ndocrinology and

N094 PhD Study Program "Endocrinology and Metabolism"

ENDOCRINOLOGY AND METABOLISM Thesis Program of the PhD Curriculum N094

Doctor of Philosophy

Coordinator Thomas M. Stulnig, Associate Professor, Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; phone: +43 1 40400 4368; fax: +43 1 40400 7790; E-mail: [email protected]

Short Description Endocrinology and metabolism are traditionally linked to each other not only in clinical settings. Due to the importance of hormones to regulate metabolism of individual cells, tissues and whole organisms, regulatory mechanisms in metabolism and endocrine axes often follow common mechanisms. Following the elucidation of endocrine regulatory mechanisms and principal metabolic pathways in the midst of the 20th century, recent developments in methods of molecular biology and in vivo investigations have now paved the way for further significant progress in the field of endocrinology and metabolism. Beginning with the molecular identification of transcription factors for genes implicated in metabolic and endocrine regulations up to in vivo NMR spectroscopy for analysis of metabolic regulation in humans these novel methods will facilitate essential contributions for the elucidation of endocrine and metabolic regulations and will enable the development of novel therapeutic approaches. A prerequisite for this progress to occur is the availability of trained researchers.

It is the aim of the PhD program "Endocrinology and Metabolism" to train students for the modern and comprehensive scientific activities in the field of endocrinology and metabolism in its broadest sense. Principles of endocrinology and metabolism are not only scientifically and clinically present in the specialty of internal medicine, but also in gynecology, pediatrics, surgery and nutritional medicine. The university lecturers that work in diverse areas from basic sciences up to clinical disciplines provide opportunities for scientific research in various aspects of the field of endocrinology and metabolism. Thematically, the program comprises theses in basic sciences, diagnostics up to novel therapeutic approaches. Methodologically, the spectrum comprises a broad spectrum of biochemistry and molecular biology up to in vivo investigations and clinical trials.

In the framework of this doctoral study, the student will scientifically work in a well-defined segment of the theme under supervision of an experienced principal investigator. Aim of the scientific work is the compilation of a doctoral thesis. In addition, the student will have the possibilities to gain basic knowledge in endocrinology and metabolism in its broadest sense and in various methods for its investigation, e.g. in the basic seminars. Own scientific works will be accompanied by

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mailto:[email protected]


critical discussion of scientific results from other groups in journal clubs. Current research projects of involved groups will be discussed in progress reports within thesis seminars. These instruments will put own scientific work put into the context of other scientific achievements to promote strategic planning of experimental work and formulation of hypothesis and results. Furthermore, progress reports advance the presentation skills and critical evaluation of own results.

The Medical University of Vienna has established a research focus concentrating scientific ressources on various aspects of metabolism including efforts on the investigation of type 2 diabetes mellitus and the metabolic syndrome, diabetic complications, high-field NMR spectroscopy of metabolic intermediates, molecular mechanisms of metabolic regulation, interference of metabolism with immunological and inflammatory mechanisms, inherited metabolic disorders, and (neuro)endocrine regulation. The PhD program "Endocrinology and Metabolism" strengthens these efforts and provides a unique opportunity for students promote their graduation while interacting with a critical mass of expert principal investigators.

The participating university teachers belong to three groups according to their roles in the PhD Program “Endocrinology and Metabolism”: 1. “Supervisors” (S) possess remarkable scientific output and are experienced

professionally and in training doctoral students. They give lectures and supervise students in their thesis projects.

2. “Young supervisors” (YS) comprise particularly ambitious principal investigators who are on the way but have not yet achieved a ”venia docendi” (“Habilitation”). Young supervisors are supported by experienced supervisors. Students guided by young supervisors meet more often with the thesis committee, i.e. every 6 months, instead of the usual yearly meetings to guarantee the highest level of education. Young supervisors contribute to the courses as do other teachers and students benefit by obtaining insight into more technical details.

3. “Lecturers” (L) comprise teachers who currently do not fulfill all criteria or abstain from supervising students but have considerable knowledge and experience in a given area. Lecturers contribute to the courses often by presenting a particularly practical approach.

Last but not least it is emphasized that the current version of the program with its contributing principal investigators and lecturers is regarded as a preliminary nucleus. The program is designed to integrate more teachers and institutions in order to cover the field of endocrinology and metabolism and related disciplines in all theoretical and practical aspects.

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Recommended Literature • The Metabolic and Molecular Bases of Inherited Disease / Charles R. Scriver

(Editor), William S. Sly (Editor), Barton Childs, Arthur L. Beaudet, David Valle, Kenneth W. Kinzler, Bert Vogelstein; McGraw-Hill Professional; 8th edition (2000) - 4 volume set, 6338 pages.

• Williams Textbook of Endocrinology / P. Reed Larsen et al.; Saunders, Philadelphia, Pa. [u.a.], 10th ed., 2003. - XXIII, 1927 pages.

• Textbook of Endocrine Physiology / ed. by James E. Griffin.; Oxford Univ. Press , Oxford, 4th ed., 2000. - X, 479 pages.

• Neuroendocrinology in Physiology and Medicine / ed. P.Michael Conn, Marc E. Freeman; Humana Press, Totowa, NJ, 2000.

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Courses

Propedeutics The propedeutics will be an obligatory part of the PhD Program. Six semester hours (SHrs) have to be completed with emphasis on natural science and medical courses for graduates from medical and non-medical studies, respectively. Please follow general regulations for the PhD Program as posted.

Basic Seminar The Basic Seminar is held in winter semsters only (2 semester hours) comprising two different sets of themes (I and II). In total 4 SHrs must be completed for the thesis program. The Basic Seminar will provide a broad overview of the field of Endocrinology and Metabolism including nutritional aspects. VO Basic Seminar "Endocrinology and Metabolism [I/II]"; 2 SHrs (compulsory course); English; personal registration by email to Prof. Th. Stulnig ([email protected])

Sabina Baumgartner-Parzer, Christian Bieglmayer, Martin Bischof, Olaf Bodamer, Wilfred Druml, Manuela Födinger, Clemens Fürnsinn, Gabriele Häusler, Jörg Michael Hiesmayr, Alexandra Kautzky-Willer, Michael Krebs, Bernhard Ludvik, Anton Luger, Wolfgang Marktl, Bruno Niederle, Peter Pietschmann, Gerhard Prager, Erich Roth, Thomas Stulnig, Walter Tschugguel, Nicole Unger-Manhart, Heinrich Vierhapper, Ludwig Wagner, Kurt Widhalm

BASIC SEMINAR I

Title Teacher Congenital adrenal hyperplasia S. Baumgartner-Parzer Modern methods of clinical laboratory analysis C. Bieglmayer In vivo studies on hepatic glycogen metabolism M. Bischof Stable isotope techniques-basics and applications O. Bodamer Clinical Nutrition and Infusion Therapy 1 W. Druml Molecular methods in research and diagnostics of

metabolic diseases 1 M. Födinger

Basics for working with experimental animals C. Fürnsinn Physiology and pathophysiology of growth G. Häusler

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Epidemiology of malnutrition M. Hiesmayr Gestational diabetes A. Kautzky-Willer Insulin resistance M. Krebs Obesity B. Ludvik Physiology of the hypothalamic-pituitary regulation A. Luger Physiology of nutrition and pathophysiology of

macronutrients W. Marktl

Endocrine surgery 1 B. Niederle Bone biology P. Pietschmann Bariatric surgery 1 G. Prager Protein catabolism, post-aggression phase,

immunonutrition 1 E. Roth

Lipid metabolism and hyperlipidemia Th. Stulnig Pathophysiology of estrogen-dependent diseases W. Tschugguel D-A-CH Reference values for food intake N. Unger-Manhart Adrenal glands H. Vierhapper Genes relevant in endocrine tumorigenesis L. Wagner Familial hypercholesterolemia in childhood and

adolescence K. Widhalm

BASIC SEMINAR II

Title Teacher Multiple Endocrine Neoplasia 2 S. Baumgartner-Parzer Interpretation of endocrinological lab results C. Bieglmayer Hypoglycemia counterregulation in type 1 diabetes M. Bischof Analytical techniques for quantification of small

molecules O. Bodamer

Clinical Nutrition and Infusion Therapy 2 W. Druml Molecular methods in research and diagnostics of

metabolic diseases 2 M. Födinger

From cell culture to the whole organism: experimental approaches

C. Fürnsinn

Basic scientific aspects of growth G. Häusler Stresshyperglycemia, nutritive intervention in

hospitalized patients M. Hiesmayr

Pregnancy in patients with type 1 and type 2 diabetes mellitus

A. Kautzky-Willer

Direct and indirect effects of nutrients on glucose metabolism

M. Krebs

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Metabolic syndrome B. Ludvik New developments in the regulation of appetite and

body weight A. Luger

Physiology of nutrition and pathophysiology of vitamins and trace elements

W. Marktl

Endocrine surgery 2 B. Niederle Bariatric surgery 2 G. Prager Pathogenesis and treatment of osteoporosis P. Pietschmann Protein catabolism, post-aggression phase,

immunonutrition 2 E. Roth

Dyslipidemias and polyunsaturated fatty acids Th. Stulnig Pathophysiology of endometriosis W. Tschugguel Polyphenols: anitoxidants and signalling molecules? N. Unger-Manhart Thyroid gland H. Vierhapper The beta cell and insulin transcription L. Wagner Principles and evidence for a preventive nutrition K. Widhalm

Journal Club The Journal Clubs (critical paper reviews) are held on a weekly basis by the program’s teachers. Currently, a single Journal Club is established each term. In total 12 SHrs must be completed for the thesis program. Title Lecturer(s) SE Journal Club "Endocrinology and Metabolism [Semester]"; 2 SHrs (compulsory course); English; personal registration by email to Prof. Th. Stulnig ([email protected]) Contents: presentation and critical discusssion of published papers

Sabina Baumgartner-Parzer, Christian Bieglmayer, Martin Bischof, Olaf Bodamer, Wilfred Druml, Manuela Födinger, Clemens Fürnsinn, Gabriele Häusler, Jörg Michael Hiesmayr, Alexandra Kautzky-Willer, Michael Krebs, Bernhard Ludvik, Anton Luger, Wolfgang Marktl, Bruno Niederle, Peter Pietschmann, Gerhard Prager, Erich Roth, Thomas Stulnig, Walter Tschugguel, Nicole Unger-Manhart, Ludwig Wagner, Kurt Widhalm

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Compulsory Optional Courses

According to the curriculum, each student must attend a total of 8 SHrs of Thesis Seminars. More elective courses are to be announced in the future. Please see the current index of courses of the Medical University of Vienna for details Title Lecturer(s) SE Thesis Seminar "Endocrinology and Metabolism [Semester]" 2 SHrs; English; personal registration by email to Prof. T. Stulnig ([email protected]) Contents: presentation and critical discussion of thesis projects

Sabina Baumgartner-Parzer, Christian Bieglmayer, Martin Bischof, Olaf Bodamer, Wilfred Druml, Manuela Födinger, Clemens Fürnsinn, Gabriele Häusler, Jörg Michael Hiesmayr, Alexandra Kautzky-Willer, Michael Krebs, Bernhard Ludvik, Anton Luger, Wolfgang Marktl, Bruno Niederle, Peter Pietschmann, Gerhard Prager, Erich Roth, Thomas Stulnig, Walter Tschugguel, Nicole Unger-Manhart, Ludwig Wagner, Kurt Widhalm

Elective Courses Please see the current index of courses of the Medical University of Vienna for details on elective courses for doctoral study programs.

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Experimental Techniques

Methods Working groups

in vitro methods apoptosis / proliferation assays Baumgartner-Parzer, Unger-Manhart,

Roth bone histomorphometry Pietschmann cell culture, cell lines Stulnig, Luger, Wagner, Bodamer,

Unger-Manhart cell culture, perfusion model Luger cell culture, primary Stulnig, Baumgartner-Parzer,

Pietschmann, Luger, Wagner, Bodamer, Häusler

enzymatics Bodamer FACS - dynamic measurements (calcium

etc.) Stulnig

FACS - immunofluorescence Stulnig, Baumgartner-Parzer, Pietschmann, Wagner, Unger-Manhart

fatty acid analysis (GC) Stulnig fluorescence microscopy Stulnig, Wagner gas chromatography Stulnig, Bodamer gene expression profiling (microarrays) Stulnig, Födinger HPLC, FPLC and other chromatographic

analyses Wagner, Bodamer, Roth

immunohistochemistry Baumgartner-Parzer, Häusler immunoassays (ELISA, FIA, RIA etc.) Pietschmann, Bodamer immunoblotting Stulnig, Baumgartner-Parzer, Fürnsinn,

Krebs, Häusler immunoprecipitation Stulnig, Wagner isolated muscle incubation Fürnsinn lipoprotein ultracentrifugation Stulnig magnetic cell sorting Stulnig mass spektrometry Bodamer metabolic labeling Stulnig, Wagner metabolic rates with radioactive tracers Fürnsinn mikronukleation in lymphocytes Bodamer

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northern blotting Stulnig, Baumgartner-Parzer, Fürnsinn, Wagner, Bodamer, Födinger

PCR, genomic Baumgartner-Parzer, Födinger PCR, on chip Bodamer PCR, real-time (quantitativ, SNP) Stulnig, Pietschmann, Wagner, Födinger,

Häusler PCR, reverse transciptase (RT-PCR) Stulnig, Pietschmann, Wagner, Födinger protein expression Wagner protein sequencing Bodamer reporter gen assay Stulnig, Baumgartner-Parzer, Wagner RFLP Baumgartner-Parzer, Födinger sequencing Baumgartner-Parzer, Födinger southern blotting Baumgartner-Parzer, Födinger spectrophotometric enzyme analyses Fürnsinn SSCP Bodamer subcellular fractionation Stulnig, Wagner tissue explants (adipose) Stulnig transfection, gene expression Stulnig, Wagner in vivo methods - animal experiments effects of antidiabetic drugs in rats Fürnsinn mouse models Stulnig, Pietschmann, Bodamer, Unger-

Manhart rat models Pietschmann stabile isotope application Bodamer in vivo methods - experiments in humans body composition measurement Widhalm epidemiology of malnutrition Hiesmayr indirect calorimetry Hiesmayr magnetic resonance spectroscopy, multi-

nuclear Roden, Bischof, Krebs, Bodamer

muscle biopsy Krebs nutritional training, assessment of nutritional

status Widhalm, Roth, Unger-Manhart, Druml,

Hiesmayr positron emission spectroscopy Bischof, Krebs

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stabile isotope technique (protein turnover, glucose turnover, gluconeogenesis, methionine-homocysteine metabolism)

Roden, Bischof, Krebs, Bodamer

tests of endocrine function Luger tests of insulin secretion and insulin sensitivity Roden, Bischof, Kautzky-Willer, Krebs

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Faculty incl. contact information and role in the program

Principal investigator E-mail Role*

Ao.Univ.Prof.DI.Dr. Sabina Baumgartner-Parzer

[email protected]

S

Ao.Univ.-Prof. Dr. Christian Bieglmayer [email protected] L

Ao.Univ.-Prof. Dr. Martin Bischof [email protected] S

Ao.Univ.-Prof. Dr. Olaf Bodamer [email protected] S

Ao. Univ.-Prof. Dr. Wilfred Druml [email protected] L

Ao. Univ.-Prof. Dr. Manuela Födinger [email protected] YS

Ao. Univ.-Prof. Dr. Clemens Fürnsinn [email protected] S

Ao. Univ.-Prof. Dr. Gabriele Häusler [email protected] L

Ao. Univ.-Prof. Dr. Michael Hiesmayr [email protected] L

Ao. Univ.-Prof. Dr. Alexandra Kautzky-Willer

[email protected]

S

Ao. Univ.-Prof. Dr. Michael Krebs [email protected] S

Ao.Univ.-Prof. Dr. Bernhard Ludvik [email protected] S

Ao.Univ.Prof. Dr. Anton Luger [email protected] S

Ao.Univ.-Prof. Dr. Wolfgang Marktl [email protected] L

Ao.Univ.-Prof. Dr. Bruno Niederle [email protected] S

Ao. Univ.Prof. Dr. Peter Pietschmann [email protected] S

Univ.-Doz. Dr. Gerhard Prager [email protected] S

Prim. ao.Univ.-Prof. Dr. Michael Roden [email protected] S

ao.Univ.-Prof. DI. Dr. Erich Roth [email protected] S

Ao.Univ. Prof. Dr. Thomas Stulnig [email protected] S

Ao.Univ.Prof. Dr. Walter Tschugguel [email protected] S

Univ.-Doz. Mag. Dr. Nicole Unger-Manhart

[email protected] L

Ao.Univ.Prof. Dr. Heinrich Vierhapper [email protected] L

Ao.Univ.Prof. Dr. Ludwig Wagner [email protected] S

Univ. Prof. Dr. Kurt Widhalm [email protected] S

* currently assigned roles: S, supervisor; YS, young supervisor; L, lecturer. page 11 of 186


Description of thesis projects and CVs of supervisors & lecturers:

Sabina BAUMGARTNER-PARZER.......................................................................... 13

Christian BIEGLMAYER ........................................................................................... 20

Martin BISCHOF....................................................................................................... 22

Olaf A. BODAMER ................................................................................................... 27

Wilfred DRUML......................................................................................................... 36

Manuela FÖDINGER................................................................................................ 38

Clemens FÜRNSINN................................................................................................ 47

Gabriele HÄUSLER .................................................................................................. 55

Michael J. HIESMAYR.............................................................................................. 59

Alexandra KAUTZKY-WILLER ................................................................................. 63

Michael KREBS ........................................................................................................ 69

Bernhard LUDVIK..................................................................................................... 77

Anton LUGER........................................................................................................... 86

Wolfgang MARKTL................................................................................................... 96

Bruno NIEDERLE ..................................................................................................... 98

Peter PIETSCHMANN............................................................................................ 115

Gerhard PRAGER .................................................................................................. 125

Michael RODEN ..................................................................................................... 131

Erich ROTH ............................................................................................................ 141

Thomas M. STULNIG ............................................................................................. 150

Walter TSCHUGGUEL ........................................................................................... 158

Nicole UNGER-MANHART..................................................................................... 164

Heinrich VIERHAPPER .......................................................................................... 169

Ludwig WAGNER ................................................................................................... 170

Kurt M. WIDHALM .................................................................................................. 178

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Sabina BAUMGARTNER-PARZER Department of Internal Medicine III, Clin. Div. Endocrinology and Metabolism [email protected] Diabetes associated micro- and macrovascular dysfunction. Analysis of cellular and molecular mechanisms. Abstract Long standing diabetes is characterized by diabetic microangiopathy (diabetic retinopathy and nephropathy) and by premature atherosclerosis. The latter represents the major cause of morbidity and mortality in patients with diabetes mellitus, whereas diabetic retinopathy is the leading cause for blindness in Europe. Recent data suggest that loss of retinal endothelial cells and pericytes due to apoptosis results in acellular capillaries and ischemia, providing the basis for the progression of diabetic retinopathy to the proliferative form of this disease. Accelerated apoptosis of endothelial cells and vascular smooth muscle cells in atherosclerotic regions is assumed to result in plaque erosion and plaque rupture and thus to favor atherothrombosis. It was only recently that bone marrow derived endothelial progenitor cells (EPCs) have been found to contribute to vascular repair and angiogenesis. In diabetic patients, however, numbers of EPCs circulating in the blood are reduced when compared to healthy control subjects. Such reduction of EPCs may contribute to diabetes associated endothelial dysfunction and to the clinical manifestation of atherosclerosis and cardiovascular disease. Therefore, it is of importance to evaluate the hypothesis that diabetes associated metabolic abnormalities (hyperglycemia, dyslipidemia and chronic elevation of free (non-esterified) fatty acids (FFA), elevated levels of proinflammatory cytokines and adhesion molecules) cause depletion of EPCs in diabetic patients. We have previously shown that vasoprotective factors (antioxidants, leptin) prevent, whereas atherosclerotic risk factors (oxidized/glycated LDL, hyperglycemia, proinflammatory cytokines, elevated free fatty acids) trigger apoptosis in cultured vascular cells, depending on stimulus and cell type. Using inhibitors of caspases, of protein kinases and of transcription factors, we could identify the respective target molecules and signal transduction pathways. Due to our extensive experience in this field of research, in future studies we want to test the hypothesis that function (apoptosis, proliferation and secretory profile) of human endothelial progenitor cells is directly affected by diabetes associated metabolic factors. It will be evaluated, whether EPCs functional alterations can be modulated by vasoprotective agents and the respective target molecules and signaling pathways will be characterized. Thesis Subjects Modulation of human endothelial progenitor cell function by metabolic factors. Techniques and infrastructure Isolation and culture of primary cultures of human vascular cells and of endothelial progenitor cells, apoptosis and proliferation assays, FACS analysis, Western and Northern blots, immunocytochemistry, transfection experiments.

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Curriculum Vitae Sabina M. Baumgartner-Parzer Address: Department of Medicine III, Division of Endocrinology & Metabolism, Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4368; Fax +43 1 404007790; Email [email protected] Personal Data Date of Birth: 5.11.1962 Place of Birth: Bad Ischl, Austria Nationality Austria Education 1985-1989 Doctoral thesis 1981-1985 Study of biotechnology 1973-1981 Secondary school: Gymnasium der Kreuzschwestern

Gmunden-Orth Career History 1998-present Associate Professor of Biochemistry at the

Department of Internal Medicine III, Div. Endocrinology & Metabolism, Medical University of Vienna Head of the working groups of vascular biology and of molecular genetics of hereditary endocrine diseases

11/1997 Habilitation at the University of Vienna 1990-1997 Post-Doc at the Research Laboratories of Department

of Medicine III, Division of Endocrinology & Metabolism, Medical University of Vienna (former Division of Endocrinology & Diabetes Mellitus, 1st Medical Department, University of Vienna)

1993 and 1994

2 months Visiting Fellow at the Havard Medical School, Boston

1989 Promotion (Dr. rer.nat.techn) 1985-1989 Thesis at the 1.Dept. of Medicine (Prof. Mannhalter /

Prof. Deutsch), University of Vienna 1985

Graduation (Dipl.-Ing) at the University of Bodenkultur

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Career-related Activities 2003 -present Editorial board of the journal Metabolic Syndrome and

Related Disorders 1998-2003 Assistent Editor of the journal Diabetologia 1996 Organization of the EASD Satellite Symposium:"Role

of adhesion molecules in Diabetes Mellitus" Awards

2005 Poster-Prize - Austrian Society of Endocrinology&Metabolism

1997 Science award of Upper Austria 1985 Dr. Karl Schleinzer-Award (University of Bodenkultur) 1984/85 Award for gifted students Memberships Austrian Diabetes Association (ÖDG), Austrian Association for Endocrinology and Metabolism (ÖGES), European Association for the Study of Diabetes (EASD) Gesellschaft für gute Labor und Analysenpraxis (GALP) Sources of funding since 2000 Period

Organization

Role

Title

kE

2005-2006 Eurasia Pacific Network (Grant to Erdenekhuu Nansalma)

Supervisor Vascular dysfunction in diabetes

10

2005-2007 FWF(Charlotte-Bühler-Program to coworker)

Supervisor Nutritional free fatty acids and diabetic vascular dysfunction. Analysis of cellular and molecular mechanisms and interactions.

80

2004-2005 Jubiläumsfonds der Österr. Nationalbank

Co-investigator

Freie Fettsäuren und Diabetes assoziierte Gefäßerkrankungen

60

1997-1999

Jubiläumsfonds der Österr. Nationalbank

Principal investigator

Bedeutung von LDL-Glykierungsprodukten bei der Entstehung von Gefäß-komplikationen im Rahmen

20

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des Diabetes Mellitus 1997-1999 FWF


Hyperglykämie und Apoptose

1993-1995 Herzfelder’sche Familienstiftung


Einfluß von Glukose auf ET-1 und EDRF Produktion in kultivierten humanen Endothelzellen verschiedener Stromgebiete

Supervision of doctoral and diploma students (since 2000) Diploma students: Andrea Lindenmayer, Kathrin Malits, Ursula Schauer, Magdalena Reithner PhD students: Name Title of thesis Period

(expected)

Acadaemic title

Karin Tobler Function of endothelial progenitor cells in gestational diabetes

2005-(2008)

(PhD)

Michaela Artwohl

Heterogeneous regulation by hyperglycemic / hyperlipidemic states as well as by an adjuvans in colon cancer therapy (levamisole) of apoptosis, proliferation and associated gene/protein expression in vascular endothelial cells.

1997-2000

Dr. rer. nat.techn

Teaching - Biochemische, molekularbiologische Arbeitsmethoden in der Endokrinologie (für Wahlfachausbildung gemäß §13 Studiengesetz Medizin, für Diplomanden und Dissertanten. - Experimentelle Arbeiten in Endokrinologie und Stoffwechsel (für Wahlfachausbildung gemäß §13 Studiengesetz Medizin, für Diplomanden und Dissertanten). - Molekulare Endokrinologie, gemeinsam mit H Cross (Pathophysiologie) - Eukaryonten - Biogenese von Zellorganellen (Wahlfachvorlesung gem. mit Prof. Glößl) - Externer Lehrauftrag an der Univ. f. Bodenkultur - Biochemische, molekularbiologische Aspekte der Endokrinologie (Dozentenvorlesung) - Ringvorlesung - ICP (Interdiscinplinary Cooperation Project of Molecular Medicine) – im SS 1999 Publications 44 peer reviewed publications and 3 reviews in scientific journals, 8 invited lectures

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Peer reviewed manuscripts since 2000 (original research and reviews) First, last or corresponding author manuscripts: M Artwohl, T Hölzenbein, L Wagner, A Freudenthaler, W Waldhäusl, SM

Baumgartner-Parzer. Levamisole induced apoptosis in cultured vascular endothelial cells. Brit J Pharmacol 131:1577-1583, 2000

SM Baumgartner-Parzer, E Schulze, S Pauschenwein, S Rondot, P Nowotny, W Waldhäusl, H Vierhapper: Mutational spectrum of the steroid 21-hydroxylase gene in Austria – Identification of a novel missense mutation. J Clin Endocrinol Metabol 86:4771-4775, 2001

SM Baumgartner-Parzer, WK Waldhäusl. The endothelium as a metabolic and endocrine organ: its relation with insulin resistance. Exp Clin Endocrinol Diabetes 109 Suppl: 166-179, 2001

SM Baumgartner-Parzer, S Pauschenwein, W Waldhäusl, K Pölzler, P Nowotny, H Vierhapper. Increased prevalence of heterozygous 21-OH germ line mutations in patients with adrenal incidentalomas. Clin Endocrinol 56, 811-816, 2002

M Artwohl, M Roden, T Hölzenbein, A Freudenthaler, W Waldhäusl, SM Baumgartner-Parzer. Modulation by leptin of proliferation and apoptosis in vascular endothelial cells. Int J Obesity 26:577-580, 2002

SM Baumgartner-Parzer, P Nowotny, W Waldhäusl, H Vierhapper. A rare duplicated 21-OH haplotype and a de novo mutation – a family analysis. J Clin Endocrinol Metabol 88: 2794-2796, 2003

M Artwohl, WF Graier, M Roden, M Bischof, A Freudenthaler, W Waldhäusl, SM Baumgartner-Parzer. Diabetic low-density lipoprotein triggers apoptosis in vasular endothelial cells. Diabetes 52:1240-1247, 2003

M Artwohl, M Roden, W Waldhäusl, A Freudenthaler, SM Baumgartner-Parzer. Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J 18: 146-148, 2004

H Vierhapper, C Bieglmayer, G Heinze, SM Baumgartner-Parzer. Frequency of RET-protooncogene mutations in patients with normal and with moderately elevated (50-100 pg/ml) pentagastrin-stimulated serum concentrations of calcitonin. Thyroid 14:580-583, 2004

SM Baumgartner- Parzer, P Nowotny, W Waldhäusl, H Vierhapper. Carrier frequency of Congenital Adrenal Hyperplasia (21-OH-deficiency) in a Middle European population. J Clin Endocrinol Metab 90: 775-778, 2004

M Artwohl, C Fürnsinn, W.Waldhäusl, T Hölzenbein, G Rainer, M Roden, A Freudenthaler, SM Baumgartner-Parzer. Thiazolidinediones inhibit proliferation of micro- and macrovascular cells. Evidence for a PPARγ-independent mitochondrial mechanism. Diabetologia, 48:586-594, 2005


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M Artwohl, T Hölzenbein, C Fürnsinn, A Freudenthaler, N Huttery, W. Waldhäusl and SM Baumgartner-Parzer. Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells. Thromb Haemost 93:810-815, 2005

SM Baumgartner-Parzer, R Lang, G Heinze, B Niederle, K Kaserer, W Waldhäusl and H Vierhapper. Polymorphisms in exon 13 and intron 14 of the RET-protooncogene: Genetic modifiers of medullary thyroid carcinoma? J Clin Endocrinol Metab 90: 6232-6236, 2005

H Vierhapper, L Wagner, S Hanslik, B Niederle, S Rondot, E Schulze, C Bieglmayer, K Kaserer and S Baumgartner-Parzer. Primary hyperparathyroidism in a patient with a seemingly homozygous Y719F RET mutation. Thyroid 15: 1303-1308, 2005

H Vierhapper, B Niederle, C Bieglmayer, K Kaserer and S Baumgartner-Parzer. Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders. Thyroid 15: 1267-1272, 2005

SM Baumgartner-Parzer, G Fischer, H Vierhapper. Predisposition for de novo gene aberrations in the offspring of mothers with a duplicated CYP21A2 gene. J Clin Endocrinol Metab 90:1164-1167, 2007

M Artwohl, K Muth, Kosulin K, R de Martin, T Hölzenbein, G Rainer, A Freudenthaler, N Huttary, L Schmetterer, WK Waldhäusl, SM Baumgartner-Parzer. R(+)-alpha-lipoic acid inhibits endothelial apoptosis and proliferation – involvement of Akt and Retinoblastoma protein / E2F. Am J Physiol Endocrinol Metab Jun 2007 (epub ahead of print)

Co-author manuscripts: H Frisch, T Battelino, E Schober, SM Baumgartner-Parzer, P Nowotny, H Vierhapper.

Salt wasting in simple virilizing congenital adrenal hyperplasia. J Pediatr Endocrinol Metab 14:1649-1655, 2001

AP Szremska, R Stoxreither, L Kenner, M Artwohl, HC Theussl, SM Baumgartner-Parzer, E. Passegue, EF Wagner, V. Sexl. Jun B inhibits proliferation and transformation in B lymphoid cells. Blood 102:4159-4165, 2003

W Gartner, T Daneva, I Mineva, SM Baumgartner-Parzer, H Vierhapper, M Weissel, B Niederle, L Wagner. Identification of a novel SNP within intron 19 of the RET gene by comparative RFLP analysis of benign and neoplastic endocrine tissue. ncbi.nlm.nih GenBank Accession AY615726; 2004

W Gartner, T Daneva, I Mineva, S Baumgartner-Parzer, B Niederle, H Vierhapper, M Weissel, L Wagner. A new identified RET proto-oncogene polymorphism is found in a high number of endocrine tumor patients. Human Genetics 117:143-153,


2005 D Stoiber, B Kovacic, C Schuster, C Schellack, M Karaghiosoff, R Kreibich, E Weisz,

Artwohl M, OC Kleine, M Müller, S Baumgartner-Parzer, J Ghysdael, M Freissmuth, V Sexl. Tyk2 is a key regulator for the tumor surveillance of B lymphoid tumors. JCI 114 (11):1650-1658, 2004

F Votava, D Török, J Kovacs, D Möslinger, SM Baumgartner-Parzer, et al. Estimation of the false negative rate in the newborn screening for congenital adrenal hyperplasia. Eur J Endocrinol 152:869-874, 2005

V Dolzan, J Solyom, G Fekete, J Kovacs, V Rakosnikova, F Votava, J Lebl, Z Pribilincova, S Baumgartner-Parzer, S Riedl, F Waldhauser, H Frisch, M Stopar-Obreza, C Krzisnik, T Battelino. Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia. Eur J Endocrinol 153:99-106, 2005

K Namiranian, F Mittermayer, M Artwohl, J Pleiner, G Schaller, BX Mayer, M Bayerle-Eder, M Roden, SM Baumgartner-Parzer, M Wolzt. Free fatty acids do not acutely increase asymmetrical dimmethylarginine concentrations. Horm Metabol Res 37: 768-772

DG Haider, F Mittermayer, G Schaller, M Artwohl, SM Baumgartner-Parzer, G Prager, M Roden, M Wolzt. Free fatty acids normalize a rosiglitazone-induced vasfatin release. Am J Physiol Endocrinol Metab 291:E885-890, 2006

Invited Talks: Hyperglycemia and endothelial cells. XIII. International Donausymposium on

Diabetes mellitus. Vienna 5.-7.10.1995 Apoptose - der programmierte Zelltod. Österr. Biochemische Ges, Biochemisches

Institut, Universität Graz, 29.6.1996 Role and mechanisms of apoptosis in endothelial cells: Zellkultur-Workshop -

European Tissue Culture Society, Wien 21/02/1997 Effect of tri-iodothyronine on cultured endothelial cells. The Vascular System in

Thyroid Disease. Heidelberg 6.10.1999 Hyperglycemia and endothelial dysfunktion. Donau-Symposium, Zürich 16.10.1999 Molekulargenetische Diagnostik des AGS. Jahrestagung der Österr. Gesellschaft für

Endokrinologie und Stoffwechsel. St. Wolfgang, 19.-21. April 2001 Molekularbiologische Diagnostik bei Nebennierentumoren. Jahrestagung der Österr.

Gesellschaft für Endokrinologie und Stoffwechsel. St. Wolfgang, 25.-27.April 2002Mechanismen des endothelialen Re-Modeling durch metabolische Faktoren.

Potsdamer Expertengespräche – Diabetes. Berlin 26.02.2005

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Christian BIEGLMAYER Clinical Institute for Medical and Chemical Laboratory Diagnostics [email protected] Curriculum Vitae Personal data: Born 09/15/1947, living in Vienna, married, one son. Education: 1965-1974: Study of chemistry at the University of Vienna. Thesis: “Function of the glyoxysomal membrane in the metabolism of growing fat storing plants", PhD graduation and basic military service. Profession: 1972-1974: Half-day employee at the Institute of General Biochemistry, afterwards full-time university assistant. 1976-1981: Hormone-Laboratory of the 1st Dept. Obstetrics and Gynaecology (General Hospital of Vienna). 1981-1991: Entrusted with the organisation and direction of the Endocrine Laboratory of the 2nd Dept. Obstetrics and Gynaecology. 1987 "Venia docendi for Biochemistry". 1988 assistant professor and since 1990 tit.a.o. Univ. Prof. 1991 till now: manager of the domain “Endocrinology” at the Clinical Institute for Medical and Chemical Laboratory Diagnostics (KIMCL) Consultant of WHO in Pyongyang, North-Korea in 1988. ÖQUASTA ring-trial leader for quality assurance of “Fertility Hormones”. Award: "Theodor Körner Award" for "Secretion of gonadotropins by pituitary cell culture" in 1978. Membership: Austrian Biochemical Society (member of the board from 1986 to 1988), Austrian Society for Clinical Chemistry, Austrian Society for Endocrinology and Metabolism (founder-member and member of the board since 1995) and New York Academy of Science. Grants: "Fonds zur Förderung der wissenschaftlichen Forschung" (1989: "Eicosanoids in menstrual blood"), "Bürgermeisterfonds der Bundeshauptstadt Wien" (1991: "Influence of cytotoxic drugs on tumor - mucin synthesis" and 1997: "Effects of 5α-reductase inhibitors on androgen metabolism in skin cells"). Scientific work: About 250 articles in scientific periodicals and books: carbohydrate metabolism in plants, steroid hormone receptors, autoimmune-reactions in pre-eclampsia, clinical and experimental endocrinology and oncology, bone marker. Lectures: “Fertility Hormones”, “Bone metabolism”, “Hormones of the adrenal gland”, “Hormones, function tests and tumor markers in gynecology”. “Modern methods of hormone analysis”, “Interpretation of hormone reports”. Outside lectures: “Principles

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of radiation protection and work with radioisotopes in medical laboratories”, “Biotechnology in diagnostic laboratories”. Guidance of 35 students during their diploma work or thesis and final examinations. Guidance of MD’s during their special training in laboratory medicine.

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Martin BISCHOF Dept. Internal Medicine III, Clin Div. Endocrinology and Metabolism [email protected] Effect of Continuous Subcutaneous Glucose Monitoring and Insulin Infusion on the Incidence of Hypoglycemia in Type 1 Diabetic Patients Abstract Hypoglycemia is a frequent complication in long-term type 1 diabetes, especially in patients with low HbA1c-levels. On average, one type 1 diabetic patient attempting to maintain near-normoglycaemia suffers two episodes of symptomatic hypoglycemia per week and one episode of severe, at least temporarily disabling, hypoglycemia approximately once a year. Long-term type 1 diabetic patients often develop hypoglycemia unawareness leading to a greater risk of severe hypoglycemia since symptom recognition and accurate detection of extreme blood glucose values are crucial for management of type 1 diabetes. With subcutaneous glucose sensors continuous blood glucose monitoring is possible. Even with older systems where glucose levels are not visible for the patient, the increased amount of blood glucose measurements allowed the physician to optimize insulin therapy resulting in reduced incidence of hypoglycemia. Only recently an improved system for continuous blood glucose measurements became available. Glucose levels are visible for the patient and alarm limits can be set. A randomized study demonstrated that this system reduces the duration of hypoglycemic episodes by 45%. The latest innovation in hypoglycemia therapy is the combination of continuous insulin supply with continuous blood glucose monitoring. This concept was implemented by the Paradigm Real Time - System which recently became available in Europe. The long-term effects of this therapeutic option on the incidence of hypoglycemia and the quality of life in type 1 diabetic patients has not yet been studied. Thesis Subjects This study plans to evaluate the hypothesis is that a combination of optimal insulin therapy by CSII combined with continuous blood glucose monitoring reduces hypoglycemia frequency and duration in type 1 diabetic patients with frequent hypoglycemia under functional insulin therapy. Furthermore we hypothesize that this therapy will improve quality of life and reduce the fear of hypoglycemia. Techniques and infrastructure Continous subcutaneous insulin infusion, Continous glucose monitoring systems

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Curriculum Vitae

Martin BISCHOF, MD Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 7257 Fax +43 1 40400 7257 email [email protected] Personal Data Date of Birth: 01.04.1969 Place of Birth: Vienna, Austria Nationality Austria Education 2003 Certification Internal Medicine 1987 – 1996 studies of Human Medicine 1979 – 1987 secondary school Career History 2005-present Clinical responsibility for the Metabolic Research Unit 2004 – present Associate Professor of Medicine at the Medical

University of Vienna Attending Physician at the Div. of Endocrinology & Metabolism

2004 “venia docendi” for Internal Medicine 1998 – 2004 Clinical training and lecturer at the Division of

Endocrinology & Metabolism, Medical University of Vienna

1996-1998 Postdoctoral fellow Department of General and Experimental Pathology, University of Vienna Medical School

1996 Fellowship Brown University, Rhode Island, USA 1992-1995 Scientific coworker of the group „Tumorpathology“

Department of General and Experimental Pathology, University of Vienna Medical School

Career-related Activities 2005-present Management Training for Medical Leaders at the

University of Krems

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Awards 2002 Aventis-Preis, University of Vienna Medical Faculty 1996 Legacy Hirtl-Buss, University of Vienna Medical

Faculty (research grant) Memberships Austrian Diabetes Society European Society for the Study of Diabetes Austrian Society for Endocrinology and Metabolism Austrian Society for Internal Medicine Sources of funding (since 2000)

Period Organization Short Title K€/yr 2005 – 2007

FWF (F17980-B11) Brain metabolism during hypoglycemia in type 1 DM

70

2004 – 2006

Austrian National Bank Project #10892

Glucose metabolism in GSD 1 26

Supervision of doctoral students (since 2000)

Name Title of thesis Period (expected) Acad.Title

Martina Mandl Measurement of unidirectional fluxes to ATP in human occipital lobe using 31PMR saturation transfer

2005 – 2008 PhD

Publications 27 peer reviewed publications in scientific journals Peer reviewed manuscripts since 2000 (original research and reviews) First, last or corresponding author manuscripts: Bischof-M, Ludwig-C, Hofer-A, Kletter-K, Krebs-M, Stingl-H, Nowotny-P, Waldhäusl-W, Roden-M. Hormonal and Metabolic Counterregulation During and After High-Dose Insulin-Induced Hypoglycemia in Diabetes Mellitus Type 2. Hormone and Metabolic Research (2000) 32:417-423 Bischof-MG, Bernroider-E, Ludwig-C, Kurzemann-S, Kletter-K, Waldhäusl-W, Roden-M. Effect of Near Physiologic Insulin Therapy on Hypoglycemia Counterregulation in Type 1 Diabetes. Hormone Research (2001) 56:151-158.

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Bischof-MG, Krssak-M, Krebs-M, Bernroider-E, Stingl-H, Waldhäusl-W, Roden-M. Effects of Short-Term Improvement of Insulin Treatment and Glycemia on Hepatic Glycogen Metabolism in Type 1 Diabetes Mellitus. Diabetes (2001) 50: 392-398 Bischof-MG, Bernroider-E, Krssak-M, Krebs-M, Stingl-H, Nowotny-P, Yu-C, Shulman-GI, Waldhäusl-W, Roden-M. Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia. Diabetes (2002) 51: 49-54 Bischof-MG, Mlynarik-V, Brehm-A, Bernroider E, Krssak-M, Bauer-E, Madl-C, Waldhäusl W, Roden-M. Brain Energy Metabolism During Hypoglycemia in Healthy and Type 1 Diabetic Humans. Diabetologia (2004) 47: 648-651 Bischof-MG, Brehm-A, Bernroider-E, Krssak-M, Mlynarik-V, Krebs-M, Roden-M. Cerebral glutamate metabolism during hypoglycemia in healthy and type 1 diabetic humans. European Journal of Clinical Investigation (2006) 36:164-169 Bischof-MG, Heize-G, Vierhapper-H. Vitamin D Status in a Healthy Population and its Relation to Age and BMI. Hormone Research (2006) 66: 211-215 Gessl-A, Bischof-M. Thyroid disorders and the Kidney. Nephro-News (2006) 8: 1-12 Co-author manuscripts: Krebs-M, Stingl-H, Nowotny-P, Weghuber-D, Bischof-M, Waldhäusl-W, Roden-M. Prevention of in Vitro Lipolysis by Tetrahydrolipstatin. Clinical Chemistry (2000) 46: 950-954 Raber-W, Raffesberg-W, Bischof-M, Scheuba-C, Niederle-B, Gasic-S, Waldhäusl-W, Roden-M. Diagnostic Efficacy of Unconjugated Plasma Metanephrines for the Detection of Pheochromocytoma. Archives of Internal Medicine (2000) 160: 2957-2963 Cross-HS, Bareis-P, Hofer-H, Bischof-MG, Bajna-E, Kriwanek-S, Bonner-E, Peterlik-M. 25-Hydroxyvitamin D3-1α-Hydroxylase and Vitamin D Receptor Gene Expression in Human Colonic Mucosa is Elevated During Early Cancerogenesis. Steroids (2001) 66:287-292 Bareis-P, Bises-G, Bischof-MG, Cross-HS, Peterlik-M. 25-Hydroxy-Vitamin D Metabolism in Human Colon Cancer Cells During Tumor Progression. Biochemical Biophysical Research Communications (2001) 285: 1012-1017 Stingl-H, Krssak-M, Krebs-M, Bischof-MG, Nowotny-P, Fürnsinn-C, Shulman-GI, Waldhäusl-W, Roden-M. Lipid-Dependent Control of Hepatic Glycogen Stores in Healthy Man. Diabetologia (2001) 44: 48-54 Krebs-M, Krssak-M, Nowotny-P, Weghuber-D, Gruber-S, Mlynarik-V, Bischof-M, Stingl-H, Fürnsinn-C, Waldhäusl-W, Roden-M. Free Fatty Acids Inhibit the Glucose-Stimulated Increase of Intramuscular Glucose-6-Phosphate Concentration in Humans. Journal of Clinincal Endocrinology and Metabolism (2001) 86: 2153-2160 Bayerle-Eder-M, Fuchsjager-Mayrl-G, Sieder-A, Polska-E, Roden-M, Stulnig-T, Bischof-MG, Waldhäusl-W, Schmetterer-L, Wolzt-M. Effect of Pravastatin on Responsiveness to N-monomethyl-L-Arginine in Patients With Hypercholesterolaemia. Atherosclerosis (2002) 160: 177-184 Bareis-P, Kallay-E, Bischof-MG, Bises-G, Hofer-H, Pötzi-C, Manhardt-T, Bland-R, Cross-HS. Clonal Differences in Expression of 25-Hydroxyvitamin D3-1α-hydroxylase,

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of 25-Hydroxyvitamin D3-24-hydroxylase, and of the Vitamin D Receptor in Human Colon Carcinoma Cells: Effects of Epidermal Growth Factor and 1α,25-Dihydroxyvitamin D3. Experimental Cell Research (2002) 276:320-327 Stingl-H, Schnedl-WJ, Krssak-M, Bernroider-E, Bischof-MG, Lahousen-T, Pacini-G, Roden-M. Reduction of Hepatic Glycogen Synthesis and Breakdown in Patients with Agenesis of the Dorsal Pancreas. Journal of Clinincal Endocrinology and Metabolism (2002) 87: 4678-4685 Anderwald-C, Bernroider-E, Krssak-M, Stingl-H, Brehm-A, Bischof-MG, Nowotny-P, Roden-M, Waldhäusl-W. Effects of Insulin Treatment in Type 2 Diabetec Patients on Intracellular Lipid Content in Liver and Skeletal Muscle. Diabetes (2002) 51: 3025-3032 Artwohl-M, Graier-W, Roden-M, Bischof-M, Freudenthaler-A, Waldhäusl-W, Baumgartner-Parzer-S. Diabetic Low-densitiy Lipoprotein Triggers Apoptosis in Vascular Endothelial Cells. Diabetes (2003) 52:1240-1247 Cauza-E, Hanusch-Enserer U, Bischof M, Spak-M, Kostner-K, Dunky-A, Ferenci-P. Increased C282Y Heterozygosity in Gestational Diabetes. Fetal Diagnosis and Therapy (2005) 20:349-354 Weghuber-D, Roden-M, Franz-C, Chmelik-M, Torabia-S, Nowotny-P, Gruber-S, Waldhäusl-W, Klingler-A, Bischof-M, Widhalm-K. Insulin resistance, but not obesity determines fatty liver in obese children. Submitted for publication. Zauner-A, Nimmerrichter-P, Anderwald-C, Bischof-M, Schiefermeier-M, Ratheiser-K, Schneeweiss-B, Zauner-C. Severity of insulin resistance in critically ill medical patients. Submitted for publication.

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Olaf A. BODAMER Dept. General Paediatrics [email protected] Mechanisms of prematurity - the potential role of genetic and metabolic factors Abstract Preterm delivery is the worldwide leading cause of infant mortality and morbidity. In the United States of America between 7 and 8% of live born newborn infants have a birth weight of 2500 g. About 20% of these weigh 1500 g or less and are mostly born prematurely. The causes for premature birth and intrauterine growth retardation are closely related and are multifactorial in origin; many social, environmental, medical and genetic factors have been suggested. Genetic factors from both mother and fetus probably play a role in determining gestational length and could confer a possible genetic predisposition towards preterm birth. Since infections seem to be most prevalent among the identifiable causes of preterm birth, it is conceivable that genetic factors that predispose to infections may play an important role. A candidate genetic study focusing on genes that encode cytokines, mediators of apoptosis and host defense found associations with allelic variants in the genes for interleukin 4 and 10 (IL4, IL10), the tumor necrosis factor alpha (TNF), and the mannose-binding lectin gene (MBL2). The possible genetic context between infection, inflammation and preterm delivery is also supported by other findings, in particular for IL4 and TNF. In addition, genetic and dietary factors conferring metabolic perturbations, such as low cholesterol during early pregnancy have been associated with adverse outcome including prematurity. The objectives of our research are twofold: First to identify novel genetic and metabolic factors that are associated with prematurity and, secondly, to identify and test appropriate mouse models of prematurity with respect to novel therapeutic approaches. Thesis Subjects) Arginine:glycine amidinotransferase (AGAT) knock-out mice - a model for prematurity and perinatal asphyxia? The role of genetic factors for the pathophysiology of prematurity - prospective multi-center, multi-national study. Techniques and infrastructure Mouse model of AGAT deficiency; phenotypic characterization of mice; primary tissue cultures; enzymatic analysis; molecular analyses (PCR, dHPLC, sequencing); chip arrays; all required equipment available.

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Curriculum Vitae

Olaf BODAMER Division of Biochemical and Paediatric Genetics, Department of General Paediatrics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria Phone +43 1 40400 3210; Fax +43 1 4063484; Email [email protected] Personal Data Date of Birth: 25.03.1963 Place of Birth: Stuttgart, Germany Nationality Germany Education 2005 Specialist in Human Genetics (Medizinische Biologie) 2001 – present Specialist in Inborn Errors of Metabolism 1999 Specialist in Paediatrics 1999 American Board Certification in Medical Genetics 1997-1999 Fellowship Medical Genetics, Baylor College of

Medicine, Houston, USA 1997 Educational Commission for Foreign Medical

Graduates (ECFMG) test passed 1994 - 1997 PhD Studies at the University College London, UK 1989 – 1992

Doctoral thesis MD at the University Medical School Heidelberg and Saarland

1982 – 1989 Studies of Human Medicine at the University of Heidelberg, Germany

1974 – 1982 secondary school in Stuttgart, Germany Career History 2004 – present Director of the Austrian National Screening Program 2004 – present Director of Biochemical and Paediatric Genetics at

the Department of General Paediatrics, Medical University of Vienna.

2002 – present Associate Professor at the Department of General Paediatrics, Medical University of Vienna. Consultant at the Children’s Hospital Mödling and Prayer Children’s Hospital Vienna

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page 29 of 186

2002 “venia docendi” for Paediatrics 2001-present Elected Fellow of the American College of Medical

Genetics 1999-2001 Assistant Professor at the Department of Human and

Molecular Genetics, Baylor College of Medicine, Houston, USA

1997 – 1999

Fellow at the Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, USA

1994 – 1999

Senior Research Associate at the Institute of Child Health, London, UK

1992 – 1993

University Assistant at the Division of Paediatric Oncology and Haematology, Univ.-Children’s Hospital Erlangen, Germany

1989– 1992 Doctoral thesis at the University Medical School Heidelberg and Saarland

1989 – 1992 Assistant Children’s Hospital Ludwigshafen, Germany and different private practices

Career-related Activities 2001 – present

Director of quality management at the Division of Biochemical and Paediatric Genetics, Medical University Vienna

2003 – present Director of the interdisciplinary working group at the University Children’s Hospital Vienna

2003 – present Director of the National Metabolic Registry Awards 2005 Wissenschaftspreis Österreichische Gesellschaft für

Kinder- und Jugendheilkunde 2001 Travel award Society of Inbron Errors of Metabolism

USA 1988 Stipend of the DAAD (Deutscher Akademischer

Auslandsdienst) Memberships Deutsche Gesellschaft für Kinderheilkunde Society for the Study of Inborn Errors of Metabolism British Inherited Metabolic Group, England American Society of Human Genetics


American College of Medical Genetics Österreichische Gesellschaft für Humangenetik International Society for Neonatal Screening Sources of funding (since 2000)


Navi Mumbai Institue of Research in Mental and Neurological Handicap

Incidence of Inborn Errors of Metabolism in India

7,5

2007 – 2009

Ministry of Science Diagnostic strategies for the molecular diagnosis of Lysosomal storage disorders

67

2006 – 2010

Ministry of Health Neonatal Screening for Lysosomal storage disorders

207

2006 – 2007

Cytonet Hepatocytes and ureacycle function 16

2006 - 2007

Milupa Threonine Metabolism in individuals with phenylketonuria

18

2004 - 2009

Genzyme Morbus Fabry, Development of a novel method for neonatal screening for lysosomal

42

2004 - 2008

SHS GmbH Development of analytical techniques 46

2002 – 2004

Austrian National Bank (#9572)

Neonatal screening for disorders of steroid genesis

63


Name Title of thesis Period (expected) Acad. Title

Karin Tuschl

therapeutic effects of oral Tetrahydrobiopterin in patients with classical phenylketonuria-a stable isotope study

2001 - 2004 MD

Rene Ratschmann

Haploid Protein Expression Test 2001 - 2004 MD

Yvonne Homocysteine and Methionine 2004 - 2007 MD page 30 of 186


Sommer Metabolism using stable isotopes Karin Tuschl

Stipend Metabolicum (€ 15.000) 2004

Denise Rauter

Maternal PKU 2002 - 2003 Mag.

Manuela Hiess

Epigenetics and Methylation 2004 – 2006 MD

Dimitri Saliabis

Tandem MS Screening 2005 - 2007 MD

Julia Vodopiutz

CDGIK – a novel disorder of glykosylation

2005 - PhD

Furhan Iqbal

AGAT Mousemodel 2006 - PhD

Ana Kiš Genetics of prematurity 2007 - PhD

Publications 61 and 10 peer reviewed publications and reviews, resp., in scientific journals, 53 invited lectures, Peer reviewed manuscripts since 2000 (original research and reviews) First, last or corresponding author manuscripts: Y. Estrov, F. Scaglia, O.A.F. Bodamer. Psychiatric symptoms in inborn errors of metabolism. J Inher Met Dis 2000; 23:2-6. (Review) O.A.F. Bodamer, A.Vellodi. Protein, glucose and energy metabolism in Gaucher disease type I. J Inher Met Dis 2000; 23:86-87. F. Feillet, O.A.F. Bodamer, S. Sequeira, M. Dixon, J.V.Leonard. Resting energy expenditure in disorders of propionate metabolism. J. Ped 2000; 136:659-663. O.A.F. Bodamer, D.Halliday, J.V. Leonard. The effects of L-alanine supplementation in late- onset glycogen storage disease type II. Neurology 2000; 55:710-712. O.A.F Bodamer, D. Halliday. Uses of stable isotopes in clinical diagnosis and research in the pediatric population. Arch Dis Child 2001; 84:444-448. (Review) O.A.F. Bodamer, D.S. Rosenblatt, S.H. Appel, A.L. Beaudet. Late-onset combined homocystinuria and methylmalonic aciduria (cblC). Neurology 2001; 56:1113. O.A.F. Bodamer, E.J. Popek, C.A. Bacino. Atypical presentation of amniotic band syndrome. Am J Med Gen 2001; 100:100-102. O.A.F. Bodamer, R.M. Bravermann, W.J. Craigen. Diagnosis of autosomal recessive

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osteopetrosis: presence of fractures in a 3-month old female. J Paed Child Health 2001; 37:520-522. O.A.F. Bodamer, S.M. Bloesch, A. Gregg, S. Stöckler-Ipsiroglu, W.E. O’Brien. Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass-spectrometry. Clin Chim Acta 2001; 308:173-178. O.A.F. Bodamer, E. Wraith, CR Scott, F. Scaglia. A New Variant Type III (Type IIID) Gaucher Disease Characterized by Dysmorphic Features, Absence of Cardiovascular Involvement, and Compound Heterozygosity for a Novel Mutation (D409H/C16S) Am J Med Genet 2002; 109:328-31. D.L. Smith, O.A.F. Bodamer. Practical management of combined MMA / homocystinuria (cblC). J Child Neurol. 2002; 17:353-6. (Review)O.A.F. Bodamer, D. Möslinger, A. Mühl und S. Stöckler-Ipsiroglu. Neugeborenen-screening in Österreich: Bestandsaufnahme, Neuentwicklungen und Zukunftsperspektiven. Pädiat Prax 2002; 61:539-549. O.A.F. Bodamer, D. Haas, M.M.P. Hermans, A.J.J. Reuser, J.V. Leonard, G.F. Hoffmann. Long-term management of childhood/non-classical infantile Glycogen Storage Disease Type II (GSD-II) with oral L-alanine supplementation. Ped Neurol 2002; 27:145-147. O.A.F. Bodamer, F. Feillet, R.E. Lane, P.J. Lee, M.A. Dixon, D. Halliday, J.V. Leonard. Utilisation of cornstarch in glycogen storage disease type Ia. Europ J Gastroenterol Hepatol 2002; 14:1251-1256. O.A.F. Bodamer, D. Bercovich, M. Schlabach, C. Ballantyne, D. Zoch, A.L. Beaudet. Use of Denaturing HPLC to provide efficient detection of mutations causing familial hypercholesterolemia. Clin Chem 2002; 48:1913-1918. K. Hussein*, O.A.F. Bodamer*, F.J. Cameron, C. Camacho-Hubner, M.A. Soos, J. Jones, F. Taylor, S. O’Rahilly, A. Aynsley-Green. A new syndrome of hemihypertrophy and severe non-ketotic hypoglycaemia without hyperinsulinism in childhood. Hormone Research 2004; 61:222-227. *joint first author O.A.F. Bodamer, R. Ratschmann, E. Paschke, T. Voigtländer, S. Stöckler-Ipsiroglu Recurrent acroparesthesia during febrile infections in a 9 year-old male. Lancet 2004; 363:1698. O.A.F. Bodamer, S. Gruber, S. Stöckler-Ipsiroglu. Nuclear magnetic resonance spectroscopy in GCDH deficiency. JIMD 2004; 27:877-883. K. Tuschl, O.A.F. Bodamer, W. Erwa, A.Mühl. Novel Method for Rapid Analysis of Total

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Plasma Homocysteine by Tandem Mass Spectrometry. Clin Chim Acta 2005; 351:139-41. K. Tuschl, A. Gal, E. Paschke, S. Kircher, S., O.A.F. Bodamer. Mucopolysaccharidosis type II in females – case report and review of literature. Ped Neurol 2005; 32:270-272. M. Holub, L. Potocki, O.A.F. Bodamer. Oral-Facial-Digital Syndrome Type 1: Review of Cerebral Malformations. Am J Med Genet 2005; 136:218? (Review). O.A.F. Bodamer, A. Mühl. Analysis of acylcarnitine ester for the diagnosis of inborn errors of metabolism using tandem mass-spectrometry. Chem Month 2005; 136:1293-1297. O.A.F. Bodamer. Genetische Polymorphismen und Prädisposition. Pädiatrie Pädiologie 2005; 1:27-31. (Review). O.A.F. Bodamer, T Sahoo, A Beaudet, W O΄Brien, L Sweetman, T Bottiglieri, C Wagner, F Scaglia. Evidence for impaired creatine synthesis in patients with combined methylmalonic aciduria and homocystinuria (cblC) – new pathomechanism and rationale for treatment of disorders of remethylation? Annals of Neurol 2005; 57:557-560. R. Ratschmann, O.A.F. Bodamer. Genetische Polymorphismen und Prädisposition. Päd. Prax 2005; 66:659-664. (Review). CB. Item, S. Stöckler-Ipsiroglu, C. Willheim, A. Mühl, O.A.F. Bodamer. Use of Denaturing HPLC to provide efficient detection of mutations causing guanidinoacetate methyltransferase deficiency. Mol Genet Metab 2005; 86:328-334. O.A.F. Bodamer, M. Beck, M. Weigl. MPS-I. Iatros Pädiatrie 2005. (Review) O.A.F. Bodamer, K Hussein, AA Morris, C-D Langhans, D Rating, E Mayatepek, JV Leonard. Glucose and leucine kinetics in children with idiopathic ketotic hypoinsulinaemic hypoglycaemia. Arch Dis Child 2006;91:483-6 O.A.F. Bodamer, W. Maurer, G. Mitterer, M.W. Mueller, A. Pollak, W.M. Schmidt. Mannose-binding lectin (MBL2) polymorphisms and the risk of preterm birth. Genetics in Medicine 2006;8:518-524 M. Holub, K. Tuschl, R. Ratschmann, K. Strnadova, W. Sperl, A. Mühl, G. Heinze, O.A.F. Bodamer. Influence of hematokrit and localisation of punch in dried blood spots on levels of amino acids and acylcarnitines measured by tandem mass spectrometry. Clin Chim Acta 2006;373:27-31 K. Strnadova, M. Holub, A. Mühl, K. Tuschl, F. Waldhauser, O.A.F. Bodamer. Long-term stability of amino acids and acylcarnitines in dried blood spots used for neonatal screening by tandem mass spectrometry. Clin Chem 2007;53:717-722

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K. Tuschl, M. Holub, M. Herle, B. Fritz, R. Stindl, C. Fonatsch, O.A.F. Bodamer. Trisomy 1q42.3-qter and monosomy 21q22.3-qter associated with ear anomaly, facial dysmorphism, psychomotor retardation and epilepsy. Am J Med Genet 2007 (accepted). M. Freilinger, D. Kalisch, A. Mühl, O. Haas, A. Moritz, O.A.F. Bodamer. Methylation status in females with Rett syndrome. J Child Neurol 2007(accepted). J. Vodopiutz, C.B. Item, M. Häusler, H. Korall, O.A.F. Bodamer. Severe speech delay as presenting symptom of guanidinoacetate methyltransferase deficiency. J Child Neurol 2007 (accepted). O.A. Bodamer, G.F. Hoffmann, M. Lindner. Expanded Newborn Screening in Europe in 2007. JIMD 2007 (accepted). Co-author manuscripts: F. Scaglia, V.R. Sutton, O.A.F. Bodamer, S.K. Shapira. Mitochondrial DNA depletion. J Child Neurol 2001; 16:136-138. S.A. Berend, O.A.F. Bodamer, S.K. Shapira, L.G. Shaffer, C.A. Bacino. A familial complex chromosomal rearrangement resulting in a recombinant chromosome. Am J Med Genet 2002; 109:311-7. C.B. Item, C. Stromberger, A. Muhl, C. Edlinger, O.A.F. Bodamer, A. Schulze, R. Surtees, V. Leuzzi, G.S. Salomons, C. Jakobs, S. Stöckler-Ipsiroglu. Denaturing gradient gel electrophoresis for the molecular characterization of six patients with guanidinoacetate methyltransferase deficiency. Clin Chem 2002; 48:767-9. C. Stromberger, O.A.F. Bodamer, S. Stöckler-Ipsiroglu. Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. J Inherit Metab Dis. 2003;26:299- 308. (Review). J. Crone, D. Moslinger, O.A.F. Bodamer, W. Schima, WD Huber, E Holme, S. Stockler Ipsiroglu. Reversibility of cirrhotic regenerative liver nodules upon NTBC treatment in a child with tyrosinaemia type I. Acta Paediatr. 2003; 92:625-8. M. Orendac, J. Zeman, S.P. Stabler, R.H. Allen, J.P. Kraus, O.A.F. Bodamer, S. Stöckler- Ipsiroglu, V. Kozich. Homocystinuria due to cystathionine β-synthase deficiency: novel biochemical findings and treatment efficacy JIMD 2003; 26:761-773. C.B. Item, S. Mercimek-Mahmutoglu, R. Battini, C. Edlinger-Horvat, C. Stromberger, O.A.F.

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Bodamer, A. Mühl, M.A. Vilaseca, H. Korall, S. Stöckler-Ipsiroglu. Characterisation of 7 novel mutations in seven patients with GAMT deficiency. Hum Mut 2004; 23:524-530. M. Holub, O.A.F. Bodamer, C. Item, A. Mühl, A. Pollak, S. Stöckler-Ipsiroglu. Correlation between disorders of fatty acid oxidation and HELLP syndrome? Acta Paediat 2005; 94:48-52. G. Mitterer, O.A.F. Bodamer, C. Harwanegg, W. Maurer, M.W. Mueller, W.M.

Schmidt. Performance of Microarray Based SNP Detection in a Routine Clinical Setting. Gene Testing 2005; 9:6-13.

S. Külkens, I. Harting, S. Sauer, A. Schulze-Bergkamen, J. Zschocke, G. F. Hoffmann, S. Gruber, O. A. F. Bodamer, S. Kölker. Late-onset neurologic disease in two patients with glutaryl-CoA dehydrogenase deficiency. Neurology 2005; 64:2142-2144. M. Huemer, B. Fowler, O.A.F. Bodamer, T. Suormala, B. Simma, J.O. Sass. Pre- and postnatal treatment in the cblC defect. J Pediatr. 2005; 147:469-472. K.A. Strnadová, F. Votava, J. Lebl, A. Mühl, C. Item, O.A.F. Bodamer, T. Torresani, Bouška, F. Waldhauser, W. Sperl. Prevalence of congenital adrenal hyperplasia and inborn errors of metabolism among sudden infant death in two Middle European countries: A retrospective analysis. Europ J Ped 2007;166:1-4 S.Fischer, G. Mann, M. Konrad, M. Metzler, G. Ebetsberger, N. Jones, B. Nadel, O. A. Bodamer, O. Haas, K. Schmitt, E. Panzer-Grunmeyer. Lack of leukemia-and clone Specific markers at birth in children with T cell precursor ALL suggests a predominantly postnatal origin. Blood 2007 Jun 8; (print)

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Wilfred DRUML Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III [email protected] Curriculum Vitae Name: Prof. Dr. med. Wilfred Johannes DRUML married with Mrs. Dr. jur. Christiane Druml 3 children (Hephzibah 22, Zino 20, Carl 16) Home address: Gottfried Keller-Gasse 13, A-1030 Vienna, Austria 31. 7. 1949 born in Mauthen/ Carinthia, Austria 1969 - 1972 Medical training (preclinical part) in Innsbruck, Austria 1972 - 1975 Medical training (clinical part) Vienna, Austria 1975 Graduation; MD 1975 - 1991 Residence/ fellow in medicine, Department of Internal Medicine I, University of Vienna, Austria 1982 Borad certification Internal Medicine 1985 - 1987 Postdoctoral research fellow Harvard University, Boston, USA 1986 US-certification (ECFMG) 1986 - 1987 Medical Fellow, Harvard University (Brigham and Women´s Hospital) Boston 1987 Board Certification in Austria : Nephrology 1987 Associate Professor of Medicine 1991 Professor of Medicine, Tenure since 1991 Director, Nephrology Intensiv Care Programme Vienna General Hospital, Vienna, Austria 1995 Board certification: Intensive Care Medicine Research Focus : Metabolism and nutrition in the critically ill, in patients with renal failure, development of the first dipeptide-containing amino acid solution worldwide and of many nutritional programs, intravenous lipids, acute renal failure, continuous renal replacement therapies, general infusion therapy. Society (Founding) Member /Officer : Austrian Society of Clinical Nutrition (AKE)(president, responsible for publication of “nutritional recomendations“), Austrian Society of Medical Intensive Care Medicine (president, responsible for “consensus reports“) European, Society of Parenteral and Enteral Nutrition, European Society of Intensive Care Medicine Congress Organization : Numerous national and international seminars and workshops in the field of intensive care medicine, clinical nutrition, of acute renal failure Editor, Editorial Board : Editor-in-Chief of Wiener klinische Wochenschrift (The Middle European Journal of Medicine), founder and editor-in-chief of an intensive care newsletter (INTENSIV-News), editorial board of several national and international journals

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Manuscript Reviewer: Regular reviewer for the major journals in the fields of clinical nutrition, of nephrology and intensive care medicine.


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Manuela FÖDINGER Clinical Institute of Medical and Chemical Laboratory Diagnostics [email protected] Effect of iron therapy on cellular iron homeostasis - safety of iron therapy? Abstract Most patients with chronic renal failure must receive erythropoietic agents and iron to maintain a hemoglobin level above 11 g/dL. Intravenous iron is more effective than oral iron substitution. Intravenously iron is mainly supplied as iron sucrose and iron gluconate. However, non-transferrin bound labile iron can produce side effects possibly by affecting endothelial cells, polymorphonuclear leukocytes and cytokines. Moreover, labile iron may act as a catalytic agent in the formation of hydroxyl radicals, and could hence contribute to cell damage. Therefore, iron must be carefully administered intravenously, particularly when supplied in high doses. Data in the literature suggest that iron is an important factor in the process of atherosclerosis, but exact mechanisms are still unknown. The ‘iron hypothesis’ suggests that iron depletion protects against ischemic heart disease. Furthermore, iron promotes bacterial growth and thus is potentially related to infectious complications. End-stage renal disease patients require iron therapy to benefit from treatment with recombinant human erythropoietin or novel erythropoiesis stimulating proteins. Monitoring of iron status in these patients includes the determination of the percentage of hypochromic red blood cells and/or the reticulocyte hemoglobin content, in addition to ferritin serum concentration and transferrin saturation. Concerning safe and optimal correction of renal anemia by intravenous iron therapy the principal questions are to be answered are the following: Does intravenous iron application indeed contribute to 1) atherogenesis, 2) infectious disease, and 3) cell damage? A first step to clarify these issues is to identify genes that are responsive to intravenous iron therapy (i.e. up- or down-regulated genes). This is to be accomplished by using gene expression microarrays in cells isolated from chronic renal failure patients that have received intravenous iron or not. Identification of genes regulated by iron therapy will provide basic information to support or reject the hypothesis of an involvement of iron in atherogenesis, infections, and cell damage. Thesis Subjects Effects of intravenous iron therapy on gene expression in human cells Molecular effects of intravenous iron therapy on oxidative stress in human cells Techniques and infrastructure Cell culture, isolation of RNA, microarray analysis; quantitative real-time PCR; all required equipment available.

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Curriculum Vitae

Manuela FÖDINGER Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 5388; Fax +43 1 40400 6752; Email [email protected] Personal Data Date of Birth: 09.02.1964 Place of Birth: Steyr, Austria Nationality Austria Education 1997 – present specialist in Laboratory Medicine 1990 International Diploma of Tropical Medicine 1982 – 1990 studies of Human Medicine 1974 – 1982 secondary school Career History 2004 – present Head of the section „Molecular Endocrinology,

Pharmacology & Metabolism“ and medical head of the division „Endocrinology“ at the Clinical Institute of Medical and Chemical Laboratory Diagnostics

2000 – present associate Professor at the Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna

2000 “venia docendi” for Laboratory Medicine 1992 - present University Assistant, Clinical Institute of Medical and

Chemical Laboratory Diagnostics, Medical University of Vienna

1991 - 1992 Research fellow at the Institute of General and Experimental Pathology and the Institute of Specific Prophylaxis and Tropical Medicine at the (Medical) University of Vienna

Career-related Activities 2001 – 2002 Postgraduate University Course for Medical Leaders

at the University of Salzburg

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2004 Section leader "Science and Development", Austrian Society for Clinical Chemistry

Awards 2001 ERA-EDTA Award of the European Dialysis and

Transplantation Association 1999

Preis der Österreichischen Gesellschaft für Nephrologie Award der National Kidney Foundation

1998

Young Investigator Award of the American Society of Transplant Physicians Best Scientific Abstract of the International Society of Peritoneal Dialysis

1996 Preis der Österreichischen Gesellschaft für Labormedizin

Memberships Austrian Society for Endocrinology and Metabolism Austrian Society for Laboratory Medicine and Clinical Chemistry Austrian Society for Good Analyses and Laboratory Praxis Society for Nephrology Sources of funding (since 2000)


Else-Kröner-Fresenius-Stiftung, Germany

Effect of homocysteine on vascular endothelial cells

17.9



Anita Jallitsch Molecular background of Anderson-Fabry disease

2007 – (2009) (Dr. scient. med.)

Publications 78 and 13 peer reviewed publications and reviews, resp., in scientific journals, 2 editorials, 3 book contributions Peer reviewed manuscripts since 2000 (original research and reviews)

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First, last or corresponding author manuscripts: Sunder-Plassmann G, Winkelmayer WC, Födinger M. 2006. Genetic aspects of hyperhomocysteinemia in chronic kidney disease. Semin Nephrol. 26:8-13. (review) Winkelmayer WC, Kramar R, Sunder-Plassmann G, Födinger M. 2005. Effects of single-nucleotide polymorphisms in MTHFR and MTRR on mortality and allograft loss in kidney transplant recipients. Kidney Int. 68:2857-62. Winkelmayer WC, Huber A, Wagner OF, Hörl WH, Sunder-Plassmann G, Födinger M. 2005. Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B in kidney transplant recipients. Kidney Int. 67:1980-5. Lorenz M, Kletzmayr J, Huber A, Hörl WH, Sunder-Plassmann G, Födinger M. 2005. Ironoverload in kidney transplants: prospective analysis of biochemical and genetic markers. Kidney Int. 67:691-7. Fritsche-Polanz R, Wallner M, Cohen G, Eberle C, Sunder-Plassmann G, Födinger M. 2004.Granulocyte function in patients with L-ferritin iron-responsive element (IRE) 39C-->T-positive hereditary hyperferritinaemia-cataract syndrome. Eur J Clin Invest. 34:701-8. Sunder-Plassmann G, Födinger M. 2004. Underuse of Hardy-Weinberg equilibrium. Kidney Int. 66:1711. (letter) Winkelmayer WC, Sunder-Plassmann G, Huber A, Födinger M. 2004. Patterns of co-occurrence of three single nucleotide polymorphisms of the 5,10 methylenetetrahydrofolate reductase gene in kidney transplant recipients. Eur J Clin Invest. 2004: 613-8. Feix A, Winkelmayer WC, Eberle C, Sunder-Plassmann G, Födinger M. 2004. Methionine synthase reductase MTRR 66A > G has no effect on total homocysteine, folate, and Vitamin B12 concentrations in renal transplant patients. Atherosclerosis. 2004 174:43-8. Födinger M, Sunder-Plassmann G. 2003. Low clinical penetrance of homozygosity for HFE C282Y: implications for genetic testing? Eur J Clin Invest. 33:737-9. (editorial) Födinger M, Veitl M, Skoupy S, Wojcik J, Rohrer C, Hagen W, Puttinger H, Hauser AC, Vychytil A, Sunder-Plassmann G. 2003. Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients. Kidney Int. 64:1095-100. Winkelmayer WC, Eberle C, Sunder-Plassmann G, Födinger M. 2003. Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney Int. 63:2280-5.

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Födinger M, Dierkes J, Skoupy S, Röhrer C, Hagen W, Puttinger H, Hauser AC, Vychytil A, Sunder-Plassmann G. 2003. Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients. J Am Soc Nephrol. 14:1314-9. Sunder-Plassmann G, Födinger M. 2003. Genetic determinants of the homocysteine level. Kidney Int Suppl. 84:S141-4. (review) Sunder-Plassmann G, Kittler H, Eberle C, Hirschl MM, Woisetschlager C, Derhaschnig U, Laggner AN, Hörl WH, Födinger M. 2002. Angiotensin converting enzyme DD genotype is associated with hypertensive crisis. Crit Care Med. 30:2236-41. Sunder-Plassmann G, Födinger M. 2002. Cost-effectiveness of homocysteine-lowering therapy to prevent coronary heart disease. JAMA. 287:190. (letter) Tröndle U, Sunder-Plassmann G, Burgmann H, Buchmayer H, Kramer L, Bieglmayer C, Hörl WH, Födinger M. 2001. Molecular and clinical characterisation of homocystinuria in two Austrian families with cystathionine beta-synthase deficiency. Acta Med Austriaca 28:145-51. Feix A, Fritsche-Polanz R, Kletzmayr J, Vychytil A, Hörl WH, Sunder-Plassmann G, Födinger M. 2001. Increased prevalence of combined MTR and MTHFR genotypes among individuals with severely elevated total homocysteine plasma levels. Am J Kidney Dis. 38:956-64. Födinger M, Buchmayer H, Heinz G, Papagiannopoulos M, Kletzmayr J, Perschl A, Vychytil A, Hörl WH, Sunder-Plassmann G. 2001. Association of two MTHFR polymorphisms with total homocysteine plasma levels in dialysis patients. Am J Kidney Dis. 38:77-84. Fritsche-Polanz R, Jordan JH, Feix A, Sperr WR, Sunder-Plassmann G, Valent P, Födinger M. 2001. Mutation analysis of C-KIT in patients with myelodysplastic syndromes without mastocytosis and cases of systemic mastocytosis. Br J Haematol. 113:357-64. Födinger M, Sunder-Plassmann G. 2001. Increased cysteine plasma levels in kidney transplants: a potential vascular disease risk factor? Transplantation. 71:713-5. Födinger M, Wagner OF, Hörl WH, Sunder-Plassmann G. 2001. Recent insights into the molecular genetics of the homocysteine metabolism. Kidney Int Suppl. 78:S238-42. (review) Sunder-Plassmann G, Winkelmayer WC, Födinger M. 2000. Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease. Expert Opin Investig Drugs. 9:2637-51. (review) Buchmayer H, Sunder-Plassmann G, Hirschl MM, Kletzmayr J, Woisetschlager C, Laggner AN, Hörl WH, Födinger M. 2000. G-protein beta3 subunit gene (GNB3)

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polymorphism 825C-->T in patients with hypertensive crisis. Crit Care Med. 28:3203-6. Födinger M, Buchmayer H, Heinz G, Papagiannopoulos M, Kletzmayr J, Rasoul-Rockenschaub S, Hörl WH, Sunder-Plassmann G. 2000. Effect of MTHFR 1298A-->C and MTHFR 677C-->T genotypes on total homocysteine, folate, and vitamin B(12) plasma concentrations in kdiney graft recipients. J Am Soc Nephrol. 11:1918-25. Floth A, Sunder-Plassmann G, Födinger M. 2000. Polymerase chain reaction amplification of bacterial 16s rRNA in biopsy samples. Urology. 55:788-9. (letter) Sunder-Plassmann G, Floth A, Födinger M. 2000. Hyperhomocysteinemia in organ transplantation. Curr Opin Urol. 10:87-94. (review) Födinger M, Fritsche-Polanz R, Buchmayer H, Skoupy S, Sengoelge G, Hörl WH, Sunder-Plassmann G. 2000. Erythropoietin-inducible immediate-early genes in human vascular endothelial cells. J Investig Med. 48:137-49. Födinger M, Hörl WH, Sunder-Plassmann G. 2000. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol. 13:20-33. (review) Co-author manuscripts:

Steiner S, Winkelmayer WC, Kleinert J, Grisar J, Seidinger D, Kopp CW, Watschinger B, Minar E, Hörl WH, Födinger M, Sunder-Plassmann G. 2006. Endothelial progenitor cells in kidney transplant recipients. Transplantation. 81:599-606. Schaeffner ES, Födinger M, Kramar R, Frei U, Hörl WH, Sunder-Plassmann G, Winkelmayer WC. 2006. Prognostic associations between lipid markers and outcomes in kidney transplant recipients. Am J Kidney Dis. 47:509-17. Lechner K, Födinger M, Grisold W, Puspok A, Sillaber C. 2005. Vitamin B12 deficiency. New data on an old theme. Wien Klin Wochenschr. 117:579-91. (review) Schaller G, Scheiber-Mojdehkar B, Wolzt M, Puttinger H, Mittermayer F, Hörl WH, Födinger M, Sunder-Plassmann G, Vychytil A. 2005. Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients. Kidney Int. 68:2814-22. Tylicki L, Födinger M, Puttinger H, Rutkowski P, Strozecki P, Tyszko S, Rutkowski B, Hörl WH. 2005. Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension relation: with the development of hypertensive end-stage renal disease. Am J Hypertens. 18:1442-8. Hauser AC, Gessl A, Lorenz M, Voigtlander T, Födinger M, Sunder-Plassmann G. 2005. High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease. J Inherit Metab Dis. 28:715-22. Krokowski M, Sotlar K, Krauth MT, Födinger M, Valent P, Horny HP. 2005.

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Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia. Am J Clin Pathol. 124:560-8. Steiner S, Schaller G, Puttinger H, Födinger M, Kopp CW, Seidinger D, Grisar J, Hörl WH, Minar E, Vychytil A, Wolzt M, Sunder-Plassmann G. 2005. History of cardiovascular disease is associated with endothelial progenitor cells in peritoneal dialysis patients. Am J Kidney Dis. 46:520-8. Valent P, Arock M, Bischoff SC, Buhring HJ, Brockow K, Escribano L, Födinger M, Grabbe J, Hartmann K, Henz BM, Horny HP, Kluin-Nelemans HC, Lima M, Marone G, Orfao A, Parwaresch RM, Sillaber C, Sotlar K, Sperr WR, Triggiani M, Van Doormaal JJ, Wolff K, Zuberbier T. 2004. The European Competence Network on Mastocytosis (ECNM). Wien Klin Wochenschr. 116:647-51. Kleinert J, Lorenz M, Hauser AC, Becherer A, Staudenherz A, Födinger M, Sunder-Plassmann G. 2005. Measurement of renal function in patients with Fabry disease. Acta Paediatr Suppl. 94:19-23. Florian S, Krauth MT, Simonitsch-Klupp I, Sperr WR, Fritsche-Polanz R, Sonneck K, Födinger M, Agis H, Bohm A, Wimazal F, Horny HP, Valent P. 2005. Indolent systemic mastocytosis with elevated serum tryptase, absence of skin lesions, and recurrent severe anaphylactoid episodes. Int Arch Allergy Immunol. 136:273-80. Huemer M, Huemer C, Ulmer H, Crone J, Födinger M, Falger J, Sailer-Hock M. 2005. No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis. J Rheumatol. 32:170-4. Valent P, Akin C, Sperr WR, Mayerhofer M, Födinger M, Fritsche-Polanz R, Sotlar K, Escribano L, Arock M, Horny HP, Metcalfe DD. 2005. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 46:35-48. (review) Sperr WR, Drach J, Hauswirth AW, Ackermann J, Mitterbauer M, Mitterbauer G, Födinger M, Fonatsch C, Simonitsch-Klupp I, Kalhs P, Valent P. 2005. Myelomastocytic leukemia: evidence for the origin of mast cells from the leukemic clone and eradication by allogeneic stem cell transplantation. Clin Cancer Res. 11:6787-92. Winkelmayer WC, Kramar R, Curhan GC, Chandraker A, Endler G, Födinger M, Hörl WH, Sunder-Plassmann G. 2005. Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: a prospective study. J Am Soc Nephrol. 16:255-60. Kleinert J, Hauser AC, Lorenz M, Födinger M, Sunder-Plassmann G. 2004. Therapy of Fabry disease. Kidney Int. 66:1288. (letter) Sengoelge G, Rainer V, Kletzmayr J, Jansen M, Derfler K, Födinger M, Hörl WH, Sunder-Plassmann G. 2004. Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients. Kidney Int. 66:295-302.

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Winkelmayer WC, Lorenz M, Kramar R, Födinger M, Hörl WH, Sunder-Plassmann G. 2004. C-reactive protein and body mass index independently predict mortality in kidney transplant recipients. Am J Transplant. 4:1148-54. Lorenz M, Wolzt M, Weigel G, Puttinger H, Hörl WH, Födinger M, Speiser W, Sunder-Plassmann G. 2004. Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients. Am J Kidney Dis. 43:1098-103. Wimazal F, Schwarzmeier J, Sotlar K, Simonitsch I, Sperr WR, Fritsche-Polanz R, Födinger M, Schubert J, Horny HP, Valent P. 2004. Splenic mastocytosis: report of two cases and detection of the transforming somatic C-KIT mutation D816V. Leuk Lymphoma. 45:723-9. Hauser AC, Lorenz M, Voigtlander T, Födinger M, Sunder-Plassmann G. 2004. Results of an ophthalmologic screening programme for identification of cases with Anderson-Fabry disease. Ophthalmologica. 218:207-9. Kotanko P, Kramar R, Devrnja D, Paschke E, Voigtlander T, Auinger M, Pagliardini S, Spada M, Demmelbauer K, Lorenz M, Hauser AC, Kofler HJ, Lhotta K, Neyer U, Pronai W, Wallner M, Wieser C, Wiesholzer M, Zodl H, Födinger M, Sunder-Plassmann G. 2004. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am Soc Nephrol. 15:1323-9. Winkelmayer WC, Skoupy S, Eberle C, Födinger M, Sunder-Plassmann G. 2004. Effects of TCN2 776C>G on vitamin B, folate, and total homocysteine levels in kidney transplant patients. Kidney Int. 65:1877-81. Vychytil A, Födinger M, Pleiner J, Mullner M, Konner P, Skoupy S, Röhrer C, Wolzt M, Sunder-Plassmann G. 2003. Acute effect of amino acid peritoneal dialysis solution on vascular function. Am J Clin Nutr. 78:1039-45. Sengoelge G, Kletzmayr J, Papagiannopoulos M, Bohle B, Hörl WH, Födinger M, Sunder-Plassmann G. 2003. TGF-beta1 impairs homocysteine metabolism in human renal cells: possible implications for transplantation. Transpl Int. 16:843-8. Jordan JH, Jäger E, Sperr WR, Schwarzinger I, Födinger M, Fritsche-Polanz R, Öhler L, Geissler K, Valent P. 2003. Numbers of colony-forming progenitors in patients with systemic mastocytosis: potential diagnostic implications and comparison with myeloproliferative disorders. Eur J Clin Invest. 33:611-8. Huemer M, Födinger M, Huemer C, Sailer-Hock M, Falger J, Rettenbacher A, Bernecker M, Artacker G, Kenzian H, Lang T, Stockler-Ipsiroglu S. 2003. Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study. Clin Exp Rheumatol. 21:249-55. Hauswirth AW, Sperr WR, Ghannadan M, Schernthaner GH, Jordan JH, Fritsche-Polanz R, Simonitsch-Klupp I, Födinger M, Lechner K, Valent P. 2002. A case of smouldering mastocytosis with peripheral blood eosinophilia and lymphadenopathy.

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Leuk Res. 26:601-6. Jordan JH, Schernthaner GH, Fritsche-Polanz R, Sperr WR, Födinger M, Chott A, Geissler K, Lechner K, Horny HP, Valent P. 2002. Stem cell factor-induced bone marrow mast cell hyperplasia mimicking systemic mastocytosis (SM): histopathologic and morphologic evaluation with special reference to recently established SM-criteria. Leuk Lymphoma. 43:575-82. Ignatescu MC, Kletzmayr J, Födinger M, Bieglmayer C, Hörl WH, Sunder-Plassmann G. 2002. Influence of mycophenolic acid and tacrolimus on homocysteine metabolism. Kidney Int. 61:1894-8. Skoupy S, Födinger M, Veitl M, Perschl A, Puttinger H, Rohrer C, Schindler K, Vychytil A, Hörl WH, Sunder-Plassmann G. 2002. Riboflavin is a determinant of total homocysteine plasma concentrations in end-stage renal disease patients. J Am Soc Nephrol. 13:1331-7. Hagen W, Födinger M, Hörl WH, Sunder-Plassmann G. 2001. Therapy of hyperhomocysteinemia in end-stage renal disease patients. Minerva Urol Nefrol. 53:159-70. (review). Jordan JH, Fritsche-Polanz R, Sperr WR, Mitterbauer G, Födinger M, Schernthaner GH, Christian Bankl H, Gebhart W, Chott A, Lechner K, Valent P. 2001. A case of 'smouldering' mastocytosis with high mast cell burden, monoclonal myeloid cells, and C-KIT mutation Asp-816-Val. Leuk Res. 25:627-34. Hauser AC, Hagen W, Rehak PH, Buchmayer H, Födinger M, Papagiannopoulos M, Bieglmayer C, Apsner R, Koller E, Ignatescu M, Hörl WH, Sunder-Plassmann G. 2001. Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients. Am J Kidney Dis. 37:758-65. Hagen W, Födinger M, Heinz G, Buchmayer H, Hörl WH, Sunder-Plassmann G. 2001. Effect of MTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients. Kidney Int Suppl. 78:S253-7. Sunder-Plassmann G, Födinger M, Buchmayer H, Papagiannopoulos M, Wojcik J, Kletzmayr J, Enzenberger B, Janata O, Winkelmayer WC, Paul G, Auinger M, Barnas U, Hörl WH. 2000. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study. J Am Soc Nephrol. 11:1106-16. Schindler K, Zauner C, Buchmayer H, Födinger M, Wölfl G, Bieglmayer C, Heinz G, Wilfing A, Hörl WH, Sunder-Plassmann G. 2000. High prevalence of hyperhomocysteinemia in critically ill patients. Crit Care Med. 28:991-5.

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Clemens FÜRNSINN Dept. Internal Medicine III, Div.Endocrinol.Metab. [email protected] Type 2 diabetes, glucose metabolism, and the role of skeletal muscle. Abstract Changes in environment and lifestyle presently cause a worldwide distinct increase in diabetes mellitus, which is particularly due to increasing numbers of patients afflicted by type 2 diabetes. This disease is strongly associated with sedentary life style and obesity. A better understanding of the natural etiology and the metabolic disturbances of type 2 diabetes, as well as the development of new therapeutic strategies and drugs is therefore among the most important challenges in medical research. In type 2 diabetes, the predominant cause of increased blood glucose, which defines the diabetic state, is resistance of target tissues to the actions of insulin, i.e., target tissues stimulated by the hormone fail to take up an appropriate amount of glucose from circulating blood. Hence, it is important to understand, how tissue insulin sensitivity is regulated and can be manipulated. In this regard, skeletal muscle is of particular interest, because muscle is the quantitatively most important target tissue for insulin-stimulated glucose lowering and accounts for up to 80% of glucose disposal under insulin-stimulated conditions. Since many years our research is focused on several aspects of the problem: (i) the description of antidiabetic potentials of new compounds in the whole organism (experimental animal); (ii) analysis of the modes and mechanisms of actions of new as well as of established antidiabetic drugs, particularly with regard to their effects on muscle insulin sensitivity; (iii) the investigation of mechanisms involved in the physiological regulation of insulin sensitivity, e.g., via adipocyte-derived hormones. More specifically, we have studied the role and demonstrated the importance of the cellular energy state for the long-term modulation of muscle insulin sensitivity. In this context, we have developed a working hypothesis that a reduced cellular energy load can serve as a trigger for delayed insulin sensitization leading to an amelioration of deranged glucose homeostasis ("the energy charge hypothesis of insulin sensitivity"). We are experienced in metabolic studies on whole animals (e.g. rat models for type 2 diabetes) and in the use of native rat soleus muscle strips in a pharmacological setting. The latter allows to analyze in detail the substrate flux rates through the most important biochemical pathways of muscle fuel metabolism and can be used for many different experiments including, e.g., ex vivo as well as in vitro approaches. Thesis Subjects Effects of antidiabetic agents on glucose metabolism of rat skeletal muscle in vivo and in vitro. Techniques and infrastructure Incubation of native rat skeletal muscle strips; analysis of muscle metabolism with radiolabelled substrates and enzymatic methods; basic methods for animal

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experimentation; hormone analysis; Northern and Western blotting; all necessary infrastructure and equipment available

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Curriculum Vitae

Clemens FÜRNSINN Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4785; Fax +43 1 40400 7790; Email [email protected] Personal Data Date of Birth: 6.3.1964 Place of Birth: Vienna, Austria Nationality Austria Education 1982 – 1990 studies of Biology (zoology/botany) 1970 – 1982 school Career History 2000 – present Associate Professor at the Department of Internal

Medicine III, Medical University of Vienna. Basic medical research on fuel metabolism and antidiabetic agents

X/1997 “venia docendi” for Metabolic Physiology 1991 – present University Assistant at the Clinical Division of

Endocrinology Metabolism, Department of Internal Medicine III, (Medical) University of Vienna, Austria

XI/1993-II/1994

4 Months of Research at the Department of Biochemistry of the University of Oxford, England, UK

X/1990 – V/1991 Civil Service V/1990 – X/1990 University Assistant at the Division of Endocrinology

& Diabetes Mellitus, 1st Medical Department, Vienna 3.4.1990 Ph.D. Graduation

1985 7 Months of Research at the Laboratory of Animal Physiology, University of Groningen, the Netherlands.

1982 Begin of Study of Biology (Zoology/Botany) at the University of Vienna

Career-related Activities 1998 – present2003 Member of the Editorial Board, Diabetologia

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Awards 1996 Winner of the Poster-Prize at the Diabetes Three

Countries Meeting at Basel, Switzerland (organized by German, Swiss, and Austrian Diabetes Associations)

1992 Winner of the Award of the HOECHST-Company Memberships Austrian Society for Endocrinology and Metabolism Austrian Diabetes Society German Diabetes Society European Society for the Study of Diabetes Sources of funding in last 5 years (2000-2005)


FFG (Nr.812095) Investigation of antidiabetic activities of established medical plants. (Project Leader: B.Brunmair)

175

2003 – 2005

FWF (P16352-B08) Antidiabetic effects caused by inhibition of cell respiration?

63

1998 – 2000

FWF (P13049-MED)

Osmosis, insulin sensitizers, and muscle glucose metabolism.

31



Susanne Neschen "Effect of GLP1/GLP1 analogues, lithium ions, and troglitazone on rat glucose metabolism; University of Vienna (Zoology)

– 2000 Dr. rer. nat.

Barbara Brunmair Wirkung und Wirkungsmechanismen von Agonisten nukleärer Rezeptoren auf den Glukose- und Fettstoffwechsel der Ratte; University of Vienna (Zoology)


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Thomas Kästenbauer

Prospektive, plazebokontrollierte, randomisierte und doppelblinde Studie zum Nachweis der Wirksamkeit einer Behandlung der peripheren diabetischen Polyneuropathie mit Ginko bilboa Extrakt Egb 761; University of Vienna (Zoology)


Florian Gras* Vergleichende Untersuchung der Wirkung von Thiazolidindionen, einem Isoxazolidindion und Dexlipotam auf den Glukosestoffwechsel der Ratte, Humboldt University, Berlin Germany

– 2004 MD

Karin Stadlbauer* Modulation von Glukosestoffwechsel und Insulinsignalkaskade durch Aminosäuren und Fettsäuren in Muskel und Leber der Ratte (Working Title); University of Vienna (Zoology)

– (2007) Dr. rer. nat.

Zsuzsanna Szöcs* Wirkung mutmaßlich antidiabetischer Naturheilmittel in einschlägigen Nagermodellen; University of Vienna (Zoology)

– (2008) Dr. rer. nat.

* Supervision together with B. Brunmair Publications 42 peer reviewed publications in scientific journals,


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4 invited lectures Peer reviewed manuscripts since 2000 (original research and reviews) Fürnsinn C, Brunmair B, Neschen S, Roden M, Waldhäusl W: Troglitazone directly inhibits CO2 production from glucose and palmitate in isolated rat skeletal muscle. Journal of Pharmacology and Experimental Therapeutics 293, 487-493, 2000. Brunmair B, Neschen S, Gras F, Roden M, Nowotny P, Waldhäusl W, Fürnsinn C: Metabolic response to anisoosmolarity of rat skeletal muscle in vitro. Hormone Metabolic Research 32, 251-255, 2000. (Erratum: Horm Metab Res 32, 440, 2000) Englisch R, Wurzinger R, Fürnsinn C, Schneider B, Frisch H, Waldhäusl W, Graf J, Roden M: Effects of insulin-like growth factor I on basal and stimulated glucose fluxes in rat liver. Biochemical Journal 351, 39-45, 2000. Oberkofler H, Neschen S, Esterbauer H, Waldhäusl W, Patsch W, Fürnsinn C: UCP3 gene expression does not correlate with muscle oxidation rates in Troglitazone-treated Zucker fatty rats. Biochimica et Biophysica Acta 1517, 113-118, 2000. Roden M, Anderwald C, Fürnsinn C, Waldhäusl W, Lohninger A: Short-term leptin exposure stimulates triglyceride deposition in rat liver. Hepatology 32, 1045-1049, 2000. Stingl H, Krssak M, Krebs M, Bischof M, Nowotny P, Fürnsinn C, Shulman GI, Waldhäusl W, Roden M: Lipid-dependent control of hepatic glycogen stores in healthy man. Diabetologia 44, 48-54, 2001. Krebs M, Krssak M, Nowotny P, Weghuber D, Gruber S, Mlynarik V, Bischof M, Stingl H, Fürnsinn C, Waldhäusl W, Roden M: Free fatty acids inhibit glucose-stimulated increase of intramuscular glucose-6-phosphate concentration in humans. Journal of Clinical Endocrinology and Metabolism 86, 2153-2160, 2001. Brunmair B, Gras F, Neschen S, Roden M, Waldhäusl W, Fürnsinn C: Direct thiazolidinedione action on rat skeletal muscle glucose handling is independent of peroxisome proliferator-activated receptor-�-mediated changes in gene expression. Diabetes 50, 2309-2315, 2001. Fürnsinn C, Nowotny P, Brunmair B, Gras F, Roden M, Waldhäusl W, Vierhapper H: Thiazolidinediones influence plasma steroids of male obese Zucker rats. Endocrinology 143: 327-330, 2002 (Rapid Communication). Anderwald C, Müller G, Koca G, Fürnsinn C, Waldhäusl W, Roden M: Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2. Molecular Endocrinology 16: 1612-1628, 2002. Fürnsinn C, Waldhäusl W: Thiazolidinediones: metabolic actions in vitro. Diabetologia 45: 1211-1223, 2002 (Review).


Anderwald C, Koca G, Fürnsinn C, Waldhäusl W, Roden M: Inhibition of glucose production and stimulation of bile flow by R (+)-�-lipoic acid enantiomer in rat liver. Liver 22: 356-362, 2002. Gras F, Brunmair B, Roden M, Waldhäusl W, Fürnsinn C: Differences in troglitazone action on glucose metabolism in freshly isolated versus long-term incubated rat skeletal muscle. British Journal of Pharmacology 138: 1140-1146, 2003. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W, Fürnsinn C: Thiazolidinediones, like metformin, inhibit respiratory complex I: A common mechanism contributing to their antidiabetic actions. Diabetes 53:1052-1059, 2004. Brunmair B, Lest A, Staniek K, Gras F, Scharf N, Roden M, Nohl H, Waldhäusl W, Fürnsinn C: Fenofibrate impairs rat mitochondrial function by inhibition of respiratory complex I. Journal of Pharmacology and Experimental Therapeutics 311:109-114, 2004. Brunmair B, Gras F, Wagner L, Artwohl M, Zierhut B, Waldhäusl W, Fürnsinn C: Expression of uncoupling protein-3 mRNA in rat skeletal muscle is acutely stimulated by thiazolidinediones: an exercise-like effect? Diabetologia 47: 1611-1614, 2004 (Short Communication) Artwohl M, Fürnsinn C, Waldhäusl W, Hölzenbein T, Rainer G, Freudenthaler A, Roden M, Baumgartner-Parzer SM: Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPAR�-independent mechanism. Diabetologia 48, 586-594, 2005. Artwohl M, Hölzenbein T, Fürnsinn C, Freudenthaler A, Huttary N, Waldhäusl W, Baumgartner-Parzer SM: Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells. Thrombosis and Haemostasis 93, 810-815, 2005 (Short Communication). Dorfmeister B, Brandhofer S, Schaap FG, Herman M, Fürnsinn C, Hagerty BP, Stangl H, Patsch W, Strobl W: Apolipoprotein AV does not contribute to hypertriglyceridemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats. Diabetologia, in press. Brunmair B, Staniek K, Dörig J, Szöcs Z, Stadlbauer K, Marian V, Gras F, Anderwald C, Nohl H, Waldhäusl W, Fürnsinn C: Activation of PPAR-� in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids. Diabetologia, 49:2713-2722, 2006. Fürnsinn C, Willson TM, Brunmair B: PPAR-�, a regulator of oxidative capacity, fuel switching, and cholesterol transport. Diabetologia, 50:8-17, 2007 (Review). Krebs M, Brunmair B, Brehm A, Artwohl M, Szendroedi J, Nowotny P, Roth E, Fürnsinn C, Promintzer M, Anderwald C, Bischof M, Roden M: The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man. Diabetes 56:1600-1607, 2007.

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Anderwald C, Brunmair B, Stadlbauer K, Krens M, Fürnsinn C, Roden M: Effects of free fatty acids on carbohydrate metabolism and insulin signalling in perfused rat liver. European Journal of Clinical Investigation, submitted

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Gabriele HÄUSLER Pediatric Department, Medical University of Vienna [email protected] An in vitro model of growth plate chondrocytes Abstract Longitudinal growth takes place at the growth plate (GP), or physis - a highly organized structure within the distal ends of long bones. Elongation of bone is established by the process of enchondral ossification, where a synchronized sequence of chondrocyte differentiation and proliferation is regulated by means of endocrine, paracrine and autocrine mechanisms. From a clinical point of view, a reduction or increase of relevant hormones (e.g., growth hormone, thyroid hormone, sex steroids, glucocorticoids) is accompanied by distinct pictures of growth failure or excess. At the level of the growth plate, the mechanisms underlying these growth disorders are poorly understood and concepts have derived from animal models, mainly rodents. While the local actions of growth stimulating factors like GH and IGF-I have been well documented, at least in animal models, the mode of action of skeletal maturation/closure of the growth plate during puberty is obscure. It has been shown that both estrogen receptors (ER) alpha and ER beta are expressed within the growth plate throughout childhood and puberty and that estrogen is the hormone mediating closure of the growth plate in both sexes. As estrogens can be synthesized locally by means of aromatization of precursors, even within the cell (intracrine), these processes are not mirrowed by serum levels of hormones. Investigation of growth plate tissue has mainly been performed in rodents (which do not close their GPs completely), and human material is very limited. In previous work our group has investigated the presence of ERs, matrix composition and the role of matrix degrading encymes (metalloproteinases) in human childhood and adolescent growth plates in vivo by immunohistochemistry. For further studies, we are currently developing an porcine in vitro model of growth plate chondrocytes. After characterization of the model and comparison with in vivo findings, it is the aim to study the effects of relevant hormones and growth factors (GH, IGF-I, estrogens) and of different treatments (chemotherapy, irradiation) on chondrocyte proliferation, differentiation and matrix production. Thesis Subjects Characterization of a porcine in vitro model of growth plate differentiation, proliferation and matrix synthesis. Effect of sex steroids on chondrocyte differentiation and matrix production in vitro. Techniques and infrastructure Tissue preparation, cell isolation, cell culture, immunohistochemistry , immunocytochemistry, quantitativeRT-PCR, Immunoblot. Collaborations within the Medical University and the University of Veterinary MedicineVienna.

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Curriculum Vitae

Gabriele HÄUSLER Department of Pediatric, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 3238; Email: [email protected] Personal Data Date of Birth: 28.04.1962 Nationality Austria Education June 1996 Habilitation 01.03.1996 Fully qualified in Paediatrics 1994-1995 Research scholarship of Austrian Ministery for

Education & Science Nov 1986 – Oct 1987 Postdoctoral research fellow 1980 – 1986 Medical School Vienna/Medical doctor Career History Since 2006 Head of the Endocrine Outpatient Clinic Since 1996 Associate Professor Since 01.06.1996 Consultant for Pediatric Endocrinology at the

University Children’s Hospital Vienna Since 1989 Registrar Oct 1987-1989 Junior physician Career-related Activities Since 1987 Participation in several clinical trials in Endocrinology.

Special fields: Growth and growth disorders. Clinical Resarch: Growth and hormone deficiency in children with brain tumors, Ullrich-Turner-Syndrom, Basic Research: Hormonal regulation of the growth plate.

05/2006 Opponent of PHD thesis at Karolisnka Hospital Since 2006 Board Member of Bone club ((ESPE) Since 2003 Board Member of Growth plate working group (ESPE)

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Memberships ESPE MESPE APED ÖGKJ Publications (since 2000) Helmreich M, Haeusler G, Egerbacher M. Distribution of Laminin, Fibronectin, Collagen I,II,IV, and X in the human adolescent and childhood growth plate. Scanning 2000 (A) Meszaros F, Vergesslich K, Riedl S, Hausler G, Frisch H: Posterior pituitary ectopy in children with idiopathic growth hormone deficiency. J Pediatr Endocrinol Metab 13(6):629-35 (2000) Frisch H, Kim C, Hausler G, Pfaffle R: Combined pituitary hormone deficiency and pituitary hypoplasia due to a mutation of the Pit-1 gene. Clin Endocrinol (Oxf) 52(5):661-665 (2000) Haeusler G, Egerbacher M, Marlovits S, Helmreich M. Integrins and extracellular matrix proteins in the childhood and adolescent growth plate. Calcif Tiss Int 71(3):212-218 (2002) Egerbacher M, Haeusler G: Estrogen receptor-alpha and estrogen-receptor-beta are present in the human growth plate in childhood and adolescence, in identical distribution. Horm Res 58: 99-103 (2002) Egerbacher M, Haeusler G: Integrins in growth plate cartilage (invited review). Pediatric Endocrinology reviews 1: 2-8 (2003) Wachstum und Pubertät. DFP Fortbildung. Ärztemagazin Ausgabe 45/20003 Binder G, Renz A, Martinez A, Keselman A, Hesse V, Riedl S, Haeusler G, Fricke-Otto S, Frisch H, Heinrich JJ, Ranke MB: SHOX Haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. J Clin Endocrinol Metab 89: 4403-4408 (2004) Haeusler G, Walter I,. Helmreich M, Egerbacher M: Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation. Calcif Tiss Int 76:326-335 (2005) Hwa V, Haeusler G, Pratt KL, Little BM, Frisch H, Koller D, Rosenfeld RG: Absence of functional acid labile subunit (ALS), resulting in severe IGF deficiency and moderate growth failure. J Clin Endocrinol Metab 91:1826-1831 (2006)

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Binder+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Renz+A%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Martinez+A%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Keselman+A%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hesse+V%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Riedl+SW%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hausler+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Fricke%2DOtto+S%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Fricke%2DOtto+S%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Frisch+H%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Heinrich+JJ%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Ranke+MB%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Haeusler+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Walter+I%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Helmreich+M%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Egerbacher+M%22%5BAuthor%5D


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Michael J. HIESMAYR Div. Cardiac- Thoracic- Vascular Anaesthesia & Intensive Care, [email protected] Stress-induced hyperglycaemia: strategies for optimal perioperative risk management Abstract: Hyperglycemia is a frequent observation during acute illness such as myocardial infarction and after major surgery. The proportion of patients with hyperglycemia may be as high as 95-100% after cardiac surgery. Stress induced hyperglycemia has a detrimental effect on the outcome after myocardial infarction and cardiac surgery. Mortality may increase by a factor of 4 especially in previously non-diabetic patients. Control of hyperglycemia in order to normalize blood glucose is associated with a clear clinical benefit. This effect is most beneficial in previously non-diabetic patients with hyperglycemia. The exact target level of glycemic is still a matter of investigation, but normalization to values between 80-125 mg/dl is probably optimal. The strategy to maintain normoglycemia has been challenged since recent findings in several categories of patients such as those in septic shock and with acute medical illnesses were less encouraging. In contrast to these patients in whom therapy can only start after injury, surgical patients have a scheduled injury where deviations can be anticipated and preventive interventions to stimulate insulin secretion or maintain insulin responsiveness can be implemented. Thus surgical patients allow a precise determination of the optimal timing of strategies to normalise glycemia. Thesis subjects: What is the time course and optimal target value for perioperative glycemia control? Do preventive nutritional interventions (preoperative carbohydrates, arginine, etc) affect the metabolic status of surgical patients? Techniques and infrastructure: epidemiological analysis of 10.000 patients from a prospective database intervention trial with preoperative nutritional supplements and determination of insulin resistance with clamp-techniques and metabolic rate with indirect calorimetry

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Curriculum Vitae

Michael J HIESMAYR Department of Cardiac Thoracic Vascular Anaesthesia & Intensive Care, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; [email protected] Personal Data Date of Birth: 08.01.1954 Place of Birth: Bregenz, Vorarlberg, Austria Nationality Austria Education 10.07.1979 Graduation: Dr. med. 1973-1979 Medical School: University Innsbruck and Vienna 1960-1972 Primary, secondary School and College: Lycée

francais de Vienna, Baccalauréat scientifique Career History 10/2002-present Administrative Director, Department of Cardiac

Thoracic Vascular Anaesthesia & Intensive Care, Medical University Vienna

1-3/2000 Visiting Professor, Department of Anaesthesia II, University Joseph Fourier, Grenoble France

Since 1992 Vice-Chairman Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care

Since 1990 Director Cardiothoracic Intensive Care Univ, University Hospital

1987 – 1988 Research Grant Erasmus University Rotterdam (5+1 month) Pathophysiological Laboratory (Prof.A.Versprille)

1987 Board Certification Anaesthesia and Intensive Care From 01.01.1984 Residency for Anaesthesia and General Intensive

Care, University School of Medicine, Vienna 1981-1983 Residency for General and Family Medicine

Regional Hospital Feldkirch, Bregenz and Dornbirn, Vorarlberg, Austria

1979-1980 Postpromotional fellowship: Department Internal Medicine, University of Zürich (Prof.W.Siegenthaler)

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Career-related Activities 1989, 1990, 1991, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 2001, 2002 1990, 1992, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 20th Meeting 2000, 2001, 2002, 2003

Organisation and Participation in the Programming of Postgraduate Educational Programs: AKE (Association for clinical nutrition):Workshop for nutritional and infusion therapy: EACTA( European Association of Cardiothoracic Anaesthetists) (since 2000 Austrian Council representative) Annual Meeting in Vienna: 1990 IZI (Interdisciplinary Centre for Research and Development in Intensive Care) (Chairman) Annual Meeting Interactive Workshops for Clinical Epidemiology and Evidence Based Medicine since 1998 in Hittisau, Vorarlberg, 11th Workshop October 2004. EWCI (Workgroup for Postoperative Intensive Care Medicine / European Society of Intensive Care Medicine) (member since 1989, president since 2001)European Workgroup for Cardiothoracic Intensivists Annual Meeting 1996 Vienna Section Perioperative Intensive Care of the ESICM: Chairman 2003

Lecturer University of Vienna: - Theory and Practice of Artificial Ventilation - Clinical Symptoms in Intensive Care - Evidence Based Medicine: Application in Intensive Care - Malnutrition & acute illness - Heart failure in the ICU - Fluid replacement in the ICU - Sepsis & septic shock

Awards 1999 Hoechst Price of the Medical Faculty Sources of funding (since 2000)

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Period Organization Short Title K€/yr 1997 Medical Scientific

Foundation of the Federal Capital Vienna

Fuzzy-KBWEAN – Expert System for Weaning from the Ventilator

Areas of research and interest: - Continuous quality assessment in Intensive Care - Performance comparison in Intensive Care between Institutions - Organ specific metabolic and nutritional interventions - Stress-induced hyperglycemia - Malnutrition in hospitals - Evidence Based Medicine Publications 6 publications Peer reviewed manuscripts since 2000 (original research and reviews) First, last or corresponding author manuscripts: Lassnigg, A., A. Punz, R. Barker, P. Keznickl, N. Manhart, E. Roth, and M. Hiesmayr,

Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Br J Anaesth, 2003. 90(2): p. 148-54.

Lassnigg, A., M.J. Hiesmayr, P. Bauer, and M. Haisjackl, Effect of centre-, patient- and procedure-related factors on intensive care resource utilisation after cardiac surgery. Intensive Care Med, 2002. 28(10): p. 1453-61.

Dworschak, M., M. Franz, C. Khazen, M. Czerny, M. Haisjackl, and M. Hiesmayr, Mechanical trauma as the major cause of troponin T release after transvenous implantation of cardioverter/defibrillators. Cardiology, 2001. 95(4): p. 212-4.

Haider, W. and M. Hiesmayr, [Glucose-insulin-potassium (GIK) in prevention and therapy of myocardial ischemia]. Wien Klin Wochenschr, 2000. 112(7): p. 310-21.

Lassnigg, A., E. Donner, G. Grubhofer, E. Presterl, W. Druml, and M. Hiesmayr, Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. J Am Soc Nephrol, 2000. 11(1): p. 97-104.

Rajek, A., T. Pernerstorfer, J. Kastner, P. Mares, M. Grabenwoger, D.I. Sessler, G. Grubhofer, and M. Hiesmayr, Inhaled nitric oxide reduces pulmonary vascular resistance more than prostaglandin E(1) during heart transplantation. Anesth Analg, 2000. 90(3): p. 523-30.

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Alexandra KAUTZKY-WILLER Dept. Internal Medicine III, Clin. Div. Endocrinology and Metabolism; [email protected] Gestational diabetes (GDM) - a model of type 2 diabetes (DM2) Abstract Women with prior GDM display a wide range of abnormalities in insulin secretion and action postpartum. The cumulative incidence of DM2 in subjects with a history of GDM ranges from 5% to 70% depending on applied diagnostic criteria, ethnicity and the length of follow-up. GDM is a heterogeneous disease reflecting any cause of diabetes emerging during pregnancy. DM 2 results from a decline in insulin sensitivity associated with a ß-cell defect. However, it is still unclear whether the molecular mechanisms that underlie the metabolic defects of DM2 are also effective in GDM, which displays an identical metabolic profile throughout pregnancy and in part also afterwards. The Viennese Post-Gestational Diabetes Project (VPGDP) therefore describes prospectively a cohort of middle European women with prior GDM with well defined glucose metabolism both during pregnancy and postpartum and aims to determine their risk to develop an impaired glucose metabolism or type 2 diabetes (DM 2) within the first ten years after delivery. We will study changes in beta-cell function and insulin sensitivity and predictive factors for the progression to prediabetes or DM 2. These results should help to better understand the pathophysiology of the disease and to establish prevention programs. Furthermore, insulin secretion and sensitivity as well as lipid metabolism are studied throughout pregnancy in women with GDM compared to women with normal glucose tolerance during pregnancy. The relationship between metabolic parameters and adipocytokines, cytokines and inflammatory parameters will be studied in order to elucidate the changes occurring during pregnancy and the factors responsible for development of diabetic fetopathy. Thesis Subjects • Adipocytokines and cardiovascular disease in Diabetes mellitus Type 2 • Gestational Diabetes – a model of Type 2 Diabetes: vascular dysfunction,

atherosclerosis, inflammation in relation to changes in adipocytokines and hormones in the natural course of the disease

• Diabetic pregnancy: impact of maternal metabolism on diabetic fetopathy Techniques and infrastructure oGTT + FSIGT with mathematical models for evaluation of insulin secretion and sensitivity parameters; clamp technique; indirect calorimetry; IMT measurements; RIA, ELISA

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Curriculum Vitae

Alexandra KAUTZKY-WILLER Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 2126; Email [email protected] Personal Data Date of Birth: 1962 Place of Birth: Vienna, Austria Nationality Austria Education 1999 Subspecialty/Boards: Encorinology and Metabolism 1998 – present Associate Professor (a.o. Univ.-Prof.) 1997 Habilitation (Univ.Doz.) 1996 Specialist in Internal Medicine 1988 Doctor Medicinae Universae Diploma (MD): Medical

School, University of Vienna Career History 1998 - present Associate Professor, tenured position, Department of

Internal Medicine III, Div. of Endocrinology and Metabolism, Medical University of Vienna

Career-related Activities Reviewer:

Diabetologia, Diabetes Care, Am J Obstet Gyn, J Endocrinol & Metab, Diabetic Medicine, Eur J Clin Invest, Horm Med Res, Wien Klin Wschr

Member of the Board: Austrian Diabetes Association 2003 - 2005 - First Secretary 2001 - 2003 - Member 1999 - 2001 - Auditor Federation of International Danube Symposia (FID) 2003 – 2007 - First Secretary Member of Expert Panels: Diabetes Guidelines (Austrian Diabetes Association

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Diabetes and Pregnancy Guidelines (German Diabetes Association)

Awards

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Poster Award of the Austrian Diabetes Association 2003 1995 Hoechst Award (AGDP) Memberships Austrian Diabetes Association; Initiation: Diabetes and Pregnancy Study Group Austrian Obesity Association Austrian Society of Internal Medicine EASD (European Association for the Study of Diabetes Diabetes Pregnancy Study Group (2001, Oxford) Sources of funding (since 2000)

Period Organization Short Title k€ 2001 – 2003

FWF, Austrian Science Foundation

P14515-B08

Austrian Diabetes Association/Clin Project Award

Austrian Gestation Diabetes Project

Österr. Nationalbank Jubiliäumsfonds

Nr. 11198



Thomas Prikoszovich

Inflammation und endotheliale Dysfunktion bei Patientinnen 5 Jahre nach Gestationsdiabetes

2005 – (2007) (Dr. scient. med.)


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Ammon Handisurya Dynamic profile of plasma ghrelin, obestatin, visfatin and retinol-binding protein 4 concentrations in relation to parameters of insulin resistance in women with gestational diabetes mellitus

2006 – (2008) (Dr. scient. med.)

Publications (2000 - 2005) 25. Modeling beta cell secretion and kinetics of proinsulin during an oral glucose

test. Tura A, Thomaseth K, Kautzky-Willer A, Ludvik B, Prager R, Pacini G. In Health Science Simulation, N, Anderson JG and Katzper M (Eds.) , SCS Press, San Diego, USA, 2000

26. Dexamethasone lowers circulating E-selectin and ICAM-1 in healthy men. Yilma B, Blann AD, Stohlawetz P, Eichler HG, Kautzky-Willer A, Wagner OF. J Lab Clin Med, 2000; 135 (3): 270-274

27. The increased insulin sensitivity in growth hormone-deficient adults is reduced by growth hormone replacement therapy. Riedl M, Ludvik B, Pacini G, Clodi M, Kotzmann H, Wagner O, Kautzky-Willer A, Prager R, Luger A. Eur J Clin Invest 2000; 30 (9): 771-778

28. Elevated plasma leptin in gestational diabetes. Kautzky-Willer A, Prager R, Ludvik B, Pacini G, Tura A, Bieglmeyer Ch, Schneider B, Waldhäusl W. Diabetologia 2001; 44: 164-172

29. Ocular Hyperperfusion following onset of intensified insulin therapy is associated with decreased plasma endothelin-1 in type 1 diabetes. G. Fuchsjäger-Mayrl, A. Kautzky-Willer, B. Kiss, G. Rainer, O. Findl, M. Roden, O. Wagner, J. Pleiner, M. Wolzt, L. Schmetterer. Diabetologia 2002; 45: 883-889

30. The effects of Ipomoea batatas (Caiapo) on glucose metabolism and serum cholesterol in patients with type 2 daibetes: a randomized study. Ludvik B, Mahdjoobian K, Waldhäusl W, Hofer A, Prager R, Kautzky-Willer A, Pacini G. Diabetes Care 2002, 25: 239-240P.

31. Influence of metabolic control on splanchnic glucose uptake, insulin sensitivity, and the time required for glucose absorption in patients with type 1 diabetes. Georg M, A. Kautzky-Willer, K. Mahdjoobian , A. Hofer , R. Prager , G. Pacini , B. Ludvik. Diabetes Care 2002, 25: 2042-2047

32. Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. F. Mittermayer, BX. Mayer, A. Meyer, C. Winzer, OF. Wagner, M. Wolzt, A. Kautzky-Willer. Diabetologia 2002, 45: 1372-1378

33. Mathematical models of glucose and free fatty acids kinetics during oral glucose tolerance tests. K. Thomaseth, A. Pavan, G. Pacini, A. Kautzky-Willer, A. Avogaro. Proceedings of the Internat. Symp. on Health Sciences Simulation 2003, p103-107

34. Increased intramyocellular lipid concentration identifies impaired glucose


metabolsim in women with previous gestational diabetes. A. Kautzky-Willer, M. Krssak, Winzer Ch, Pacini G, A. Tura, Farhan S, Wagner W, Brabant G, Horn R, Stingl H, Schneider B, Waldhäusl W, Roden M. Diabetes 2003, 52: 244-251

35. Basal and dynamic proinsulin-insulin relationship to assess b-cell function during OGTT in metabolic disorders. A. Tura, G. Pacini, A. Kautzky-Willer, B. Ludvik, R. Prager, K. Thomaseth. Am J Physiol 2003, 285: E155-E162

36. Mode of action of Ipomoea Batatas (Caiapo) in type 2 diabetic patients. B. Ludvik, W. Waldhäusl, R. Prager, A. Kautzky-Willer, G. Pacini. Metabolism 2003, 52: 875-880

37. Plasma adiponectin, insulin sensitivity and subclinical inflammation in women with prior gestational diabetes. Ch. Winzer, A. Festa , B. Schneider , D. Bancher-Todesca, G. Pacini , T. Funahashi , OF. Wagner , A. Kautzky-Willer. Diabetes Care 2004, 27: 1721-1727

38. Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus. Ch. Worda, H. Leipold, Ch. Gruber, A. Kautzky-Willer, Köfler M., D. Bancher-Todesca. Am J Obstet Gynecol 2004, 191: 2120-2124

39. Haptoglobin phenotype and gestational diabetes. S Mustafa, Th Vukovich, Th Prokiszovich, Ch Winzer, B. Schneider, H. Ester-bauer, OF Wagner, A. Kautzky-Willer Diabetes Care 2004, 27: 2103-2107

40. Fetal hyperinsulinism and maternal one hour postload plasma glucose level. H. Leipold, A. Kautzky-Willer, Özbal A., Ch. Worda, Bancher-Todesca D., Ch. Worda. Obstet Gynecol 2004, 104: 1301-1306

41. Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control. H. Leipold,Ch. Worda, Ch. J. Gruber, A. Kautzky-Willer, PW. Husslein, D. Bancher-Todesca. Wien Klin Wochenschr 2005, 117: 521-5

42. Severe diabetic fetopathy despite strict metabolic control. H Leipold, J Schwindt, A Kautzky-Willer, D Bancher-Todesca, Ch Worda, PW. Husslein. Wien Klin Wochenschr 2005, 117: 561-4

43. Metabolic indices for improved characterization of subjects with impaired glucose tolerance. Tura A., Mari A., Winzer Ch., Kautzky-Willer A., Pacini G. In Proc. X Mediterranean Conf. On Medical and Biological Engineering (MEDICON 2004), CD-ROM, ISSN 1727-1983, ISBN 88-7780-308-8, paper # 295

44. Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not the second trimester. Leipold H, Worda C, Gruber CJ, Prikoszovich T, Wagner O, Kautzky-Willer A. Eur J Clin Invest 2005, 35: 752-7

45. Tura A, Kautzky-Willer A, Pacini G. Insulinogenic indices from insulin and C-peptide: comparison of beta-cell function from OGTT and IVGTT. Diab Res & Clin Pract 2006, 72: 298-301

46. Tura A, Mari A, Winzer C, Kautzky-Willer A, Pacini G. Impaired beta cell function in lean normotolerant former gestational diabetic women. Eur J Clin Invest 2006, 36: 22-8

47. Kautzky-Willer A, Tura A, Winzer C, Wagner OF, Ludvik B, Hanusch-Enserer U, Prager R, Pacini G. Insulin sensitivity during OGTT and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinediones. Diab Obesity Metab 2006, in press

48. S. Farhan, C. Winzer, P Quehenberger, C Bieglmaier, O. F. Wagner, G. Pacini,

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A. Tura, K. Huber, W. Waldhäusl, A. Kautzky-Willer. PAI-1 plasma levels in women with a history of gestational diabetes. Eur J Clin Invest 2006, 36: 345-352

49. Morbiducci U, Di Benedetto G, Kautzky-Willer A, PaciniG, Tura A. Improved usability of the minimal model of insulin sensitivity based on automated approach and genetic algorithisms for parameter estimation. Clinical Science 2007, 112: 257-263

50. Mittermayer F, Kautzky-Willer A (corresponding author), Winzer Ch, Krzyzanoska K, Prikoszovich Th, Demehri S, Wagner O, Wolzt M. Elevated concentrations of asymmetric dimethylarginine are associated with deterioration of glucose tolerance in women with previous gestational diabetes mellitus. Journal of Internal Medicine 2007, 261: 392-398

51. Gasic S, Winzer Ch, Bayerle-Eder M, Roden A, Pacini G, Kautzky-Willer A.Impaired cardiac autonomic function in women with prior gestational diabetes. Eur J Clin Invest 2007, 37: 42-47

52. Haider D, Handisurya A, Storka A, Vojtassakova E, Luger A, Pacin G, Tura A, Wolzt M, Kautzky-Willer A. Visfatin response to glucose is reduced in women with gestational diabetes mellitus. Diabetes Care 2007, in press

53. Riedl M, Maier C, Handisury A, Luger A, Kautzky-Willer A. Ghrelin regulation in pregnancy is independent of glucose metabolism. Journal of Internal Medicine 2007, in press

Reviews 1. Epidemiologie, Ätiologie und neue therapeutische Konzepte bei Adipositas. B

Ludvik, A. Kautzky-Willer, R Prager. Therapiewoche Österreich 1992, 7:10-16. 2. Gestationsdiabetes. Kautzky-Willer A. Diabetes und Stoffwechsel 1998, 7: 197-

203 3. Diabetes-Screening in der Schwangerschaft. D. Bancher-Todesca, H. Leipold,

P. Husslein, A. Kautzky-Willer. Geburtshilfe und Frauenheilkunde 2003, 63: 223-229

4. Übergewicht und Diabetes in der Schwangerschaft. A. Kautzky-Willer, Ch. Winzer. Journal für Ernährungsmedizin 2002, 3: 7-12

5. Gestationsdiabetes. Kautzky-Willer A und Bancher-Todesca Dagmar. Wien. Med. Wochenschr. 2003, 153: 478-485

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Michael KREBS Dept. Internal Medicine III, Clin. Div. Endocrinology and Metabolism; [email protected] Hepatic glycogen metabolism and profiles of glucose and glucoregulatory hormones in patients with type 1 diabetes mellitus after pancreatic transplantation Abstract Background: Subjects with poorly controlled type 1 diabetes mellitus have a major defect in postprandial hepatic glycogen synthesis resulting in lower hepatic glycogen content and higher hepatic glucose output. Pancreatic transplantation is an effective treatment of diabetes mellitus and results in postprandial glucose metabolism similar to that in nondiabetic subjects on comparable immunosuppressive agents. However, in contrast to the physiological secretion of insulin into the portal vein, insulin is usually drained into the systemic circulation in pancreas transplanted patients. Therefore, this operation results in peripheral hyperinsulinemia and relative low portal insulin concentrations.

Hypothesis: An optimized peripheral insulin supplementation achieved by pancreas transplantation might correct not only hyperglycaemia but also defects in postprandial glycogen synthesis in liver associated with type 1 diabetes. Alternatively, peripheral hyperinsulinemia and portal insulin deficiency associated with pancreas transplantation and systemic drainage of insulin might augment the impairment in postprandial hepatic glycogen storage observed in patients with type 1 diabetes treated with s.c. insulin. The successfully pancreas transplanted type 1 diabetic patients might also serve as a model to elucidate the question whether an optimized peripheral insulin therapy (including s.c. insulin application which is the current standard of care) is in principal able to correct impaired hepatic glycogen metabolism observed in type 1 diabetes.

Objectives: To evaluate glycogen metabolism in liver, rates of endogenous glucose production as well as day-time profiles of plasma glucose and glucoregulatory hormones in patients with type 1 diabetes mellitus after pancreas-kidney transplantation compared to nondiabetic patients after successful kidney transplantation and healthy humans.

Population: Three groups will be studied: 10 patients with type 1 diabetes mellitus and functioning pancreas-kidney transplants with systemic venous drainage, 10 nondiabetic subjects with functioning kidney transplants, and 10 healthy control subjects

Outcome Variables: Postprandial glycogen synthesis (µmol·l-1 liver·min-1) in liver as calculated from the slope of the glycogen concentration over time before and after ingestion of a standardized meal. Repetitive in vivo NMR spectroscopy of natural abundance 13C glycogen in the liver to calculate net hepatic glycogen synthesis after standardized test-meals. Rates of fasting endogenous glucose production will be calculated as the tracer (D-[6,6-2H2]-glucose) infusion rate divided by the average percentage of 2H2 enrichment in C6 of plasma glucose under steady-state conditions. Thesis Subjects • Hepatic glycogen metabolism and profiles of glucose and glucoregulatory

hormones in patients with type 1 diabetes mellitus after pancreatic transplantation

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• Morbid obesity and weight reduction: Impact on molecular mechanisms of insulin resistance

Techniques and infrastructure metabolic research ward; various clamp techniques, nuclear magnetic resonance spectroscopy, tracer studies -glucose turnover, analysis of signaling events in biopsies of skeletal muscle by immunoblotting, all equipment available

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Curriculum Vitae

Michael KREBS Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4310; Fax +43 1 40400 7790; Email [email protected] Personal Data Date of Birth 28.07.1971 Place of Birth: Nationality Austria Education 1996-07-02 MD degree Jan 1994 – June 1996 Research work for my MD-thesis „Function of

heparin cofactor II outside the hemostatic system at the Department for Vascular Biology and thrombosis Research (Head: Prof.B.R. Binder, MD)

Nov 1992 – Feb 1993 Research training in the Laboratory for Clinical & Experimental Physiology

Oct 1990 – July 1996 University of Vienna Medical School Career History Oct 2005 Associate Professor of Internal Medicine Aug 1999 – Aug 2005 Residency in Internal Medicine at the Division of

Endocrinology and Metabolism, Department of Internal Medicine III, (Head: Prof.W.Waldhäusl) with rotations in Endocrinology and Metabolism, Gastroenterology and Hepatology, Hematology, Nephrology and Transplantation, Emergency Medicine and Intensive Care

Aug 1999 Successful participation at the EASD Clinical Scientist’s Training Course in Uppsala

Oct 1998 – Aug 1999 Post doctoral training in the group of Prof.M.Roden at the Dep. of Internal Medicine III, Div. of Endocrinology & Metabolism (Head:

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Prof.Dr.W.Waldhäusl) July 1996 – Dec 1998 Postdoctoral training at the Department of

Vascular Biology and thrombosis Research (Head: Prof.BR Binder), Univ of Vienna, Medical School

Career-related Activities Research experience:

I received an in depth training in all basic biochemical techniques (protein purification, affinity- and gel chromatography, FPLC, ELISA, PAGE, W - blot, various activity assays for enzymes and inhibitors). In addition I gained comprehensive experience in the field of tissue culture and cell biology (FACS, Northern-Blot, Immunohistochemistry). A major focus of my research work was the pathogenesis of vascular disease associated with the insulin resistance syndrome and renal insufficiency. During the recent years I performed studies on glucose metabolism in normal volunteers and diabetic subjects using NMR spectroscopy (non-invasive determination of glycogen concentrations in skeletal muscle and liver, muscular glucose-6-phosphate, and intracellular lipids). Our group also applies various tracer techniques and biopsies of skeletal muscle in combination with hyperinsulinemic- and pancreatic-clamp tests to determine rates of glucose turnover, gluconeogenesis, and molecular mechanisms insulin resistance. I am especially interested in elucidating the mechanisms of nutrient induced insulin resistance in humans.

Awards 1992, 1993, 1994, 1995 1994

I received achievement awards from the Faculty of Medicine, University of Vienna for excellent performances in medical school Research award granted by the University of


February, 1997 June, 2002 December, 2002 April, 2003 November, 2003 April, 2004 October, 2005

Vienna for the project „Inhibition of serine proteases of the alternative pathway of complement by heparin cofactor II Best abstract award for „Complex formation of heparin cofactor II (HCII) and complement factor D (Adipsin)“ at the 41st Annual Meeting of the Society for Thrombosis and Hemostasis Research Aventis-Award for: Effects of short-term improvement of insulin treatment and glycemia on hepatic glycogen metabolism in type 1 diabetes mellitus Theodor Billoth-Award for: Mechanism of amino acid-induced skeletal muscle insulin resistance in humans Theodor Körner-Award for: „ Investigation of direct Effects of Amino Acids on Insulin Resistance and Glucose Metabolism in Humans.“ Project award by the Austrian Diabetes Association (35.000 €) for: „Molecular mechanisms of amino acid induced insulin resistance in human skeletal muscle“ Best abstract award of the European Society for Clinical Investigation for: Amino acid induced hepatic and skeletal muscle insulin resistance in humans. Josef Skoda-Project Award of the Austrian Society of Internal Medicine (40 000 €) for: “Morbid obesity and weight reduction: Impact on molecular mechanisms of insulin resistance”

Memberships Austrian Society of Internal Medicine Austrian Diabetes Association Austrian Society of Nephrology European Association for the Study of Diabetes Sources of funding (since 2000)

Period Organization Short Title K€

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2003-2005 Austrian Diabetes Association

Molecular mechanisms of amino acid induced insulin resistance in human skeletal muscle“

35

2005 - Austrian Society of Internal Medicine

Morbid obesity and weight reduction: Impact on molecular mechanisms of insulin resistanc

40

2007 - Austran National Bank

Hepatic glycogen metabolism and profiles of glucose and glucoregulatory hormones in patients with type 1 diabetes mellitus after pancreatic transplantation

54

Supervision of doctoral students (since 2000) Name Title of thesis Period (expected) Acad.Ti

Miriam Promintzer

Morbid obesity and weight reduction: Impact on molecular mechanisms of insulin resistanc

11.2005 – (11.2008)

(PhD)

Publications A. Original research: Krebs M, Stingl H, Nowotny P, Weghuber D, Bischof M, Waldhäusl W, Roden M: Prevention of in vitro lipolysis by tetrahydrolipstatin. Clin Chem 46:950-954, 2000 (IP: 5.538) Bischof MG, Ludwig C, Hofer A, Kletter K, Krebs M, Stingl H, Nowotny P, Waldhäusl W, Roden M: Hormonal and metabolic counterregulation during and after high dose insulin induced hypoglycemia in diabetes mellitus type 2. Hormon Metabol Res 32:417-423, 2000 (IP: 1.669) Polak K, Schmetterer L, Luksch A, Gruber S, Polska E, Peternell V, Bayerle-Eder M, Wolzt M, Krebs M, Roden M: Free fatty acids/triglycerides increase ocular and subcutaneous blood flow. Am J Physiol Regulatory Integrative Comp Physiol 280:R56-R61, 2001 (IP: 3.627) Bischof MG, Krssak M, Krebs M, Bernroider E, Stingl H, Waldhäusl W, Roden M: Effects of short-term improvement of insulin treatment and glycemia on hepatic glycogen metabolism in type 1 diabetes mellitus. Diabetes 50:392-398, 2001 (IP: 8.298) Stingl H, Krssak M, Krebs M, Bischof M, Nowotny P, Fürnsinn C, Shulman GI, Waldhäusl W, Roden M: Lipid-dependent control of hepatic glycogen stores in healthy man. Diabetologia 44:48-54, 2001 (IP: 5.689)

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Krebs M, Krssak M, Weghuber D, Nowotny P, Gruber S, Mlynarik V, Bischof MG, Stingl H, Fürnsinn C, Waldhäusl W, Roden M: Free fatty acids inhibit the glucose-stimulated increases of intramuscular glucose-6-phosphate concentrations in man. J Clin Endocrinol Metab 86:2153-2160, 2001 (IP: 5.876) Bischof MG, Bernroider E, Krssak M, Krebs M, Stingl H, Nowotny P, Yu C, Schulman G, Waldhäusl W, Roden M: Hepatic glycogen metabolism in type 1 diabetes mellitus after long-term near normoglycemia. Diabetes 51:49-54, 2002 (IP: 8.298) Krebs M, Krssak M, Bernroider E, Nowotny P, Anderwald C, Brehm A, Roth E, Waldhäusl W, Roden M: Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 51:599-605, 2002 (IP: 8.298) Krebs M, Brehm A, Krssak M, Anderwald C, Bernroider E, Nowotny P, Roth E, Chandramouli V, Landau BR, Waldhäusl W, Roden M: Direct and indirect effects of amino acids on hepatic glucose metabolism. Diabetologia, 46:917-925, 2003 (IP: 5.689) Krebs M, Geiger M, Polak K, Vales A, Schmetterer L, Waldhäusl W, Binder BR, Roden M: Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. Thromb Heamostas 90:422-428, 2003 (IP: 4.950) Tremblay F*, Krebs M*, Brehm A, Bernroider E, Pfeiler G, Novotny P, Waldhäusl W, Marette A, Roden M: Overactivation of S6K1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 54: 2674-84, 2005 (IP: 8.298) *both authors equally contributed to this work Bischof MG, Brehm A, Bernroider E, Krssak M, Mlynarik V, Krebs M, Roden M: Cerebral glutamate metabolism during hypoglycemia in healthy and type 1 diabetic humans. Eur J of Clin Invest, 36:164-9, 2006 (IP: 2.346) Krebs M, Brunmair B, Brehm A, Artwohl M, Szendrödi J, Nowotny P, Roth E, Fürnsinn C, Promintzer M, Anderwald C, Bischof M, Roden M: The mTOR-pathway regulates nutrient sensitive glucose uptake in man. Diabetes 56:1600-1607,2007 Anderwald C, Anderwald-Stadler M, Promintzer M, Prager G, Mandl M, Nowotny P, Bischof MG, Wolzt M, Ludvik B, Kästenbauer T, Pacini G, Luger A, Krebs M: Clamp-like Index: a Novel, Highly Sensitive Insulin Sensitivity Index to Calculate Hyperinsulinemic Clamp Glucose Infusion Rates from Oral Glucose Tolerance Test in Nondiabetic Humans. Diabetes Care 2007; E-pub B. Reviews: Geiger M, Krebs M, Jerabek I, Binder BR: Protein C inhibitor (PCI) and heparin

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cofactor II (HCII): Possible alternative roles of these heparin-binding serpins outside the hemostatic system. Immunopharmacology 36:279-284, 1997 (IP: 0.776) Binder BR, Christ G, Gruber F, Grubic N, Hufnagl P, Krebs M, Mihaly J, Prager GW: Plasminogen activator inhibitor 1: physiological and pathophysiological roles. News Physiol Sci 17:56-61, 2002 (IP:3.682) Krebs M, Roden M: Nutrient induced insulin resistance in human skeletal muscle. Current Medicinal Chemistry, 11:901-908, 2003 (IP: 4.409) Krebs M, Roden M: Molecular mechanisms of lipid induced insulin resistance. Diabetes Obes Metab, 7:621-32, 2005 (IP: 1.528) Krebs M: Amino acid-dependent modulation of glucose metabolism in humans. Eur J of Clin Invest, 35:351-354, 2005 (IP: 2.346)

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Bernhard LUDVIK Dept. of Internal Medicine III, Clin. Div. Endocrinology & Metabolism [email protected] Metabolic, nutritional and endocrine characteristics of morbid obesity and their changes following weigth loss Abstract Morbid obesity is characterized by an increased morbidity and mortality. The pathogenesis involves a variety of disturbed patterns of adipocytokines and satiety factors. The standard treatment of morbid obesity is bariatric surgery, which involves several methods such as gastric banding, gastric bypass or pace makers that help to reduce weight. The success rate of the respective methods is highly variable and not predictable. In addition, the enormous weight loss following bariatric surgery leads to profound changes in body composition, among them an undesirable loss of muscle mass. Current research focuses on three major topics related to surgery-induced weight loss: 1. Profiles of satiety factors and adipocytokines before and following weight reduction. Among other factors, recent research in our laboratory focused on visfatin, which for the first time has been shown to decrease following weight loss as well as on adipocyte fatty acid binding protein (AFABP), which, again for the first time, has been found to be increased in morbid obesity and reduced following weight reduction. 2. A major focus lies on the changes in body composition and the nutritional status before and after weight loss. We have demonstrated that the decrease in muscle mass cannot be prevented by additional oral protein supplementation. In the future we plan to investigate the impact of several surgical approaches on nutritional status and body composition and whether they can be prevented by appropriate nutritional intervention. 3. Morbid obesity is characterized by an increased incidence of psychiatric comorbidity such as eating disorders, which have to be taken into account as regards to optimizing treatment outcome. Current research focuses on the quality of life in these patients and whether the health benefits following weight loss correspond with improvement in general well being. Thesis Subjects Assessment of endocrine (adipocytokines), nutritional and psychological parameters in morbid obesity and their impact on overall efficacy following bariatric surgery Techniques and infrastructure Measurement of body composition (MRI, DEXA, BIA), analysis of adipocytokines and satiety factors (RIA, ELISA), assessment of nutritional (eating questionnaire) and

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psychological status, measurement of parameters of insulin secretion and insulin sensitivity, all equipment at site

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CURRICULUM VITAE Bernhard LUDVIK Department of Internal Medicine III, Division of Endocrinology and Metabolism,

Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Phone/Fax:: ++43 (01) 40 400

4364,

Mobile: 0664-308 67 63; E-mail: [email protected],

Homepage: http://www.bernhard-ludvik.at

Personal Data Date of Birth: June 21, 1961

Place of Birth: Vienna

Nationality: Austria

Education June 19, 1979 High School, Schottengymnasium in Vienna,

graduation

Languages: English, French

Feb. 7, 1985 Medical School, University of Vienna, graduation,

MD

Career History 1985 – 1992 Internship and residency from March 1, 1985 to

June 30, 1992 at the Medical Department II,

University of Vienna

Since July 1, 1991 Specialist in Internal Medicine

1991 – 1992 Military Service in the Austrian Army Hospital

1992 - 1994 Research Fellow at the University of California San

Diego

Since June 27, 1995 Assistant Professor of Medicine

Since 1996 Specialist in Endocrinology and Metabolism

Since October 01, 1998 Associate Professor of Medicine

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current employment Associate Professor of Medicine, University of

Vienna; Attending in Internal Medicine and

Endocrinology at the Division of Endocrinology and

Metabolism, Department of Internal Medicine III,

University of Vienna (Vienna General Hospital)

Leader of the working group on Obesity and Endocrinology

Honors and Awards 1992 Research Grant „Erste Österreichische Sparkasse“;

presented by the Austrian Medical Association

1992-1994 Fellowship Max Kade Foundation; Research at the

University of San Diego, California

1995 Hoechst Award presented by the Dean of the

Faculty of Medicine of Vienna in

1995 2nd Secretary of the Austrian Society of Internal

Medicine

1996-1997 1st Secretary of the Austrian Diabetes Association

1996-1999 1st Secretary of the Federation of the International

DONAU-SYMPOSIA on Diabetes mellitus

1996-1998 Vice President of the Austrian Obestiy Association

1998-2000 President of the Austrian Obestiy Association

2001 Chairman of the European Congress of Obestiy

ECO 2001

2002 2nd Secretary of the Austrian Society of Internal

Medicine

2002-2003 Vice President of the Austrian Obestiy Association

1998-2003 Assistant Editor of DIABETOLOGIA

2004 Founding Fellow of the SCOPE program (EASO)

2004

Memberships Austrian Medical Association

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Austrian Society of Internal Medicine

Austrian Society of Endocrinology

Austrian Obesity Association

Austrian Diabetes Association

American Diabetes Association

European Association for the Study of Obesity (EASO)

European Association for the Study of Diabetes (EASD)

European Group on Insulin Resistance (EGIR)

Federation of International Donau Symposia on Diabetes mellitus

Lipidforum Austriacum Current Positions Member of the Editoral Board „Current Diabetes Reviews” Advisory Board „Jatros. Zeitschrift für Diabetologie und Stoffwechsel“

Member of the Editorial Board and Editor in Chief of „Journal für Ernährungsmedizin“

2nd Secretary of the Austrian Society of Internal Medicine (2005)

Sources of funding (since 2000)

Period Organization Short Title K€ 2003 – 2007 Austrian National

Bank Jubilee Fund Project no. 10329

Einfluß von akuter und chronischer Alkoholaufnahme auf Insulinsensitivität und Endothelfunktion bei Typ 2 Diabetes Mellitus

70

1996 – 2000 Austrian National Bank Jubilee Fund Project no. 6138

Anwendung einer neuen, nicht- invasiven Methode (OG- Clamp) zur Evaluierung der splanchnischen Glukoseaufnahme

22



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Barbara Trip Der Einfluss einer proteinreichen (v.a. ovolactovegetabilen) Diät auf Parameter des Glukose- und Fettstoffwechsels bei mit Insulin behandelten Typ 2 Diabetikern

2004 – 2007 PhD

Raphaela Riener Selbstwirksamkeitserwartungen bei extremer Adipositas und deren Einfluss auf die Lebensqualitätsäußerungen nach operativer Therapie anhand der Diskrepanzen zwischen Befund und Befinden

2005 – (2008) (PhD)

Publications since 2000 Original papers and reviews Ludvik B: [Diabetes therapy related to etiology. Indications, uses and side effects of new insulin sensitizers]. MMW.Fortschr.Med. 142:27-28, 2000

Riedl M, Ludvik B, Pacini G, Clodi M, Kotzmann H, Wagner O, Kautzky-Willer A, Prager R, Luger A: The increased insulin sensitivity in growth hormone-deficient adults is reduced by growth hormone replacement therapy. Eur.J.Clin.Invest 30:771-778, 2000

Kautzky-Willer A, Pacini G, Tura A, Bieglmayer C, Schneider B, Ludvik B, Prager R, Waldhausl W: Increased plasma leptin in gestational diabetes. Diabetologia 44:164-172, 2001

Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ: A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539-548, 2001

Tura A, Ludvik B, Nolan JJ, Pacini G, Thomaseth K: Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT. Am.J.Physiol Endocrinol.Metab 281:E966-E974, 2001

Ludvik B, Mahdjoobian K, Waldhaeusl W, Hofer A, Prager R, Kautzky-Willer A, Pacini G: The effect of Ipomoea batatas (Caiapo) on glucose metabolism and serum cholesterol in patients with type 2 diabetes: a randomized study. Diabetes Care 25:239-40, 2002


Georg P, Kautzky-Willer A, Mahdjoobian K, Hofer A, Prager R, Pacini G, Ludvik B: Influence of metabolic control on splanchnic glucose uptale, insulin sensitivity, and the time required for glucose absorption in patients with type 1 diabetes. Diabetes Care 25:2042-2047, 2002

Ludvik B, Thomaseth K, Nolan, JJ, Clodi M, Prager R, Pacini G: Inverse relation between amylin and glucagon secretion in healthy and diabetic human subjects. Eur J Clin Invest 33, 316-322, 2003

Tura A, Pacini G, Kautzky-Willer A, Ludvik B, Prager R, Thomaseth K: Basal and dynamic proinsulin-insulin relationship to assess {beta}-cell function during OGTT in metabolic disorders. Am J Physiol Endocrinol Metab 285, E155-E162, 2003

Ludvik B, Waldhaeusl W, Prager R, Kautzky-Willer A, Pacini G: Mode of Action of Ipomoea batatas (Caiapo) in type 2 diabetic patients. Metabolism 52:875-880, 2003

Pichler B, Ludvik B: Future perspectives of pharmacotherapy of obesity. Journal für Kardiologie 10:427-429, 2003

Ludvik B, Neuffer B, Pacini G: Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic patients. Diabetes Care 27:436-440, 2004

Schindler K, Prager G, Ballaban T, Kretschmer S, Riener R, Buranyi B, Maier C, Luger A, Ludvik B: The Impact of Laparoscopic Adjustable Gastric Banding (LABG) on Plasma Ghrelin, Eating Behaviour and Body Weight. Eur J Clin Invest 34(8):549-54, 2004

Schindler K, Ludvik B: Methodische und praktische Aspekte der Bestimmung der Körperzusammensetzung [Assessment of Body Composition - methods and practical aspects]. Wien Med Wochenschr 154(13-14):305-12, 2004

Tripp B, Ludvik B: Medikamentöse Therapie der Adipositas [Pharmacotherapy of Obesity]. Wien Med Wochenschr 154(13-14):320-8, 2004

Bohdjalian A, Langer FB, Hoda A, Felberbauer FX , Silberhumer G, Zacherl J, Schindler K, Luger A, Ludvik B, Prager G: Chirurgische Therapie der Adipositas. Wien Med Wochenschr 154(13-14):329-33, 2004

Tripp B, Ludvik B: Neue Antiadiposita [Novel Anti-Obesity Drugs]. Acta Medica Austriaca 31(4):133–138, 2004

Cauza E, Hanusch-Enserer U, Strasser B, Ludvik B, Metz-Schimmerl S, Pacini G, Wagner O, Georg P, Prager R, Kostner K, Dunky A, Haber P: The Relative Benefits of Endurance and Strength Training on the Metabolic Factors and Muscle Function of People with Type 2 Diabetes Mellitus. Arch Phys Med Rehabil 86(8):1527-33, 2005

Langer FB, Reza Hoda MA, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzl E, Schindler K, Luger A, Ludvik B, Prager G: Sleeve Gastrectomy and Gastric Banding: Effects on Plasma Ghrelin Levels. Obes Surg 15(7):1024-9, 2005

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Cauza E, Hanusch-Enserer U, Strasser B, Ludvik B, Kostner K, Dunky A, Haber P: Continuous Glucose Monitoring in Diabetic Long Distance Runners. Int J Sports Med 26(9):774-80, 2005

Abrahamian H, Ludvik B, Schernthaner G, Prager R, Zellenka U, Knudsen L, Wascher T: Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).Horm Metab Res. 37(11):684-9, 2005

Langer FB, Bohdjalian A, Felberbauer FX, Fleischmann E, Reza Hoda MA, Ludvik B, Zacherl J, Jakesz R, Prager G: Does gastric dilatation limit the success of sleeve gastrectomy as a sole operation for morbid obesity? Obes Surg 16 (2):166-71, 2006

Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B: Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab. 91(4):1578-81, 2006

Riener R, Schindler K, Ludvik B: Psychosocial Variables, Eating Behavior, Depression and Binge Eating in Morbidly Obese Subjects. Eating Behaviors, 2006, in press

Bohdjalian A, Prager G, Aviv R, Policker S, Schindler K, Kretschmer S, Riener R, Zacherl J, Ludvik B: One year experience with Tantalus™: a New Surgical Approach to Treat Morbid Obesity. Obes Surg, 2006, in press

Schindler K, Haider D, Wolzt M, Rieger A, Gmeinhart B, Luger A, Nowotny P, Ludvik B: Impact of Antiretroviral Therapy on Visfatin and Retinol Binding Protein 4 in HIV+ Subjects, Eur J Clin Invest, 2006, submitted

Haider DG, Schindler K, Mittermayer F, Müller M, Nowotny P, Rieger A, Ludvik B, Wolzt M: Effect of rosiglitazone on visfatin and retinol binding protein-4 plasma concentrations in HIV-positive patients. Metabolism, 2006, submitted

Ludvik B, Hanefeld M, Pacini G: Improved Metabolic Control by Ipomoea (Caiapo) is Associated with Increased Adiponectin and Decreased High Sensitive C-reactive Protein and Fibrinogen Levels. Diabetes Care, 2006, submitted

Chapters in Books Ludvik B: Adipositas – Diagnostik und Therapie. In Ernährungsmedizin. Widhalm K, Diallo-Ginstl E, Eds. ÖAK 2000, 334-346 Ludvik B: Konservative Therapie der morbiden Adipositas. In Morbide Adipositas – Klinik und Therapie. Hell E, Miller K, Eds. Ecomed 2000, 20-25 Ludvik B: Sekundäre Diabetesformen. In Diabetes in der Praxis. Waldhaeusl W, Gries FA, Scherbaum W, Eds. Springer Verlag Berlin 2004 Ludvik B: Diabetes mellitus: ein progerones Krankheitsbild. Therapie, Prävention und Einfluss von Lifestyle. In Angewandte Anti-Aging-Medizin. Gasser R (Hg). Verlagshaus der Ärzte 2004

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Abrahamian+H%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Ludvik+B%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Schernthaner+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Prager+R%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Zellenka+U%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Knudsen+L%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Wascher+T%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Langer+FB%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Bohdjalian+A%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Felberbauer+FX%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Fleischmann+E%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Reza+Hoda+MA%22%5BAuthor%5D



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Zacherl+J%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Jakesz+R%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Prager+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Haider+DG%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Schindler+K%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Schaller+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Prager+G%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Wolzt+M%22%5BAuthor%5D



Books Ludvik B (Hrsg.): Risikofaktor Diabetes – Konzepte für ein Langzeitproblem. Uni-Med-Verlag Bremen, 1.Aufl. 2004 [ISBN: 3-89599-824-9]

Ludvik B, Toplak H: Medikamentöse Therapie der Adipositas. Springer Verlag Wien, 1.Aufl. 2006 [ISBN: 3-211-83815-5] Mihaljevic K, Feffer S, Ludvik B: Essen mit Spass + Aktivsein mit Mass. So entkommen Sie dem Metabolischen Syndrom, Verlagshaus der Ärzte, 1. Aufl. 2006

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Anton LUGER Dept. Internal Medicine III, Div. Endocrinology and Metabolism; [email protected] Non-genomic effects of glucocorticoids on carbohydrate metabolism Abstract Glucocorticoids are known to bind to intracellular receptors and initiate genomic signaling mechanisms leading to combined actions on glucose metabolism (suppression of insulin secretion, inhibition of glucose uptake in peripheral tissues and promotion of gluconeogenesis in the liver). The final result is an increase in blood glucose levels. Although glucocorticoids are released at high levels within minutes in response to any stress or threat to homeostasis (e.g. hypoglycemia), the discovery of intracellular receptors that translocate to the nucleus and modify the transcription of target genes has focused research on genomic signaling mechanisms, which lead to effects more than 30 min after glucocorticoid exposure. In the last decade, there is a booming research in the field of non-genomic steroid signaling whose effects occur within minutes. Nevertheless, very little is known about rapid effects of glucocorticoids on carbohydrate metabolism and there are no data on the respective signaling mechanisms. Such work dates many decades ago and is mainly focused on the rapid impact on insulin secretion in vivo and peripheral glucose uptake in vitro. Glucocorticoids are important therapeuticals with, unfortunately, major metabolic side effects. A full knowledge of other signaling mechanisms and possibly receptors, mediating glucocorticoid effects would help in discovering novel drug targets with an optimized benefit-risk-ratio. Starting from this current knowledge, we began to study the rapid (within minutes) effects of glucocorticoids on carbohydrate metabolism and found a significant increase in insulin secretion from the INS-1E and Rinm5F rat beta-cell lines after stimulation with 100nM Dexamethasone for 15 minutes. Therefore, we plan to study the second messengers and other signaling mechanisms involved in this effect and to check the presence of possible glucocorticoid membrane binding sites using fluorescence correlation spectroscopy (FCS), a method recently established in our laboratory. At the same time we plan to study the rapid effects of glucocorticoids in the periphery, namely their effect on glucose uptake in primary cultures of adipocytes and muscle cells. Glucocorticoid membrane binding will be investigated in both these models using FCS. The 3T3-L1 fibroblast pre-adipocyte cell line will be used for studying the signaling mechanisms involved. In summary, this work could contribute to a hitherto unknown part of the physiology of glucocorticoid effects on carbohydrate metabolism. Thesis Subjects Rapid (non-genomic) effects of glucocorticoids on insulin release in beta cells and peripheral glucose uptake. Signaling mechanisms (receptors, second messengers, etc.) mediating these effects. Techniques and infrastructure

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Models: rat beta-cell lines, murine pre-adipocyte cell line, primary cultures of human adipocyte and muscle cells. Experiments: stimulation experiments, RIA, intracellular free calcium & cAMP measurement, Western Blotting. All required equipment available.

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Curriculum Vitae Anton LUGER Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4310; Fax +43 1 405 93 234; Email [email protected] Personal Data Date of Birth: 03.10.1952 Place of Birth: Vienna Nationality Austria Education June 1978 MD Degree, University of Vienna, Austria 1987 Habilitation Career History 01.10.2005 – present Acting Head/Division of Endocrinology and Metabolism

of the Department of Medicine III, Unviersity of Vienna, Austria

1991 − present Department of Medicine III, Unviersity of Vienna, Austria

1986 – 1991 Department of Medicine II, University of Vienna 1985 – 1986 Visiting Fellow at the Developmental Endocrinology

Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

1980 – 1985 Resident, Departments of Medicine II and Cardiology, University of Vienna, Austria

1978 – 1980 Institute of Pharmacology, University of Vienna, Austria Career-related Activities 1995 – 2005 Deputy Head/Division of Endocrinology and

Metabolism/Department of Medicine III, Unviersity of Vienna, Austria

2005 – present Member of the Executive Committee of the European Neuroendocrine Association

2003 – 2004 President of the Austrian Society for Endocrinology and

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Metabolism 1999 – present Austrian Delegate at the Section of Endocrinology at

the UEMS (European Union of Medical Specialists) 1998 – 2002 Deputy Chairman of the Medical Faculty Assembly,

University of Vienna 1985 – 1986 Max Kade Fellowship Awards 2004 Award of the Erste Bank 1986 Award of the Austrian Society of Nephrology 1986 Max Kade Fellowship 1985 Max Kade Fellowship 1985 Hoechst Award 1982 Hoechst Award Memberships Austrian Diabetes Society European Society for the Study of Diabetes Austrian Society for Endocrinology and Metabolism Austrian Society for Internal Medicine Sources of funding (since 2000)

Period Organization Short Title total K€

2002 – 2006

FWF (P15958-B08) Membrane bound Glucocorticoid-Receptors

166

2003 – 2006

Jubiläumsfond der Österr.Nationalbank (10321)

Ghrelin: Regulation der Ausschüttung und Zusammenspiel mit autonomem Nervensystem und Nährstoffen

70

2004 – 2006

Bürgermeisterfonds der Bundeshauptstadt Wien

Microarray-Analyse von Hypophysentumoren

30

2004 – 2005

Hochschuljubiläums stifung Stadt Wien

Microarray-Analyse von Hypophysentumoren

6

2002 – 2003

Bürgermeisterfonds der

Untersuchungen zur physiologischen und pathophsiologischen Regulation des

27

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Bundeshauptstadt Wien (2179)

Peptidhormons Ghrelin

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Maier Christina (toghether with J.Smolen)

SLE & IDDM – eine seltene Kombination

2000-2001 Thesis MD

Schmidt Adele Untersuchungen zur Regulation der Ghrelin-Sekretion

2002-2003 Thesis MD

Altenberger Tibor (toghether with L.Wagner)

Aberrant Gene Expression Patterns in Pituitary Tumors

2004-2006 Thesis PhD

Kasses Dominik Auswirkungen der Stoffwech-seleinstellung auf das Endokrinium bei Diabetikern

ongoing Diploma MD

Gorczyca Monika Hypercortisolismus als Ursache einer unzureichenden Stoff-wechseleinstellung bei Typ 2 Diabetikern

ongoing Diploma MD

Publications Peer reviewed manuscripts since 2000 (original research and reviews)

First, last or corresponding author manuscripts:

Blank D, Riedl M, Reitner A, Schnack C, Schernthaner G, Clodi M, Frisch H, Luger A 2000 Growth hormone replacement therapy is not associated with retinal changes. J Clin Endocrinol Metab 85:634-636 Luger A 2000 Trau keinem über 30, Testosteron für alle Männer über 50? Wien Klin Wochenschr 112:339-340 Riedl M, Clodi M, Kotzmann H, Hainfellner JA, Schima W, Reitner A, Czech T, Luger A 2000 Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administrastion of hypothalamic releasing hormones: MR features. Eur J Radiol 36:1-4 Riedl M, Ludvik B, Pacini G, Clodi M, Kotzmann H, Wagner O, Kautzky-Willer A, Prager R, Luger A 2000 The increased insulin sensitivity in growth hormone-deficient adults is reduced by growth hormone replacement therapy : Eur J Clin Invest 30:771-778

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Kotzmann H, Yilmaz N, Lercher P, Riedl M, Schmidt A, Schuster E, Kreuzer S, Geyer G, Frisch H, Hörl WH, Mayer G, Luger A 2001 Differential effects of growth hormone therapy in malnourished hemodialysis patients. Kidney Int 60:1578-1585 Riedl M, Kotzmann H, Luger A 2001 Wachstumshormon beim älteren Mann. Wien Med Wochenschr 151:426-429 Hernberg-Stahl E, Luger A, Abs R, Bengtsson B, Feldt-Rasmussen U, Wilton P, Westberg B, Monson JP 2001 Healthcare consumption decreases in parallel with improvements in quality of life during growth hormone (GH) replacement in hypopituitary adults with GH deficiency. J Clin Endocrinol Metab 86:5277-5281 Kehely A, Bares PC, Frewer P, Birkett M, Blum WF, Mamessier P, Ezzat S, Ho KKY, Lombardi G, Luger A, Marek J, Russell-Jones D, Sönksen P, Attanasio AF 2002 Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms. J Clin Endocrinol Metab 87:1974-1979 Schmidt A, Luger A, Hörl WH 2002 Sexual hormone abnormalities in male patients with renal failure. Nephrol Dial Transplant 17:368-371 Maier C, Rünzler D, Wagner L, Grabner G, Köhler G, Luger A 2002 Evidence for specific glucocorticoid binding sites on the cell membrane by fluorescence correlation spectroscopy. Single Mol 3:211-216 Schaller G, Schmidt A, Pleiner J, Woloszczuk W, Wolzt M, Luger A. 2003 Plasma ghrelin concentrations are not regulated by glucose or insulin: a double-blind, placebo-controlled cross-over clamp study. Diabetes 52:16-20. Kotzmann H, Schmidt A, Riedl M, Schuster E, Geyer G, Frisch H, Hörl WH, Mayer G, Luger A. 2003 One year growth hormone therapy improves granulocyte function, but not nutritional and anthropometric parameters in malnourished hemodialysis patients. Nephron Clin Pract 93:c75-c82. Mogensen CE, Viberti G, Halimi S, Ritz E, Ruilope L, Jermendy G, Widimsky J, Sareli P, Taton J, Rull J, Erdogan G, De Leeuw PW, Ribeiro A, Sanchez R, Mechmeche R, Nolan J, Sirotiakova J, Hamani A, Scheen A, Hess B, Luger A. 2003 Effect of low-dose perindopril/ indapamide on albuminuria in type 2 diabetes. Preterax in albuminuria regression: PREMIER. Hypertension 41:1063-1071. Weitgasser R, Lechleitner M, Luger A, Klingler A. 2003 Effects of glimepiride on HbA1C and body weight in type 2 diabetes: results of a 1.5 year follow-up study. Diabetes Res Clin Pract 61:13-19. Pfeiffer C, Winkler F, Luger A, Pieber T, Saudek F, Skrha J, Hermansen K, Lervang HH, Nistrup-Holmegaard S, Bergkulla S, Lembcke HJ, Schulze J, Petersen KG, Haslbeck M, Jonker JJC, Vaaler S, Rolstad OJ, Distiller LA, Robertson LI, Omar MAK, Wing J, Arner P, Arnqvist H, Lager I, Lennerhagen P, Borthwick LJ, Hattersley A, Owens DR, Mathews DR, Nattrass M. 2003 Safety and efficacy of insulin glargine (HOE 901) versus NPH insulin in combination with oral treatment in Type 2 diabetic patients. Diabetic Med 20:545-551. Luger A. 2003 Erkrankungen der Hypophyse: Klinische Symptomatik und biochemische Diagnostik. Wien Klin Wochenschr 115 (Suppl 2):19-22. Feinböck C, Luger A, Klingler A, Egger T, Kacerovsky Bielesz G, Winkler F, Siebenhofer A, Großschädl F, Frank E, Irsigler K 2003 Prospective multicentre trial

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comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type diabetes not controlled with diet alone. Diab Nutr Metab 16:214-221 Kotzmann H, Riedl M, Pietschmann P, Schmidt A, Schuster J, Kreuzer S, Frisch H, Geyer G, Hörl WH, Mayer G, Luger A 2004 Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in malnourished patients on chronic hemodialysis. J Nephrol, 17:87-94 Schmidt A, Maier C, Schaller G, Nowotny P, Bayerle-Eder M, Buranyi B, Luger A, Wolzt M 2004 Acute exercise has no effect on ghrelin plasma concentrations. Horm Metab Res 36:174-177 Maier C, Riedl M, Clodi M, Bieglmayer C, Mlynarik V, Trattnig S, Luger A 2004 Dynamic contrast-enhanced MR imaging of the stimulated pituitary gland, Neuroimage 22:347-352 Schmidt A, Fabrizii V, Maier C, Riedl M, Schmidt A, Kotzmann H, Geyer G, Luger A. 2004 Normal regulation of elevated plasma ghrelin concentrations in dialysis patients. Wien Klin Wochenschr 116:235-239 Köller MD, Templ E, Riedl M, Clodi M, Wagner O, Smolen JS, Luger A 2004 Pituitary function in patients with newly diagnosed untreated systemic lupus erythematosus. Ann Rheum Dis 63:1677-1680 Maier C, Schaller G, Buranyi B, Nowotny P, Geyer G, Wolzt M, Luger A 2004 The cholinergic system controls ghrelin release and ghrelin induced GH release in humans. J Clin Endocrinol Metab 89:4729-4733 Schindler K, Prager G, Ballaban T, Kretschmer S, Riener R, Buranyi B, Maier C, Luger A, Ludvik B 2004. The impact of laparoscopic banding (LABG) on plasma ghrelin, eating behaviour and body weight. Eur J Clin Invest 34:549-554 Maier C, Luger A 2004 Endokrinologie und Adipositas. Acta Med Austriaca 31:112-114 Frossard M, Blank D, Joukhadar C, Bayegan K, Schmid R, Luger A, Müller M 2005 Interstitial glucose in skeletal muscle of diabetic patients during an oral glucose tolerance test. Diabetic Med 22:56-69 Maier C, Rünzler D, Schindelar J, Grabner G, Waldhäusl W, Köhler G, Luger A 2005 G-protein coupled glucocorticoid receptors on the pituitary cell membrane. J Cell Sci 118:3353-3361 Langer FB, Reza Hoda MA, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzel E, Schindler K, Luger A, Ludvik B, Prager G 2005 Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg 15: 1024-1029 Ziegler S, Kudlacek S, Luger A, Minar E 2005 Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease. Atherosclerosis 182:175-180 Luger A 2005 Schilddrüse und Polyendokrinopathien. Wiener Med Whschr, 155: 454-457 Maier C, Mustapic D, Schuster E, Luger A, Eher R 2006 Effect of a pocket-size tablet dispensing device on glycemic control in type 2 diabetic patients. Diabetic Medicine 23:40-45 Altenberger T, Bilban M, Auer M, Knosp E, Wolfsberger S, Gartner W, Mineva I, Zielinski C, Wagner L, Luger A 2006 Identification of DLK1 variants in pituitary and

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neuroendocrine tumors. Biochem Biophys Res Comm 340:995-1005 Riedl M, Maier C, Zettinig G, Nowotny P, Schima W, Luger A 2006 Long term control of hypercortisolism with fluconazole: case report and in vitro studies. Eur J Endocrinol 154:519-524 Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M 2006 The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia 49: 1909-1914 Gartner W, Koc F, Nabokikh A, Daneva T, Niederle B, Luger A, Wagner L 2006 Long-term in vitro growth of human insulin-secreting insulinoma cells. Neuroendocrinol 83: 123-130 Schindler K, Haider D, Wolzt M, Rieger A, Gmeinhart B, Luger A, Nowotny P, Ludvik B 2006 The adipocytokines visfatin and retinol binding protein 4 (RBP-4) before and following 12 months of antiretroviral therapy in HIV infected subjects. Eur J Clin Invest 36: 640-646 Zettinig G, Wrba F, Trautinger F, Peloschek P, Luger A 2006 Necrobiotic panniculitis due to repeated Insulin injection: A rare cause of a “false positive” Somatostatin receptor scintigraphy. Nuklearmedizin 45: N64-N66 Wieselthaler G, Riedl M, Templ E, Wolner E, Wagner O, Luger A, Clodi M 2007 Endocrine function is not impaired in patients with a continuous MicroMed-DeBakey axial flow pump. J Thorac Cardiovasc Surg 133: 2-6 Haider DG, Schindler K, Mittermayer F, Müller M, Nowotny P, Rieger A, Luger A, Ludvik B, Wolzt M 2007 Effect of rosiglitazone on visfatin and retinol binding protein-4 plasma concentrations in HIV-positive patients. Clin Pharmacol Ther 81: 580-585 Maier C, Mustapic D, Schuster E, Luger A, Eher R 2007 Effect of a pocket-size tablet-dispensing device on glycaemic control in type 2 diabetic patients. Author’s response. Diabet Med 24: 102 Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, Ludvik B 2007 Serum retinol-binding protein-4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 92: 1168-1171 Haider DG, Schindler K, Mittermayer F, Müller M, Nowotny P, Rieger A, Luger A, Ludvik B, Woltz M 2007 Plasma adipocyte and epidermal fatty acid binding protein is reduced after weight loss in obesity. Diabetes Obes Metab, in press Haider DG, Handisurya A, Storka A, Vojtassakova A, Luger A, Pacini G, Tura A, Wolzt M, Kautzky-Willer A 2007 Visfatin response to glucose is reduced in women with gestational diabetes mellitus. Diabetes Care, 30: 1889-1891 Gartner W, Vila G, Daneva T, Nabokikh A, Koc-Saral F, Ilhan A, Majdic O, Luger A, Wagner L 2007 New functional aspects of the neuroendocrine marker secretagogin based on the characterization of its rat homologue. Am J Physiol-Endoc M, 293: E347-354 Riedl M, Maier C, Handisurya A, Luger A, Kautzky-Willer A 2007 Insulin resistance has no impact on ghrelin suppression in pregnancy. J Int Med, in press Anderwald C, Stadler M, Promintzer M, Prager G, Mandl M, Nowotny P, Bischof M, Wolzt M, Ludvik B, Pacini C, Luger A, Krebs M 2007 Clamp-like index: a novel, highly sensitive insulin sensitivity index to calculate hyperinsulinemic clamp glucose infusion rates from oral glucose tolerance test in nondiabetic humans. Diab Care, in press

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Nabokikh A, Ilhan A, Bilban M, Gartner W, Vila G, Niedlere B, Nielsen JH, Wagner O, Base W, Luger A, Wagner L 2007 Reduced TGF-β1 expression and its target genes in human insulinomas. Exp Clin Endocr Diab, in press

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Wolfgang MARKTL Zentrum für Physiologie und Pathophysiologie der Medizinischen Universität Wien [email protected] Curriculum Vitae Geboren am 14. 5. 1944 in Waiern/Kärnten. Besuch der Volksschule in den Jahren 1950 bis 1954 in Klagenfurt. Besuch des Realgymnasiums in Klagenfurt von 1954 bis 1962, Matura am 4. 7. 1962. Medizinstudium in Innsbruck und Wien in den Jahren 1962 bis 1968. Promotion zum Dr.med.univ. am 15. 6. 1968 in Innsbruck. Vom 1.11.1968 bis 31.12. 1969 sowie vom 1. 4. 1970 bis zum 31. 5. 1972 Assistenzarzt am Institut für allgemeine und experimentelle Pathologie der Universität Wien, vom 1. 1. 1970 bis zum 31. 3. 1970 Assistenzarzt an der 1. Chirurgischen Univ. Klinik in Wien. Seit 1. 6. 1972 am Institut für Medizinische Physiologie der Universität Wien. Erlangung des Ius practicandi im Jahre 1976. Habilitation für medizinische Physiologie am 14. 1. 1983. Leiter der Abteilung für Umweltphysiologie und Balneologie am Zentrum für Physiologie und Pathophysiologie der Med.Univ. Wien Seit 1. 4. 1986 Leitung des Ludwig Boltzmann Institutes zur Erforschung physiologischer Rhythmen in Bad Tatzmannsdorf. Juni 1994 Anerkennung als Facharzt für medizinische Leistungsphysiologie Ernennung zum tit.a.o.Univ.Prof. mit 4.10.1994 Verleihung des Ehrenkreuzes für Wissenschaft und Kunst, I. Klasse, durch den Bundespräsidenten mit Datum von 28.09.2001 Wissenschaftliche Arbeitsgebiete: Ernährungs- und Stoffwechselphysiologie, Balneologie und medizinische Klimatologie, Chronobiologie Funktionen in wissenschaftlichen Vereinigungen und Verbänden: Leitung der Abteilung Wissenschaft im Österr. Heilbäder- und Kurorteverband, Mitglied des erweiterten Vorstandes und Ehrenmitglied des Verbandes Österr. Kurärzte, derzeit 1. Vorsitzender der Österr. Gesellschaft für Balneologie und medizinische Klimatologie, Gründungsmitglied der European Society for Chronobiology, Mitglied der International Society for Chronobiology, Vorstandsmitglied der Österreichischen Gesellschaft für Ernährung, korrespondierendes Mitglied der geologischen Bundesanstalt, Mitglied der European Academy of Nutritional Sciences, sowie Mitglied zahlreicher weiterer wissenschaftlicher Gesellschaften des In- und Auslandes. Schriftleiter der Zeitschrift “Forschende Komplementärmedizin” des Karger-Verlags bis 2007 Mitglied des Redaktionskollegiums der Zeitschrift “Physikalische Medizin, Rehabilitationsmedizin, Kurortemedizin” des Thieme-Verlags,

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Vorsitzender des Akademischen Rates der Wr. Internat. Akademie für Ganzheitsmedizin; von Juni 2000 bis Juni 2003 Vizepräsident der Wr. Internat. Akademie für Ganzheitsmedizin, Seit 24.06.2003 Präsident der Wr. Internat. Akademie für Ganzheitsmedizin, Mitglied der Codex-Kommission bis 2007 Seit 01.01.2002 Med.-Wiss. Leiter der Akademie für den Diätdienst und ernährungsmedizinischen Beratungsdienst im AKH Wien, Seit 29.01.2002 Vizepräsident des Akademischen Institutes für Ernährungsmedizin Publikationstätigkeit: derzeit 271 wissenschaftliche Publikationen, wissenschaftlicher Redakteur des Handbuchs der natürlichen Heilmittel Österreichs 1985, laufende Vortragstätigkeit im In- und Ausland, Teilnahme an Sendungen von Rundfunk und Fernsehen.

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Bruno NIEDERLE Section Endocrine Surgery, Division of General Surgery, Department of Surgery [email protected] Surgical strategy in thyroid nodules classified as "follicular neoplasia" Abstract The surgical strategy in thyroid nodules classified as "follicular neoplasia" by fine-needle aspiration (FNA) is still under discussion. The treatment of follicular adenoma is hemithyroidectomy (lobectomy and isthmectomy) while follicular thyroid carcinoma has to be treated by total thyroidectomy. If follicular lesions cannot be classified in frozen-sections completion thyroidectomy has to be performed in a second procedure. Therefore the role of frozen section, gender, age and tumor size in the differentiation of follicular adenoma from carcinoma has to be analyzed retrospectively to define risk factors. As a consequence a prospective protocol for the surgical treatment of "follicular thyroid lesions" should be developed. Molecular genetic studies on fresh tissue and on tissue samples will help to differentiate follicular adenoma, follicular carcinoma and the follicular variant of papillary thyroid cancer. Thesis Subjects Is it justified to treat follicular thyroid lesions larger than 25 mm by total thyroidectomy to avoid re-operations? Techniques and infrastructure Retrospective multivariate analysis of demographic, clinical, surgical, histopathological and follow-up data of 150 patients with follicular thyroid lesions classified as "follicular lesions" by FNA: Correlation of FNA - frozen section - histopathology and clinical outcome

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Curriculum Vitae

Bruno NIEDERLE Department of Surgery , Division of General Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 6943; 5621, 5622; Fax +43 1 40400 6827; Email [email protected] Personal Data Date of Birth: 25-08-1953 Place of Birth: Steyr, Upper Austria Nationality Austria Education Oct. 1st, 197 – May 20th, 1976 University of Vienna, Medical School - MD Career History May 1,1974 - April 30, 1976 June 1, 1976 - Sept 30, 1977 June 1, 1977 -Nov 30, 1977 Sept 19, 1978 – Sept 16, 1979 March 1, 1982 - August 31, 1982 March 1, 1983 - September 1, 1983 March 1, 1987 - August 31, 1987 Oct 1, 1988 - Feb 28, 1989

Student Lecturer, Department of Anatomy, University of Vienna Assistant Lecturer, Department of Anatomy, University of Vienna Intern, Department of Internal Medicine, Cardiology, University of Vienna Resident, Department of Traumatology I, University of Vienna Resident, Department of Anesthesiology, Intensive Care Unit, University of Vienna Senior Resident, Department of Surgery (incl. traumatology, pediatric surgery) Provincial Hospital Oberpullendorf Intern, Department of Pediatric Surgery , Mautner Markhof'sche Kinderspital Resident, Department of Surgery II, University of Vienna (Thoracic/Heart Surgery)

Since Oct 1, 1977 - pres. June 1, 1989/July 7, 1989

Resident/Chief Resident/ Senior Resident Department of Surgery, Division of General Surgery, University of Vienna, Medical School Assistant Professor of Surgery (Venia docendi)

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Nov 25, 1992/Sept 8, 1993 July 1, 1999/March 1, 2000

Associate Professor of Surgery Professor of Surgery (Endocrine Surgery)

December 7, 1983 May 15, 1992 April 6. 2003

Registration: Registered to practice surgery in Austria Registered to practice vascular surgery in Austria Qualification for “Endocrine Surgery” - European Board of Surgery

Fellowships Feb 1, 1977 - April 30, 1977 Research Fellowship at the University of Fribourg,

Switzerland, Department of Anatomy Career-related Activities 2002 – 2003 Management Training for Medical Leaders at the

Univ. Salzburg 2004 – present Section leader "Obesity and Lipid Disorders", Austrian

Society for Endocrinology and Metabolism 1980 1984 1985 1986 1987 1989 1990 1991 1993 1989

Visiting Physician National Institutes of Health, Cancer Institute, Surgical Branch, Bethesda, USA Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, USA Toronto General Hospital, Division of Thoracic Surgery, Toronto, Canada Mayo Clinics, Department of Surgery, Rochester, Minnesota, USA Department of Surgery, University of Chicago, Chicago, USA Department of General Surgery, Division of Endocrine Surgery, University of Michigan, Ann Arbor, USA Department of General Surgery, Division of Endocrine Surgery, University of Michigan, Ann Arbor, USA Baylor College of Medicine, Department of Surgery, Methodist Hospital and M.D. Anderson, Cancer Center, University of Texas, Houston, USA Department Surgery II, University of Nagoya, Japan Visiting Professor: Invited Guest Speaker - 1st International Postgraduate Course in Endocrine Surgery


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1990 1991 1993 1993 1993 1995 1997 1997 1999 1999 2001 2001 2002 2003 2003

Department of Surgery, The Mary Imogene Bassett Hospital Cooperstown, New York, USA Faculty Member: 2nd International Postgraduate Course in Endocrine Surgery (British Virgin Islands) Faculty Member/Organizer: 3rd International Postgraduate Course in Endocrine Surgery (Austria) Invited Guest Speaker - 26th Annual Meeting of the Japanese Society of Thyroid Surgeons, Nagoya Department of Endocrine Surgery, Tokyo Women's Medical College, Tokyo, Japan Surgical Training Course “Endocrine Surgery”, Department of Surgery, Martin Luther University Halle Wittenberg, Germany Surgical Training Course “Endocrine Surgery”, Department of Surgery, Heinrich Heine University Düsseldorf, Germany Surgical Training Course “Endocrine Surgery”, Department of Surgery, Martin Luther University Halle Wittenberg, Germany 1st Postgraduate Course in Endocrine Surgery, Chirurgische Arbeitsgemeinschaft für Endokrinologie (CAEK), German Association of Surgery, Braunlage/Harz, Germany Surgical Training Course “Endocrine Surgery”, Department of Surgery, Philipps University Marburg, Germany 2nd Postgraduate Course in Endocrine Surgery, Chirurgische Arbeitsgemeinschaft für Endokrinologie (CAEK), German Association of Surgery, St. Johann, Austria 4th International Post-graduate Course of Minimal-invasive Endocrine Surgery, IRCAD/EITS Strasbourg, France Faculty Member: 7th International Postgraduate Course in Endocrine Surgery, France 3nd Postgraduate Course in Endocrine Surgery, Chirurgische Arbeitsgemeinschaft für Endokrinologie (CAEK), German Association of Visceralsurgery, Wernigerode, Germany


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2003 2004 2005 2005

5th International Post-graduate Course of Minimal-invasive Endocrine Surgery, IRCAD/EITS Strasbourg, France 1. Internationaler Operationskurs für minimal-invasive endokrine Chirurgie – Klinik für Chirurgie und Zentrum für Minimla-invasive Chirurgie der Kliniken Essen-Mitte (10.11. – 11.11.2003) 2. Internationaler Operationskurs für minimal-invasive endokrine Chirurgie – Klinik für Chirurgie und Zentrum für Minimla-invasive Chirurgie der Kliniken Essen-Mitte (8.11. – 9.11.2004) 4. Postgradualer Kurs für Endokrine Chirurgie , Chirurgische Arbeitsgemeinschft für Endokrinologie der Deutschen Gesellschaft für Viszeralchirurgie,, Bad Blumau, Austria (3. - 5. März 2005) (6th) International Post-graduate Course of Minimal-invasive Endocrine Surgery, IRCAD/EITS Strasbourg, France

1992 1993 1996 1996 1996 2001 1997 1998 1999

Coordinator/Organizer of International Congresses and Workshops How to treat parathyroid hyperplasia, Vienna, Austria 3rd Postgraduate Course of the International Association of Endocrine Surgeons (IAES), St. Johann, Austria Carcinoids (Jejunum, ileum, colon. rectum, other localization), 15. u– CAEK, Feldkirch – Austria How to treat lymph node metastases in differentiated thyroid cancer, Vienna, Austria 8th Annual Meeting of Euro-MEN, Vienna, Austria 2nd Postgraduate Course in Endocrine Surgery, Chirurgische Arbeitsgemeinschaft für Endokrinologie (CAEK), German Association of Surgery, St. Johann, Austria Member of Organizing- and Scientific Committee of International Congresses and Workshops International Conference on the Management of “Non-functioning” Adrenal Tumors, Athens, Greek Advanced Course on Endocrine Surgery, Rome, Italy


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2000 2002 2004 2004 2005

Local Organizer “IAES-International Surgical Week”, Vienna, Austria Thyroid Two, Linz, Austria Thyroid Three, Pichlarn, Austria Endocrine Surgery – International Meeting, Rom, ItalyThyroid Four, Pichlarns, Austria Member of International Consensus Conferences Consensus Conference on the ENETS: Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumors

Awards 1985 1986 1986 1987 1987 1988 1989 1991 1998 2003 2004 2005

Theodor Billroth Preis, Österreichische Gesellschaft für Chirurgie Wissenschaftlicher Förderungspreis der Österreichischen Gesellschaft für Gefäßchirugie Wissenschaftlicher Förderungspreis der Ersten Österreichischen Sparkasse Austrotransplantpreis Wissenschaftlicher Anerkennungspreis des Landes Niederösterreich Wissenschaftlicher Förderungspreis der Ersten Österreichischen Sparkasse Billroth Preis, Ärztekammer für Wien Wissenschaftlicher Förderungspreis der Österreichischen Gesellschaft für Gefäßchirugie BRAHMS Forschungspreis für Schilddrüsenerkrankungen together with the Österreichischen Gesellschaft für Nuklearmmedizin BRAHMS Forschungspreis für Schilddrüsenerkrankungen together with the Österreichischen Gesellschaft für Nuklearmmedizin Sandoz Forschungspreis für Schilddrüsenerkrankungen together with the Österreichischen Gesellschaft für Nuklearmedizin Sandoz Forschungspreis für Schilddrüsenerkrankungen together with the Österreichischen Gesellschaft für Nuklearmedizin


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Editorial Board 1991 – 2002 Editor-in-Chief: European Surgery - Acta Chirurgica

Austriaca 2002- present British Journal of Surgery Consultant Board 1998 - 2002 Minimal Invasive Chirurgie (Germany) 2001 – 2002 The European Journal of Surgery (Sweden) 1998 - 2002 Onkologie Aktuell (Germany) 1998 - present Langenbeck`s Archives of Surgery (Germany) 2006 - present Wiener Klinsiche Wochenschrift – Middle European

Journal of Medicine (Austria) Invited Reviews for Surgery (USA) World Journal of Surgery (USA) Onkologie (Germany) Transplant International (Germany) European Journal of Endocrinology (Switzerland) European Journal of Clinical Investigation (Great Britain) European Journal of Surgical Oncology (Great Britain) Wiener klinische Wochenschrift (Austria) Memberships Member of National Societies: 1978 - Vienna Medical Association 1979 - Austrian Society of Surgeons 1979 - Austrian Society for Gastroenterology 1981 - Society of Surgeons in Vienna 1985 - Austrian Society of Surgical Research 1987 - Austrian Society of Vascular Surgeons 1990 - Austrian Society of Bone and Mineral Electrolyte Metabolism1994 - Austrian Society of Endocrinology and Metabolism Member of International Societies 1984 - International Association of Endocrine Surgeons (IAES) 1985 - International Society of Surgery (ISS)


1985 - German Society of Surgeons 1985 - German Association of Endocrine Surgeons (CAEK) 1987 - German Society of Endocrinology 2002 - Fellow of the Royal College of Surgeons – FRCS (London)2003 - German Society of Viszeral Surgery 2003 - Fellow of the American College of Surgeons - FACS 2004 Eurpean Neuroendocrine Tumour Society (ENETS) Corresponding Member of International Societies 1992 - Society of Head and Neck Surgeons, USA 1994 - American Association of Endocrine Surgeons (AAES); USA Council Member of National Societies 1991 – 2002. Austrian Society of Surgeons 1992 – pres. Austrian Society of Surgical Oncology (ASSO) [1992-1996 Chairman “Thyroid Section”; Secretary General 2003 - ] 1994 – pres. Austrian Society of Endocrinology and Metabolism [2002-pres Coordinator: Section “Endocrine Surgery”] 1996 – pres. Society of Surgeons in Vienna [President 1999 – 2000; Past-President 2000-2001] Council Member of International Societies 1991 - 1997 International Association of Endocrine Surgeons (IAES) 1991 - 1996 Member of the Scientific Committee European School of Oncology (ESO) Vienna Office 1996 – pres. Chirugische Arbeitsgemeinschaft für Endokrinologie (CAEK), German Association of Viszeral Surgeons [Co-chairman 1996 – 2000; Chairman 2003- ] 2003 - European Society of Endocrine Surgeons (ESES) – [Member of the founding committee; 2003 - Secretary Treasurer] Sources of funding (since 2000)

Period Organization Short Title K€ 2001-2003 Hochschuljubiläums

fonds (project no. H-144/2001; together with M. Schindl/K. Kaczirek)

Irinotecan (Campt®) und Paclitaxel (Taxol®) in der Behandlung neuroendokriner Tumore

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2001-lfd Austrian National Bank Jubilee Fund (project no. 9307; together with K. Kaczirek, G. Prager)

Intraoperatives Parathomron-Monitoring: Untersuchungen zur Parathormonkinetik bei primärem und sekundärem Hyperparathyreoidismus



Philipp Riss Primärer Hyperparathyreoidismus – intraoperatives PTH-Monitoring

Martin Bruno Niederle

Gastro-Enteropankreatische neuroendokrine Tumore – GEP-NET. Eine prospektive Studie zur Inzidenz in Österreich

2006 – (2008) Dr. scient. med.

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Publications 586 peer reviewed publications in scientific journals (263 Original Papers, 10 invited Commentaries, 6 Letters, 66 Short Papers, 29 Invited Reviews) List of Original Publications (since 2000) 168 Wagner, B., Ludwig, C., Riedl, M., Niederle, B., Cejna, M., Vierhapper, H.,

Waldhäusl, W., Roden, M.: Severe chronic hypoglycemia in a lean young woman. PANCREAS 21, 97-99 (2000)

169 Raderer, M., Kurtaran, A., Leimer, M., Angelberger, P., Niederle, B., Vierhapper, H., Vorbeck, F., Hejna, M.,H.,L., Scheithauer, W., Pidlich, P Virgolini, I.: Value of peptide receptor scintigraphy using 123-I Vasoactive Intestinale Peptide and 111-In DTPA-D-Phe- Octreotide in 194 carcinoid patients: Vienna University experience, 1993 to 1998. J CLIN ONCOL 18, 1331-1336 (2000)

170 Muhm, M., Polterauer, P., Gstoettner, W., Temmel, A., Losert, H., Richling, B., Undt, G., Niederle, B., Staudacher, M., Kretschmer, G., Ehringer, H.,.: Glomus caroticum - Chemotectom., Übersicht über die aktuelle Diagnostik und Therapie. WIEN KLIN WOCHENSCHR 112, 115 - 120 (2000)

171 Hörandner, H., Mürzl, E., Neyer, U., Breiteneder-Geleff, S., Niederle, B., Haid, A., Breitfellner, G.: Fokale Proliferationen in reaktiv hyperplastischen Nebenschilddrüsen bei terminaler Niereninsuffizienz - Implikation für die Autotransplantation nach totaler Parathyreoidektomie. WIEN KLIN WOCHENSCHR 112, 353 - 357 (2000)

172 Raber, W., Raffesberger, W., Kmen, E., Hamwi, A., Niederle, B., Waldhäusl, W., Roden, M.: Pheochromocytoma with normal urinary and plasma catecholamines but elevated plasma free metanephrines in a patient with adrenal incidentaloma. ENDOCRINOLOGIST 10, 65 - 68 (2000)

173 Scheuba, Ch., Kaserer, K., Kortzmann, H., Bieglmayer, Ch., Niederle, B., Vierhapper, H.: Prevalence of C-cell hyperplasia in patients with normal basal and pentagastrin-stimulated calcitonin. THYROID 10, 413 - 416 (2000)

174 Schindl, M., Kaczirek, K., Kaserer, K., Niederle, B.: Is the new classification of neuroendocrine pancreatic tumors of clinical help? WORLD J SURG 24, 312 - 318 (2000)

175 Zacherl, J., Scheuba, Ch., Prager, G., Zacherl, M., Jakesz, R., Niederle, B.: Wie kostengünstig ist die laparoskopische Adrenalektomie wirklich? MINIMAL INVASIVE CHIRURGIE 9, 79 - 84 (2000)

176 Neunteufl, Th., Heher, S., Prager, G., Katzenschlager, R., Abela, C., Niederle, B., Stefenelli, Th.: Effects of sucessful parathyroidectomy on altered arterial reactivity in patients with hypercalcemia: results of a 3-year follow-up study. CLIN ENDOCRINOL 53, 229 - 232 (2000)

177 Raber, W., Kaserer, K., Niederle, B., Vierhapper, H., Raber, W., Kaserer, K., Niederle, B., Vierhapper, H.: Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of 120 patients. THYROID 10, 709 - 712 (2000)

178 Zettinig, G., Kaserer, K., Passler, Ch., Flores, J.,A., Niederle, B., Dudczak, R.: Advanced insular thyroid carcinoma in a fourteen-year old girl: twenty-four years of follow-up. THYROID 10, 435 - 437 (2000)

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179 Raber, W., Raffesberger, W., Bischof, M., Scheuba, Ch., Niederle, B., Gasic, S., Waldhäusl, W., Roden, M.: Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytoma. ARCH INTERN MED 160, 2957 - 2963 (2000)

180 Virgolini, I., Traub, T., Leimer, M., Novotny, C., Pangerl, T., Ofluoglu, S., Halvadjieva, E., Smith-Jones, P., Flores, J., Li, S.,R., Angelberger, P., Havlik, E., Andreae, F., Raderer, M., Kurtaran, A.,. Niederle, B., Dudczak, R.: New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy. Q J NUCL MED 44, 50 - 58 (2000)

181 Weinhaeusel, A., Vierhapper, H., Schlegl, R., Wagner, T., Muhr, D., Scheuba, Ch., Niederle, B., Haas, O.,A.: A novel mutation E 179K of the MEN1 gene predisposes for multiple endocrine neoplasia-type 1 (MEN1). HUMAN MUTATION 16, 533 (2000)

182 Niederle, B., Prager, G., Scheuba, Ch., Passler, Ch., Schindl, M.: Minimal invasive chirurgische Endokrinologie. ACTA CHIR AUSTRIACA 32, Suppl 165, 39-46 (2000)

183 Schindl, M., Kaserer, K., Niederle, B.: Treatment of gastric neuroendocrine tumors. ARCH SURG 136, 49 - 54 (2001)

184 Kaserer, K., Knezevic, V., Passler, Ch., Niederle, B., Krizmann, D.: Expressionsanalyse follikulärer Schilddrüsenläsionen mittels cDNA Arrays auf Basis mikrodissezierter Zellen: Anwendungsmöglichkeiten für die präoperative Schilddrüsen Punktionszytologie. VERH DTSCH GES ZYT 22, 29-34 (2001)

185 Zettinig, G., Leitha, Th., Niederle, B., Kaserer, K., Becherer, A., Kletter, K., Dudczak, R.: FDG positron emission tomographic, radioiodine, and MIBI imaging in a patient with poorly differentiated insular thyroid carcinoma. CLIN NUCL MED 26, 599-601 (2001)

186 Roden, M., Raber, W., Bernroider, E., Niederle, B., Waldhäusl, W., Gasic, S.: Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen. CLIN CHEM 47, 1061-1067 (2001)

187 Prager, G., Czerny, Ch., Kurtaran, A., Passler, Ch., Scheuba, Ch., Bieglmayer, Ch., Niederle, B.: Minimally invasive open parathyroidectomy in an endemic goiter area. ARCH SURG 136, 810 - 816 (2001)

188 Kaserer, K., Scheuba, Ch., Neuhold, N., Weinhaeusl, A., Vierhapper, H., Haas, O.,A., Vierhapper, H., Niederle, B.: Sporadic versus familial medullary thyroid microcarcinoma - A histopathological study of 50 consecutive patients. AM J SURG PATHOL 25, 1245-1251 (2001)

189 Passler, Ch., Avanessian, R., Kaczirek, K., Paregr, G., Scheuba, Ch., Schindl, M., Niederle, B.: Schilddrüsenchirurgie im Alter. ACTA CHIR AUSTRIACA 33, 288-293 (2001)

190 Schmaldienst, S., Dittrich, E., Pietschmann, P., Niederle, B., Becherer, A., Watschinger, B.: A patient with evidence of two underlying diseases causing hypercalcemia. NEPHROL DIAL TRANSPLANT 16, 2413-2425 (2001)

191 Prager, G., Heinz-Peer, Gertraud Passler, Ch., Kaczirek, K., Schindl, M., Scheuba, Ch., Niederle, B.: Surgical strategy in adrenal masses. EUR J RADIOL 41, 70-77 (2002)

192 Hönigschnabl, Selma., Gallo, Sylvia., Niederle, B., Prager, G., Kaserer, K., Lechner, G., Heinz-Peer, Gertraud: How accurate is MR imaging in characterisation of adrenal masses: update of a long-term study. EUR J RADIOL 41, 113-122 (2002)

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193 Kandioler-Eckersberger, Daniela, Niederle, B., Herbst, F., Wenzl, E: A magnetic probe to retrieve broken matallic parts of instruments during laparoscopuic procedures. SURGICAL ENDOSCOPY 16, 208-209 (2002)

194 Steurer, M., Passler, Ch., Denk, Doris M., Schneider, Berit Niederle, B., Biegenzahn, W.: Advantages of recurrent laryngeal nerve identification in thyroidectomy and parathyroidectomy and the importance of preoperative and postoperative laryngoscopic examination in more than 1000 nerves at risk. LARYNGOSCOPE 112, 124-133 (2002)

195 Bachleitner-Hofmann, T., Stift, A Friedl, J., Pfragner Roswitha., Radelbauer, K., Dubsky, P., Schüller, G., Benkö, T., Niederle, B., Brostjan, C., Jakesz, R., Gnant, M.: Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells. J CLIN ENDOCRINOL METAB 87, 1098-1104 (2002)

196 Niederle, B., Haas, O.,A.: Multiple endocrine neoplasia syndromes. WIEN KLIN WOCHENSCHR 114, 239-245 (2002)

197 Weinhäusel, A., Kaserer, K., Vierhapper, H., Niederle, B., Haas, O.,A., : Multiple endocrine neoplasia type 1 (MEN1) in Austria. WIEN KLIN WOCHENSCHR 114, 252-257 (2002)

198 Kaczirek, K., Prager, G., Schindl, M., Kaserer, K., Gessl, A., Vierhapper, H., Niederle, B.: Multiple endocrine neoplasia 1- current recommendations for diagnosis and treatment. WIEN KLIN WOCHENSCHR 114, 258-266 (2002)

199 Bieglmayer, C., Scheuba, C., Niederle, B., Flores, J., Vierhapper, H.: Screening for medullary thyroid carcinoma: Experience with different immunoassays for human calcitonin. WIEN KLIN WOCHENSCHR 114, 267-273 (2002)

200 Kaserer, K., Scheuba, C., Neuhold, N., Weinhäusel, A., Vierhapper, H., Niederle, B.: Recommendations for reporting C cell pathology of the thyroid. WIEN KLIN WOCHENSCHR 114, 274-278 (2002)

201 Pfragner, R., Wirnsberger, G., H., Ingolic, E., Niederle, B.: Medullary thyroid cartcinoma in cell culture - models for future therapies. WIEN KLIN WOCHENSCHR 114, 279-283 (2002)

202 Zettinig, G., Fueger Barbara J., Passler, Ch., Kaserer, K., Pirich, Ch., Dudczak, R., Niederle, B.: Long-term follow-up of patients with bone matastases from differentated thyroid cancer-surgery or conventional treatment? CLIN ENDOCRINOL 56, 377-382 (2002)

203 Neyer, U., Hörandner, H., Haid, A., Zimmermann, G., Niederle, B.: Total parathyroidectomy with autotransplantation in renal hyperparathyroidism: low recurrence after intra-operative tissue selection. NEPHROL DIAL TRANSPLANT 17, 625-629 (2002)

204 Zettinig, G., Prager, G., Kurtaran, A., Kaserer, K., Czerny, Ch., Dudczak, R., Niederle, B.: Stellenwert eines strukturierten Befunsschemas zur Interpretation der Nebenswchilddrüsenszintigraphie bei primärem Hyperparathyreoidismus. ACTA MED AUSTRIACA 29, 68 - 71 (2002)

205 Zettinig, G., Kurtaran, A., Prager, G., Kaserer, K., Dudczak, R., Niederle, B.: ""Suppressed"" double adenoma - a rare pitfall in minimally invasive parathyroidectomy. HORMONE RES 57, 57 -60 (2002)"

206 Prager, G., Heinz-Peer, G., Passler, Ch., Kaczirek, K., Schindl, M., Scheuba, Ch., Vierhapper, H., Niederle, B.: Can dynamic Gadolinium-enhanced magnet resonance imaging with chemical shift studies predict the status of adrenal masses? WORLD J SURG 26, 958 - 964 (2002)

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207 Schindl, M., Kaczirek, K., Passler, Ch., Kaserer, K., Prager, G., Scheuba, Raderer, M., Niederle, B.: Treatment of small intestinal neuroendocrine tumos: Is an extended multimodal approach justified? WORLD J SURG 26, 976 - 984 (2002)

208 Bieglmayer, C., Prager, G., Niederle, B.: Kinetic analyses of parathyroid hormone clearence as measured by three rapid immunoassays during parythyroidectomy. CLIN CHEM 48, 1731-1738 (2002)

209 Passler, Ch., Avanessian, R., Kaczirek, K., Prager, G., Scheuba, Ch., Niederle, B.: Thyroid surgery in the elderly. ARCH SURG 137, 1243 - 1248 (2002)

210 Prager, G., Kalaschek, A., Kaczirek, K., Passler, Ch., Scheuba, Ch., Sonneck, G., Niederle, B.: Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism. SURGERY 132 , 930 - 936 (2002)

211 Gimm, O., Niederle, Barbara.,E., Weber, Theresia Bockhorn, M., Ukkat, J., Brauckhoff, M., Nguyen Thanh, P., Frilling, Andreja Klar, E., Niederle, B., Dralle, H.: RET proto-oncogene mutations affecting codon 790/791: a mild form of MEN 2A? SURGERY 132 , 952 - 952 (2002)

212 Kaserer, K., Knezevic, V., Pichlhofer, B., Scheuba, C., Passler, C., Worth, J., Niederle, B., Krizman, D.: Construction of cDNA libraries from microdissected benign and malignant thyroid tissue. LAB INVEST 82, 1707-1714 (2002)

213 Passler, C., Prager, G., Scheuba, C., Kaserer, K., Zettinig, G., Niederle, B: Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodin substitution. ANN SURG 237, 227-234 (2003)

214 Saeger, W., Fassnacht, M., Chita, R., Prager, G., Nies, C., Lorenz, K., Bährlehner, E., Simon, D., Niederle, B., Beuschlein, F., Allolio, B., Reincke, M.: High diagnostic accuracy of adrenal core biopsy: Results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. HUMAN PATHOL 34, 180-186 (2003)

215 Prager, G., Czerny, Ch., Ofluoglu, S., Kurtaran, A., Passler, Ch., Kaczirek, K., Scheuba, Ch., Niederle, B.: Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region. J AM COLL SURG 196, 541-548 (2003)

216 Loewe, Ch., Schindl, M., Cejna, M., Niederle, B., Lammer, J., Thurnher, S.: Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: Assessment of mid- and long-term results. AM J ROENTGENOL 180, 1379-1384 (2003)

217 Kaczirek, K., Soleiman, A., Schindl, M., Passler, Ch., Scheuba, C., Prager, G., Kaserer, K., Niederle, B.: Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism. EUR J CLIN INVEST 33, 488-492 (2003)

218 Niederle, B., Prager, G: Advanced endoscopic adrenal surgery - new developments., EUR SURG 35, 71-75 (2003)

219 Brauckhoff, M., Kaczirek, K., Than, PN., Gimm, O., Bär Anette Niederle, B., Dralle, H.: Technikal aspects of subtotal endoscopic adrenalectomy. EUR SURG 35, 84-88 (2003)

220 Rauhofer, U., Prager, G., Hoermann, M., Auer, H., Kaserer, H., Niederle, B.: Cystic echninococcosis of the thyroid gland in children and adults. THYROID 13, 497-502, (2003)

221 Kaczirek, K., Prager, G., Kienast, O., Dobrozemsky, G., Dudczak, R., Niederle, B., Kurtaran, A.: Combined transmission and 99Tc-Sestamibi emission

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tomography for localization of mediastinal parathyroid glands. NUKLEARMEDIZIN 42, 220-223 (2003)

222 Passler, C., Prager, G., Scheuba, C., Niederle, Barbara E., Kaserer, K., Zettinig, G., Niederle, B.: Follicular Variant of Papillary Thyroid Carcinoma - A long-term follow-up. ARCH SURG 138, 1362-1366 (2003)

223 Niederle, B., Prager, G., Kaczirek, K., Scheuba, C., Passler, C., Asari, R.: Minimal-invasive Chirurgische Endokrinologie: Aspekte der Radiodiagnostik. WIEN KLIN WOCHENSCHR 115, SUPPL 2, 10 - 18 (2003)

224 Weinhäusel, A., Behmel, A., Ponder, BAJ., Haas, OA., Niederle, B., Gessl, A., Vierhapper, H., Pfragner, R.: Long-term follow-up revealed ""sporadic"" pheochromocytoma as multiple endocrine neoplasia type 2A-2 (MEN2A-2). ENDOCRINE PATHOLOGY 14, 375 - 382 (2003)"

225 Prager, G., Riss, P., Bieglmayer, C., Niederle, B: The role of intraoperative quick PTH measurements in primary hyperparathyroidism., ANN ITAL CHIR 74, 395-399 (2003)

226 Prager, G., Heinz-Peer, G., Passler, C., Kaczirek, K., Scheuba, C., Niederle, B.: Applicability of laparoscopic adrenalectomy in 150 consecutive patients – a prospective study. ARCH SURG 139, 46-49 (2004)

227 Karges W, Dralle, H, Raue, F, Mann, K., Reiners, C, Grussendorf M, Hüfner, M, Niederle, B, Brabant, G, : Calcitonin Measurement to Detect Medullary Thyroid Carcinoma in Nodular Goiter: German Evidence-Based Consensus Recommendation. EXP CLIN ENDOCRINOL DIABETES 112, 42-58 (2004)

228 Karanikas G, Moameni A, Poetzi C, Zettinig G, Kaserer K, Bieglmayer C, Niederle B, Dudczak R, Pirich Ch.: Frequency and Relevance of Elevated Calcitonin Levels in Patients with Neoplastic and Nonneoplastic Thyroid Disease and in Healthy Subjects. J CLIN ENDOCRINOL METAB 89, 1098-1104 (2004)

229 Passler, C., Scheuba, C., Prager, G., Kaczirek, K., Kaserer, K., Zettinig, G., Niederle, B.: Prognostic factors of papillary and follicular thyroid cancer: Differences in an iodine-repleted endemic goiter region. ENDOCRINE-RELATED CANCER 11, 129-137 (2004)

230 Stadler A, Schima W, Prager G, Homolka P, Heinz G, Saini S, Eisenhuber E, Niederle B.: CT Density Measurements for Characterization of Adrenal Tumors Ex Vivo: Variability Among Three CTScanners. AM J ROENTGENOL 182, 671-675 (2004)

231 Kaczirek, K., Schindl, M., Weinhäusl, A., Scheuba, C., Passler, C., Prager, G., Raderer, M., Hamilton, G., Mittlböck, M., Siegl, V., Pfrganer, Roswitha Niederle, B: Cytotoxic Activity of Camtothecin and Palitaxel in Newly Established continuous Human Medullary Thyroid Carcinoma Cell Lines. J CLIN ENDOCRINOL METAB 89, 2397-2401(2004)

232 Stift, A., Sachet, Monika Yagubian, Rubina Bittermann, C., Dubsky, P., Brostjan, Christina Pfragner, Roswitha Niederle, B., Jakesz, R., Gnant, M., Friedl, J.: Dendritic Cell Vaccination in Medullary Thyroid Carcinoma. CLIN CANCER RES 10, 2944-2953 (2004)

233 Zierhut, Barbara Mechtler, K., Gartner, W., Daneva, T., Base, W., Weissel, M., Niederle, B., Wagner, L.: Heat shock protein 70 (Hsp70) subtype expression in neuroendocrine tissue and identification of neuroendocrine tumour-specific Hsp70 truncation. ENDOCRINE-RELATED CANCER 11, 377-389 (2004)

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234 Kaczirek, K., Ba-Ssalamh, A., Schima, W., Niederle, B.: The importance of preoperative localisation procedures in organic hyperinsulinism -Experience in 67 patients. WIEN KLIN WOCHENSCHR 116, 373-378, (2004)

235 Zettinig, G., Mitterhauser, M., Wadsak, W, Becherer, A., Pirich, C., Vierhapper, H., Niederle, B., Dudczak, R., Kletter, K.: Positron emission tomography imaging of adrenal masses: 18F-fluorodeoxyglucose and the 11-hydroxylase tracer 11C-metomidate. EUR J NUCL MED MOL IMAGING 31, 1224-1230 (2004)

236 Özer, S., Dobrozemsky, G, Kienast, O., Beheshti, M., Becherer, A., Niederle, B., Kainberger, F., Dudczak, R., Kurtaran, A.: Value of combined XCT/SPECT technology for avoiding false positive planar 123I-MIBG scintigraphy. NUCLEAR MEDICINE 43, 164-170, (2004)"

237 Kaczirek, K, Niederle, B.: Nesidioblastosis: an old term and a new understanding. WORLD J SURG 28, 1227-1230 (2004)

238 Gimm, O., Ukkat, J., Niederle, Barbara.,E., Weber, Theresia Nguyen Thanh, P., Brauckhoff, M., Niederle, B., Dralle, H.: Timing and extent of surgery in patients with familial medullary thyroid carcinoma/Multiple endocrine neoplasia 2A-related RET mutations not affecting codon 634. WORLD J SURG 28, 1312 -1316 (2004)

239 Passler, C., Scheuba, C., Asari, R., Kaczirek, K., Kaserer, K., Niederle, B: Importance of tumour size in papillary and follicular thyroid cancer. BR J SURG 92, 184-189 (2005)

240 Kaczirek, K., Asari, R., Scheuba, C., Niederle, B.: Organic hyperinsulinism and endoscopic surgery. WIEN KLIN WOCHENSCHR 117 (2005)

241 Kaczirek, K., Prager, G., Bieglmayer, C., Asari, R., Scheuba, C., Niederle, B: Quick PTH assay cannot predict incomplete parathyroidectomy in patients with renal hyperparathyroidism. SURGERY 137, 431-435 (2005)

242 Gartner, W., Mineva, I., Daneva, T., Baumgartner.,Parzer, Sabine., Niederle, B., Weissel, M., Wagner, L.: A new identified RET proto-oncogen polymorphism is found in a high number of endocrine tumor patients. HUM GENET 117, 143-153 (2005)

243 Deicher, R., Kirsch, B., Mullner, M., Kaczirek, K., Niederle, B., Horl, WH.: Impact of parathyroidectomy on neutrophil cytosolic calcium in chronic kidney disease patients: a prospective parallel group trial. J INTERN MED., 258, 67-76 (2005)

244 Baumgartner-Parzer, S.,M., Lang, R., Wagner, L., Heinze, G., Niederle, B., Kaserer, K., Waldhäusl, W., and Vierhapper, H.: Polymorphism in exon 13 and intron 14 of the RET protooncogen: Genetic modifiers of medullary thyroid carcinoma? J CLIN ENDOCRINOL METAB 90, 6323-6236 (2005)

245 Pfragner, R., Skowitsch, G., Höger, H., Jech, M., Rinner, B., Siegl, V., Niederle, B., Gnant, M., Friedl, J., Stift, A.: Medullary thyroid carcinoma: Autologous tumor cell lines for dendritic cell vaccinationin. ANTICANCER RESEARCH 25, 4121-4126 (2005)

246 Vierhapper, H., Niederle, B., Bieglmayer, C., Kaserer, K., Baumgartner-Parzer; S.: Early Diagnosis and Curative Therapy of Medullary Thyroid Carcinoma by Routine Measurement of Serum Calcitonin in Patients with Thyroid Disorders. THYROID 15, 1267-1272.(2005)"

247 H., Vierhapper, H., Rondot, S., Schulze, E., Wagner, L., Hanslik, S., Niederle, B., Bieglmayer, C., Kaserer, K., Baumgartner-Parzer, S.: Primary

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Hyperparathyroidism as the Leading Symptom in a Patient with an Y791F RET Mutation. THYROID 15, 1303-1308 (2005)

248 Niederle, B.,E., Schmidt, G., Organ, C.,H., Niederle, B.: Albert J and His Surgeon: A Historical Reevaluation of the First Parathyroidectomy. J AM COLL SURG 202, 181-190 (2006)

249 Kaczirek, K., Prager, G., Riss, Ph., Wunderer, G., Asari, R., Scheuba, C., Bieglmayer, C., Niederle, B.: Novel Parathyroid Hormone (1-84) Assay as Basis for Parathyroid Hormone Monitoring in Renal Hyperparathyroidism. ARCH SURG 141, 129-134 (2006)

250 Schuetz, M., Beheshti, M., Oezer, S., Novotny, C., Paul, M., Hofmann, A., Bieglmayer, C., Niederle, B., Kletter, K., Dudczak, R., Karanikas, G., Pirich, C.: Calcitonin measurements for early detection of medullary thyroid carcinoma or its premalignant conditions in Hashimoto´s thyroiditis. ANTICANCER RESEARCH 26, 723-728 (2006)

251 Scheuba, C. Kaserer, K. Kaczirek, K. Asari, R. Niederle, B.: Desmoplastic stromal reaction in medullary thyroid cancer - an intraoperative "marker" for lymph node metastases. WORLD J SURG 30, 853-859 (2006)

252 Bieglmayer, C., Kaczirek, K. Prager, G. Niederle, B.: Parathyroid hormone monitoring during total parathyroidectomy for renal hyperparathyroidism: pilot study of the impüact of renal function and assay specifity. CLIN CHEM 52, 1112-1119 (2006)

253 Gartner W, Koc F, Nabokikh A, Daneva T, Niederle B, Luger A, Wagner L: Long-Term in vitro Growth of Human Insulin-Secreting Insulinoma Cells. NEUROENDOCRINOLOGY 83, 123-130 (2006)

254 Schima W, Ba-Ssalamah A, Plank C, Kulinna-Cosentini C, Prokesch R, Tribl B, Sautner T, Niederle B.: Pankreas : Teil II Tumore. RADIOLOGE 46, 421-438 (2006)

255 Asari R, Scheuba, C, Kaczirek, K., Niederle B: Estimated risk of pheochromocytoma recurrence after adrenal sparing surgery in patients with MEN 2A. ARCH SURG 141,1199-1205 (2006)

256 Jensen, R.T. Niederle, B. Mitry, E. Ramage, J.K. Steinmüller, T. Lewington, V. Scarpa, A. Sundin, A. Perren, A. Gross, D. O'Connor, J.M. Pauwels, S. Klöppel, G.: Gastrinoma (Duodenal and Pancreatic). NEUROENDOCRINOLOGY 84:173-182 (2006)

257 de Herder, W.W. Niederle, B. Scoazec, J.-Y. Pauwels, S. Klöppel, G. Falconi, M. Kwekkeboom, D.J. Öberg, K. Eriksson, B. Wiedenmann, B. Rindi, G. O'Toole, D. Ferone, D.: Well-Differentiated Pancreatic Tumor/Carcinoma: Insulinoma. NEUROENDOCRINOLOGY 84:183-188 (2006)

258 Heinz-Peer G, Memarsadeghi M, Niederle B.: Imaging of adrenal masses. CURR OPIN UROL 17, 32-38 (2007)

259 Scheuba C, Bieglmayer, C, Asari R, Kaczirek K, Izay B, Kaserer K, Niederle B.: The value of intraoperaitve pentagastrin testing in medullary thyroid cancer. SURGERY 141 (2007)

260 Bieglmayer C., Vierhapper, H., Dudczak, R., Niederle, B.: Measurement of calcitonin by immunoassay analyzers. CLIN CHEM LAB MED 45, 662-666 (2007)

261 Koperek O, Scheuba C, Puri C, Birner P, Haslinger C, Rettig W, Niederle B, Kaserer K, Garin Chesa P.: Molecular characterization of the desmoplastic tumor stroma in medullary thyroid carcinoma. INT J ONCOL 3: 59-67 (2007)

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262 Riss P, Kaczirek K, Bieglmayer C, Niederle B: PTH spikes during parathyroid exploration-a possible pitfall during PTH monitoring? LANGENBECKS ARCH SURG 392: 427-30 (2007)

263 Neumayer C, Moritz A, Asari R, Weinhäusel A, Hölzenbein T, Kretschmer G, Niederle B, Haas OA: Novel SDHD germ-line mutations in pheochromocytoma patients. EUR J CLIN INVEST 37, 544-551 (2007)

## Riss P, Kaczirek K, Heinze G, Bieglmayer C, Niederle B: A “defined baseline” in PTH monitoring increases surgical success in patients with multiple gland disease. Surgery, in press (2007)

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Peter PIETSCHMANN Institute of Pathophysiology [email protected] Osteoblastic gene expression patterns and microarchitecture of bone in male osteoporosis Abstract Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. In osteoporosis histomorphometric findings typically include reduced trabecular bone volume, low trabecular number, reduced trabecular thickness and poor connectivity. Osteoporosis results from an imbalance of bone resorption and bone formation and traditionally has been regarded as a disease of postmenopausal women. Nevertheless, although definitely underestimated, osteoporosis in men is a frequent and severe disease. In the European Vertebral Osteoporosis Study, which enrolled over 15.000 men and women from 36 countries, the mean prevalence of vertebral deformities was 12% in women and 12% in men. The prevalence increased with age in both sexes, nevertheless, the curve was steeper in women than in men. Moreover, poor outcome following hip fracture is gender-dependent; it has been reported that male gender increases mortality risk after hip fracture by fourfold.

No pathogenetic model for idiopathic male osteoporosis has reached common consent yet; nevertheless a number of factors influencing the male skeleton have been discussed. Estrogen deficiency traditionally has been associated with postmenopausal osteoporosis but also plays a prominent role in the pathogenesis of male osteoporosis. Several studies have suggested that increased serum levels of sex hormone binding globulin lead to a decrease in free androgens and estrogen. Moreover, calcium absorption is low in osteoporotic men; renal calcium loss and hypercalciuria may be further pathogenetic aspects. In addition, low plasma levels of insulin-like growth factor-1 have been found. In studies on bone histomorphometry in idiopathic osteoporosis in men, some authors described an impaired bone formation while others found that bone resorption is increased. Studies from our laboratory on biochemical markers demonstrated that in men with idiopathic osteoporosis bone resorption is increased and exceeds bone formation.

In order to further elucidate the pathogenesis of male osteoporosis, we will analyze osteoblastic gene expression patterns in bone from men with hip fractures due to primary osteoporosis. Femoral heads will be obtained from men undergoing hip arthroplasty either for hip fracture or osteoarthritis (as a control group). We will assess the gene expression of osteoblast specific transcription factors (such as runx2 or osterix) as well as cytokines that control osteoclast generation (e.g. RANKL and osteoprotegerin at the mRNA and protein level). Gene expression patterns will be related to parameters that reflect the microarchitecture of bone as assessed by bone histomorphometry and microCT. Thesis subjects Molecular mechanisms of excessive bone resorption and defective bone formation in male osteoporosis. / Relationship between the microarchitecture of bone and gene expression patterns of osteoblasts. / Pathogenesis of osteoporosis in elderly subjects. / Bone metabolism in a model of ankylosing spondylitis Techniques and infrastructure

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Cell and RNA isolation from tissues, primary culture, quantitative real time PCR, Western blotting, FACS analysis, bone histomorphometry, microCT; all required equipment available.

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Curriculum Vitae Peter PIETSCHMANN Department of Pathopyhsiology, Medical University of Vienna, Waehringer Gürtel 18-20, A – 1090 Vienna, Austria, Phone +43-1-40400-51-22; Fax: +43-1-40-400-51-30; E-mail [email protected] Personal Data Date of Birth: May 13, 1960 Place of Birth: Vienna Nationality Austria Education 2006-present Deputy Head of the Department of

Pathophysiology 2006-present Head of the Division of Molecular and

Biochemical Pathology 2002 Appointment as Associate Professor of

Pathophysiology, Medical School,University of Vienna

2001 Certification as Specialist of Pathophysiology 1994

Certification as Specialist of Rheumatology

1992 Appointment as Associate Professor of Internal Medicine, Medical School,University of Vienna

1990 Certification as Specialist of Internal Medicine 1984 Graduation as Medical Doctor 1979 – 1984 Medical School, University of Vienna 1978 – 1979 Military Service 1970-1978 Secondary School (Vienna) 1966-1970 Elementary School (Vienna)

Career History 2002 – present Associate Professor of Pathophysiology at the

Department of Pathophysiology,Medical University of Vienna

1999-present Head of the “Bone, Cartilage and Connective Tissue Research Group”

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1998-present Department of Pathophysiology (former Department of General and Experimental Pathology), University of Vienna (since 2004: Medical University of Vienna)

1997-1998 Institute of Immunology, University of Vienna 1992-1997 Division of Rheumatology/Department of Internal

Medicine 3, University of Vienna 1992-present Associate Professor of Internal

Medicine,(Medical) University of Vienna 1991-1992 Rheumatic Diseases Division, Department of

Internal Medicine, Southwestern Medical Center at Dallas, University of Texas, Dallas, TX, USA

1990-1991 Department of General and Experimental Pathology, University of Vienna

1984-1990 Department of Medicine 2, University of Vienna

Career-related Activities 2000-present Treasurer of the Austrian Society for Bone and

Mineral Research 1998-present Board member of the Austrian Society for

Geriatrics and Gerontology 1993-present Scientific colaborationwith the Luwdig Boltzmann

Institute of Aging Research, Vienna Awards 1986 Paracelsus Award Austrian Society for

Internal Medicine 1996 Young Investigator Award World congress on

Osteoporosis Memberships International Bone and Mineral Society Austrian Society for Bone and Mineral Research (Member of the Board) Austrian Society for Geriatrics and Gerontology (Member of the Board) Society for Internal Medicine of Vienna and Lower Austria Austrian Society for Rheumatology Austrian Society for Endocrinology and Metabolism Austrian Society for Cytometry Austrian Diabetes Society Medical Society of Vienna


Affiliation with the Ludwig Boltzmann Institute for Aging Research, Vienna Sources of funding in last 5 years (2000-2005) Only FWF and equivalent projects

Period Organization Short Title K€ 2007-2009 Jubiläumsfonds der

Österreichischen Nationalbank Projekt # 12544

Vergleichsstudie von Hüftknochen von Männern mit Schenkelhaslfrakturen bzw. Hüftarthrosen

47

2002-2004 Medizinisch-wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien, Projekt # 2240

Die Wirkung von Bone morphogenetic protein-5 auf die Generation von Osteoklasten in Knochenmarkskulturen.

26

2002-2004 Hochschuljubiläumsstiftung der Stadt Wien, Projekt # H-1166/2003

The role of lymphocyte subpopulations in osteoclast generation in murine bone marrow cultures.

4

2001 – 2006

FWF Forschungsprojekt P16060-B05 (Co-aplicant)

Extended studies on the modulation of the ageing processes in the rat by physical exercise and food restriction

204

2001 Medizinisch-wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien

Die Bedeutung des Vitamin D-Rezeptors für die Zytokinproduktion von T-Lymphozyten

6

2000-2001 Jubiläumsfonds der Österreichischen Nationalbank

The relationship of cytokines, sex steroids and bone turnover in aging men and women.

36


Name Title of thesis Period (expected)

Acad. Title

Ing. Susanne Die Wirkung von 1999-2001 MD

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Brosch Bisphosphonaten auf die Osteoklastogenese und das Immunsystem

Maria Winzer The effects of phytoestrogens on the generation of osteoclasts

2003-2006 MD

Mag. Pharm. Brigitte Behal

Metaanalysis of the spontaneous course of osteoporosis

2005-2007 Dr. scient. med.

Mag.rer.nat. Daniela Stupphann

Bone metabolism in ankylosing spondylitis


Dr. med. univ. Janina Patsch

Microarchitecture of bone in osteoporotic men: Relation with osteoblastic gene expression patterns and treatment effects


Dipl. Ing. (FH) Martina Rauner

Molecular mechanisms of osteoblast differentiation: Relevance to senile osteoporosis


Publications 99 original publications and 28 reviews in peer reviewed scientific journals, 9 book chapters, >100 invited lectures, Peer reviewed manuscripts 2000-2005 (original research and reviews) First, last or corresponding author manuscripts: Pietschmann P, Hahn P, Kudlacek S, Thomas R, Peterlik M (2000) Surface markers and transendothelial migration of dendritic cells from elderly subjects. Exp Gerontol 35: 213 - 224 Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P, Bernecker P, Kainberger F, Grampp S, Kudlacek S, Woloszczuk W, Smolen JS, Pietschmann P (2000) Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis 59: 308 – 310

Pietschmann P, Stöckl J, Draxler S, Majdic O, Knapp W (2000) Functional and phenotypic characterization of dendritic cells generated in human plasma supplemented medium. Scand J Immunol 51: 377 – 383

Grisar J, Hahn P, Brosch S, Peterlik M, Smolen JS, Pietschmann P (2001)


Phenotypic characteristics of human monocytes undergoing transendothelial migration. Arthritis Res 3: 127 - 132 Pietschmann P, Kudlacek S, Grisar J, Spitzauer S, Woloszczuk W, Willvonseder R, Peterlik M (2001) Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Eur J Clin Invest 31: 444 – 451

Pietschmann P, Grisar J, Thien R, Willheim M, Kerschan-Schindl K, Preisinger E, Peterlik M (2001) Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures. Exp Gerontol 36: 1749-1759 Grisar J, Bernecker PM, Aringer M, Redlich K, Sedlak M, Wolozcszuk W, Spitzauer S, Grampp S, Kainberger F, Ebner W, Smolen JS, Pietschmann P (2002). Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation. J Rheumatol 29: 1430 – 1436 Lernbass I, Wutzl A, Grisar J, Schett G, Redlich K, Spitzauer S, Grampp S, Imhof H, Peterlik M, Pietschmann P (2002) Quantitative ultrasound in the assessment of bone status of patients suffering from rheumatic diseases. Skeletal Radiol 31: 270 – 276

Kerschan-Schindl K, Strametz-Juranek J, Heinze G, Grampp S, Biegelmayer C, Pacher R, Maurer G, Fialka-Moser V, Pietschmann P (2003) Pathogenesis of bone loss in heart transplant candidates and recipients. J Heart Lung Transpl 22: 843 – 850

Pietschmann P, Gollob E, Brosch S, Hahn P, Kudlacek S, Willheim M, Woloszczuk W, Peterlik M, Tragl KH (2003) The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism. Exp Gerontol 38: 1119 – 1127 Kerschan-Schindl K, Mitterbauer M, Füreder W, Kudlacek S, Grampp S, Biegelmayer C, Fialka-Moser V, Pietschmann P, Kahls P (2004) Post- transplant complications – Bone metabolism in patients more than five years after bone marrow transplantation. Bone Marrow Transplantation 34:491-496 Sipos W, Willheim M, Hofbauer G, Pietschmann P (2005) Evaluation of the suitability of monoclonal antibodies for flow cytometric intracellular cytokine detection in peripheral blood lymphocytes. J Vet Med A 52: 55-60

Kerschan-Schindl K, Hawa G, Kudlacek S, Woloszczuk W, Pietschmann P (2005) Serum levels of cathepsin K decrease with age in both women and men. Exp Gerontol 40: 532 – 535

Sipos W, Duvigneau JC, Hofbauer G, Schmoll F, Baravalle G, Hartl R, Exel B, Dobretsberger M, Pietschmann P (2005) Characterization of the cytokine pattern of porcine bone marrow-derived cells treated with 1α,25(OH)2D3. J Vet Med A52: 382-387

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Wutzl A, Brozek W, Lernbass I, Rauner M, Hofbauer G, Schopper C, Watzinger F, Peterlik M, Pietschmann P (2006) Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation. J Biomed Mater Res A 77 (1): 75-83 Mikosch P, Igerc I, Kudlacek S, Woloszczuk W, Gallowitsch HJ, Kresnik E, Stettner H, Grimm G, Lind P, Pietschmann P (2006) Receptor activator of nuclear factor κB ligand and osteoprotegerin in men with thyroid cancer. Eur J Clin Invest 36: 566-573 Brosch S, Shehata M, Hofbauer G, Peterlik M, Pietschmann P (2006) Alendronate stimulates expression of functional surface molecules ICAM-1, HLA-DR and B7-2 on human monocytes. Osteol 15: 188-196 Rauner M, Winzer M, Stupphann D, Krenbek D, Pietschmann P (2007) RANKL and OPG gene expression in bone marrow stromal cells and calvarial osteoblasts in mouse and rat. Osteol 16: 19-28

Co-author manuscripts: Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Silverman S, Felsenberg D, Vandormael K, Daifotis A, Lombardi A (2000) Alendronate treatment of osteoporosis in men. N Engl J Med 343: 604 – 610 Barnas U, Schmidt A, Seidl G, Kaider A, Pietschmann P, Mayer G (2001) A comparison of quantitative computed tomography and dual X-ray absorptiometry for evaluation of bone mineral density in patients on chronic hemodialysis. Am J Kidney Dis 37: 1247 – 1252 Kallay E, Pietschmann P, Toyokuni S, Bajna E, Hahn P, Mazzucco K, Bieglmayer C, Kato S, Cross HS (2001) Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Carcinogenesis 22: 1429-1435 Redlich K, Hayer S, Maier A, Dunstan CR, Tohidast-Akrad M, Lang S, Türk B, Pietschmann P, Woloszczuk W, Haralambous S, Kollias G, Steiner G, Smolen JS, Schett G (2002) Tumor necrosis factor α-mediated joint destruction is inhibited by targeting osteoclasts with osteoprotegerin. Arthritis Rheum 46: 785 – 792 Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R (2003) Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone 32: 681 –686 Sipos W, Duvigneau CJ, Pietschmann P, Willheim M, Höller K, Hartl RT, Wahl K, Steinborn R, Gemeiner M, Schmoll F (2003) Parameters of humoral and cellular immunity following vaccination of pigs with a European modified-live strain of porcine reproductive and respiratory syndrome virus (PRRSV), Viral Immunol 16: 335 – 346

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Schett G, Kiechl S, Redlich K, Oberhollenzer F, Weger S, Egger G, Mayr A, Jocher J, Xu Q, Pietschmann P, Teitelbaum S, Smolen J, Willeit J (2004) Soluble RANKL and risk of non-traumatic fracture. JAMA 291: 1108 – 1113 Kotzmann H, Riedl M, Pietschmann P, Schmidt A, Schuster E, Kreuzer S, Kainberger F, Frisch H, Geyer G, Hörl WH, Mayer G, Luger A (2004) Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis. J Nephrol 17: 87 – 94 Sipos W, Duvigneau JC, Willheim M, Schilcher F, Hartl RT, Hofbauer G, Exel B, Pietschmann P, Schmoll F (2004) Systemic cytokine profile in feeder pigs suffering from natural postweaning multisystemic wasting syndrome (PMWS) as determined by semiquantitative RT-PCR and flow cytometric intracellular cytokine detection. Vet Immunol Immunopathol 99: 63 – 71 Grisar J, Aringer M, Köller MD, Stummvoll GH, Eselböck D, Zwölfer B, Steiner CW, Zierhut B, Wagner L, Pietschmann P, Smolen JS (2004) Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells. Ann Rheum Dis 63: 1632-1637 Cavanagh LL, Boyce A, Smith L, Padmanabha J, Filgueira L, Pietschmann P, Thomas R (2005) Rheumatoid arthritis synovium contains plasmacytoid dendritic cells. Arthritis Res Ther 7: R230-40 Karanikas G, Schütz M, Wahl K, Paul M, Kontur S, Pietschmann P, Kletter K, Dudczak R, Willheim M (2005) Relation of anti-TPO antibody titre and T-lymphocyte cytokine production patterns in Hashimoto’s thyroiditis. Clin Endocrinol 63: 191 – 196 Thien R, Baier K, Pietschmann P, Peterlik M, Willheim M (2005) Interactions of 1α,25-dihydroxyvitamin D3 with IL-12 and IL-4 on cytokine expression of human T lymphocytes. J Allergy Clin Immunol 116: 683 – 689 Sipos W, Duvigneau JC, Pietschmann P, Schilcher F, Hofbauer G, Hartl RT, Schmoll F (2005) Porcine dermatitis and nephropathy syndrome (PDNS) is associated with a systemic cytokine expression profile indicative of proinflammation and a Th1 bias. Vet Immunol Immunopathol, A52: 382-387 Gugatschka M, Dobnig H, Fahrleitner-Pammer A, Pietschmann P, Kudlacek S, Strele A, Obermayer-Pietsch B (2005) Molecularly-defined malabsorption, milk consumption and anthropometric differences in adult males. Q J Med 98: 857-863 Fischer P, Gruenblatt E, Pietschmann P, Tragl KH (2006) Serotonin Transporter Polymorphism and LDL-Cholesterol. Mol Psychiatry 11 (8): 707-709 Wutzl A, Eisenmenger G, Hoffmann M, Czerny C, Moser D, Pietschmann P, Ewers R, Baumann A. (2006) Osteonecrosis of the jaws and bisphosphonate

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treatment in cancer patients. Wien Klin Wochenschr 118 (15-16): 473-478 Gugatschka M, Hoeller A, Fahrleitner-Pammer A, Dobnig H, Pietschmann P, Kudlacek S, Obermayer-Pietsch B (2007) Calcium supply, bone mineral density and genetically defined lactose maldigestion in a cohort of elderly men. J Endocrinol Invest 30 (1): 46-51 Reviews: Kudlacek S, Willvonseder R, Stohlawetz P, Hahn P, Pietschmann P (2000) Immunology and aging. The aging male 3: 137 – 142 Resch H, Gollob E, Kudlacek S, Pietschmann P (2001) Die Osteoporose beim Mann. Wien Med Wschr 151: 457-463 Pietschmann P (2001) Geschlechtsunterschiede bei Gelenkserkrankungen: pathophysiologische Grundlagen. Wien Med Wschr 151: 573-575 Mitringer A, Pietschmann P (2002) Osteoporose bei prämenopausalen Frauen. Wien Med Wschr 152: 586 - 590 Dimai HP, Pietschmann P, Resch H, Klaushofer K (2002) Leitfaden zur medikamentösen Therapie der postmenopausalen Osteoporose. Wien Med Wschr 152: 596 - 612 Brosch S, Redlich K, Pietschmann P. (2003) Pathogenese der Osteoporose bei chronischer Polyarthritis. Acta Med Austriaca 30: 1 – 5 Pietschmann P, Kerschan-Schindl K (2004) Osteoporosis: Gender specific aspects. Wien Med Wschr 154/17-18: 411- 415 Rauner M, Sipos W, Pietschmann P (2007) Osteoimmunology. Int Arch Allergy Immunol 143: 31-48 Patsch J, Muschitz C, Resch H, Pietschmann P (2007) Of mice and men: pathophysiology of male osteoporosis. JMHG 4(1): 87-93

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Gerhard PRAGER Dept. of Surgery, Med. Univ. of Vienna [email protected] Influence of bariatric surgery on gastrointestinal hormones Abstract In the last decades there has been a dramatic increase in the incidence of morbid obesity in the western world. Bariatric surgery is the most effective current treatment of morbid obesity. Different surgical approaches (restrictive, malabsorptive, gastric pacing) are nowadays applied to achieve permanent weight loss. Although bariatric surgery provides excellent results concerning weight loss and improvement of comorbidities its exact mode of action is still not completely understood. Several recently discovered gastrointestinal peptide hormones play an important role in the regulation of hunger and satiety. Only little is known about the regulation of these hormones after different bariatric procedures. Based on that knowledge we plan to determine the levels of different gastrointestinal (GI) hormones (ghrelin, glucagon-like peptide (GLP) 1, GLP 2, gastric inhibitory polypeptide (GIP), apelin, etc.) before and after bariatric surgery (gastric banding, gastric bypass, gastric stimulation) to improve and optimize our understanding of current procedures and gain further insight in the regulation of hunger and satiety. Determination of GI hormones is done in cooperation with the lab facilities of Dept. Internal Medicine III. Thesis Subjects GI hormones play a key role in satiety-hunger control. Bariatric surgery has significant impact on the levels of different GI hormones. Techniques and infrastructure More than 100 patients per year operated. Blood samples from the surgical department. Analysis and determination in cooperation with Dept. Internal Medicine III. All required equipment available.

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Curriculum Vitae Gerhard PRAGER

Address: Clinical Division of General Surgery, Department of Surgery, Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Vienna, Austria; Email [email protected]

Born 11th July 1967 in Vienna; Austrian citizen; married with DI Silvia Prager née Ertl; architect), 1 daughter, 1 son

Graduation Doctor of Medicine, 08th July 1992

1st October 1992 – 31st Mai 1993 Military service (military anesthetist)

1st December 1993 – 13th April 1997 and 1st October 1997 – 28th February 1998 Resident, Hospital Mistelbach, Dept of Surgery (Chief: Univ. Prof. Dr. E. Schima)

14th April 1997 – 30th September 1997 Guest surgeon, Surgical Endocrinology, Univ. Prof. Dr. B. Niederle, at the Clinical Division of General Sugery (Chief: o. Univ. Prof. Dr. R. Jakesz), University Clinics for Surgery, Vienna

Since 1st March 1998 Resident at the Clinical Division of General Surgery, University Clinics for Surgery, Vienna

30th April 1999 Certificate in Surgery of the Austrian Medical Association

April 2003 Appointment Consultant at the University Clinics for Surgery

23rd March 2004 Habilitation at the Medical University of Vienna (Univ. Doz.)

April 2004 Chief Working Group “Bariatric Surgery“ at the Clinical Division of General Surgery, Dept of Surgery

April 2005 Chief Working Group “Minimal Invasive Surgery“ at the Clinical Division of General Surgery, Dept of Surgery

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List of Publications (since 2000)

First Author 4 Prager, G. Czerny, Ch. Kurtaran, A. Passler, Ch. Scheuba, Ch. Bieglmayer, Ch.

Niederle, B.: Minimally invasive open parathyroidectomy in an endemic goiter area. ARCH SURG 136, 810 - 816 (2001)

5 Prager, G. Heinz-Peer, G. Passler, Ch. Kaczirek, K. Schindl, M. Scheuba, Ch. Niederle, B.: Surgical strategy in adrenal masses. EUR J RADIOL 41, 70-77 (2002)

6 Prager, G. Kalaschek, A. Kaczirek, K. Passler, Ch. Scheuba, Ch. Sonneck, G. Niederle, B.: Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism. SURGERY 132, 930 - 936 (2002)

7 Prager, G. Heinz-Peer, G. Passler, Ch. Kaczirek, K. Schindl, M. Scheuba, Ch. Vierhapper, H. Niederle, B.: Can dynamic Gadolinium-enhanced magnet resonance imaging with chemical shift studies predict the status of adrenal masses?. WORLD J SURG 26, 958 - 964 (2002)

8 Prager, G. Czerny, C. Ofluoglu, S. Kurtaran, A. Passler, C. Kaczirek, K. Scheuba, C. Niederle, B.: Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region. J AM COLL SURG 196, 541-548 (2003)

9 Prager, G. Heinz-Peer, G. Passler, Ch. Kaczirek, K. Scheuba, Ch. Niederle, B.: Applicability of laparoscopic adrenalectomy in 150 consecutive patients - a prospective study. Arch Surg, 2004. 139(1): 46-9

Coauthor and Senior Author 13 Zacherl, J. Scheuba, Ch. Prager, G. Zacherl, M. Jakesz, R. Niederle, B.: Wie

kostengünstig ist die laparoskopische Adrenalektomie wirklich?. MINIMAL INVASIVE CHIRURGIE 9, 79 - 84 (2000)

14 Neunteufl, Th. Heher, S. Prager, G. Katzenschlager, R. Abela, C. Niederle, B. Stefenelli, Th.: Effects of sucessful parathyroidectomy on altered arterial reactivity in patients with hypercalcemia: results of a 3-year follow-up study. CLIN ENDOCRINOL 53, 229 - 232 (2000)

15 Niederle, B. Prager, G. Scheuba, Ch. Passler, Ch. Schindl, M.: Minimal invasive chirurgische Endokrinologie. ACTA CHIR AUSTRIACA 32, [Suppl165] 39 - 46 (2000)

16 Passler, Ch. Avanessian, R. Kaczirek, K. Prager, G. Scheuba, Ch. Schindl, M. Niederle, B.: Schilddrüsenchirurgie im Alter. ACTA CHIR AUSTRIACA 33, 288-293 (2001)

17 Hönigschnabl, S. Gallo, S. Niederle, B. Prager, G. Kaserer, K. Lechner, G. Heinz-Peer, G.: How accurate is MR imaging in characterisation of adrenal masses: update of a long-term study . EUR J RADIOL 41, 113-122 (2002)

18 Kaczirek, K., Prager, G., Schindl, M., Kaserer, K., Gessl, A., Vierhapper, H., Niederle, B.: Multiple endocrine neoplasia 1- current recommendations for diagnosis and treatment. WIEN KLIN WOCHENSCHR 114, 258-266 (2002)

19 Zettinig, G. Prager, G. Kurtaran, A. Kaserer, K. Czerny, Ch. Dudczak, R. Niederle, B.: Stellenwert eines strukturierten Befundschemas zur Interpretation

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der Nebenschilddrüsenszintigraphie bei primärem Hyperparathyreoidismus. ACTA MED AUSTRIACA 29, 68 - 71 (2002)

20 Zettinig, G. Kurtaran, A. Prager, G. Kaserer, K. Dudczak, R. Niederle, B.: "Suppressed" double adenoma - a rare pitfall in minimally invasive parathyroidectomy. HORMONE RES 57, 57 -60 (2002)

21 Schindl, M. Kaczirek, K. Passler, Ch. Kaserer, K. Prager, G. Scheuba, Raderer, M. Niederle, B.: Treatment of small intestinal neuroendocrine tumos: Is an extended multimodal approach justified?. WORLD J SURG 26, 976 - 984 (2002)

22 Bieglmayer, C. Prager, G. Niederle, B.: Kinetic analyses of parathyroid hormone clearence as measured by three rapid immunoassays during parythyroidectomy. CLIN CHEM 48, 1731-1738 (2002)

23 Hoda, M. R. Rasoul-Rockenschaub, S. Felberbauer, F. X. Prager, G. Szeles, J. C. Dadgar, N. Wenzl, E.: Pregnancy and labor after adjustable gastric banding for therapy of morbid obesity. WIEN KLIN WOCHENSCHR 114, 781-784 (2002)

24 Passler, Ch. Avanessian, R. Kaczirek, K. Prager, G. Scheuba, Ch. Niederle, B.: Thyroid surgery in the geriatric patient. ARCH SURG 137, 1243 - 1248 (2002)

25 Passler, C. Prager, G. Scheuba, C. Kaserer, K. Zettinig, G. Niederle, B.: Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodin substitution. ANN SURG 237, 227-234 (2003)

26 Saeger, W. Fassnacht, M. Chita, R. Prager, G. Nies, C. Lorenz, K. Bährlehner, E. Simon, D. Niederle, B. Beuschlein, F. Allolio, B. Reincke, M.: High diagnostic accuracy of adrenal core biopsy: Results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. HUMAN PATHOL 34, 180-186 (2003)

27 Kaczirek, K. Soleiman, A. Schindl, M. Passler, Ch. Scheuba, C. Prager, G. Kaserer, K. Niederle, B.: Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism. EUR J CLIN INVEST 33, 488-492 (2003)

28 Niederle, B. Prager, G.: Advanced endoscopic adrenal surgery-new developments. EUR SURG 35, 71-75 (2003)

29 Rauhofer, U. Prager, G. Hoermann, M. Auer, H. Kaserer, H. Niederle, B.: Cystic echninococcosis of the thyroid gland in children and adults. THYROID 13, 497-502, (2003)

30 Passler, C. Prager, G. Scheuba, C. Niederle, BE. Kaserer, K. Zettinig, G. Niederle, B.: Follicular variant of papillary thyroid carcinoma - a long term follow up. Arch Surg, 2003. 138(12): 1362-6.

31 Stift, A. Prager, G. Selzer, E. Widder, J. Kandioler, D. Friedl, J. Teleky, B. Herbst, F. Wrba, F. Bergmann, M.: The early response of p53-dependant proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue. Int J Oncol, 2003. 23(5): 1269-75.

32 Bohdjalian, A. Langer, F. Reza Hoda, M. A. Felberbauer, F. Silberhumer, G. Zacherl, J. Schindler, K. Luger, A. Ludvik, B. Prager, G.: Surgical treatment of obesity. Wien Med Wochenschr, 2004. 154(13-14): 329-33.

33 Kaczirek, K. Schindl, M. Weinhausel, A. Scheuba, C. Passler, C. Prager, G. Raderer, M. Hamilton, G. Mittlbock, M. Siegl, V. Pfragner, R. Niederle, B.: Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines. J Clin Endocrinol Metab, 2004. 89(5): 2397-401.

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34 Passler, C. Scheuba, C. Prager, G. Kaczirek, K. Kaserer, K. Zettinig, G. Niederle, B.: Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region. Endocr Relat Cancer, 2004. 11(1): 131-9.

35 Schindler, K. Prager, G. Ballaban, T. Kretschmer, S. Riener, R. Buranyi, B. Maier, C. Luger, A. Ludvik, B.: Impact of laparoscopic adjustable gastric banding on plasma ghrelin, eating behaviour and body weight. Eur J Clin Invest, 2004. 34(8): 549-54.

36 Stadler, A. Schima, W. Prager, G. Homolka, P. Heinz, G. Saini, S. Eisenhuber, E. Niederle, B.: CT density measurements for characterization of adrenal tumors ex vivo: variability among three CT scanners. AJR Am J Roentgenol, 2004. 182(3): 671-5.

37 Widhalm, K. Dietrich, S. Prager, G.: Adjustable gastric banding surgery in morbidly obese adolescents: experiences with eight patients. Int J Obes Relat Metab Disord, 2004. 28 Suppl 3: S42-5.

38 Fleischmann, E. Kurz, A. Niedermayr, M. Schebesta, K. Kimberger, O. Sessler, D. I. Kabon, B. Prager, G.: Tissue oxygenation in obese and non-obese patients during laparoscopy. Obes Surg, 2005. 15(6): 813-9.

39 Kaczirek, K. Riss, P. Wunderer, G. Prager, G. Asari, R. Scheuba, C. Bieglmayer, C. Niederle, B.: Quick PTH assay cannot predict incomplete parathyroidectomy in patients with renal hyperparathyroidism. Surgery, 2005. 137(4): 431-5.

40 Langer, F. B. Wenzl, E. Prager, G. Salat, A. Miholic, J. Mang, T. Zacherl, J.: Management of postoperative esophageal leaks with the Polyflex self-expanding covered plastic stent. Ann Thorac Surg, 2005. 79(2): 398-403; discussion 404.

41 Langer, F. B. Reza Hoda, M. A. Bohdjalian, A. Felberbauer, F. X. Zacherl, J. Wenzl, E. Schindler, K. Luger, A. Ludvik, B. Prager, G.: Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg, 2005. 15(7): 1024-9.

42 Langer, F. B. A. Bohdjalian, A. Felberbauer, F. X. Fleischmann, E. Reza Hoda, M. Ludvik, B. Zacherl, J. Jakesz, R. Prager, G.: Does Gastric Dilation Limit the Success of Sleeve Gastrectomy as a Sole Operation for Morbid Obesity?. Obes Surg, 2006. 16: 166-171

43 Langer, F. B. A. Bohdjalian, A. Hoda, A Silberhumer, G Felberbauer, F. X. Rasoul-Rockenschaub, S Zacherl, J. Wenzl, E Prager, G.: Early Results of Laparoscopic Adjustable GastricBanding using the new Low Pressure Soft Gastric Band. EUR SURG 2004. 36: 345-349

44 Silberhumer, G Miller, K. Krivanek, S. Widhalm, K. Pump, A. Prager, G.: Laparoscopic adjustable Gastric Banding in Adolescents: The Austrian Experience. Obes Surg, 2006. 16: 1062-1067

45 Haider, D. Schindler, K. Schaller, G. Prager, G. Wolzt, M. Ludvik, B.: Increased Plasma Visfatin Concentrations in Morbidly Obese Subjects are reduced after Gastric Banding. J Clin Endocrinol Metab, 2006. 91: 1578-1581.

46 Bohdjalian, A. Prager, G. Aviv, R. Policker, S. Schindler, K. Kretschmer, S. Riener, R. Zacherl, J. Ludvik, B.: One-year experience with Tantalus: a new surgical approach to treat morbid obesity. Obes Surg, 2006. 16(5): 627-634

47 Kaczirek, K. Prager, G. Riss, P. Wunderer, G. Asari, R. Scheuba, Ch. Bieglmayer, Ch. Niederle, B.: Novel parathyroid hormone (1-84) assay as basis for parathyroid hormone monitoring in renal hyperparathyroidism. Arch Surg 2006. 141: 129-134

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48 Bieglmayer, C. Kaczirek, K. Prager, G. Niederle, B.: Parathyroid Hormone Monitoring during Total Parathyroidectomy for Renal Hyperparathyroidism: Pilot Study of the Impact of Renal Function and Assay Specificity. Clin Chem 2006. 52: 1112-1119

49 Haider, D.G. Mittermayer, F. Schaller, G. Artwohl, F. Baumgartner-Parzer, S.M. Prager, G. Roden, M. Wolzt, M.: Free fatty acids normalize a rosiglitazone-induced visfatin release. Am J Physiol Endocrinol Metab 2006

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Michael RODEN 1st Med. Dept. & Landsteiner-Institute, Hanusch Hospital [email protected] Pathogenesis of insulin resistance, obesity and diabetes in humans Abstract Obesity and type 2 diabetes are becoming the most important health problems all over the world. Although treatment and prevention can be effective the underlying causes defining success or failure of lifestyle intervention are still not well understood. We have previously contributed to the current hypothesis that increased lipid availability is mainly responsible for insulin resistance in obesity and type 2 diabetes. Now, we focus our research on the mechanisms underlying these defects in lipid metabolism, particularly on the role of mitochondrial energy metabolism by noninvasive measurement of ATP synthesis. We test the efficacy of various forms of intervention (diet, exercise and antidiabetic drugs) in patient groups with different genetic risk to develop diabetes mellitus. Further, we analyze changes in hormone secretion in those patients as well as in morbidly obese before and after severe weight loss. Thesis Subjects Effects of exercise on mitochondrial function Assessment of early defects in energy metabolism in the development of fatty liver disease Effects of different dietary composition on insulin action Techniques and infrastructure Clinical metabolic lab, stable isotope dilution techniques to assess whole body glucose and lipid metabolism, noninvasive measurement of intracellular lipids and glucose metabolites as well as quantification of tissue specific metabolic fluxes using magnetic resonance spectroscopy, tissue biopsies

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Curriculum Vitae

Michael RODEN 1.Medical Department, Hanusch Hospital, Heinrich Collin Strasse 30, A-1140 Vienna, Austria; Phone +43 1 91021 85011; Fax +43 1 91021 85019; Email [email protected] Personal Data Date of Birth: 11.02.1961 Place of Birth: Vienna, Austria Nationality Austria Education 2004 Certificate of Achievement, Continuing Research

Education Credit Program (CREC) in compliance with NIH, Case Western Reserve University, Cleveland, OH

1997 Specialist in Endocrnology and Metabolism 1994 Specialist in Internal Medicine 1993 Certificate in Emergency Medicine 1986 Graduation as Medical Doctor (Dr.med.) Career History 2005 – present Director of the Karl-Landsteiner-Institute for

Endocrinology and Metabolism; Vienna 2003 – present Head of the I. Medical Department, Hanusch Hospital,

Vienna 1997 Associate Professor of Medicine, University of Vienna1994-1995 Max-Kade Fellowship, Division of Endocrinology,

Department of Internal Medicine, Yale University, New Haven, CT, USA

1994 “Venia docendi”in Internal Medicine, Univ. Vienna 1988 – 2003 University Assistant , Division of Endocrinology

Metabolism, Department of Internal Medicine I, then III, (Medical) University of Vienna, Austria

1986-1988 University Assistant, Pharmacological Institute, University of Vienna

1982-1984 Instructor, Anatomical Institute, University of Vienna

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1979 and 1986 Regular Military Service Career-related Activities 1996-present

EU Liason Person, Council Member, Advisory Board Member of the Annual Meeting, European Association for the Study of Diabetes (EASD)

2000-2007 Past-President, President, Vice-President and Councillor, Austrian Diabetes Association (ÖDG)

2000-2007 Councilor, Treasurer, First Secretary, Federation of International Danube Symposia (FID)

1996-2002 Vice-President, Honorary Secretary-Treasurer, Councilor, European Society for Clinical Investigation (ESCI)

1997-present Editorial Boards Assistant Editor Diabetologia (-2003) Associate Editor Eur. J. Clin. Invest. (present) Associate Editor Diabetic Medicine (present) Editorial Board Am. J. Physiol. (present)

1995 Management Training for Leadership in Medicine, University of Vienna and University of Salzburg

Awards 2006 ESCI (formerly Mack-Foster) Award for Excellence in

Clinical Sciences, European Society for Clinical Investigation

2004 International Novartis Award for Innovative Patient Oriented Research - Young Investigator, Europe-USA

2002 Novartis (formerly Sandoz) Award for Chemistry, Biology and Medicine, Austria

2001 Ferdinand-Bertram Award, German Diabetes Association

1999 Kardinal-Innitzer Award, Austria 1996 Joseph-Skoda-Research Award, Austrian Society of

Internal Medicine Hoechst Award, Faculty of Medicine, University of Vienna

1994 Theodor Körner Award Austria Research Award, City of Vienna by the Mayor of the City of Vienna

1992 Friedrich Wewalka Memorial Award by the Austrian Society for Gastroenterology and Hepatology

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Memberships Diabetes Associations: USA, Europe, Germany, Austria Endocrinology / Obesity: USA, Germany, Austria European Society for Clinical Investigation Austrian Society for Internal Medicine Sources of funding (since 2000)

Period Organization Short Title K€/yr 2006 – present

Juvenile Diabetes Research Foundation International (JDRF), New York, NY

Noninvasive measurement of hepatic glycogen synthesis kinetics in type 1 diabetics

2005 – present

Austrian National Bank

Vergleich der Effekte von Kraft-Ausdauer (REsistance )- mit aeroben Konditionstrainings (COnditioning) Training - RECO Studie

2002 – present

Austrian Science Fund (FWF)

Metabolic regulation in human skeletal muscle Effects of lipids on cellular metabolism

2002-2004 European Foundation for the Study of Diabetes (EFSD)

Metabolic effects of long-term suppression of lipolysis



Martin Krssak (Mitbetreuuer, ormal- und Naturwissenschaftl. Fakultät, 2000)

Applications of 1H-NMR methods in the experimental liver transplantation


Harald Stingl Die Bedeutung freier Fettsäuren für die Regulation der hepatischen Glukoneogenese des Menschen

– 2000 MD

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Elisabeth Bernroide Hepatischer Glykogenstoffwechsel bei Patienten mit Diabetes mellitus Typ 1

– 2000 DM

Daniel Weghuber Effekte freier Fettsäuren auf muskulären Glukosetransport / phosphorylierung und den intramyozellulären Lipidgehalt beim Menschen

– 2001 MD

Christian Anderwald Die residuale Insulinresistenz von Leber und Muskel bei Diabetes mellitus Typ 2

– 2002 MD

Attila Breh Regulation des postprandialen Leberglykogenstoffwechsels bei Typ-2 Diabetes

– 2003 MD

Rainer Englisch Effects of insulin-like growth factor I on basal and stimulated glucose fluxes in rat liver

– 2004 Dr. rer. nat. techn.

Goran Mitkovski (Mitbetreuer)

Nutrient dependent regulation of signal transduction in human skeletal muscle

– 2006 MD

Christian Toth The role of mitochondiral dysfunction in muscle insulin resistance of type 2 diabetes mellitus

– 2007 MD

Michaela Farukuoye Ernährungsintervention bei Gesunden und Nachkommen von Typ-2 Diabetikern

2005 - (2007) Dr. scient med.

Romana Stark Automated applications of high resolution magnetic resonance spectroscopic imaging (MRSI) in metabolic studies

2005 - (2007) Dr. scient med.


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Michaela Kacerovsky

Noninvasive measurement of liver glycogen kinetics in type 1 diabetes

2006 - (2009) PhD

Publications More than 100 original papers in peer reviewed journals More than 30 reviews in peer reviewed journals More than 90 invited lectures Only original and published papers (since 2000)

1. Krssak M, Falk Petersen K, Bergeron R, Price T, Laurent D, Rothman DL, Roden M, Shulman GI (2000) Intramuscular glycogen and intramyocellular lipid utilization during prolonged exercise and recovery in man: a 13C and 1H nuclear magnetic resonance spectroscopy study. J Clin Endocrinol Metab 85:748-754

2. Stulnig T, Berger M, Roden M, Stingl H, Raederstorff D, Waldhäusl W (2000) Inhibition of T lymphocyte signaling by elevated serum concentrations of unsaturated free fatty acids. FASEB J 14:939-947

3. Roden M, Stingl H, Chandramouli V, Schumann WC, Hofer A, Landau BR, Nowotny P, Waldhäusl W, Shulman GI (2000) Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in man. Diabetes 49:401-407

4. Fürnsinn C, Brunmair B, Neschen S, Roden M, Waldhäusl W (2000) Troglitazone directly inhibits CO2 production from glucose and palmitate in isolated rat skeletal muscle. J Pharmacol Exp Ther 293:487-493

5. Roden M, Ludwig C, Nowotny P, Schneider B, Roden A, Waldhäusl W (2000) Relative hypoleptinemia in type 1 and type 2 diabetes mellitus. Int J Obesity 24:976-981

6. Schatzl G, Reiter WJ, Thürridl T, Waldmüller J, Roden M, Söregi S, Madersbacher S (2000) Endocrine patterns in patients with benign and malignant prostatic diseases. Prostate 44:219-224

7. Krebs M, Stingl H, Nowotny P, Weghuber D, Bischof M, Waldhäusl W, Roden M (2000) Prevention of in vitro lipolysis by tetrahydrolipstatin. Clin Chem 46:950-954

8. Englisch R, Wurzinger R, Fürnsinn C, Schneider B, Frisch H, Waldhäusl W, Graf J, Roden M (2000) Effects of insulin-like growth factor I on basal and stimulated glucose fluxes in rat liver. Biochem J 351:39-45

9. Brunmair B, Neschen S, Furtmüller R, Roden M, Waldhäusl W, Fürnsinn C (2000) Metabolic response to anisoosmolarity of rat skeletal muscle in vitro. Horm Metab Res 32:251-255

10. Raber W, Raffesberg W, Bischof M, Scheuba C, Niederle B, Gasic S, Waldhäusl W, Roden M (2000) Diagnostic efficacy of plasma free metanephrines for the detection of pheochromocytoma. Arch Intern Med 160:2959-2963

11. Bischof MG, Ludwig C, Hofer A, Kletter K, Krebs M, Stingl H, Nowotny P, Waldhäusl W, Roden M (2000) Hormonal and metabolic counterregulation


during and after high dose insulin induced hypoglycemia in diabetes mellitus type 2. Horm Metab Res 32:417-423

12. Roden M, Anderwald C, Fürnsinn C, Waldhäusl W, Lohninger A (2000) Effects of short-term leptin exposure on triglyceride deposition in rat liver. Hepatology 32:1045-1049

13. Polak K, Schmetterer L, Luksch A, Gruber S, Polska E, Peternell V, Bayerle-Eder M, Wolzt M, Krebs M, Roden M (2001) Free fatty acids/triglycerides increase ocular and subcutaneous blood flow. Am J Physiol 280:R56-R61

14. Bischof MG, Krssak M, Krebs M, Bernroider E, Stingl, H, Waldhäusl W, Roden M (2001) Intensive insulin therapy does not normalise all defects of hepatic carbohydrate metabolism in type 1 diabetes mellitus. Diabetes 50:392-398

15. Stingl H, Krssak M, Krebs M, Bischof M, Nowotny P, Fürnsinn C, Shulman GI, Waldhäusl W, Roden M (2001) Lipid-dependent control of hepatic glycogen stores in healthy man. Diabetologia 44:48-54

16. Krampl E, Kametas N, Cacho Zegarra AM, Roden M, Nicolaides KH (2001) Maternal blood glucose at high altitude. Brit J Obstet Gynaec 108:254-257

17. Krampl E, Kametas N, Nowotny P, Roden M, Nicolaides KH (2001) Glucose metabolism in pregnancy at high altitude. Diabetes Care 24:817-822

18. Krebs M, Krssak M, Weghuber D, Nowotny P, Gruber S, Mlynarik V, Bischof M, Stingl H, Fürnsinn C, Waldhäusl W, Roden M (2001) Free fatty acids inhibit glucose-stimulated increases of intramuscular glucose-6-phosphate concentrations in man. J Clin Endocrinol Metab 86:2153-2160

19. Roden M, Raffesberg W, Raber W, Bernroider E, Niederle B, Waldhäusl W, Gasic S (2001) Quantification of unconjugated metanephrines in human plasma without interference with acetaminophen. Clin Chem 47:1061-1067

20. Wurzinger R, Englisch R, Roka S, Langer R, Gajdzik L, Roden M, Graf J (2001) Intracellular calcium in the isolated rat liver: correlation to glucose release, K+ balance and bile flow. Cell Calcium 30:403-412 (doi:10.1054/ceca.2001.0248)

21. Brunmair B, Gras F, Neschen S, Roden M, Wagner L, Waldhäusl W, Fürnsinn C (2001) Direct thiazolidinedione action on isolated rat skeletal muscle fuel handling is independent of PPARγ-mediated changes in gene expression. Diabetes 50:2309-2315

22. Starcuk Jr Z, Starcuk Z, Mlynarik V, Roden M, Horky J, Moser E (2001) Low power water suppression by hyperbolic secant pulses with controlled offsets and delays (WASHCODE). J Magn Reson 152:168-178

23. Széles JC, Csapó B, Klarhöfer M, Balássy C, Hoda R, Berg A, Roden M, Polterauer P, Waldhäusl W, Moser E (2001) In vivo magnetic resonance micro-imaging of the human toe at 3 tesla. Magn Reson Imaging 19:1235-1238

24. Bischof MG, Bernroider E, Ludwig C, Kurzemann S, Kletter K, Waldhäusl W, Roden M: (2001) Hypoglycemia counterregulation during near physiologic insulin therapy. Horm Res 56:151-158

25. Fürnsinn C, Nowotny P, Brunmair B, Gras F, Roden M, Waldhäusl W, Vierhapper H (2002) Thiazolidinediones influence plasma steroids of male obese Zucker rats. Endocrinology 143:327

26. Bayerle-Eder M, Fuchsjäger-Mayrl G, Sieder A, Polska E, Roden M, Stulnig T, Bischof M, Waldhäusl W, Schmetterer L, Wolzt M (2002) Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia. Atherosclerosis 160:177-184

27. Bischof MG, Bernroider E, Krssak M, Krebs M, Stingl H, Nowotny P, Yu C,

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Shulman GI, Waldhäusl W, Roden M (2002) Hepatic glycogen metabolism in type 1 diabetes mellitus after long-term near normoglycemia. Diabetes 51:49-54

28. Krebs M, Krssak M, Bernroider E, Anderwald C, Brehm A, Meyerspeer M, Nowotny P, Roth E, Waldhäusl W, Roden M (2002) Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 51:599-605

29. Artwohl M, Roden M, Hölzenbein T, Freudenthaler A, Waldhäusl W, Baumgartner-Parzer S (2002) Modulation by leptin of proliferation and apoptosis in vascular endothelial cells. Int J Obesity 26:577-580

30. Schmidt A, Pleiner J, Schaller G, Roden M, Dallinger S, Mayer G, Schmetterer L, Wolzt M (2002) Renal hemodynamic effects of somatostatin are not related to inhibition of endogenous insulin release. Kidney Int 61:1788-1793

31. Pleiner J, Schaller G, Mittermayer F, Bayerle-Eder M, Roden M, Wolzt M (2002) FFA-induced endothelial dysfunction can be corrected by Vitamin C. J Clin Endocrinol Metab 87:2913-2917

32. Anderwald C, Müller G, Koca G, Fürnsinn C, Waldhäusl W, Roden M (2002) Leptin-dependent inhibition of hepatic gluconeogenesis is modulated by insulin receptor substrate-2. Mol Endocrinol 16:1612-1628

33. Fuchsjäger-Mayrl G, Kautzky-Willer A, Kiss B, Rainer G, Findl O, Wagner O, Roden M, Pleiner J, Wolzt M, Schmetterer L (2002) Ocular hyperperfusion following onset of intensified insulin therapy is inversely correlated with plasma endothelin-1 in type 1 diabetes. Diabetologia 45:883-890

34. Anderwald C, Koca G, Fürnsinn C, Waldhäusl W, Roden M (2002) Inhibition of glucose production and stimulation of bile flow by R(+)-α-lipolic acid in rat liver. Liver 22:356-362

35. Anderwald C, Bernroider E, Krssak M, Stingl H, Brehm A, Bischof MG, Roden M, Waldhäusl W (2002) Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes 51:3025-3032

36. Stingl H, Schnedl WJ, Krssak M, Bernroider E, Bischof MG, Lahousen T, Pacini G, Roden M (2002) Reduction of hepatic glycogen synthesis and breakdown in patients with agenesis of the dorsal pancreas. J Clin Endocrinol Metab 87:4678-4685

37. Stingl H, Raffesberg W, Nowotny P, Waldhäusl W, Roden M (2002) Reduction of plasma leptin concentrations by arginine but not lipid infusion in humans. Obes Res 10:1111-1119

38. Herkner H, Klein N, Joukhadar C, Lackner E, Langenberger H, Frossard M, Bieglmayer, Wagner O, Roden M, Müller M (2003) Transcapillary insulin transfer in human skeletal muscle. Europ J Clin Invest 33:141-146

39. Kautzky-Willer A, Krssak M, Winzer C, Pacini G, Tura A, Serdat F, Wagner OF, Brabant G, Horn R, Stingl H, Waldhäusl W, Roden M (2003) Increased intramyocellular lipid concentrations identify impaired glucose and energy metabolism in women with prior gestational diabetes. Diabetes 52:244-251

40. Artwohl M, Graier WF, Roden M, Waldhäusl W, Bischof M, Freudenthaler A, Baumgartner-Parzer SM (2003) Glycated low-density lipoprotein modulates apoptosis and proliferation in vascular endothelial cells. Diabetes 52:1240-1247

41. Gras F, Brunmair B, Roden M, Waldhäusl W, Fürnsinn C (2003) Differences in troglitazone action on glucose metabolism in freshly isolated versus long-term incubated rat skeletal muscle. Brit J Pharmacol 138:1140-1146

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42. Raber W, Raffesberg W, Waldhäusl W, Gasic S, Roden M (2003) Exercise induces excessive normetanephrine responses in hypertensive diabetic patients. Europ J Clin Invest 33:480-487

43. Krebs M, Brehm A, Krssak M, Anderwald M, Bernroider M, Nowotny P, Roth E, Chandramouli V, Landau BR, Waldhäusl W, Roden M (2003) Direct and indirect effects of amino acids on hepatic glucose metabolism in humans. Diabetologia 46:917-925

44. Anderwald C, Brabant G, Bernroider E, Horn R, Brehm A, Waldhäusl W, Roden M (2003) Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. Diabetes 52:1792-1798

45. Krebs M, Polak K, Vales A, Geiger M, Schmetterer L, Wagner OF, Waldhäusl W, Binder BR, Roden M (2003) Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. Thromb Haemost 90:422-428

46. Kunert O, Stingl H, Rosian E, Krššák M, Bernroider E, Seebacher W, Zangger K, Staehr P, Chandramouli V, Landau BR, Nowotny P, Waldhäusl W, Haslinger E, Roden M (2003) Measurement of fractional whole-body gluconeogenesis in humans from blood samples using 2H nuclear magnetic resonance spectroscopy. Diabetes 52:2475-2482

47. Artwohl M, Roden M, Waldhäusl W, Freudenthaler A, Baumgartner-Parzer SM (2004) Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J 18:146-148

48. Bischof MG, Brehm A, Bernroider E, Krssak M, Mlynarik V, Bauer E, Madl C, Waldhäusl W, Roden M (2004) Brain energy metabolism during hypoglycemia in healthy and type 1 diabetic humans. Diabetologia 47:648-651

49. Krssak M, Mlynarik V, Meyerspeer M, Moser E, Roden M (2004) 1H NMR relaxation times of skeletal muscle metabolites at 3 Tesla. Magn Reson Mater Phy 16:155-159

50. Brunmayr B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W, Fürnsinn C (2004) Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanisms contributing to their antidiabetic actions? Diabetes 53:1052-1059

51. Hills SA, Blakau B, Coppack SW, Dekker JM, Mari A, Natali A, Walker M, Ferrannini E, on behalf of the EGIR-RISC Study Group (… Roden M) (2004) The EGIR-RISC STUDY (The European group for the study of insulin resistance: relationship between insulin sensitivity and cardiovascular disease risk): I. Methodology and Objectives. Diabetologia 547:566-570

52. Hanusch-Enserer U, Cauza E, Brabant G, Dunky A, Rosen A, Pacini G, Tüchler H, Prager R, Roden M (2004) Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding. J Clin Endocrinol Metab 89:3352-3358

53. Winzer C, Wagner O, Festa A, Schneider B, Roden M, Bancher-Todesca D, Pacini G, Funahashi T, Kautzky-Willer A (2004) Plasma adiponectin, insulin sensitivity and subclinical inflammation in women with prior gestational diabetes. Diabetes Care 27:1721-1727

54. Brunmayr B, Lest A, Staniek K, Gras F, Scharf N, Roden M, Nohl H, Waldhäusl W, Fürnsinn C (2004) Fenofibrate impairs rat mitochondrial function by inhibition of respiratory complex I. J Pharmacol Exp Ther (PMID 15166256)

55. Bayerle-Eder M, Polska E, Kopf A, Roden M, Waldhäusl W, Pleiner H, Wipler

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B, Wolzt M, Schmetterer L (2004) Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects. Europ J Clin Invest 34:519-529

56. Brehm A, Pfeiler G, Pacini G, Vierhapper H, Roden M (2004) Relationship of plasma lipoprotein ratios and insulin resistance in obesity. Clin Chem 50:2316-2322

57. Krssak M, Brehm A, Bernroider E, Anderwald C, Dalla Man C, Nowotny P, Cobelli C, Shulman GI, Waldhäusl W, Roden M (2004) Postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes 53:3048-3056

58. Brabant G, Nave H, Horn R, Anderwald C. Müller G, Roden M (2004) In vivo and in vitro evidence for a hepatic modulation of the leptin signal in rats. Europ J Clin Invest 34:831-837

59. Bayerle-Eder M, Pleiner J, Mittermayer F, Schaller G, Roden M, Waldhäusl W, Bieglmayer C, Wolzt M (2004) Effect of systemic vitamin C on free fatty acid-induced lipid peroxidation. Diabetes Metab 30:433-439

60. Artwohl M, Fürnsinn C, Waldhäusl W, Hölzenbein T, Rainer G, Freudenthaler A, Roden M, Baumgartner-Parzer S (2005) Thiazolidendiones inhibit proliferation of micro- and macrovascular cells by a PPARγ-independent mechanism. Diabetologia 48:586-594

61. Charbonnel B, Roden M, Urquhart R, Mariz S, Johns D, Mihm MJ, Widel M, Tan M (2005) Pioglitazone elicits long-term improvements in insulin sensitivity and lipids in patients with type 2 diabetes: comparisons with gliclazide-based regimen. Diabetologia 48:553-560

62. Brabant G, Müller G, Horn R, Roden M, Nave H (2005) Hepatic leptin signalling in obesity. FASEB J 19:1048-1050

63. Bernroider E, Brehm A, Krssak M, Anderwald C, Trajanoski Z, Cline G, Shulman GI, Roden M (2005) The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes. J Clin Endocrinol Metab 90:5559-5565

64. Roden M, Laakso M, Johns D, Widel M, Urquhart R, Richardson C, Mariz S, Tan MH (2005) Long-term effects of pioglitazone and metformin on insulin sensitivity in patients with type 2 diabetes. Diabetic Med 22:1101-1106

65. Lechleitner M, Roden M, Haehling E, Müller M (2005) Insulin glargine in combination with oral antidiabetic drugs as a cost equivalent alternative to conventional insulin therapy in type 2 diabetes mellitus. Wien Klin Wschr 117:593-598

66. Tremblay F, Krebs M, Dombrowski L, Brehm A, Bernroider E, Roth E, Nowotny P, Waldhäusl W, Marette A, Roden M (2005) Overactivation of the S6 kinase 1 a cause of human insulin resistance duirng increased amino acid availability. Diabetes 54:2674-2684

67. Meyerspeer M, Krssak M, Kemp GJ, Roden M, Moser E (2005) Dynamic Interleaved 1H/31P STEAM MRS at 3 Tesla using a pneumatic force-controlled plantar flexion exercise rig. MAGMA 18:257-262

68. Brehm A, Krssak M, Schmid AI, Nowotny P, Waldhäusl W, Roden M (2006) Increased lipid availability impairs insulin stimulated ATP synthesis in human skeletal muscle. Diabetes 55:136-140

69. Stingl H, Chandramouli V, Brehm A, Nowotny P, Waldhäusl W, Landau BR, Roden M (2006) Changes in glycogen cycling during a glucose load in healthy humans. Diabetologia http://dx.doi.org/10.1007/s00125-005-0099-x

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http://dx.doi.org/10.1007/s00125-005-0099-x


Erich ROTH Surgical Research Laboratory, Surgical University Clinic [email protected] Metabolism and Clinical Nutrition in Critically Ill Patients Abstract Clinical nutrition is of high importance for the outcome of critically ill patients. Recently it was shown that certain macronutrients have an immunomodulating capacity. Therefore immunonutrition contains several potentially immunomodulating agents such as glutamine, arginine, omega-3 fatty acids, and nucleotides. In general, results with these agents demonstrate a reduction in rate of infectious complications, reduction in the number of days in hospital, but no effect on mortality. Our research unit was mainly interested to investigate the effect of glutamine on metabolism and immunoreactivity. The amino acid glutamine (Gln) plays a central role in nitrogen transport within the body and is a fuel for rapidly dividing cells, such as in the gut and the immune system. The plasma Gln levels decline during critical illness and therefore these cells suffer from Gln-starvation under these conditions. Gln-starvation leads to energy depletion, which is associated with a reduced responsiveness to exogenous stimuli. In addition, Gln-starving cells show a reduced expression of the 70 kDa heat shock protein, which is an important factor for cell survival and contain a reduced level of the antioxidant glutathione. Recent findings show that the extracellular Gln level affects the susceptibility of cells to different apoptosis triggers: while Gln-starving cells are more sensitive to Fas-ligand mediated apoptosis they are desensitized against the cytotoxic effects of TNF-alpha. In addition, we are interested in the investigation of the molecular mechanisms of Gln-sensing and the role of AMP-activated protein kinase, the cellular redox state, osmosignaling, regulation of translation, and amino acyl tRNA synthetases. Moreover, there is increasing evidence that oxidative stress plays an important role during development and progression of inflammatory diseases. Recent publications have shown that an oxidized cytosolic environment amplifies activation of nuclear factor kappa B (NFĸB), which plays a critical role during inflammatory processes by activating many genes encoding for proinflammatory cytokines and immunoregulatory mediators. The cytosolic redox state of a cell depends on the equilibrium between oxidative and antioxidative substances. One of the most important intracellular antioxidative defense systems against oxidative stress is the tripeptide glutathione (GSH), which is oxidized to glutathione disulfide (GSSG) while it scavenges free radicals. As during inflammatory diseases reduced levels of GSH and/or increased levels of free radicals are detected, recent therapies against inflammatory diseases focus on antioxidant administration to diminish oxidative stress and thereby arrest inflammatory processes. Therefore we are interested in investigating new substances with antioxidative capacities especially of natural polyphenols such as cachexins, curcumine, alpha-lipoic acid, which has become already of particular clinical interest. Thesis Subjects Immunomodulating nutrients - mode of action and clinical relevance Influence of natural antioxidants on the redox potential Techniques and infrastructure

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Inflammatory models: Critically ill patients, endotoxic mouse model, cell cultures models. HPLC Lab, immunomonitoring by FACS, ELISA techniques, Western plot, proteomic analysis, genomic analysis

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Curriculum Vitae

Erich ROTH Surgical Research Laboratory, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 6949; Fax +43 1 40400 6782; Email: [email protected] Personal Data Date of Birth: 17.08.1946 Place of Birth: Trofaiach, Austria Nationality Austria Education 1977 – present Specialist for Nutritional and Meatbolic Research 2000 – 2006 Study of Social- and Cultural Anthropology, University

of Vienna” 1973-1976 PhD degree in Natural Science at the University of

Agronomics of Vienna. Doctoral thesis work at the Vienna Sandoz-Research Institute (now: Novartis Research Institute) on “Enterotoxines of Escherichia coli: Determination of single Parameters for the Production of Vaccine”

1967-1973 Combined studies of Microbiology and Biochemistry at the University of Agronomics of Vienna, University of Vienna, Technical University of Vienna

1957 – 1966 secondary school in Leoben, Styria, Austria Career History 1993 – present Associate Professor at the Department of Surgery,

Surgical Research Laboratory, Medical University of Vienna.

1994 Administrative director of the Surgical Research Laboratory

1993 Conferment of the title “Associate Professor” 1986 “venia docendi” for Medical Biochemistry 1977 Research State at the St. Eric Hospital Stocholml

1976-1977 Biochemical Adviser for the Kontron company, Vienna

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1973 Graduation: Engineer of Microbiology and Biochemistry, Diplomawork: “Autoinhibitory and Autostimulating Substances of Aspergillus orycae”

1966-1967 regular Military Service 1993 – 1994 temporary University Assistant at the Clinical Division

of Endocrinology & Metabolism, Univ. of Vienna Career-related Activities 1998- 2003 President of the Austrian Society for clinical Nutrition 2003 Organizer of the International Congress on Nutrtion 2000 Congress President of the International Nutrition

Congress, Hofburg, Vienna Awards 2006 Honorary Cuthbertson Lecture of the European

Society of Enteral, Parenteral Nutrition and Metabolism, Istanbul, Turkey

1985 Conferment of the Konrad Lang Award of AKE/DAKE in Heidelberg for: “fundamental investigations on the metabolism of amino acids and proteins of critically ill patients”

1986-2005 Several research awards in Austria Editorial Board Clinical Nutrition Journal Parenteral Enteral Nutrition Nutrition Current Opinion in Clinical Nutrition and Metabolic Care European Journal of Nutrition Aktuelle Ernährungsmedizin Journal für Ernährungsmedizin


Period Organization Short Title K€ 2007 - 2003 Fresenius Kabi

Deutschland Influence of substances with antioxidative capacity on the cellular redox potential

150

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2000 – 2003 Novartis Nutrition Austria/International

Glycine as an immunomodulator 148

2002 Abbot Laboratory Immune enhancing effects of FOS 40 2000 – 2001 BASF Immunmodilation by Liponic acid and

Glutamine 72



Nicole Manhart Modulation of intestinal immune response by protein malnutrition and amino acids

1998 – 2000 Dr.rer. nat. techn.

Alexander Gornikiewicz

Catecholamine induced immunomodulation in sepsis

1998-2000 Dr. rer.nat.techn

Carmen Ludwig P53 Status and response to neoadjuvant therapy in breast cancer patients

1999-2002 Dr.rer.nat. techn

Barbara Wessner Influence of nutritive antioxidants on the cellular redox potential under inflammatory conditions

2002-2004 Dr.rer.nat.

techn

Brigitte Wolf Importance of individual gene profiles and mismatch repair genes in colorectal cancer biology

2002-2005 Dr.rer.nat.

techn

Melanie Baumgartner

Polyunsaturated fatty acids enhance arsenic trioxide-mediated cytotocity in tumor cells by increasing oxidative stress

2003-2005 Dr.rer.nat. techn.

Sonja Kappel Genetic tumor profiling using the p53 tumor suppressor gene as diagnostic and predictive marker

2002-2005 Dr.rer.nat.

Techn.

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Anja Bernhardt Influence of hepatic growth factor on wound healing and tumor growth

2007- Dr.med.sci.

Publications 170 peer reviewed publications and reviews, in scientific journals, over 100 plenary, invited or guest lectures on national or international congresses, workshops, and symposia in the field of clincial nutrition and metabolism Original Publications since 2000 119. Zauner C., Schneeweiß B., Kranz A., Madl C., Ratheiser K., Kramer L., Roth E.,

Schneider B., Lenz K. Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine. Am.J.Clin.Nutr. 71:1511-1515 (2000)

120. Gornikiewicz A., Sautner T., Brostjan C., Schmierer B., Függer R., Roth E., Mühlbacher F., Bergmann M. Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells. FASEB J. 14:1093-1100 (2000)

121. Oehler R., Weingartmann G., Manhart N., Salzer U., Meissner M., Schlegel W., Spittler A., Bergmann M., Kandioler D., Oismüller C., Struse H.M. Roth E. Polytrauma induces increased expression of pyruvate kinase in neutrophils. Blood 95: 1086-1092 (2000)

122. Oehler R., Schmierer B., Zellner M., Prohaska R., Roth E. Endothelial cells downregulate expression of the 70 kDa Heat shock protein during hypoxia. Biochemical and Biophysical Research Communications 274:542-547 (2000)

123. Manhart N., Vierlinger K., Akomeah R., Bergmeister H., Spittler A., Roth E. Influence of enteral diets supplemented with key nutrients on lymphocyte subpopulations in Peyer’s patches of endotoxin-boostered mice. Clinical Nutrition 19:265-269 (2000)

124. Manhart N., Vierlinger K., Habel O., Bergmeister H., Götzinger P., Sautner T., Spittler A., Boltz-Nitulescu G., Marian B., Roth E. Lipopolysaccaride causes atrophy of Peyer’s patches and an increased expresssion of CD28 and B7 costimulatory ligands. Shock 14: 478-483 (2000)

125. Manhart N., Vierlinger K., Bergmeister H., Boltz-Nitulescu G., Spittler A., Roth E. Influence of short-term protein malnutrition of mice on the phenotype and costimulatory signals of lymphocytes from spleen and Peyer’s patches. Nutrition 16:197-201 (2000)

126. Gebhard B., Gnant M., Schütz G., Roka S., Weigel G., Kandioler D., Taucher S., Grünberger T., Roth E., Jakesz R., Spittler A. Different transendothelial migration behaviour pattern of blood monocytes derived from patients with benign and malignant diseases of the breast. Anticancer Research 20:4599-4604 (2000)

127. Spittler A., Razenberger M., Kupper H., Kaul M., Hackl W., Boltz-Nitulescu G., Függer R., Roth E. Relationship between interleukin-6 plasma concentration in patients with sepsis, monocyte phenotype, monocyte phagocytic properties, and


cytokine production. Clinical Infectious Diseases 31:1338-42 (2000) 128. Manhart N., Vierlinger K., Spittler A., Bergmeister H., Sautner T., Roth E. Oral

feeding with glutamine prevents lymphocyte and glutathione depletion of Peyer’s patches in endotoxemic mice. Annals of Surgery 234:92-97 (2001)

129. Spittler A., Sautner T., Gorniekiewicz A., Manhart N., Oehler R., Bergmann M., Függer R., Roth E. Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery -induced decreases in HLA-DR expression on monocytes. Clinical Nutrition 20:37-42 (2001)

130. Krebs M., Krssak M., Bernroider E., Anderwald C., Brehm A., Meyerspeer M., Nowotny P., Roth E., Waldhäusl W., Roden M. Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 51:599-605 (2002)

131. Roth E., Oehler R., Manhart N., Exner R., Wessner B., Strasser E., Spittler A. Regulative potential of glutamine-relation to glutathione metabolism. Nutrition 18:217-221 (2002)

132. Zellner M., Hergovics N., Roth E., Jilma B., Spittler A., Oehler R. Human monocyte stimulation by experimental whole body hyperthermia. Wien.Klin.Wochenschr. 114/3:102-107 (2002)

133. Oehler R., Pusch E., Dungel P. Zellner M., Eliasen M.M., Brabec M., Roth E. Glutamine depletion impairs cellular stress response in human leucocytes. British Journal of Nutrition 87:S17-S21 (2002)

134. Wekerle Th., Blaha P., Asari R., Schmid M., Kiss Ch., Roth E., Mühlbacher F. Tolerance induction through mixed chimerism. Eur.Surg. 34:131-135 (2002)

135. Exner R., Weingartmann G., Eliasen M.M., Gerner Ch., Spittler A., Roth E., Oehler R. Glutamine deficiency renders human monocytic cells more susceptible to specific apoptosis triggers. Surgery 131:75-80 (2002)

136. Manhart N., Akomeah R., Bergmeister H., Spittler A., Ploner M., Roth E. Administration of proteolytic enzymes bromelain and trypsin diminish the number of CD4+ cells and the interferon-� response in Peyer’s patches and spleen in endotoxemic balb/c mice. Cellular Immunology 215:113-119 (2002)

137. Bauer E., Gendo A., Madl C., Garo F., Roth E., Kramer L. Effects of sorbent suspension dialysis on plasma amino acid levels in cirrhotic patients with refractory hepatic encephalopthy . The International Journal of Artificial Organs 25:923-928 (2002) 138. Exner R., Tamandl D., Goetzinger P., Mittlboeck M., Fuegger R., Sautner T., Spittler A., Roth E. Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression. Annals of Surgery 237:110-115 (2003)

139. Lassnig A., Punz A., Barker R., Keznickl P., Manhart N., Roth E., Hiesmayr M. Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. British Journal of Anaesthesia 90:148-154 (2003)

140. Blaha P., Bigenzahn S., Koporc Z., Schmid M., Langer F., Selzer E., Bergmeister H., Wrba F., Kurtz J., Kiss Ch., Roth E., Muehlbacher F., Sykes M., Wekerle T. The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade. Blood 101:2886-2893 (2003)

141. Oehler R., Roth E.Regulative capacity of glutamine. Current Opinion in Clinical Nutrition and Metabolic Care 6:277-282 (2003)

142. Manhart N., Spittler A., Bergmeister H., Mittlböck M., Roth E. Influence of fructooligosaccharides on Peyer’s patch lymphocyte numbers in healthy and

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endotoxemic mice. Nutrition 19:657-660 (2003) 145. Spittler A., Roth E. Is monocyte HLA-DR expression predictive for clinical

outcome in sepsis ? Intensive Care Medicine (2003) 146. Sturlan S., Baumgartner M., Roth E., Bachleitner-Hofmann T. Docosahexaenoic

acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells. Blood 101:4990-4997 (2003)

147. Wessner B., Strasser E.-M. Spittler A., Roth E. Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R,S-�-lipoic acid on glutathione content of myelomonocytic cells. Clinical Nutrition 22:515-522 (2003)

148. Nanobashvili J., Neumayer C., Fügl A., Punz A., Blumer R., Prager M., Mittlböck M., Gruber H., Polterauer P., Roth E., Malinski T., Huk I. Ischemia/reperfusion injury of skeletal muscle: Plasma taurine as a measure of tissue damage. Surgery 133:91-100 (2003)

149. Roth E., Zellner M., Wessner B., Strasser E., Manhart N., Oehler R., Spittler A. Glycine – An inert amino acid comes alive. Nutrition 19:817-818 (2003)

150. Tamandl D., Bahrami M., Wessner B., Weigel G., Ploder M., Fürst W., Roth E., Boltz-Nitulescu G., Spittler A. Modulation of toll-like receptor 4 expression on human monocytes by tumor necrosis factor and interleukin-6: tumor necrosis factor evokes lipopolysaccharide hyporesponsiveness, whereas interleukin-6 enhances lipopolysaccharide activity. Shock 20:224-229 (2003)

151. Krebs M., Brehm A., Krssak M., Anderwald C., Bernroider E., Nowotny P., Roth E., Chandramouli V., Landau B.R., Waldhäusl W., Roden M. Direct and indirect effects of amino acids on hepatic glucose metabolism in humans. Diabetologia 46:917-925 (2003)

152. Bergmann M., Gornikiewicz A., Tamandl D., Exner R., Roth E., Függer R., Götzinger P., Sautner T. Continuous therapeutic epinephrine but not norepinephrine prolongs splanchnic IL-6 production in porcine endotoxic shock. Shock 20:575-581 (2003)

153. Varga P., Griffiths R., Chiolero R., Nitenber G., Leverve X, Pertkiewicz M., Roth E., Wernerman J., Pichard C., Preiser J.-C. Is parenteral nutrition guilty? Intensive Care Med 29:1861-1864 (2003)

154. Roth E., Manhart N., Wessner B. Assessing the antioxidative status in critically ill patients. Current Opinion in Clinical Nutrition and Metabolic Care 7:161-168 (2004)

155. Hallwirth U., Pomberger G., Pollak A., Roth E., Spittler A. Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. Pediatr Allergy Immunol 15:513-516 (2004)

156. Baumgartner M., Sturlan S., Roth E., Wessner B., Bachleitner-Hofmann T. Enhancement of arsenic trioxide-mediated apoptosis using docosahexaenoic acid in arsenic trioxide-resistant solid tumor cells. Int J Cancer 112:707-712 (2004)

157. Roth E., Manhart N. Einfluss der Mangelernährung auf die Immunitätslage. Mangelernährung, S. 94-97. In: Ernährungs- und Infusionstherapie – Standards für Klinik, Intensivstation und Ambulanz. Hg.: Hartig W., Biesalski H.K., Druml W., Fürst P., Weimann A. Thieme-Verlag (2004)

158. Oehler R., Roth E. Glutamine metabolism. In: Metabolic and therapeutic aspects of amino acids in clinical nutrition. Hg.: Cynober L.A. CRC Press (2004)

159. Roth E., Kudsk KA. Immunonutrition: Back to Science. J Par Ent Nutr 28:278 (2004)

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160. Pollheimer J., Zellner M., Eliasen M.M., Roth E., Oehler R. Increased susceptibility of glutamine-depleted monocytes to fever-range hyperthermia. Ann Surg 241:349-355 (2005)

161. Zellner M., Winkler W., Hayden H., Diestinger M., Eliasen M., Gesslbauer B., Miller I., Chang M., Kungl A., Roth E., Oehler R. Quantitative validation of different protein precipitation methods in proteome analysis of blood platelets. Electrophoresis 26:2481-91 (2005)

162. Roth E., Wessner B. L-arginine: an amino acid with multiple effects. Wien Klin Wochenschr 117:666-72, 2005

163. Strasser E.-M., Wessner B., Manhart N., Roth E. The relationship between the antioxidative, anti-inflammatory effects of curcumin and cellular glutathione content in myelomonocytic cell. Biochemical Pharmacology 70:552-559, 2005

164. Roth E. L-Arginin-Gabe bei chirurgischen Patienten. Ist das gefährlich? Schweizer Zeitschrift für Ernährungsmedizin 3:12-15, 2005

165. Tremblay F., Krebs M., Dombrowski L., Brehm A., Bernroider E., Roth E., Nowotny P., Waldhausl W., Marette A., Roden M. Overactivation of S6 kinase as a cause of human insulin resistance during increased amino acid availability. Diabetes 54:2674-84, 2005

166. Wessner B., Strasser EM., Manhart N., Roth E. Supply of R-alpha-Lipoic acid and glutamine to casein-fed mice influences the number of B lymphocytes and tissue glutathione levels during endotoxemia. Wien Klin Wochenschr. In press 2006

167. Kappel S., Kandioler D., Steininger R., Längle F., Wrba F., Ploder M., Berlakovich G., Soliman T., hetz H., Rockenschaub S., Roth E., and Mühlbacher F. Genetic Detection of Lymph Node Micrometastases: A Selection Criterion for Liver Transplantation in Patients with Liver Metastases after Colorectal Cancer. Transplantation 81: 64-70, 2006

168. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zugel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A.Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 36:361-70, 2006

169. Eliasen MM, Brabec M, Gerner C, Pollheimer J, Auer H, Zellner M, Weingartmann G, Garo F, Roth E, Oehler R.Reduced stress tolerance of glutamine-deprived human monocytic cells is associated with selective down-regulation of Hsp70 by decreased mRNA stability. J Mol Med. 84:147-58, 2006

170. Ploder M., Pelinka L., Schmuckenschlager C., Wessner B., Ankersmit HJ., Fürst W., Redl H., Roth E., and Spittler A. Lipopolysaccharide- induced tumor necrosis factor alpha production and not monocyte human leukocyte antigen-DR expression is correlated with survival in septic trauma patients. Shock 25:1-7, 2006

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Thomas M. STULNIG Dept. Internal Medicine III, Clin. Div. Endocrinology and Metabolism; [email protected] Polyunsaturated fatty acids in morbid obesity

Abstract Obesity is associated with a chronic state of subclinical inflammation that resides in adipose tissue. This subclinical inflammation is associated with the development of metabolic disorders such as insulin resistance and diabetes mellitus and cardiovascular complications. Therefore, obesity-associated adipose tissue inflammation has become a novel aspect of the pathophysiology of type 2 diabetes and its complications. Molecular mechanisms underlying macrophage immigration and activation are currently investigated in order to discover novel drug targets.

Polyunsaturated fatty acids (PUFAs), particularly those of the n-3 series, ameliorate insulin resistance and development of diabetes mellitus type 2. Previous studies in our laboratory revealed that feeding a diet rich in saturated and monounsaturated fatty acids to obese diabetic mice leads to extensive adipose tissue infiltration with macrophages together with increased expression with a number of inflammatory genes. Notably, macrophage infiltration of adipose tissue in obese diabetic mice under high-fat diet could be totally prevented by including marine n-3 PUFA in the diet. Moreover, adipocytes of animals on high-fat diets showed signs of dedifferentiation by reduced expression of cell type-specific genes and those involved in lipid metabolism that were also prevented by n-3 PUFA. Since macrophage infiltration and activation selectively occurs in adipose tissue and only in obese mice, adipocytes that are heavily loaded with lipids appear to provoke macrophage infiltration by unknown mechanisms.

Starting from this knowledge from animal models, effects of n-3 PUFA on metabolic regulation and adipose tissue inflammation are to be analyzed. Within a clinical study, morbidly obese patients are to treated with n-3 PUFA or not immediately prior to a planned bariatric operation. Within the thesis, metabolic control is studied before and at the end of the treatment period. Moreover, samples from visceral and subcutaneous adipose tissue are taken at the bariatric operation in order to study possible effects on adipose tissue inflammation. Tissue specimens obtained during these clinically oriented investigations will facilitate studies on the factors underlying n-3 PUFA effects in adipose tissue of morbidly obese patients. These studies will not only allow translation of basic research into clinical application but also training of students with various methods to investigate body composition, metabolic control and nutrition in an increasingly prevalent population of patients. Thesis Subjects PUFA effects on metabolic control in morbidly obese patients PUFA effects on adipose tissue inflammation in morbidly obese patients Techniques and infrastructure Assessment of insulin sensitivity; dietary assessment and interventions; explant and primary cell culture; analyses of cytokines by ELISA and bead assays; immunofluorescence analyses; immunoblotting; FACS analysis; quantitative real-time RT-PCR; all required equipment is available.

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Curriculum Vitae

Thomas STULNIG Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4368; Fax +43 1 40400 7790; Email [email protected] Personal Data Date of Birth: 31.05.1964 Place of Birth: Burghausen, Obb., Germany Nationality Austria Education 2003 – present specialist in Endocrinology and Metabolism 1999 specialist in Internal Medicine 1991 Educational Commission for Foreign Medical

Graduates (ECFMG) test passed 1982 – 1990 studies of Human Medicine 1974 – 1982 secondary school Career History 2002 – 2005 principal Investigator of the CeMM – Center of

Molecular Medicine of the Austrian Academy of Sciences (ID#20020)

2001 – 2002 Marie-Curie Individual Fellowship of the European Commission at the Karolinska Insitute, Dept. of Medical Nutrition at Novum Research Center, Huddinge, Sweden with Prof. Jan-Åke Gustafsson

2000 – present Associate Professor at the Department of Internal Medicine III, Medical University of Vienna. Clinical duties and supervising physician at the inpatient and various outpatient departments

2000 “venia docendi” for Internal Medicine 1998 – 2003 Coapplicant in the Interdisciplinary Cooperation

Project “Molecular Medicine” at the University of Vienna

1995 – present University Assistant at the Clinical Division of Endocrinology Metabolism, Department of Internal

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Medicine III, (Medical) University of Vienna, Austria 1994 – 1995 regular Military Service 1993 – 1994 temporary University Assistant at the Clinical Division

of Endocrinology & Metabolism, Univ. of Vienna 1991 – 1993 University Assistant at the Institute for General and

Experimental Pathology, Univ. of Innsbruck 1990 – 1991 Research Assistant at the Institute for General and

Experimental Pathology, Univ. of Innsbruck 1986 – 1989 Doctoral Thesis at the Insitute for Medical Biology and

Genetics, Univ. of Innsbruck Career-related Activities 2002 – 2003 Training Course for Medical Management at the

University of Salzburg 2004 – present Section leader "Obesity and Lipid Disorders", Austrian

Society for Endocrinology and Metabolism Awards 2005 Novartis Prize 2004 for Medicine 2003 Research Award of the Erste Österreichische

Sparkasse in cooperation with the Medical Association of Vienna

2003 Josef-Skoda Research Award of the Austrian Association of Internal Medicine (research grant)

2000 Ludwig-Heilmeyer Medaille in Silver of the Association for Progress in Internal Medicine

1995 Johannes-Tuba-Prize of the Tyrolean Medical Association

1991 Talentförderungsprämie of the country Upper Austria Memberships Austrian Society for Allergology and Immunology Austrian Society for Biochemistry and Molecular Biology Austrian Diabetes Society European Society for the Study of Diabetes American Diabetes Association Austrian Society for Endocrinology and Metabolism Austrian Society for Internal Medicine



Period Organization Short Title K€ 2007 European Science

Foundation (EW06-007)

Exploratory Workshop on Targeting Obesity-driven Inflammation

14

2006 – 2009 Austrian Science Fund (FWF) Doctoral program (W1205-B09)

Cellular communication in health and disease (own share)

129

2006 – 2008 FWF (P18776-B11) The role of osteopontin in adipose tissue inflammation

296

2003 – 2006 FWF (P16788-B13) Polyunsaturated fatty acids and dendritic cells

191

2003 – 2005 Austrian Society for Internal Medicine, Joseph-Skoda Research Award 2003

Proteomic analysis of insulin signaling via adipocyte lipid rafts

40

2002 – 2005 CeMM (ID# 20020), Austrian Academy of Sciences

Fatty acids as molecular modulators of insulin sensitivity in adipocytes (own share)

600

2001 – 2002 Marie-Curie-Fellowship, European Commission

The biological role of nuclear oxysterol receptors LXRa and LXRb

78

1999 – 2003 FWF (P13507-B01) The role of lipid rafts for lymphocyte activation

290



Maximilian Zeyda Molecular mechanisms of T cell inhibition by polyunsaturated fatty acids

1998 – 2001 Dr. nat. techn.

René Geyeregger Impact of polyunsaturated fatty acids on the formation of the immunological synapse

2001 – 2005 Dr. rer. nat.

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Jelena Todoric Mechanisms of adipose tissue macrophage infiltration and their prevention by polyunsaturated fatty acids

3.2005 – (6.2007) (PhD)

Florian Kiefer Role of MCP-1 and osteopontin in adipose tissue inflammation

5.2006 – (2.2009) (PhD)

Publications 61 and 6 peer reviewed publications and reviews, resp., in scientific journals, 7 invited lectures, Peer reviewed manuscripts since 2000 (original research and reviews) First, last or corresponding author manuscripts: Stulnig T.M., M. Berger, M. Roden, H. Stingl, D. Raederstorff, W. Waldhäusl:. 2000.

Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling. FASEB J 14:939-947.

Stulnig T.M., J. Huber, N. Leitinger, E.M. Imre, P.Angelisová, P. Nowotny, W. Waldhäusl. 2001. Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J. Biol Chem. 276:37335-37340.

Zeyda M., T. Sigmund, G. Staffler, V. Horejsí, W. Waldhäusl, T.M. Stulnig. 2002. LAT displacement from lipid rafts as molecular mechanism of T cell inhibition by polyunsaturated fatty acids. J. Biol. Chem. 277: 28418-28423.

Stulnig T.M., U. Oppermann, K.R. Steffensen, G.U. Schuster, J.-Å. Gustafsson. 2002. Liver X receptors downregulate 11beta-hydroxysteroid dehydrogenase type 1 expression and activity. Diabetes 51:2426-2433.

Stulnig T.M., K.R. Steffensen, H. Gao, M. Reimers, K. Dahlman-Wright, G.U. Schuster, J.-Å. Gustafsson. 2002. Novel roles of liver X receptors exposed by gene expression profiling in liver and adipose tissue. Mol. Pharmacol. 62:1299-13095.

Zeyda M., A. Szekeres, M.D. Säemann, R. Geyeregger, H. Stockinger, G.J. Zlabinger, W. Waldhäusl, T.M. Stulnig. 2003. Suppression of T Cell signaling by polyunsaturated fatty acids: Selectivity in inhibition of mitogen-activated protein kinase and nuclear factor acitivation. J. Immunol. 170:6033-6039.

Stulnig T.M. 2003. Immunomodulation by polyunsaturated fatty acids: mechanisms and effects. Int. Arch. Allergy Immunol. 132:310-321. (Review)

Stulnig T.M., W. Waldhäusl. 2004. 11beta-hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes. Diabetologia 47:1-11. (Review)

Stulnig T.M., M. Zeyda. 2004. Immunomodulation by polyunsaturated fatty acids: impact on T cell signaling. Lipids 30:1171-1175. (Review)

Zeyda M., M.D. Säemann, K.M. Stuhlmeier, G.J. Zlabinger, W. Waldhäusl, T.M.


Stulnig. 2005. Polyunsaturated fatty acids inhibit dendritic cell activation and function independently of NF-kappaB activation. J. Biol. Chem. 280:14293-14301.

Geyeregger R., M. Zeyda, G. Zlabinger, W. Waldhäusl, T.M. Stulnig. 2005. Polyunsaturated fatty acid treatment of T cells alters formation of the immunological synapse. J. Leukoc. Biol. 77:680-688.

Zeyda M., R. Geyeregger, B.M. Kirsch, K.M. Stuhlmeier, W.H. Hörl, G.J. Zlabinger, M.D. Säemann, T.M. Stulnig. 2005. Inhibition of human dendritic cell maturation and function by the novel immunosuppressant FK778. Transplantation, 80:1105-1111 (2005).

Geyeregger R., Zeyda M., Stulnig T.M. 2005. Liver X receptors in cardiovascular and metabolic disease. Cell. Mol. Life Sci. 63:524-539 (2006). (Review)

Zeyda M., Stulnig T.M. 2005. Lipid rafts & Co.: an integrated model of membrane organization in T cell activation. Progr. Lipid Res., submitted for publication. (Review)

Löffler M., M. Bilban, M. Reimers, W. Waldhäusl, T.M. Stulnig. 2006. Blood glucose lowering nuclear receptor agonists do not normalize hepatic gene expression in db/db mice. J. Pharmacol. Exp. Therap., 316:797-804.

Todoric J., M. Löffler, J. Huber, M. Bilban, M. Reimers, A. Kadl, M. Zeyda, W. Waldhäusl, T.M. Stulnig: Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids. Diabetologia 49:2109-2119 (2006).

Zeyda M., T.M. Stulnig: Lipid rafts & Co.: an integrated model of membrane organization in T cell activation. Progr. Lipid Res. 45:187-202 (2006). (Review)

Huber J., M. Löffler, M. Bilban, M. Reimers, A. Kadl, J. Todoric, N. Leitinger, W. Waldhäusl, T.M. Stulnig: Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by polyunsaturated fatty acids. Int. J. Obes. 31:1004-1013 (2007).

Geyeregger R., M. Zeyda, W. Bauer, E Kriehuber, M.D. Säemann, G.J. Zlabinger, D. Maurer, T.M. Stulnig: Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin bundling protein fascin. Blood 109:4288-4295 (2007).

Zeyda M., D. Farmer, O. Aszmann, M. Speiser, G. Zlabinger, T.M. Stulnig: Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int. J. Obes., in press (2007).

Co-author manuscripts: Schmaldienst S., S. Banyai, T.M. Stulnig, G. Heinz, M. Jansen, W.H. Hörl, K. Derfler.

2000. Prospective randomised cross-over comparison of three LDL-apheresis systems in statin pretreated patients with familial hypercholesterolemia. Atherosclerosis 151:493-399.

Van Laethem V., X. Liang, F. Andris, J. Urbain, M. Vandenbranden, J.-M.Ruysschaert, M.D. Resh, T.M. Stulnig, O. Leo. 2003. Glucocorticoids alter the lipid and protein composition of membrane rafts of a murine T cell hybridoma. J. Immunol. 170:2932-2939.

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Säemann M.D., M. Zeyda, C. Diakos, A. Szekeres, G.A. Bömig, P. Kelemen, O. Parolini, H. Stockinger, E. Prieschl, T. Stulnig, T. Baumruker, G.J. Zlabinger. 2003. Pharmacological targeting of JAK3 impairs early T cell receptor (TCR)-triggered cellular activation. Transplantation 75:1864-1872.

Sanzone S., M. Zeyda, M.D. Säemann, M. Soncini, W. Holter, G. Fritsch, W. Knapp, F. Candotti, T.M. Stulnig, O. Parolini. 2003. SAP deficiency causes imbalanced early signal transduction and blocks downstream activation in T cells from XLP patients. J. Biol. Chem. 278:29593-29599.

Steffensen K.R., M. Nilsson, G.U. Schuster, T.M. Stulnig, K. Dahlmann-Wright, J.-Å. Gustafsson. 2003. Gene expression profiling in adipose tissue indicates different transcriptional mechanisms of liver X receptors alpha and beta, respectively. Biochem. Biophys. Res. Commun. 310:589-593.

Staffler G., A. Szekeres, G.J. Schütz, M.D. Säemann, E. Prager, M. Zeyda, K. Drbal, I. Hilgert, G.J. Zlabinger, T.M. Stulnig, H. Schindler, V. Horejsí, H. Stockinger. 2003. Selective inhibition of T cell activation via CD147 through novel modulation of lipid rafts. J. Immunol171:1707-1714.

Seo J.B. H.M. Moon, W.S. Kim, Y.S. Lee, H.W. Jeong, E.J. Yoo, J. Ham, H. Kang, M.-G. Park, K.R. Steffensen, T.M. Stulnig, J.-Å. Gustafsson, S.D. Park, J.B. Kim. 2004. Activated liver X receptors stimulate adipocyte differentiation through induction of PPARgamma expression. Mol. Cell. Biol. 24: 3430-3444.

Jaksits S., W. Bauer, E. Kriehuber, M. Zeyda, T.M. Stulnig, G. Stingl, E. Fiebiger, D. Maurer. 2004. Lipid raft-associated GTPase signaling controls morphology and CD8+ T cell stimulatory capacity of human dendritic cells. J. Immunol. 173: 1628-1639.

Corton J.C., U. Apte, S.P. Anderson, P. Limaye, L, Yoon, J. Latendresse, C. Dunn, J.X. Everitt, K.A. Voss, C. Swanson, C. Kimbrough, J.S. Wong, S.S. Gill, R. Chandraratna, M.K. Kwak, T.W. Kensler, T.M. Stulnig, K.R. Steffensen, J.-Å. Gustafsson, H.M. Mehendale. 2004. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. J. Biol. Chem. 270: 46204-46212.

Steffensen K.R., S.Y. Neo, T.M. Stulnig, V.B. Vega, S.S. Rahman, G.U. Schuster, J.-Å. Gustafsson, E.T. Liu. 2004. Genome-wide expression profiling: a panel of mouse tissues discloses novel biological functions of LXRs in adrenal. J. Mol. Endocrinol. 33:609-622.

Anderson S.P., C. Dunn, A. Laughter, L. Yoon, C. Swanson, T.M. Stulnig, K.R. Steffensen, R.A.S. Chandraratna, J.-Å. Gustafsson, J.C. Corton. 2004. Overlapping transcriptional programs regulated by peroxisome proliferator-activated receptor alpha, retinoid X receptor and liver X receptor in the mouse liver. Mol. Pharm. 66:1440-1452.

Säemann M.D., M. Zeyda, T.M. Stulnig, G.A. Böhmic, T. Wekerle, W.H. Hörl, G.J. Zlabinger. 2004. Janus kinase-3 (JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation. Transplant. Int. 17:481-489. (Review)

Säemann M.D., T. Weichhart, M. Zeyda, G. Staffler, K. Stuhlmeier, Y. Sobanov, T.M. Stulnig, W.H. Hörl, G.J. Zlabinger. 2005. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a TLR4-dependent mechanism. J. Clin. Invest. 115:468-475.

Kirsch B., M. Zeyda, K. Stuhlmeier, J. Grisar, J. Smolen, B. Watschinger, T.M. Stulnig. W.H. Hörl, G.J. Zlabinger, M.D. Säemann. 2005. The active metabolite of leflunomide A77 1726 potently interferes with dendritic cell maturation via

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inhibition of NFkappaB signaling. Arthritis Res. Ther. 7:R694-R703. Zeyda M., M, Poglitsch, R. Geyeregger, J. Smolen, G.J. Zlabinger, W.H. Hörl, W.

Waldhäusl, T.M. Stulnig, M.D. Säemann. 2005. The active leflunomide metabolite teriflunomide disrupts the interaction of T cells with antigen-presenting cells: involvement of impaired integrin activation and immunological synapse formation. Arthritis Rheum., 52:2730-2739.

Schuster G., L. Johansson, S. Kietz, T.M. Stulnig, P Parini, J.-Å. Gustafsson: Improved metabolic control by depletion of liver X receptors in mice. Biochem. Biophys. Res. Commun. 348:176-182 (2006).

Nilsson M., T.M. Stulnig, C.Y. Lin, A.L. Yeo, P. Nowotny, E.T. Liu, K.R. Steffensen: Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback. Mol. Endocrinol. 21:126-137 (2007).

Zeyda M., R. Geyeregger, M. Poglitsch, T. Weichhart, G.J. Zlabinger, S. Koyasu, W.H. Hörl, T.M. Stulnig, B. Watschinger, M.D. Säemann: Impairment of T cell interactions with antigen-presenting cells by immunosuppressive drugs reveals involvement of calcineurin and NF-kappaB in immunological synapse formation. J. Leukoc. Biol. 81:319-327 (2007).

Haidinger M., R. Geyeregger, M. Poglitsch, T. Weichhart, M. Zeyda, B. Vodenik, T.M. Stulnig, G.A. Böhmig, W.H. Walter, M.D. Säemann: Anti-thymocyte globulin impairs T cell/antigen-presenting cell interaction: disruption of immunological synapse and conjugate formation. Transplantation, in press (2007).

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Walter TSCHUGGUEL Dept. Obstetrics and Gynecology [email protected] Endometriosis, a sequel of diseased eutopic endometrium Abstract Endometriosis is a common, benign, estrogen dependent, chronic gynecological disorder associated with pelvic pain and infertility. It is characterized by the presence of uterine endometrial tissue outside of the normal location (i.e. ectopic sites) — mainly on the pelvic peritoneum, but also on the ovaries and in the rectovaginal septum, and more rarely in the pericardium, pleura, and even in the brain. The prevalence of pelvic endometriosis approaches 6–10% in the general female population in the reproductive age (Giudice and Kao, 2004). The answer to the question how uterine endometrial tissue following retrograde menstruation is able to migrate towards and to invade extrauterine sites is presently missing. However, it implies the existence of a not yet described mechanism responsible for this process. Due to recent findings that eutopic endometrium of endometriosis patients, in contrast to endometrium of healthy patients, contains the enzyme aromatase (also known as CYP19) (Noble et al., 1996; Kitawaki et al., 1997; Wolfler et al. 2005), we speculate aromatase expression is a major hallmark of this disease. Understanding the links between aromatase expression, abnormal cell migration and invasion may give us the additional possibility to speculate on other facets of endometriosis, e.g., how ectopic lesions survive apoptosis, but do not become metastatic. Furthermore, such investigations could disclose novel early eutopic markers of endometriosis that can help to identify the disease out of menstrual discharge, which makes uninformative, invasive procedures, i.e. laparoscopy or laparotomy unnecessary. Thesis Subjects Does the eutopic endometrium of endometriosis vs. healthy patients contain a fully developed principle making endometrial cells able to proliferate, migrate and translocate towards ectopic sites? Techniques and infrastructure Primary endometrial cell culture, Western blotting, Raf-1 kinase assay, immunohistochemistry, immunofluorescence, RT-PCR and Real-Time RT-PCR, FACS analysis, migration assay, transfection of cells, all required equipment available.

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CURRICULUM VITAE

Walter TSCHUGGUEL Medical University of Vienna, Department of Obstetrics & Gynecology, Division of

Gynecological Endocrinology & Reproductive Medicine, A-1090 Vienna/Austria,

Waehringer Guertel 18-20 +43 1 40400 7828, +43 676 924 2 924; FAX +43 1

40400 7842

[email protected]

Personal Data Date of Birth: 02-06-1966

Place of Birth: Vienna, Austria


Education 1972 - 1976 Primary School, Vienna, Austria

1976 - 1984 High School, Vienna, Austria, Matura

1984 - 1990 Medical School, University of Vienna, Austria, MD degree

Career History 1986 - 1990 Academic Tutor, Institute of Anatomy, University of Vienna

1991 Resident, Department of Urology, University of Vienna

School of Medicine

1992 Military Service in the Austrian Armed Force

1992 - 1993 Coordinator for Liver and Kidney

Transplantation at the Department of Surgery, University of Vienna 1993-1996 Rotation Internship, Departments of Surgery and Internal

Medicine, Krankenhaus Floridsdorf, Vienna, Austria

1996 General Physician´s degree

1992 - 1996 Postdoc, Department of General & Experimental

Pathology, Division of Cellular Pathology, University of

Vienna

1996 - 2000 Resident, Department of Obstetrics and Gynecology,

University of Vienna School of Medicine

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2000 - Present Fellow, Department of Obstetrics and Gynecology,

Division of Gynecological Endocrinology & Reproductive

Medicine, University of Vienna School of Medicine

2000 Habilitation (Universitätsdozent), Associate Professor,

Department of Obstetrics and Gynecology, Division of

Gynecological Endocrinology & Reproductive Medicine,

University of Vienna School of Medicine

Career-related Activities 2003 Chief Officer for Education and Training of Residents at

the Department of Obstetrics and Gynecology, Division of

Gynecological Endocrinology & Reproductive Medicine,

Medical University of Vienna

2005 Education in the program Klinischer Studienleiter”, part I,

collaboration between the Medical University of Vienna

and the Vienna school of Clinical Research (VSCR)

Awards 1998 International Organon Award for Assisted Reproduction

2002 Wyeth´s President´s Presenter Award of the Society for Gynecologic

Investigation (SGI), Toronta, Canada, USD $ 1000. - to Mentee Dr. Felix

Stonek


Investigation (SGI), Los Angeles, CA, USD $ 1000. - to Mentee Dr. Monika

Wölfler


Investigation (SGI), Toronta, Canada, USD $ 1000. - to Mentee Mag. Cristina

Rubiolo

Memberships Austrian Society of Gynecology and Obstetrics (OEGGG)

Society for the Study of Reproduction (SSR)

page 160 of 186 Society for Gynecological Investigation (SGI, Full Member)


Reviewing Activities British Journal of Cancer (since 1999)

Molecular Human Reproduction (since 2000)

Human Reproduction (since 2000)

Breast Cancer Research and Treatment (since 2001)

Molecular Endocrinology (since 2004)

Lancet (since 2005)


Period Organization Short Title K€ 1998 Jubilee Fund of the

Austrian National Bank

Inducible Nitric Oxide Synthase (iNOS) Induction in Human Endometrium

18

2000 Jubilee Fund of the Austrian National Bank

Inducible Nitric Oxide Synthase (iNOS) as a Regulator of Apoptosis and Collagenolysis in Cultured Steroid-hormone treated Endometrial Stromal Cells

22

2007 – 2009 Austrian Science Fund (P19327-B02)

Endometriosis, a Sequel of Diseased Eutopic Endometrium

328



Gudrun Brunnmayr The Psychiatric Co-morbidity (DSM-IV) between Chronic Pelvic Pain Patients (CPP) and Chronic Polysymptomatic Patients is equal

2004 – 2005 MD

Joanna Pong Comparison of the Methylation Status of the CpG-island neighboring Exon 1 of the Aromatase Gene in Human Myomas and their adjacent Myometria by using Methylation-specific PCR

2004 – 2006 MD

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Publications 1. Wolfler MM, Facchinetti F, Venturini P, Huber A, Helmer H, Husslein P,

Tschugguel W. Induction of labor at term using isosorbide mononitrate

simultaneously with dinoprostone compared to dinoprostone treatment alone:

a randomized, controlled trial . (2006). Am J Obstet Gynecol; 195, 1617-22.

2. Dietrich W, Haitel A, Holzer G, Huber JC, Kolbus A, Tschugguel W. Estrogen

receptor-beta is the predominant estrogen receptor subtype in normal human

synovia. (2006). J Soc Gynecol Investig. 13, 512-7.

3. Demyanets S, Pfaffenberger S, Kaun C, Rega G, Speidl WS, Kastl SP, Weiss

TW, Hohensinner PJ, Dietrich W, Tschugguel W, Bochkov VN, Awad EM,

Maurer G, Huber K, Wojta J. The estrogen metabolite 17beta-dihydroequilenin

counteracts interleukin-1alpha induced expression of inflammatory mediators

in human endothelial cells in vitro via NF-kappaB pathway. (2006). Thromb

Haemost. 95, 107-16.

4. Wolfler, M.M., Nagele, F., Kolbus, A., Seidl, S., Schneider, B., Huber, J.C,

Tschugguel W. A predictive model for endometriosis. (2005). Hum Reprod; 20

(6): 1702-08.

5. Eppel, W., Facchinetti, F., Schleussner, E., Piccinini, F., Pizzi, C., Gruber,

D.M., Schneider, B., Tschugguel, W. Second trimester abortion using

isosorbide mononitrate in addition to gemeprost compared with gemeprost

alone: a double-blind randomized, placebo-controlled multicenter trial. (2005).

Am J Obstet Gynecol, 192, 856-61.

6. Fuchsjager-Mayrl, G., Nepp, J., Schneeberger, C., Sator, M., Dietrich, W.,

Wedrich, A., Huber,

7. J., Tschugguel, W. Identification of estrogen and progesterone receptor mRNA

expression in the conjunctiva of premenopausal women. (2004). Invest

Ophthalmol Vis Sci, 43, 2841-4.

8. Stonek, F., Dietrich, W., Schneeberger, C., Vycudilik, W., Tschugguel, W.

Quantitative determination of carbon monoxide in cell culture supernatants by

spectrophotometric analysis. (2004). J Biochem Biophys Methods, 58, 49-58.

9. Tschugguel, W., Berga, S.L. Treatment of functional hypothalamic

amenorrhea with hypnotherapy. (2003). Fertil Steril, 80, 982-5. page 162 of 186

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16723101&query_hl=1&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16543969&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum




10. Tschugguel, W., Dietrich, W., Zhegu, Z., Stonek, F., Kolbus, A., Huber, J.C.

Differential regulation of proteasome-dependent estrogen receptor alpha and

beta turnover in cultured human uterine artery endothelial cells. (2003). J Clin

Endocrinol Metab, 88, 2281-7.

11. Gruber, C.J., Tschugguel, W., Schneeberger, C., Huber, J.C. Production and

actions of estrogens. (2002). N Engl J Med, 346, 340-52.

12. Singer, C.F., Kronsteiner, N., Marton, E., Walter, I., Kubista, M., Czerwenka,

K., Schreiber, M., Tschugguel, W., Wieser, F., Kubista, E. IL-1alpha gene

expression in human endometrial cancer is independent of ovarian steroid

receptor expression. (2002). Eur J Cancer, 38 Suppl 6, S76-7.

13. Singer, C.F., Kronsteiner, N., Marton, E., Walter, I., Kubista, M., Czerwenka,

K., Schreiber, M., Tschugguel, W., Wieser, F., Kubista, E. Interleukin-1 system

and sex steroid receptor gene expression in human endometrial cancer.

(2002). Gynecol Oncol, 85, 423-30.

14. Wieser, F., Schneeberger, C., Hudelist, G., Singer, C., Kurz, C., Nagele, F.,

Gruber, C., Huber, J.C., Tschugguel, W. Endometrial nuclear receptor co-

factors SRC-1 and N-CoR are increased in human endometrium during

menstruation. (2002). Mol Hum Reprod, 8, 644-50.

15. Tschugguel, W., Stonek, F., Zhegu, Z., Dietrich, W., Schneeberger, C.,

Stimpfl, T., Waldhoer, T., Vycudilik, W., Huber, J.C. Estrogen increases

endothelial carbon monoxide, heme oxygenase 2, and carbon monoxide-

derived cGMP by a receptor-mediated system. (2001). J Clin Endocrinol

Metab, 86, 3833-9.

16. Stonek, F., Tschugguel, W., Huber, J.C., Schneeberger, C. Calculated

background elimination in quantifying nitric-oxide synthase enzyme activity.

(2001). J Biochem Biophys Methods, 50, 29-32.

17. Wieser, F., Hosmann, J., Tschugguel, W., Czerwenka, K., Sedivy, R., Huber,

J.C. Progesterone increases the number of Langerhans cells in human

vaginal epithelium. (2001). Fertil Steril, 75, 1234-5.

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Nicole UNGER-MANHART Dept. Surgery, Research Labaratories [email protected] Influence of green tea extract on immunological and redox parameters during endotoxemia Abstract Both clinical and experimental studies have shown that intestinal dysfunction and failure of the gut barrier function are involved in the development of distant organ injury under septic conditions. Generally the portal venous route is considered as the primary route of translocating bacteria and the liver has become one of the most intensively studied organs during septic conditions. On the other hand it has been proposed that translocation to the mesenteric lymph and subsequent lung injury plays a role in the onset of multiorgan failure. With respect to gut dysfunction during sepsis the intestinal immune system has gained particular interest. Previous studies in our laboratory revealed that endotoxemia induces an atrophy of Peyer’s patch (PP) lymphocytes, which is associated with a decrease in PP glutathione content. We showed that PP lymphocytes react very sensitively to different dietary interventions and that diets rich in immune modulatory substances are able to diminish PP atrophy and glutathione depletion. From this data we assumed that not only inflammation but also oxidative stress plays an important role. Recently it has been shown that green tea extract (GTE) exerts antioxidative as well as anti-inflammatory effects. These effects are attributed to the high flavonoid content of green tea. The main flavonoids in green extract are epigallocatechingallat, epicatechin, gallocatechin, and catechin. Several experimental studies show that catechins inhibit cellular signaling of the NF-kB pathway thereby reducing the production of pro-inflammatory mediators. This turns GTE into an interesting dietary additive during endotoxemia. In contrast to the described antioxidative effects of GTE, recent studies reveal a potent prooxidative potential of this extract. Therefore we want to evaluate the pro/anti-oxidative and anti-inflammatory effects of GTE under endotoxemic conditions. In a current project the effect of GTE on inflammatory as well as on oxidative parameters is to be investigated during murine endotoxemia. In particular, the most effective concentration of GTE and the most appropriate feeding time has to be evaluated. We focus on the main inductive site of the intestinal immune system, the PP lymphocytes, and the remote organs lung and liver. Methods to evaluate pro- or anti-oxidative effects on PP lymphocytes as well as on lung and liver tissues have to be established. Furthermore, anti-inflammatory properties of GTE are to be investigated on molecular level. Thesis Subjects Techniques and infrastructure Mouse model of endotoxemia, dietary intervention, cell isolation from tissues, primary culture, FACS analysis, ELISA, real-time PCR, western blot, HPLC

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CURRICULUM VITAE

Unger-Manhart Nicole

Division of Surgery, Department of surgical research laboratories, Medical University

of Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria;

Phone + 43 1 40400 6959, Fax +43 1 40400 6782;

E-mail: [email protected]

Personal data: Date of birth: 26.04.1970

Place of Birth: Vienna


Education: 2004-present Assistant professor since 2004

2000 Doctor rerum naturalium technicarum

University of agricultural sciences, Institute of applied

microbiology, Vienna

1997 Master of science (April 1997); University of Vienna, Department

of Surgical Research, Vienna

1991-1997 Study of Nutritional Science, University of Vienna, Institute of

Nutritional Science, Vienna

Career History: 2002 – present University of Vienna, Department of Surgical Research

Modulation of the mucosal immunsystem by antioxidative

nutrients

Islet cell transplantation

Collaborations and support of clinical studies

Training of ungraduated students

2001 – 2002 University of Bonn, Department of Nutritional Science

University assisent

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Training of ungraduated students in basics of nutrition

(performance of lectures, seminars and practical training)

Collaboration and support of physicians in accomplishing clinical

nutritional studies

1997 – 2000 University of Vienna, Department of Surgical Research

Ph.D. student: Set-up of a mouse model to investigate mucosal and systemic

immune response

Application of methods to investigate immune response (ELISA,

flow cytometry, real time PCR)

Support of diploma theses

Support of clinical studies

1998 University of Memphis Tennessee, Department of Traumatology

Research training Training of experimental parenteral administration of nutrients

and pharmaceuticals to mice

1996 -1997 University of Vienna, Department of Surgical Research

Undergraduate student Establishment of a flow cytometrical method to measure the

respiratory burst of immune cells

Performance of cell culture

Awards: 2000 Best original article published in Clinical Nutrition during the year

2000

2000 Travel fellowship for the ESPEN congress

1999 Travel fellowship for the ESPEN congress

Membership Arbeitsgemeinschaft für klinische Ernährung

Career-related Activities

• Laboratory training (February 1996) in the routine laboratory of the hospital

Wr. Neustadt, Austria

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• Seminar on nutrition assessment, planning and communication in developing

countries (February 1996 – March 1996) University of Giessen, Institute of

Nutritional Science, Germany

• Laboratory training (July 1995 - August 1995) in the laboratory of the health

insurance organisation Vienna, Wr. Gebietskrankenkasse, Vienna, Austria

• Laboratory training (August 1994) in the laboratory of the health insurance

organisation Vienna, Wr. Gebietskrankenkasse, Vienna, Austria

• Practical training (July 1994) in the dietitian group of the hospital

Rudolfstiftung, Vienna, Austria

• secretary (July 1993) Semperit technical products GmbH, Wimpassing, Austria

• executive officer (May 1992 – September 1992) Wichem med. Laser-

Systeme GmbH, Vienna, Austria

• executive officer (October 1990 – June 1991) Wichem International GmbH,

Vienna, Austria

Publications: 11 and 9 peer reviewed publications and reviews, resp., in scientific journals, 15 invited lectures Orginal Manuscripts: The relationship between the anti-inflammatory effects of Curcumin and cellular glutathione content in myelomonocytic cells Strasser EM., Wessner B., Manhart N., Roth E. Biochem.Pahrmacol 15: (70):552-559 2005 Influcence of fructooligosaccharides on Peyer´s patch lymphocyte numbers in healthy and endotoxemic mice. Manhart N., Spittler A., Bergmeister H., Mittlbock M., Roth E. Nutrition 2003, 19(7-8):657-660 Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. A.Lassnigg, A. Punz, R.Barker, P. Keznickl, N.Manhart, E.Roth and M.Hiesmayr Br J Anaesth 90:148-154; 2003 Oral feeding with glutamine prevents lymphocyte and glutathione depletion of Peyer´s patches in endotoxemic mice. N.Manhart, K.Vierlinger, A.Spittler, H.Bergmeister, T.Sautner, E.Roth Ann Surg 234:92-97; 2001 Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression of monocytes A.Spittler, T.Sautner, A.Gornikiewicz, N.Manhart, R.Öhler, M.Bergmann, R.Függer, E.Roth Clin Nutr 20:37-42; 2001

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Lipopolysaccharide causes atrophy of Peyer´s patches and an increased expression of CD28 and B7 costimulatory ligands N.Manhart, K.Vierlinger, O.Habel, H.Bergmeister, P.Götzinger, T.Sautner, A.Spittler, G.Botz-Nitulescu, B.Marian, E.Roth Shock 14:478-483; 2000 Influence of enteral diets supplemented with key nutrients on lymphocyte subpopulations in Peyer´s patches of endotoxin-boostered mice N.Manhart, K.Vierlinger, R.Akomeah, H.Bergmeister, A.Spittler, E.Roth Clin Nutr 19:265-269; 2000 Influence of short-term protein malnutrition of mice on the phenotype and costimulatory signals of lymphocytes from spleen and Peyer´s patches N.Manhart, K.Vierlinger, H.Bergmeister, G.Boltz-Nitulescu, A.Spittler, E.Roth Nutrition 16:197-201; 2000 Polytrauma induces increased expression of pyruvate kinase in neutrophils. R.Öhler, G.Weingartmann, N.Manhart, U.Salzer, M.Meissner, W.Schlegel, A.Spittler, M.Bergmann, D.Kandioler, C.Oismüller, H.Struse, E.Roth. Blood 95:1086-1092; 2000 Reviews: Assessing the antioxidative status in critically ill patients Roth E, Manhart N, Wessner B. Curr Opin Clin Nutr Metab Care. 2004; 7:161-8 Glycine--an inert amino acid comes alive Roth E, Zellner M, Wessner B, Strasser E, Manhart N, Oehler R, Spittler A Nutrition. 2003 Sep;19(9):817-8. Nutritive amino acids – effective modulators of the immune response Manhart N., Stehle P. Forum Nutr 56:151-154 2003 Regulative potential of glutamine – relation to glutathione metabolism. E.Roth, R.Oehler, N.Manhart, R.Exner, B.Wessner, E.Strasser, A.Spittler Nutrition 18:217-21;2002 Nutritive amino acids – effective modulators of the immune response N. Manhart, P. Stehle Forum of Nutrition, book series Karger, Basel, Switzerland, submitted October 2001 Therapeutic potential of glutathione R.Exner, B.Wessner, N.Manhart, E.Roth Wien Klin Woschenschr 112/14:610-616; 2000

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Heinrich VIERHAPPER Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III [email protected] Curriculum Vitae Date and place of birth: April 29, 1951; Ernstbrunn, Austria

Nationality: Austrian

Civil status: married, to Maria Sofia Puelma-Lugones

Studies:

1. Primary school in Ernstbrunn, Austria (1956-1960).

2. Realgymnasium der Theresianischen Akademie,Vienna, Austria (1960 -

1968)

3. University of Vienna Medical School, ViennaAustria (1968 - 1974); M.D.:

March, 1974.

Training in Internal Medicine: I. Medizinische Universitätsklinik,

University of Vienna Medical School (1974-1980).

Training in Laboratory Medicine: I. Medizinische Universitätsklinik and Institute of Clinical Chemistry

University of Vienna Medical School (1980-1985).

Scientific work: Since 1976, predominantly in the field of Endocrinology;

at the Division of Clinical Endocrinology and Diabetes mellitus; I. Med. Univ.-

Klinik

University of Vienna Medical School.

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Ludwig WAGNER Dept. Internal Medicine III, [email protected] Mechanism of action of mutated RUVBL1/TIP49a versions in neuroendocrine tumorigenesis Abstract Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, which arise from the system of neuroendocrine cells. In general, oncogenesis is caused by an imbalance between cell death and cell proliferation. A reduced rate of cells undergoing apoptosis is the reason for the development of NETs. Three genes (bcl-2, c-myc, p53) are mainly involved in deregulation of the homeostasis between cell proliferation and apoptosis observed in NETs. TIP49a, a DNA-helicase, is a newly identified interaction partner of c-myc and ß-cathenin. Its name originates from the property to play a role in the RNA-polymerase II holoenzyme complex. Due to its homology to the bacterial protein RuvB, it was also termed RUVBL1. Remarkable presence of this predominantly intranuclear protein in cytoplasm was one of our previous interesting findings. Immunofluorescence microscopy using the recently developed anti-RUVBL1/TIP49a mAb IB3 demonstrated that in apoptotic cells the characteristic staining was lost. Using these immunoreagents we found that RUVBL1/TIP49a can interact with microtubules during mitosis of U937 cells. The correct formation of the mitotic spindle is a central point for mitotic rates and cell proliferation. These data and tumor-specific overexpression as well as results from other authors demonstrated that the molecule might play an important role in carcinogenesis. We performed Southern analysis, using DNA from various NET samples. These exhibited a characteristic band pattern, which was comparable to genomic DNA obtained from leukocytes. Strikingly, the RFLP derived from one carcinoid tumor differed from the other analyzed NETs. This patient had been diagnosed with a carcinoid tumor and, having already metastasis, he died shortly after surgery due to rapid tumor growth. The deranged findings in the Southern blot motivated us to investigate the protein-morphology in this tumor. Immunoblots comparing this tumor with other NETs presenting with normal RUVBL1/TIP49a RFLP patterns, identified a truncated version of this protein. Therefore, we aim at identifying the mutated sequence of RUVBL1/TIP49a in the tumor and to continue to perform RFLP analyses in a larger number of tumors. In addition, malignancy associated mutations were identified in adult leukemias. Thesis Subjects Biological relevance of identified tumor-specific mutations within the RUVBL1/TIP49a gene in tumorigenesis. Techniques and infrastructure RLFP, tumor DNA analysis, long range PCR, cDNA cloning, cellular overexpression of mutants, cell cycle analysis, expression analysis, protein analysis (immunoblot, 2D-gel and proteomics),

page 170 of 186


page 171 of 186


Curriculum Vitae

Ludwig Wagner Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Phone +43 1 40400 4319; Fax +43 1 40400 7790; Email [email protected] Personal Data Date of Birth: 16.04.1955 Place of Birth: Waidhofen/Ybbs, NÖ., Austria Nationality Austria Education 1997 – present Ass. Professor of Internal Medicien 1989 1977-1982

specialist in Internal Medicine studies in Medicine

1975 – 1977 studies of Human Human Sciences 1967 – 1975 secondary school Career History 1982-85 1986-87 1987-92 1993 1994-95

Training at the Department of Medicine I in order to specialize in Internal Medicine (Head Prof. Deutsch), University of Vienna. Postgraduate training at the University College Hospital London (immunohematological laboratory: Head: Prof. Goldstone) Clinical and part time research work at the Department of Medicine I, University of Vienna. Postgraduate training at the Harvard Medical School in the Laboratory of Infectious Disease, Massachusetts General Hospital East. Research at the laboratory of the Department of Medicine III, Div. of Clinical Endocrinology &

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1996-97 1997-2000 1998 and 1999 2000 2001-

Metabolism (Head: o.Prof. Waldhäusl). University of Vienna. Research at the Infectious Disease Laboratory, Massachusetts General Hospital East, Harvard Medical School, Boston. Part-time research and clinical work at the Department of Medicine III, University of Viennna (Head o.Prof. Waldhäusl) During the summer months, research at the Infectious Disease Laboratory, Massachusetts General Hospital East, Harvard Medical School, Boston September-December: Research at National Center of Biotechnology, Campus Cantoblanco, Madrid Part-time research at the Research Laboratory and clinical work at the Department of Medicine III, University of Viennna (Head o.Prof. Walter Hörl)

Awards and Fellowship Research fellowship from the Austrian Ministery of Science 1986-1987 Research fellowship of the Max Kade foundation 1993 Biochemie-Research award for Thyroid disease 2002 Memberships European Society for Calcium binding Proteins Austrian Society for Internal Medicine Sources of funding (since 2000)

Period Organization Short Title K€/yr 2001– 2003

Akademie der Wissenschaften: Doc Stipendium

Phänotypische und Genotypische Klassifizierung neuroendokriner Neoplasien

21

2002 Biochemie-Forschungspreis für

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Schilddrüsen-erkrankungen

Collaborative research agreement between University of Vienna and Biosite: Neurobiochemical Marker proteins indicative for brain microembolism. 2003-2005 Collaborative research agreement between Medical University of Vienna and Biosite: Development of a tumor marker device specific for brain tumors and evaluation of neuropathological markers in multiple sclerosis and peripheral polyneuropathy. 2005-2007 Supervision of doctoral students (since 2000)


Barbara Zierhut Phänotypische und genotypische Klassifizierung neuroendokriner Neoplasien

– 2003 MD

Teodora Daneva The involvement of calcium binding proteins, DREAM/Calsenilin and Secretagogin in pancreatic beta cell function

– 2004 PhD

Tibor Altenberger Aberrant gene expression patterns in pituitary tumors

– 2004 PhD

Ivelina Mineva Differential expression of alphaB-crystallin and Hsp27-1 in anplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene silencing (Univ. Sofia)

– 2007 PhD

Anastasiya Nabokikh

Genes influencing insulinoma growth

pending

Aysegul Ilhan Molecular cloning and renal expression analysis of the C20orf3 gene product

pending

Publications 57 peer reviewed publications in scientific journals.

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30) Wagner L. , O. Oliyarnyk, W. Gartner, P. Nowotny, M. Groeger, K. Kaserer, W. Waldhäusl, and MS. Pasternack. Cloning and Expression of Secretagogin, a Novel Neuroendocrine- and Pancreatic Islet of Langerhans-specific Ca2+-binding Protein. J Biol Chem 2000 275: 24740-24751

31) B. Lamkhioued, EA. Garcia-Zepeda, S. Abi-Younes, H. Nakamura, S.

Jedrzkiewicz, L. Wagner, PM. Renzi, Z. Allakhverdi, C. Lilly, Q. Hamid, and AD. Luster. Monocyte Chemoattractant Protein (MCP)-4 Expression in the Airways of Patients with Asthma. Induction in Epithelial Cells and Monocuclear Cells by Proinflammatory Cytokins. Am J Resp Crit Care Med 2000 162: 723-732

32) Artwohl M, Hoelzenbein T, Wagner L, Freudenthaler A, Waldhaeusl W,

Baumgartner-Parzer. Levamisole induced apoptosis in cultured vascular endothelial cells. Br J Pharmacol 2000 131: 1577-1583

33) E. Templ, G. Mostbeck, L. Wagner and M. Weissel. Reversibility of

Retroperitoneal Fibrosis after Successful Treatment of Colon Cancer. Acta med Austriaca 2000 27: 168-170

34) D. Zhang, M. Pasternack, P. Beresford, L. Wagner, A. Greenberg, J. Lieberman.

Induction of rapid histon degradation by the cytotoxic T lymphocyte protease granzyme A. J Biol Chem 2001 276: 3683-3690

35) W. Gartner, W. Lang, F. Leutmetzer, H. Domanovits. W. Waldhaeusl, L. Wagner.

Cerebral expression and serum detectability of secretagogin, a recently cloned EF-hand Ca2+-binding Protein. Cerebral Cortex 2001 11:1161-1169.

36) Brunmair, B., F. Gras, S. Neschen, M. Roden, L. Wagner, W. Waldhäusl, C.

Fürnsinn. Direct thiazolidinedione action on isolated rat skeletal muscle fuel handling is independent of peroxisome proliferator-activated receptor- gamma-mediated changes in gene expression. Diabetes, 2001. 50(10): 2309-15.

37) Sauty, A., RA. Colvin, L. Wagner, S. Rochart, F. Spertini, AD. Luster. CXCR3

internalization following T cell-endothelial cell contact: preferential role of IFN-inducible T cell alpha chemoattractant (CXCL11). J Immunol, 2001. 167(12): 7084-93.

38) Meier, C., D. Rüzler, L. Wagner, G. Grabner, G. Köhler, A. Luger. Evidence for

specific glucocorticoid binding sites on the cell membrane by fluorescence correlation spectroscopy. Single Mol. 2002.3: 211-216.

39) Gartner, W., J. Rossbacher, B. Zierhut, T. Daneva, W. Base, M. Weissel, W.

Waldhäusl, M.S. Pasternack, L.Wagner. The ATP-dependent Helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motility and Cytoskel. 2003.56:79-93.

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40) Zierhut, B., Mechtler, K., Gartner, W., Daneva, T., Base, W., Weissel, M., Niederle, B., and Wagner, L. Heat shock protein 70 (Hsp70) subtype expression in neuroendocrine tissue and identification of a neuroendocrine tumour-specific Hsp70 truncation. Endocr Relat Cancer. 2004. 11: 377-389.

41) Grisar J, Aringer M, Koller MD, Stummvoll GH, Eselbock D, Zwolfer B, Steiner

CW, Zierhut B, Wagner L, Pietschmann P, Smolen JS. Leflunomide inhibits

transendothelial migration of peripheral blood. Cell Ann Rheum Dis. 2004 Dec;63(12):1632-7. 42) Barbara Zierhut, Teodora Daneva, Wolfgang Gartner, Barbara Brunnmaier, Tord

Berggård, L Wagner. Setagin and secretagogin-R22: Posttranscriptional modification products of the secretagogin gene (SCGN). Biochem Biophys Res Commun (2005) 329:1193-1199.

43) Brunmair B., F. Gras, L. Wagner, M. Artwohl, B. Zierhut, W. Waldhäusl, C.

Fürnsinn. Expression of uncoupling protein-3 mRNA in rat skeletal muscle is acutely stimulated by thiazolidinediones: an exercise-like effect? . Diabetologia (2004) 47: 1611-1614.

44) T. Altenberger, M. Bilban, M. Auer, E. Knosp, S. Wolfsberger, W. Gartner, I.

Mineva, C. Zielinski, L. Wagner, and A. Luger. Identification of DLK1 variants in pituitary- and neuroendocrine tumors, Biochem Biophys Res Commun 340 (2006) 995-1005.

45) S. M. Baumgartner-Parzer, R. Lang, L. Wagner, G. Heinze, B. Niederle, K.

Kaserer, W. Waldhausl, and H. Vierhapper. Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?, J Clin Endocrinol Metab 90 (2005) 6232-6236.

46) W. Gartner, I. Mineva, T. Daneva, S. Baumgartner-Parzer, B. Niederle, H.

Vierhapper, M. Weissel, and L. Wagner. A newly identified RET proto-oncogene polymorphism is found in a high number of endocrine tumor patients, Hum Genet 117 (2005) 143-153.

47) D. Haubenberger, R. E. Bittner, S. Rauch-Shorny, F. Zimprich, C. Mannhalter, L.

Wagner, I. Mineva, K. Vass, E. Auff, and A. Zimprich. Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene, Neurology 65 (2005) 1304-1305.

48) I. Mineva, W. Gartner, P. Hauser, A. Kainz, M. Loffler, G. Wolf, R. Oberbauer, M.

Weissel, and L. Wagner. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing, Cell Stress Chaperones 10 (2005) 171-184.

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49) H. Vierhapper, S. Rondot, E. Schulze, L. Wagner, S. Hanslik, B. Niederle, C. Bieglmayer, K. Kaserer, and S. Baumgartner-Parzer. Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation, Thyroid 15 (2005) 1303-1308.

50) K. Birkenkamp-Demtroder, L. Wagner, F. Brandt Sorensen, L. Bording Astrup, W.

Gartner, H. Scherubl, B. Heine, P. Christiansen, and T. F. Orntoft. Secretagogin is a novel marker for neuroendocrine differentiation, Neuroendocrinology 82 (2005) 121-138.

51) W. Gartner, F. Koc, A. Nabokikh, T. Daneva, B. Niederle, A. Luger, and L.

Wagner. Long-term in vitro growth of human insulin-secreting insulinoma cells, Neuroendocrinology 83 (2006) 123-130.

52) K. Adolf, L. Wagner, A. Bergh, P. Stattin, P. Ottosen, M. Borre, K. Birkenkamp-

Demtroder, T. F. Orntoft, and N. Torring. Secretagogin is a new neuroendocrine marker in the human prostate, Prostate (2007) in press.

53) J. Attems, M. Quass, W. Gartner, A. Nabokikh, L. Wagner, S. Steurer, S. Arbes,

F. Lintner, and K. Jellinger. Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons, Exp Gerontol 42 (2007) 215-222.

54) A. Rogstam, S. Linse, A. Lindqvist, P. James, L. Wagner, and T. Berggard.

Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin, Biochem J 401 (2007) 353-363.

55) I. Pipp, L. Wagner, K. Rössler, H. Budka, M. Preusser. Secretagogin expression

in tumors of the human brain and ist coverings, APMIS 2007 in press 56) A. Nabokikh, A. Ilhan, M. Bilban, W. Gartner, G. Vila, B. Niederle, JH. Nielsen, O.

Wagner, W. Base, A. Luger, L. Wager, Reduced TGF-ß1 expression and its target genes in human insulinomas. Experimental and Clinical Endocrinology & Diabetes 2007 in press

57) W. Gartner, G. Vila, T. Daneva, A. Nabokikh, F. Koc-Saral, A. Ilhan, O. Majdic, A.

Luger, L. Wagner, New functioanl aspects of the neuroendocrine marker secretagogin based on the characterization of ist rat homolog. Am J Physiol Endocrinol Metab 2007 in press

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Kurt M. WIDHALM Div.of Clin Nutrition and Metabolism, Dept of Pediatrics, Med.Univ Vienna [email protected] Early detection and treatment of children and adolescents affected with familial hypercholesterolemia (FH) Abstract (area of research, most recent results; <3000 characters) Thesis Subjects Association between genotype and phenotype in families affected with FH Effect of ApoE pattern on the effect of diet on serum lipoproteins in children with FH Dose effect of soy proteins and isoflavons Clinical characteristics of Apo-B-100-Defect Postprandial Hypertriglyceridemia in parents with familial comb. Hyperlipidemia Effekt of w-3 fatty acids in infants and children with homozygous LPL-deficiency Intima Media thickness in young children with homozygous familial hypercholesterolemia undergoing LDL-apheresis Techniques and infrastructure Outpatient clinic for lipid and lipoprotein disorders Dietary intervention for affected subjects. Lipoprotein research laboratory including ultracentrifuge, isoelectric, focusing, electrophoresis etc. Cooperations to detect LDL-receptor gene mutations Unit for clinical drug trials

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CURRICULUM VITAE Kurt WIDHALM, Dr.med. Professor for Clinical Nutrition, Head, Div. Nutrition and Metabolism, dept. of

Pediatrics, Med.Univ. of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria,

Phone: +43-1-404002337 or 3232, Fax: +43-1-40400 2338 or 3194, E-Mail:

[email protected]

Personal Data Date of Birth : 02.02.1946

Place of Birth: Linz, Austria


Education: 1964: Graduated at Academic Gymnasium Linz, with honors;

Jan.1971: Dr.med.univ., Univ.Vienna Nov.1977: Board

Certification: Pediatrics ("Facharzt für Kinderheilkunde")

Jan.1998: Board Certification: Clinical Chemistry ("Facharzt für

medizinische und chemische Labordiagnostik")

Brief Chronology of Employment: Feb.1971-May 1973: Dept.of Physiology, Univ. Vienna

1973-1992: Dept.of Pediatrics, Univ.Vienna

1992-1994: Director and Head of Internal Dept. Mautner Markhof

Childrens Hospital Vienna

1994-: Dept. of Pediatrics, Med. Univ. of Vienna

Career History: Since 1974: Head of Outpatient Clinic for Obesity, Feb.1978:

Senior Lecturer in Pediatrics Lipid Disorders and Nutrition

Conseling

1980: Assoc.Prof.of Pediatrics

July 1986: Professor for Pediatrics

1987: Head of the "Academy of Clinical Nutrition" of the Austrian

Nutrition Society and of the Physicians Board of Vienna

1.1.1988-1992: Director of the Austrian Screening Program for

Inborn Errors of Metabolism (incl.Treatment Program), located on

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the Dept. of Pediatrics, Univ.Vienna

15.10.1992: Director and Head of Internal Department of the

Mautner Markhof Children's Hospital, Vienna

1994: Professor for Clinical Chemistry

1995: Professor for Pediatrics, Dept. for Pediatrics, Univ.Vienna

1997: President Austrian Academy for Medical Nutrition

2003: Full Professor for Clinical Nutrition and Head of Dept.

Nutrition and Metabolism

Foreign studies: May/June 1975: Clin. Institute for Research on Myocardial

Infarction, Med.Clinics, Univ. Heidelberg, Germany.

Oct.1977: Lipid Res.Clinics, Dept.Pediatrics, Johns Hopkins

Univ., Baltimore, Md. (Prof.Dr. P.O.Kwiterovich)

May 1982: Invited Tour Speaker, Amer.Ass.Clin. Chem.

Oct.1983: The Cleveland Clinic Foundation, Dept.of

Biochemistry, Section Lipids, Nutrition and Metabolic Dis.

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Oct.1985: Children's Hospital Melbourne

Oct./Nov.1988: University Riberao Preto, Sao Paulo, Brasil

Jan.1992: Inst.for Genetic Diseases, Academy of Science,

Moscow

Military Service: July/August 1976

Committees and Boards: Secretary of the Austrian Society for Pediatrics (1982-86)

Council Member and Vice President (1992-96) of the Austrian

Society for Nutrition (1990-2000)

President Austrian Medical Academy of Nutrition (since 1997)

President of the Austrian Lipid Society (until 1994)

Member of the Health Council of the City of Vienna (1991-1999)

President of the Federation of European Societies of Nutrition

(FENS) 1995-99

President European Childhood Obesity Group (since 2003)


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Editorial Scientific Boards: Aktuelle Ernährungsmedizin (G.Thieme, Stuttgart)

Nutrition Research (Pergamon Press)

Klinische Pädiatrie (F.Enke-Verlag)

J.Amer.Coll.Nutrition

Int.Pediatrics

Editor: J. für Ernährungsmedizin (Wien)

Publications: (Alan R.Liss, New York) K.Widhalm, H.K. Naito

(Books) (Eds.): Detection and Treatment of Lipid and Lipoprotein

Disorders of Childhood 1985 (Progress in Clin. and Biol.

Res.Vol.88)

K.Widhalm, H.K. Naito (Eds.): Recent Aspect of Diagnosis and

Treatment of Lipoprotein Disorders 1988 (Progress in Clin. and

Biol.Res.Vol. 255)

Apolipoproteins in Lipid Disorders, Springer, Wien, New York-

1991

Ernährungsmedizin, Verlag d. Österr. Ärztekammer, Wien, 2000,

2006

Kinderernährung, Verlag d. Österr. Ärztekammer, Wien, 2002

350 scientific papers, most of them in International Journals

Reviewer: Pediatric Research, Pediatrics, Annals of Nutrition and

Metabolism, European Journal of Pediatrics,J. Nutrition,

Metabolism and Cardiovascular Diseases, Journal of Pediatric

Gastroenterology and Nutrition, Gene Therapy,

J.Inher.Metab.Dis., Int.J.Obesity etc.


Period Organization Short Title K€ 2005 – 2008 EU (partner Project

no. 007034) HELENA – Healthy Lifestyle in Europe by Nutrition in Adolescence


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– 2007 Medpace Randomized Double-Blind Placebo-Controlled Efficacy and Safety Study of Colesevelam HCI Administered to Pediatric patients with Heterozygous Familial Hypercholesterolemia on a Stable of Statins or Treatment Naive to Lipid-Lowering Therapy

– 2007 Aesca Klin. Prüfung von Ezemibide/ Simvastatin bei Kindern und Jugendlichen mit familiärer Hypercholesterinämie

2003 – 2006 Fresenius, Graz Ernährungszustand/Malnutrition bei hospitalisierten Patienten

– 2005 Alpro Foundation, Brüssel

Effekt von Sojaprotein bei Kinder und Jugendlichen mit familiärer Hypercholesterinämie

– 2005 Numico Int., Wageningen, The Netherlands

Glucosestoffwechsel bei übergewichtigen Jugendlichen

– 2005 Rudolf Mach CLA Studie – 2005 Abbott Anwendungsbeobachtung der Wirkung

von Sibutramine bei morbid adipösen Jugendlichen

– 2004 EU (QULRT-2000-00716)

QULRT – Quality of life in chronically ill children

– 2004 Agrana, BM, FGÖ (Projetknummer 323/III/48)

PRESTO – Prevention Study of Obesity

– 2004 Nährstoffakademie Salzburg

Mikronährstoffe in Österreich

– 2004 ARC Seibersdorf Altersabhängigkeit – HF Strahlungsabsorption

finished Nestlé Familial Hypercholesterolemia




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Irene Mann Homozygote, familiäre Hypercholesterinämie: Klinik, Diagnose und Therapie an Hand von drei pädiatrischen Fällen

– 2006 Dr.

Michaela Kiss Glucosetoleranz bei morbid obesen Patienten

– 2006 Dr.

Marie-Therese Heine- Geldern

Malnutrition: Ernährungszustand von ambulanten Patienten

– 2005 Dr.

Christina Denninger Mögliche Assoziation zwischen unterschiedlichen Mutationen des LDLR - Gens u. des Gesamtcholesterins bzw. LDL - Cholesterins

– 2005 Dr.

Philipp Kahl Anwendungsbeobachtung der Wirkung von Sibutramine bei morbid adipösen Jubendlichen

– 2005 Dr.

Iris Ciba Nonalcoholic Fatty Liver Disease“ und deren Korrelation mit Insulinresistenz bei adipösen Kindern und Jugendlichen

– 2005 Dr.

Barbara Öller Das Polycystische Ovarialsyndrom und die nicht-alkoholischen Fettlebererkrankungen im Kindes- und Jugendalter

– 2005 Dr.

Eva Rettenbacher Mutationsanalyse des Melanocortin-4-Rezeptorgens bei extrem adipösen Kindern und Jugendlichen (Univ. Marburg, Germany)

– 2004 Dr.


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Bettina Bandur Bericht über in Österreich durchgeführte Untersuchungen zur Versorgung der Bevölkerung mit Vitaminen und Spurenelementen

– 2004 Dr.

Christian Denzer Adipostias im Kindes- und Jugendalter: Profil einer universitären Adipositasambulanz

– 2003 Dr.

Andrea Preisinger Pediatric Obesity – A review of literature and 3,5-year-follow-up of an outpatient weight reduction program in obese children and adolesents

– 2002 Dr.

Publications

Widhalm K., Schönegger K., Huemer C., Auterieth A.: Does the BMI reflect body fat in obese children and adolescents? A study using the TOBEC method. Int.J.Obesity 25, 279-285 (2001), IF 3,199 Eisenkölbl J., Katasurya M., Widhalm K.: Underestimation of body fat mass percentage measured by bioelectrical bioimpedance. Eur.J.Clin.Nutrition 55, 423-429 (2001) IF 1,668 Boeck A., Zeitlhofer J., Widhalm K.: Visual evoked potential changes in asymptomatic children with biotinidase deficiency: Wien.Klin.Wschr. 113: 527-530 (2001) IF 0,588 Widhalm K.: Adipositas. State of the Art. Österr. Ärztezeitung 6, 34-38 (2001) Dirisamer A., Widhalm K.: Homocysteine in children and adolescents from families with premature cardiovascular disease. Abstr. Ped.Res. 49, 257A (2001), IF 2,661 Widhalm K. Miranda da Cruz B., de Sonneville LMJ.: Information processing characteristics and uridine treatment in children with classical galactosemia. Nutr.Research 22, 257-270 (2002) IF 0,716 Standard, Original


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Gulesserian T., Widhalm K.: Effect of a rapeseed oil substituted diet on serum lipids and lipoproteins in children and adolescents with familial hypercholesterolemia. J.Amer.Coll.Nutr. 21: 103-108 (2002) IF 1,546 Standard, Original Widhalm K.: Diagnosis and treatment of hyperlipoproteinemias in children and adolescents. In: Pediatric Endocrinology; F. Lifshitz, Ed., 859-64 M. Dekker, New York (2002) Review Hofmann U., Dirisamer A., Heher S., Kostner K., Widhalm K., Neunteufel Th.: Relation of peripheral flow-mediated Vasodilatation and coronary artery calcium in young patients with heterozygous familial hypercholesterolemia. Am.J.Cardiol. 90, 70-73 (2002) IF 2,762 Top Original Widhalm K., Schwabl R.: Nutrient intakes of children and adolescents with morbid obesity In: Study on „Obesity and functional foods in Europe“; EU-Cost Action 918, 396-401 (2002) K.Bauer, et al.K.Widhalm: Cholesterin 2. ACCC 2002, Konsensus-Statement CliniCum, Sonderausgabe Oktober 2002 Dirisamer A., Widhalm K.: Lipoprotein (a) as a potent risk indicator for early cardiovascular disease. Acta Paediatr. 91:1313-17 (2002), IF 1,315 Dirisamer A., Hachemian N., Bucek R. A., Wolf F., Reiter M., Widhalm K.: The effect of low-dose simvastatin in children with familial hypercholesterolemia: a 1-year observation. Eur J Pediatr. 162: 421-425 (2003) IF 1,22 Widhalm K., Reithofer E.: Effect of Two Diets in Children and Adolescents with Familial Hypercholesterolemia: Soy-Protein Diet Versus Low Saturated Fat Diet. Nutrition and Biochemistry of Phospholipids. 16: 171-174, 563-564 (2003) Denzer C., Reithofer E., Wabitsch M., Widhalm K.: The outcome of childhood obesity management depends highly upon patient compliance. Eur. J. Pediat. 163:99-104 (2004) Dirisamer A., Reiter M., Bucek R.A., Widhalm K.: Plasma homocysteine concentration in children of families with proven myocardial infarction before the age of 55 years. Acta Paed. 93:1-2 (2004) Dietrich S, Widhalm K: A multidisciplinary Therapy Program for Morbidly Obese Children and Teenagers: Results After 7 Months. Int. Pediatrics 19:83-89 (2004) Flodmark CE, Lissau I, Moreno L, Pietrobelli A, Widhalm K: New Insights into the Field of Children and Adolescents Obesity: The European Perspective. Int. J. Obesity 28:1189-1196 (2004) Widhalm K, Dietrich S, Prager G: Adjustable Gastric Banding Surgery in morbidly obese Adolescents: Experiences with 8 patients; Int. J. Obesity 28:42-45 (2004)


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Widhalm K, Weghuber D: Treatment of Children and Adolescents with Familial and Polygenic Hypercholesterolemia with Classical and Soy Substituted Diet in: Koen Descheemaeker, Ignace Debruyne (Hrsg.) Soy & Health 2004 Clinical Evidence Dietetic Applications 41-47 (2005) Pietrobelli A, Flodmark CE, Lissau I, Moreno LA, Widhalm K:From birth to adolescence: Vienna 2005 European Childhood Obesity Group International Workshop. Int J Obesity 29:S1-S6 (2005) Widhalm K, Fussenegger D: Actions and programs of European countries to combat obesity in children and adolescents: a survey. Int J Obesity 29:S130-S135 (2005)

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