INDEX

Acellular tissue matrix, 5~58, 93-96; see also Ex-tracellular matrix

Actin, 65-66, 68, 100, 138, 145-148,438 Action potential, 245, 289 Adenocarcinoma, 54, 56 Adenosine receptors, 312 Adherence factors, 341 Adherence markers, 439--442 Adhesins, 327-329, 340, 344-345, 352-353, 356 Adhesion molecules, 19--20, 44, 53-54, 332 Adrenoceptors, 242-243, 286 Adrenoceptor antagonists, 28~289 Aerobactin, 329 Aging, 84 Aldose reductase pathway, 298 Alpha blockers, 317, 320 AMPA receptor antagonists, 275 Androgen receptors, 55 Angiogenesis, 75-77 Angiotensin 11,133,184,231 Anodal block technique, 306 Anticancer agents, 375, 383 Anticholinergic therapy, 49, 304 Antigens, 353-354, 374, 388 Antimotility drugs, 469, 472 Antitumor agents, 324 Apoptosis, 77, 95, 437, 449--450, 452-453 Aromatic amines, 396 Asymmetric unit membrane, 8--13,15,20,44,51

plaques, 8--13, 20, 44 Asymptomatic bacteriuria, 334, 339 ATP, 157-158,245,272 Augmentation, 49--50, 54, 5~58, 129, 131-133,

193 Autoaugmentation, 43-44, 50 Autocrine motility factor receptor, 470 Azacytidine, 421

Bacillus Calmette--Guerin immunotherapy, 360, 371, 374,381

Bacterial adhesion, 325-326

Bacterial colonization, 325-327, 340-341, 352-356 host factors in, 333-334 as prerequisite in urinary tract infections, 352-356

Bacterial infection, 325; see also Urinary tract infec­tions

Barrier function, 44 Basement membrane proteins, 19,25, 54, 75-77,

400-401,403-404,407-409 Benign prostate hyperplasia, 143, 148,215,283 Beta receptors, 313-314 Bethanechol,70, 124-125,314 Biopharming strategy, 14-15 Bladder, 3,31,43,49, 63,93, 103, 117, 121,129,137,

155,171,183,193,201,215,237,253, 265,293,303,323,371,387,395,399, 413,419,425,437,449,469,477

p-adrenoceptors on, role of, 242-243 anatomical studies, 254-256

pathways in brain, 256 in spinal chord, 256

angiotensin II, role of, 183-189 collagen production, 184, 187-189 future directions, 188--189 hypothesis of, 189 in vitro cell culture studies, 187-188 in vivo animal studies, 185-187 physiologic effects on function, 184 smooth muscle growth, 184-185

augmentation, 49--50, 54, 5~58, 129, 131-133, 193 autoaugmentation, 43-44, 50 calcium ion homeostasis in, 155-167

excitation contraction coupling, 157-159 ontogeny, 159--162 outlet obstruction, 156, 162-166 regulation, 15~157

cancer in humans, 437-446 cancer progression, 425-433 carcinogenesis of, 56, 449--450

experimental investigations in humans, 454-463 gene expression, 457-463

485

486

Bladder (cant.) carcinogenesis of (cant.)

mechanistic models, 451-463 modeling system for, 449, 461-463 retinoid signaling, 449-463 role of retinoids, 452-454 strategy for cure, 461-463 Vogelstein-Kinzler model, 450-451

cell phenotypic changes in, 67-70 cell proliferation, 187-188 cellular factors in development/function of, 132-133 compliance, 68,122-123,137,155,166,209-213,

241-247 central nervous system, role of, 253 collagen in filling of, role of, 215-223 contractile proteins on smooth muscle, role of, 137-149 cycling, 155-156,216-220 decompensation, 137, 144, 149, 163-165,216 detrusor smooth muscle, role of, 241-242

ion channels on, 245-247 relaxation pathways, 241-242

cyclic AMP pathway, 242-244 cyclic GMP pathway, 244-245

diabetic cystopathy, 294-298 diagnosis of disorders, 38-41 diseases of, 39, 49-50, 54 disorders of, 31

from mucosal function, 266 distention model, 178 DNA methylation in cancer of, role of, 419-423

CpG islands, 420 endothelin B receptor gene, 422 P19/P1610cus,420 PAX-6 gene, 422-423 T24 cells, 421 tumor suppressor genes, 421-422

dysfunction, 266, 271 effects of adrenoceptor antagonists, 286-289 effects of hypertension on function, 283-290 Ehlers-Danlos syndrome in, 201-213 enlargement of, 49 epithelial cells in, role of, 32-36, 50-56 epithelial-mesenchymal interactions in, 3-4, 49-58,

103-114 implications for augmentation, 49-50, 54

exteroceptive perineaJ.-.bladder reflex mechanism, 254

exteroceptive somato-bladder reflex mechanism, 253

extracellular matrix, 53-54 protein, 193

fetal physiology of, studies in, 121-127 animal,124-126 during obstructed development, 126-127 human, 121-124

fetal urine output of, 100 fibrotic response of, 49 functions of, 49-50,121,137-138,155,159,215 gene expression during development of, 64, 66-68

Bladder (cant.) growth and differentiation of, 65-66, 68 hyperelasticity of, 212 hypertension vs. voiding behavior, 284-285 hypertropy of, 65-68, 185

Index

immunohistochemical markers of disease progres­sion, 425-433

measurement of cellular proliferation, 430-431 in vitro physiological studies, 258-262

brain stem-spinal chord-bladder, 258 spinal chord, 258

in vivo physiological studies, 256-258 innervation, 65, 71, 285-288 insight into nerve growth factor regulation, 286-290 instability,216 ion channels on behavior, 245-247 markers in study of, 445 maturation of reflex pathways, 253-262

postnatal development, 254 animal studies, 256-262

prenatal development, 253 membrane depolarization, 158, 299-300 model for submesothelial mesenchymal cell activa­

tion, 73-75 modulation of in vitro invasiveness, 399-410

urokinase expression studies, 400-410 flow cytometry, 401-403, 405 immunohistochemical staining, 403, 405 Matrigel invasion assays, 403-409 tumor cel1lines, 401, 408

molecular mechanisms for muscle contraction, 138 neonatal perineal-bladder reflex mechanism, 254 neurogenic, 49 new concepts of development of, 193-198 normal development of, 54 observations from hypertensive rat, 283-290 ontogeny of, 4 outlet obstruction, 137, 185-187 overactivity of, 241-247, 300 overview of cancer of, 395-397, 419, 437-446 parasympathetic pathways, 254, 262 parathyroid hormone-related protein, role of, 247 pathophysiology of bacterial cystitis, 325-334

clinical studies, 329 colonization, 325-327 cynomologous monkeys, studies in, 332-333 fimbrial adhesins, 327-330 host factors, 333-334

bacterial colonization, 333-334, 352-356 inflammatory response, 332-333, 389 overview of infections, 325-330 phagocytosis, 331-332 urinary tract infections, 325, 327-330, 333-334 virulence factors, 330-333

adherence, 331-332 cellular receptors, 332-333 immunity, 333 surface, 330-331 vaccines, 333

Index

Bladder (cant.) prostaglandins, 171-179

cyclooxygenase isofonns, 173--179 fetal development, 175 regulation of, 173-177 therapeutic use, 177-179

functions of, 172-178 regulation of synthesis, 171-172 role in mucosal cytoprotection, 173 site for, 172

rabbit, studies in, 63-78, 157-167,265--272,294 cell differentiation, 71-73, 77 detrusor smooth muscle function, 265, 272 effect of diabetes, 294-298 endogenous lipase activity, 267-272 fatty acid distribution, 265--272 mucosa function, 265, 272 Na + -K+ -ATPase activity, 293-298 obstruction modeling, 63, 69-73, 77

serosal thickening, 68-70 smooth muscle growth, 66-{j8

phospholipids, 267-272 regeneration, 70-72, 77

freezing model, 71, 77 serosal thickening, 70-72 smooth muscle growth, 70-71

submesothelial-mesenchymal cell activation, 73-75, 78

urothelial-mesenchymal interactions, 75--77 rat, studies in, 275--280

effects of glutamate receptor antagonists, 275, 280 smooth muscle ontogeny, 93-101

methodology, 96 urethral activities, 275, 280

reconstruction of, 32-38 by autoaugmentation, 43-46

use of de-epithelialized bowel, 44,50 through regeneration, 129

overview of, 129-130 use ofsmall intestine submucosa, 129-134

augmentation study in rats, 131-132 graft preparation, 130 in vitro contractility and compliance studies,

130, 132-133 intrinsic properties, 133-134 long-tenn augmentation in dogs, 132

regeneration of, 52, 56--58, 96 regulation of smooth muscle contractility, 293-294

diminition by diabetes, 294-298 effects

of carbachol, 294-297, 299 of diabetes, 294-298 of ouabain, 294-296, 299

intraccellular Na" 298-299 role ofNa+-K+-ATPase activity, 293-300

replacement of, 50 restoration of function, 303-307

neurostimulation techniques, 304-305 sacral anterior root stimulation, 304

487

Bladder (cant.) restoration off unction (cont.)

sacral deafferentation, 303, 305 selective neurostimulation, 305--307 stimulation-induced detrusor-sphincter dyssyner-

gia, 304-305 sarcoplasmic reticulum, role of, 155--156 smooth muscle proteins, 53 spinal reflex mechanisms, 253-254, 262 spinobulbospinal bladder-bladder reflex mecha-

nism, 254, 256 stress-strain relationships of, 167, 189, 210-213 stromal cells of, 53

ontogeny of, 53 structural-functional interfaces in, 64-65 tissue creation

in vitro, 31-41 in vivo, 31-41

tissue repair and replacement, 31, 36--38 animal studies, 37-38 engineering strategies of, 32-34, 36--38, 40

cell characterization, 32 cell cultures, 32 cell delivery vehicles, 34-36 cell expansion, 32 fetal tissue, 38-41 use of polymers, 35--38

human studies, 33-35 transitional cell carcinoma of, 425--433

cellular proliferation, 430-433 prognostic markers in, 426-433 role of regulatory proteins, 431-433 role of tumor suppressor genes, 426-430

treatrnentofcancer, 371-383 combination therapies, 380-382

toxicity assessment, 382, 392 future directions, 382-383

with Bacillus Calmette-Guerin modifiers, 381-383,392

mechanism of action, 374-375 prevention of tumor recurrence, 377-380 therapy, 375--377

interferon in, 371-372, 392 clinical trials, 375 co-application with intravesical chemotherapy,

380-382 intravesical therapy, 372-373

eradication of residual cancer, 376--377 prevention of tumor recurrence, 377-380

management issues, 383 overviewof,371-373

tumor cell motility in, 469-470 carcinoma studies in mice, 472-474 second line therapy, 474-476 signal transduction pathway, 470-472 therapeutic approach to carcinoma, 469-476

tumor invasion, 413-416 in vitro model, 414-416 role of matrix metaloproteinases, 413

488

Bladder (cont.) tumors, 50, 56 urinary incontinence, 43 urothelial cell propagation, 44-45

animal studies, 44 human studies, 44-45 in vitro organ culture models, 45 monolayer cultures, 44-45

urothelial cells, role of, 32~36, 44-45, 50--56 urothelial differentiation in cancer of, role of, 437-446

adherence markers, 439-442 desmosomes, 439 E-cadherin, 439-441 hemidesmosomes, 441-442 integrins, 441

cell surface markers, 442-443 blood group antigens, 442 epidermal growth factor receptor, 442 uroplakins, 442

cytoskeletal markers, 438-439 actin, 438 cytokeratins, 439

proliferation markers, 438 urothelium, role of, 20, 44-45, 49, 247~248 use of bowel in augmentation of, 50 wall characteristics, 20 1~213

Bladder cancer cell lines, 20, 56 Blood group antigens, 442 Blood pressure, 284, 317

role in urinary frequency, 284, 288-290 Bombesin, 471 Bone demineralization, 50 Bradykinin, 471 Burst stimulation, 305

Ca2+/calmodulin-dependent myosin light chain phos-phorylation, 138

Ca2+-Mg2+-ATPase, 156 Calcium-channel blocker, 124 Calcium-induced calcium release, 157 Calcium ion homeostasis, 155-167 Caldesmon, 137-138, 140, 147~148 Calmodulin, 137-138, 147 Calponin, 140, 148, 315 Calsequestrin, 157 Cancer cell lines, 399, 40 1,408 Capsaicin, 172~173, 178, 311~312 Capsular antigen, 330 Captopril, 185-186 Carbachol, 133,294-297,299,312 Carboplatin,474-476 Carcinogens, 56

environmental, 395 Carcinoma in situ, 371, 419 Cell surface antigen, 470 Cell surface markers, 353, 442-443 Cell transplantation, 32, 35, 45 Cell-associated fluorescence, 401-402 Cellular signalling, 54

Central nervous system, 253 Chemokines, 360

synthesi s, 68 Chemoprevention, 437-438, 446, 452 Chemotherapy, 372, 380--382 Choline acetyltransferase, 126,314-315 Cigarette smoking, 395-396 Cloaca, 3

Index

Collagen, 25, 53-54, 94, 96-97, 100, 122~123, 129, 131,134,183-185,188, 193, 202~212, 215-223, 229-230

Colon cancer, 406-407, 450, 482 Contractile proteins, 65-fJ7, 73 Contraction coupling, 157~159 Cromakalim, 246 Cross bridge cycling, 140, 149 Cross-species transplantation, 130 Cryotechnique, 306-307 Cyclins, 83-90, 426 Cyclooxygenase, 171, 173~ 179 Cystectomy, 38 Cystic fibrosis, 341 Cystitis, 270, 325, 339-340, 359, 387

pathophysiology of bacterial cystitis, 325-334 clinical studies, 329 colonization, 325-327 cynomologous monkeys, studies in, 332-333 fimbrial adhesins, 327~330 host factors, 333-334

bacterial colonization, 333~334, 352~356 inflammatory response, 332~333, 389 overview of infections, 325-330 phagocytosis, 331~332 urinary tract infections, 325, 327~330, 333-334 virulence factors, 330--333

adherence, 331~332 cellular receptors, 332-333 immunity, 333 surface, 330--331 vaccines, 333

Cystograms, 38-40 Cytokeratin, 21, 197, 439 Cytokine/growth factor receptors, 19 Cytokines, 66, 72, 332~333, 360, 366, 40 I, 408, 413 Cytotoxic T cells, 374, 381

Deafferentation, 305 Decompensation, 137, 144, 149, 163-165,216 De-epithelialized bowel, 44, 50 Denervation,314-316 Derjaguin-Landau--Verwey-Overbeek theory, 326 Derusor-sphincter dyssynergia, 193-194 Desmin, 53, 65, 70, 94, 100 Desmosomes, 439 Detrusor reserve, 163, 167 Detrusor smooth muscle, 53, 63-66, 143, 155-166,

205-206, 212; see also Smooth muscle animal studies, 93-101, 246, 265, 272 contractile proteins, 53, 137~149

Index

Detrusor smooth muscle (cont.) contractility of, 293-294 dysfunction in diabetes, 294-298 growth of, 184-185 human, 246-247 innervation of, 242 in vitro studies in rats, 285-286

adrenoceptor antagonists, 286, 289 blood pressure, 284, 289 hyperactivity,287-289 innervation, 285, 289 nerve growth factor metabolism, 286-290 voiding behavior, 284-285, 289

ion channel, 245-247 calcium, 246-247 potassium, 245-246

relaxation pathways, 241-242 cyclic AMP pathway, 242-244

f3-adrenoceptor agonists, 242-243 forskolin, 243-244 phosphodiesterase inhibitors, 244 vasoactive intestinal polypeptide, 243

cyclic GMP pathway, 244-245 ATP,245 nitric oxide, 244-245

role in bladder compliance, 241-242 role of Na + -K+ -ATPase activity on contractility,

293-300 role in outflow obstruction, 66-68 studies in rabbit bladder, 265-272

Detrusor-sphincter dyssynergia, 275, 303-305, 314 Detrusor-sphincter synergia, 280 Dexamethasone, 173 Diabetes mellitus, 294 Diabetic cystopathy, 294-298 Differentiation markers, 63, 68, 396 DiItiazem, 124 Distention model, 178 Diverticulectomy, 201-202 Diverticulum, 209-213 DNA methylation, 419-423, 478

role in bladder cancer, 419-423 DNA synthesis, 425 Doxazosin, 318 Doxorubicin, 371, 380 Dunning tumor, 6, 56 Dupuytren's disease, 95 Dysfunctional voiding, 387 Dystrophin, 228

E. coli, 12-13,325-332,339-347,351-356 role in urinary tract infection in women, 340-347

E-cadherin, 32-33,45,413, 439-441,470 Ehlers-Danlos syndrome, 201-213 Elastin, 54, 206, 209, 212 Embryogenesis, 443 Endogenous lipase activity, 267-272 Endothelin, 133

receptor gene, 422

Endotoxin, 332, 334, 360 Enterobacteriaceae, 325, 327, 329 Enterococci, 330, 339 Enterocystoplasty, 43-45, 56 Environmental carcinogens, 395 Epidermal growth factor, 399, 401-403, 410

receptors, 33-34, 442 Epirubicin, 383 Epithelial cells

in rat bladder development, 94 role in urinary tract infections, 341

Epithelial tissue, 19-20; see also Urothelium cell regulation of, 21, 25 cytodifferentiation of, 19, 23-24 disease progression, 19-20 histioarchitecture, 19, 22 homeostasis, 19-20 organization of, 19-20

cell lineage markers, 19 functional issues, 19 structural issues, 19-20

proliferation, 19,24-25 role of stroma, 19

Epitope masking, 21 Estrogen replacement therapy, 340 Eukaryotic cell cycle, 425-426 Excitation contraction coupling, 157-159 Exstrophy, 38-40 Extracellular matrix, 53-54, 57, 117,225; see also

Acellular tissue matrix protein, 193

Fetal hydronephrosis, 125 Fibrillin, 54, 206, 209, 212 Fibroblast growth factor, 52-53, 66

489

Fibroblasts, 57, 6S-70, 77, 84-90, 94-95, 97, 100, 131 Fibronectin, 25, 54 Fibronexus, 95 Fibrosis, 44-45 Flow cytometry, 401-403, 405 Forskolin, 243-244 Free calcium, 138 Free fatty acids, 265-272 Freezing model, 71, 77

Gelsolin, 438 Gene switching, 419 Gene therapy, 41, 46 Genetic variability, 396 Genitourinary reconstruction, 133-134 Gestation, 96-101 Gibbs free energy equation, 156 Glandular budding, 197 Glibenclamide, 299-300 Glutamate receptor antagonists, 275

effects on lower urinary tract function, 275-280 G1ycolipids, 389-390 Glycoproteins, 341, 346-347, 391

matrix-associated, 54

490

Glycosphingolipids, 352-353, 389 Glycosyltransferases, 353 Graft preparation, 130 Grafts, 101, 129

heterotropic, 54 preparation of, 130

Growth factors, 4, 66, 78, 401, 408; see also Nerve growth factor

Hemagglutination, 327, 344-345 Hemidesmosomes, 441-442 Hemolysin, 329---331, 334, 340 Herpes zoster, 388 Heterotypic grafts, 54 High-performance liquid chromatography, 354-355 High-performance thin layer chromatography, 354-355 Histamine, 471 Homeostasis, 21-22, 25-26, 49 Homeostatic range, 66 Host defense, 334 Host factors, 323, 333-334, 356 Host genetic factors, 353 Host tissue, 58 Human cancer, 427 Human epithelial cells, 83; see also Epithelial cells

markers, 85-90 proliferation of, 85-88 replicative senescence, 83-90

cells and culture methods, 85-86 flow cytometric analysis, 86 Northern blot analysis, 86 Western blot analysis, 86

response to serum stimulation, 88 role of cell cycle proteins, 83-90 viability of, 87

Human growth hormone, 14 Human uroepithelial cells, 83; see also Normal human

urothelial cells markers, 85-90 proliferation of, 85-88 replicative senescence, 83-9

cells and culture methods, 85-86 flow cytometric analysis, 86 Northern Blot analysis, 86 Western analysis, 86

response to serum stimulation, 88 role of cell cycle proteins, 83-90 viability of, 87

Hydroxyproline, 207 Hyperactivity, 31 ~319 Hyperelasticity,212 Hyperglycemia, 298 Hyperplasia, 65, 68, 77 Hyperploidy, 65, 68, 77 Hyperreflexia, 304-305 Hypertension, 283, 290, 317

on bladder function, 283-290 studies in rats, 283-290 vs. voiding behavior, 284-285

Index

Hypertrophy, 65-68, 144, 155, 163, 185,226-227, 232,271,316,318,319

Hypoxia, 270-272

Immortal cell lines, 84 Immune system, 333, 374-375, 381, 388 Immunologic markers, 438 Incontinence, 193,270,304 Indomethacin, 172, 177 Inflammatory mediators, 360, 363-366 Inflammatory response, 131 Innervation, 65, 71,285-288 Integrin, 22, 25, 54, 438, 441 Interferon, 324, 374, 399, 401-403, 410

administration of, 375-376, 383 mechanism of action, 374-375 overview of, 374 treatment of superficial bladder cancer, 374-382

Interleukin, 332, 334, 360, 366 Interstitial cystitis, 271 Intracellular calcium, 123-124, 157 Intravesical therapy, 372-373, 376-383 Ion channels, 245-247 Ion homeostasis, 156 Ischemia, 265, 270-271, 332-333 Isoproterenol, 243 Isoreceptors, 328

Junctional complexes, 19---20, 44

Keratin, 69---70, 75, 197 Keratinocyte growth factor, 52-53, 66 KI-67 labeling, 325

Lamina proparia, 65, 69, 219---220, 206 Laminin, 25, 53, 100 Latch, 140, 148 Lewis genes, 353 Lipopolysaccharide, 330, 332,360, 364,366 Losartan, 187, 23 I Lysophosphatidic acid, 471

Magnesium sulfate, 125 Major histocompatibility complex, 374 Malignant progression, 21 Markers, 445

adherence, 439-442 cell lineage, 19 cell surface, 353,442-443 cytoskeletal, 438-439 differentiation, 63, 68, 396 human epithelial cells, 85-90 immunohistochemical, 425-433 immunologic, 438 prognostic, 426-433 proliferation, 438 tumor cell motility, 469-470 urothelial cell, 438-443

Matrigel invasion assays, 403-409 Matrigel surface, 33, 399-400, 403 Matrix-associated glycoproteins, 54 Membrane depolarization, 158, 299---300

Index

Metabolic acidosis, 50 Metalloproteinases, 126,396,413-414,416,482 Metastasis, 399-400, 408, 410, 481-482 Metastatic disease, 395 Methaxamine, 123 Methylation, 396, 461, 477-481 Mitomycin, 371, 375, 380, 382 Mitosis, 425, 438 Monensin, 299 Monolayer culture, 414-415 Mucosa

cytoprotection of, 173 functions of, 265, 272 studies in rabbit bladders, 265--272

Mucus, 341, 346 Myelomeningocele, 122, 183, 193-194 Myelotoxicity,476 Myofibroblasts, 63, 69-71, 94-95,100,133,148 Myosin, 53, 65, 68--69, 100, 138, 140--141, 144,

147-148, 158,232

Na+-K+-ATPase, 156, 159,293-300 Natural killer cells, 374 Necrotizing factor, 329 Neoplasia, 21 Neoplastic disease, 426 Nerve growth factor, 284, 286-290, 318; see also

Growth factors insight into regulation, 286-290

Neuroplasticity, 254 Neurostimulation, 305--307 Neurotropic virus, 254 Nifedipine, 159,249 Nitric oxide, 313, 359, 361, 244-245

synthesis, 359, 243 urinary tract infections, role in, 359-363

Nitrosamines,56 NMDA receptor antagonists, 275 Norepinephrine, 289 Normal human urothelial cells, 413-416

Obstructive uropathy, 215, 271 Organ culture model, 45, 413 Organ replacement, 31-41 Ouabain, 292-296, 299 Outflow obstruction, 66-70

modeling of, 63, 69-73, 77 serosal response, 68-70 smooth muscle response, 66-68

Outlet obstruction, 122, 137, 156, 162-166, 185--187 overview of, 137 role of smooth muscle, 137-149

P21 tumor suppressor gene, 429-430 P53 tumor suppressor gene, 427-428 Paclitaxel,474-476 Papillary tumors, 371,395,419,451 Parasympathetic pathways, 254, 262 Parathyroid hormone-related protein, 249 Pathogenesis, 21, 26

Pathological threshold, 66 Pathways

aldose reductase, 298 brain, 256 cyclic AMP, 242-244 cyclic GMP, 244-245 exteroceptive perineal-bladder reflex, 254 exteroceptive somato-bladder reflex, 253 maturation of reflex, 253-262 neonatal perineal-bladder reflex, 254 parasympathetic, 254, 262 primitive reflex, 253 relaxation, 241-242 signal transduction, \39,470-472 spinal chord, 256

PAX-6 gene, 422-423 Pelvic afferents, 3 II Permeability barrier function, 20, 266, 270 Pertussis toxin, 471-476 Phagokinetic track motility assay, 472 Phenotypic variability, 396

491

Phorbol-12-myristate 13-acetate, 399, 401-403, 410 Phosphodiesterase inhibitors, 244 Phospholipids, 262-272 Phosphorylation, 21, 158, 359, 427 Physiological remodeling, 65 Pili, 340, 342 Pinacidil, 246 Plaques, 8-13, 20, 44 Plasma membrane, 20, 157-159 Plasminogen activators, 400-401, 410 Plasminogen receptors, 481 Potassium chloride, 70, \33,294 Primitive reflex pathway, 253 Prognostic markers, 426-433 Prostaglandin endoperoxide synthase, 172-173 Prostaglandins, 171-179,332,361 Prostate, 55--56 Protein kinase C, 298 Proteolysis, 413, 416 Proteolytic enzymes, 84 Proteus mirabilis, 325, 339 Protoncogenes, 66 Pseudomonas cepacia, 325, 330, 339, 341 Pseudorabies virus, 254-258 Pyelonephritis, 328, 339-340, 387

Reciprocal signaling, 4 Reflex pathways, 253; see also Pathways Reflex voiding, 253-254, 262 Refractoriness, 460 Regeneration, 25--26 Regulatory proteins, 425, 431-433 Relaxation, 140, 157-158,3\3

agents, 312 Renal failure, 121, 175,339 Reperfusion, 266, 271 Replicative senescence, 83 Retinoblastoma tumor suppressor gene, 426-427

492

Retinoid signaling, 449-463 Retinoids, 452-463 Reverse differentiation, 197 Reverse transcriptase polymerase chain reaction,

443-444 study of urothelial cell differentiation, 443-444,

457-463 Ritodrine, 125 Ryanodine, 124, 158--159

Sacral anterior Toot stimulation, 304 Sacral deafferentation, 305 Sacroplasmic endoplasmic reticulum calcium ATPase,

158--166 Sarcoplasmic reticulum, ISS, 157-158,225-226 Schistosoma haematobium, 395 Secretor gene, 353--354 Senescence, 480; see also Replicative senescence Serosa, 68--71 Serosal dislocation, 75 Serosal thickening, 68--72 Serum stimulation, 84, 88, 90 Sesquiterpene thapsigargin, 160 Shrinkage, 44-45 Signal transduction pathway, 139,470-472 Small intestine submucosa, 129-134 Smooth muscle, 53--58, 66--68, 93, 226, 232, 241-242;

see also Detrusor smooth muscle characteristics of, 94 contractile proteins on, 53, 137-149 development of, 93, 100-101 differentiation, 94, 100 effect of gestation on, 96-101 factors in cell differentiation, 71-73 functional aspects in urinary bladder, 137-149

molecular mechanism for contraction, 138--140 regulation ofactin-myosin interaction, 138--140 role in outlet obstruction, 137-138

animal model, 143--144, 148 contractive dysfunction, 148--149

role of contractile proteins, 140-148 signal transduction pathway, 139

functions of, 265, 272 human adult bladder, 94, 97, 99 human fetal bladder, 94-97, 100 obstruction modeling of, 63, 66-73, 77,137-149 ontogeny of, 93--101

rat bladder, 93--101 progression, 96-97, 100 regeneration of, 70-72, 77 regulation of contractility, 293--294 role of angiotensin 11 in, 184-185 ultrastructural changes due to obstruction, 95, 100 urothelium-mesenchymal interactions, 75-77

Spina bifida, 183, 229 Spinal chord, 256, 258

injury, 304-305, 307, 311 Spinalreflex,253-254,262 Spontaneous hypertensive rat, 284-285, 318--319

Squamous cell carcinoma, 395 Squamous metaplasia, 20, 24

Index

Staphylococcus saprophyticus, 325, 327,330, 339 Stress proteins, 66 Stress-strain relationships, 167, 189, 209-213 Stroma, 19,53,55-56,413,416

role in urothelial tissue regulation, 19-26 signalling, 55

Surface energy theory of adhesion, 326 Surrogate endpoints, 437

Tadenan, 315-316 Telomere shortening, 85 Tenascin, 54 Thrombin, 471 Thromboxane, 361 Tis, 395 Tissue damage, 332-334 Tissue engineering, 32-41, 46 T lymphocytes, 332 Topical therapy, 371, 374 Tortuosity,220 Toxicity assessment, 382, 392 Transcription factors, 231 Transcriptional activators, 453 Transforming growth factor, 66,360,399,401-403,

410 Transitional cell carcinoma, 20, 371-372, 395,

425-433 Transneuronal virus tracing, 254-255 Transrectal electrostimulation, 305 Transurethral resection, 372 Tropomyosin, 138, 140, 147-148 Tumor, 50, 56,395-396,400,410,427-429

cell lines, 401, 408 cell motility, 469-470 heterogeneity, 433 invasion, 413-416 marker studies, 470 necrosis factor, 332, 360 papillary, 371, 395, 419, 451 progression, 23, 25-26 recurrence, 377-380 signal transduction pathway, 470-472 suppressor genes, 419, 421-422, 426-430 suppressor mechanism, 84 therapeutic approach to bladder carcinoma, 469-476

Tumorigenesis, 90, 452 Tumorigenicity, 438, 441 Tyrosine kinase, 158

Umbrella cell, 438 Urinary continence, 50 Urinary incontinence, 43 Urinary tract infections, 325, 327-330, 333--334

animal models, 363--366 bacterial colonization as prerequisite to, 325-327,

340-341,352-356 economic consequences of, 339

Index

Urinary tract infections (cont.) fluid-pathogen interactions, 340-347, 352-356 host factors in susceptibility to, 351-357, 388 incidence of, 339 induction of nitric oxide synthase, 359-366 inflammatory responses, 363--366 pathophysiology of bacterial cystitis, 325--334 recurrence of, 351-353, 356, 373

acquired host factors, 356 host genetic factors, 353-356

role of ad he sins in, 352-353 in women, 340-344, 351-356, 388--391

E. coli investigations, 340-347, 352-356 vaginal colonization by bacteria, 340-347

Urokinase, 399 expression studies, 400-410

Uropathogens, 333, 339, 353; see also E. coli Uroplakins, 21, 51, 196, 332, 390, 442

identification of, 9-10 markers ofurothelial differentiation, 7-16

early studies of, 8--9 molecular structure of, 10-12 perspectives on future research, 15--16 role as receptors for uropathogenic bacteria, 12-13

Urothelial cells, 332 bacterial cystitis, 325--334 differentiation in rat bladder, 94 markers, 438--443 role in urinary tract infection in women, 352-356,

366 role of differentiation in bladder cancer,

437-446 Urothelium, 3-4, 9-16, 20, 44-45, 49-56, 65, 75,196,

266,312-313,387,396,438--446 antigen expression, 51 asymmetric unit membrane, role of, 20 barrier function, 20 bladder carcinoma, effect on, 20 cell culturing, 51 cytodifferentiation, 20-21, 23--24 epithelial cell regulation, as model for, 20, 26 functions of, 20, 50, 270-271 histology of, 50 human, 21, 23

Urothelium (cant.) in vitro cell systems, 21-23,26

intact organ cultures, 22 monocultures, 21-23 organoids, 22

markers of cell phenotype, 21, 23 permeability, 20 phenotype, 50-51, 54 proliferation, 24-25, 44-45, 52 regeneration, 25--26 regulatory role, 196 stratification, 22-23, 45 transitional cell carcinoma progression, 22-23 wound healing, 25--26

Urovirulence factors, 340

Vaccines, 333 Vaginal infection: see Urinary tract infections Vascularity, 395--396 Vasculogenesis, 75--76 Vasoactive intestinal polypeptide, 243 Verapamil,226 Vimentin, 53, 65, 68, 94, 100 Vinculin, 53, 100 Virulence factors, 330-333

adherence, 331-332 cellular receptors, 332-333 immunity, 333 surface, 330-331 vaccines, 333

Viscero-motoric spasticity, 305 Vitamin E, 315 Vitronectin, 54 Vogel stein-Kinzler model, 450-451 Voiding reflex, 312

effect of hypertension on, 284-285 Voltage operated calcium, 158--160

Wi star-Kyoto hyperactive rat, 287-288 Wi star-Kyoto hypertensive rat, 287-288 Wound healing, 25--26, 52, 70, 95

Yersinia enterocolitica, 341

Zymograms,414-415

493