antibodies in cells

2
1269 enabled to compete on an equal basis in the employment market. At the same time social workers and social agencies will be required to give them support and reassurance during this very difficult transitional stage. Here the settlements, community centres, youth clubs, churches, and schools have a vital role to play in encouraging these submerged people to achieve social competence and to assimilate the norms of the wider community. Sociologists have revealed the existence of these subcultural pockets. Social justice and social hygiene alike demand that a strenuous endeavour should be made to eliminate them once and for all. 1. Noise Control in Hospitals. King Edward’s Hospital Fund for London, 34, King Street, E.C.2. Annotations NOISE IN HOSPITALS " DEPRIVED of rest, all prematurely die ", wrote Ovid. It is by no means easy to ensure that hospital patients have the rest they need; necessary nursing and medical attention is itself a disturbance, and lights which must be left burning during the night make sleep difficult for some patients. But the main cause of disturbed rest is usually noise; that much of this is unnecessary has been shown by an inquiry by King Edward’s Hospital Fund For London.l A questionary was sent to more than two thousand patients in fifteen hospitals; they were asked to comment on the noises which disturbed them most. Most patients are not worried by a background roar of traffic, at least by day, but this and all other noises become more disturbing at night. Most of the disturbing noises arise either within, or just outside the ward, and are due to faulty (and therefore noisy) equipment, or to thought- lessness on the part of the staff. These internal disturb- ances can usually be prevented at little cost, whereas those arising further away (milk crates, a dance hall next door to the hospital) cannot usually be prevented without heavy expenditure. Many patients returned the ques- tionary without comment, and the report concludes that " nearly 50% were not bothered by noises ". This is a surprising conclusion-surprising, at any rate, to those of us who have been patients ourselves-and it may be ,-suspected that some of the patients were unable to express their views. Trolleys, telephones, and lifts are often the noisiest equipment. Trolleys can be greased and lift doors adjusted, but the only solution to the telephone problem is to change the call system. Perhaps the suggestion which patients will welcome most is that polyethylene bowls should replace those of aluminium. To be woken up in what, for most people, is the middle of the night is un- pleasant enough; to be woken to the nerve-tearing sound of aluminium bowls clanging against a stainless-steel sink is very much worse. But the best results will probably be achieved by encouraging staff not only to be quiet them- selves, but to report noisy equipment. Nurses are not the only offenders; many doctors, called to the ward in the middle of the night, would do well to recall what Hilton said a hundred years ago. In many cases patients them- selves are the cause of the disturbance. This is a more intractable problem, and probably the side-ward is the only solution at present. Perhaps the hospitals of the future will include a sound-proof ward for senile patients who become manic at about 3 A.M. The extent to which illness is prolonged by lack of rest cannot be assessed. Many sound-proofing schemes are considered impracticable owing to their expense; but, now that the care of each inpatient costs over E20 a week, nothing that will hasten recovery can be lightly set aside because of its price. 1. Lancet, 1958, i, 1321. 2. Nature, Lond., 1958, 181, 1419. 3. Coons, A. H. Int. Rev. Cytol. 1956, 5, 1. 4. Chadwick, C. S., McEntegart, M. G., Nairn, R. C. Lancet, 1958, i, 412. 5. White, R. G. Nature, Lond., 1958, 182, 1383. ANTIBODIES IN CELLS MUCH work has been done to determine the site of anti- body formation and to identify the cells in the body responsible for the synthesis of antibodies.1 Ingenious techniques have been devised to determine whether a single cell can produce a variety of antibodies simul- taneously or whether there must be a separate cell or clone of cells to synthesise each kind of antibody. Nossal and Lederberg 2 (the winner of a Nobel prize this year) used a micromanipulation technique to study isolated single cells from the lymph-nodes of rats immunised with two distinct strains of salmonella. Some of the isolated cells formed agglutinating antibodies to one of the strains and some to the other, but no single cell produced detectable amounts of antibody to both strains. It can be concluded therefore that when an animal is stimulated with two con- ’ trasting antigens, individual cells tend to form only one kind of antibody. Antibodies labelled with fluorescent dyes 3 4 have now been used to investigate the problem. 5 Frozen sections of tissues suspected of containing anti- bodies to an antigen are first treated with the antigen and then with specific antibody coupled to a fluorescent dye. Cells containing the antibody will bind the antigen and then the labelled antibody so that they will show fluores- cence when exposed to ultraviolet light. Two different modifications of the technique are used to detect the presence of two different antibodies. In the first modifica- tion the tissue section is first exposed to one of the anti- gens and the corresponding labelled antibody, and the distribution of fluorescent cells is noted. This fluorescence is quenched by exposure to long-wave ultraviolet irradia- tion. Then the section is treated with the second antigen, and fluorescent antibody and the distribution of fluores- cence are again noted. The second method depends on labelling the two antibodies with dyes which fluoresce different colours, so that the presence of two antibodies can be detected simultaneously in the tissue section after treating it first with the mixed antigens and then with the mixture of antibodies each labelled with a different dye. These methods have been applied to sections of spleen and popliteal lymph-nodes from rabbits immunised with mixtures of two different antigens, either pneumococci and hen-egg albumin or diphtheria toxoid and hen-egg albumin. In each case the immunisation caused prolifera- tion of plasma cells and their precursors in the pulp of the spleen and the medulla of the lymph-nodes. Both methods revealed that the two antibodies were located within distinct systems of plasma-cell elements. In no case was evidence obtained of two different antibodies within the same cell-which confirms the view that individual cells tend to form only one kind of antibody. If the two groups of cells forming different antibodies were derived by repeated division from widely dispersed precursors, there tended to be a characteristic grouping of

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1269

enabled to compete on an equal basis in the employmentmarket. At the same time social workers and social

agencies will be required to give them support andreassurance during this very difficult transitional stage.Here the settlements, community centres, youth clubs,churches, and schools have a vital role to play in

encouraging these submerged people to achieve socialcompetence and to assimilate the norms of the wider

community. Sociologists have revealed the existenceof these subcultural pockets. Social justice and socialhygiene alike demand that a strenuous endeavour shouldbe made to eliminate them once and for all.

1. Noise Control in Hospitals. King Edward’s Hospital Fund for London,34, King Street, E.C.2.

Annotations

NOISE IN HOSPITALS" DEPRIVED of rest, all prematurely die ", wrote Ovid.

It is by no means easy to ensure that hospital patientshave the rest they need; necessary nursing and medicalattention is itself a disturbance, and lights which mustbe left burning during the night make sleep difficult forsome patients.But the main cause of disturbed rest is usually noise;

that much of this is unnecessary has been shown by aninquiry by King Edward’s Hospital Fund For London.lA questionary was sent to more than two thousand

patients in fifteen hospitals; they were asked to commenton the noises which disturbed them most.Most patients are not worried by a background roar of

traffic, at least by day, but this and all other noises becomemore disturbing at night. Most of the disturbing noisesarise either within, or just outside the ward, and are dueto faulty (and therefore noisy) equipment, or to thought-lessness on the part of the staff. These internal disturb-ances can usually be prevented at little cost, whereas thosearising further away (milk crates, a dance hall next doorto the hospital) cannot usually be prevented withoutheavy expenditure. Many patients returned the ques-tionary without comment, and the report concludes that" nearly 50% were not bothered by noises ". This is a

surprising conclusion-surprising, at any rate, to those ofus who have been patients ourselves-and it may be

,-suspected that some of the patients were unable to expresstheir views.

Trolleys, telephones, and lifts are often the noisiest

equipment. Trolleys can be greased and lift doors

adjusted, but the only solution to the telephone problemis to change the call system. Perhaps the suggestion whichpatients will welcome most is that polyethylene bowlsshould replace those of aluminium. To be woken up inwhat, for most people, is the middle of the night is un-pleasant enough; to be woken to the nerve-tearing soundof aluminium bowls clanging against a stainless-steel sinkis very much worse. But the best results will probably beachieved by encouraging staff not only to be quiet them-selves, but to report noisy equipment. Nurses are not theonly offenders; many doctors, called to the ward in themiddle of the night, would do well to recall what Hiltonsaid a hundred years ago. In many cases patients them-selves are the cause of the disturbance. This is a moreintractable problem, and probably the side-ward is the

only solution at present. Perhaps the hospitals of the

future will include a sound-proof ward for senile patientswho become manic at about 3 A.M.The extent to which illness is prolonged by lack of rest

cannot be assessed. Many sound-proofing schemes areconsidered impracticable owing to their expense; but,now that the care of each inpatient costs over E20 a

week, nothing that will hasten recovery can be lightlyset aside because of its price.

1. Lancet, 1958, i, 1321.2. Nature, Lond., 1958, 181, 1419.3. Coons, A. H. Int. Rev. Cytol. 1956, 5, 1.4. Chadwick, C. S., McEntegart, M. G., Nairn, R. C. Lancet, 1958, i, 412.5. White, R. G. Nature, Lond., 1958, 182, 1383.

ANTIBODIES IN CELLS

MUCH work has been done to determine the site of anti-body formation and to identify the cells in the bodyresponsible for the synthesis of antibodies.1 Ingenioustechniques have been devised to determine whether asingle cell can produce a variety of antibodies simul-taneously or whether there must be a separate cell or cloneof cells to synthesise each kind of antibody. Nossal and

Lederberg 2 (the winner of a Nobel prize this year) useda micromanipulation technique to study isolated singlecells from the lymph-nodes of rats immunised with twodistinct strains of salmonella. Some of the isolated cellsformed agglutinating antibodies to one of the strains andsome to the other, but no single cell produced detectableamounts of antibody to both strains. It can be concludedtherefore that when an animal is stimulated with two con- ’

trasting antigens, individual cells tend to form only onekind of antibody. Antibodies labelled with fluorescentdyes 3 4 have now been used to investigate the problem. 5

Frozen sections of tissues suspected of containing anti-bodies to an antigen are first treated with the antigen andthen with specific antibody coupled to a fluorescent dye.Cells containing the antibody will bind the antigen andthen the labelled antibody so that they will show fluores-cence when exposed to ultraviolet light. Two differentmodifications of the technique are used to detect the

presence of two different antibodies. In the first modifica-tion the tissue section is first exposed to one of the anti-gens and the corresponding labelled antibody, and thedistribution of fluorescent cells is noted. This fluorescenceis quenched by exposure to long-wave ultraviolet irradia-tion. Then the section is treated with the second antigen,and fluorescent antibody and the distribution of fluores-cence are again noted. The second method depends onlabelling the two antibodies with dyes which fluorescedifferent colours, so that the presence of two antibodiescan be detected simultaneously in the tissue section aftertreating it first with the mixed antigens and then with themixture of antibodies each labelled with a different dye.

These methods have been applied to sections of spleenand popliteal lymph-nodes from rabbits immunised withmixtures of two different antigens, either pneumococciand hen-egg albumin or diphtheria toxoid and hen-eggalbumin. In each case the immunisation caused prolifera-tion of plasma cells and their precursors in the pulp of thespleen and the medulla of the lymph-nodes. Both methodsrevealed that the two antibodies were located withindistinct systems of plasma-cell elements. In no case wasevidence obtained of two different antibodies within thesame cell-which confirms the view that individual cellstend to form only one kind of antibody.

If the two groups of cells forming different antibodieswere derived by repeated division from widely dispersedprecursors, there tended to be a characteristic grouping of

1270

the two kinds of cells. But although some tendency wasdiscerned for some cells to occur in small clumps con-taining the same antibody, there were no marshalled clonesof identical cells. This does not necessarily mean thatthere is no clonal individuation in antibody formation,since there is evidence of motility of cells in both spleenand lymph-nodes. In the case of germinal centres oflymph nodules there was some indication that the cellsnearly all contained the same antibody.

1. Studies on Medical and Population Subjects. No. 14. MorbidityStatistics from General Practice. Vol. I (General). Pp. 174. H.M.Stationery Office. 15s. 6d.

THE MOSAIC MAKERS

GENERAL practitioners and medical statisticians are

good companions indeed, for each has the means to

supply the other’s need. A practitioner’s work consists ofinnumerable items of service or consultations which

singly may mean little but in sum total represent analmost unexplored field for research. The statisticians,like the makers of the mosaics in Roman temples, arefamiliar with the management and handling of small bitsand pieces, tiny fragments of information, and theirmethods can be applied to the doctor’s material withoutdifficulty.Although attempts have been made in the past to fit the

fragments of information gained in individual practices,and in small groups, into a useful picture, there havehitherto been no studies whose results can be related to awhole community. Such a study-appropriately a jointundertaking by the College of General Practitioners andthe General Register Office-has now been made.lThe object of the survey was simple-to measure in

total, and for each disease, the amount of sickness encoun-tered in general practice in England and Wales in one year.The attainment of this object was more difficult since itrequired the recording of every item of service by 170general practitioners in over a hundred separate practicesduring the twelve months of the survey. To ensure thatthe results represented conditions in the populationgenerally, the sample examined had to be large; and totake account of the changes of the seasons the study hadto be lengthy. In all, 382,829 patients were covered bythe study, and records were made at 1,436,155 consulta-tions with the family doctors. The mosaic had manypieces.The diagnosis at each consultation was recorded, and

from these diagnoses tables were prepared (in terms of theInternational Classification of Diseases) which show thenumbers of patients attending their doctor for a givendisease, as well as the number of consultations. The

patient-consulting rate expresses the actual number ofpersons with a disease, and is the truest guide to theincidence of sickness in the community.The main content of this volume, the first of a series

of three, lies in the tables, which have been produced bymechanical analysis after coding and checking-itself atremendous undertaking-of the cards completed by thedoctors. These tables contain the most accurate anddetailed information on the distribution of illness yetcompiled for any community, and will be studied byadministrators and others as a basis for planning. The

fragments of this mosaic will be rearranged many timesbefore all the possible pictures can be recognised andconclusions drawn from them; and the second and thirdvolumes in the series will deal respectively with thedistribution of sickness by occupation and with the more

clinical implications of general practioners’ morbiditystatistics:

So the picture builds up, with doctor, people, diseases,items of service, geographical regions, and age-groups asthe pieces. The tables show that during the year therewas an average of 3-8 consultations per patient on thedoctors’ lists, and confirm the general impression that thecommon cold is the most widespread national affliction,with a patient-consulting rate of 81.1 per 1000. Bronchitis

required most medical attention, with a consultation-rateof 261-1 per 1000. The rate of patients consulting forrespiratory tuberculosis was 2-9 per 1000. The patient-consulting rate for psychoneurotic disorders was 45’7 per1000-again confirming the impression of more frequentrecognition of mental illness-and it is suggested that anational total of 2 million patients come under theirdoctors’ care for conditions within this group at some time

during the year. The number of patients consulting forcancer was 5-2 per 1000-a rate suggesting that about230,000 cases come under general-practitioner care duringa year; while arthritis and rheumatism were both wide-spread and disabling, having the second highest con-sultation-rates and patient-consulting rates.A full account is given of the way in which this large

survey was planned, showing the steps taken to ensureaccuracy in recording and true relation of the morbidityseen by each doctor to the people for whom he wasmedically responsible. The background was the NationalHealth Service " list ", which itself changed in everypractice, by births, deaths, and movements of the popula-tion during the survey year. The procedures for estab-lishing the dimensions and age-sex structure of a practicepopulation are described and will be valuable to all whoplan future studies. It is noteworthy that one partner inthis enterprise, the College of General Practitioners, is

planning a modified survey to be carried out on a con-tinued basis.2 This is as great an evolutionary step as

that from the still photograph to the " movie ".

The modern mosaic makers have much to do, andmuch to learn as they do it. Sampling techniques must bedeveloped and improved so that information of equalaccuracy may be obtained for less effort and disturbanceof general-practice routine. Methods of recording mustbe adapted to the special circumstances of general prac-tice, and means must be found of presenting the informa-tion so obtained in its most convenient and useful form.The Survey now published is at once the foundation forfuture work and a challenge to future activity.

2. See Lancet, Nov. 29, 1958, p. 1164.3. Siller, W. G. J. Path. Bact. 1958, 76, 431.

SEPTAL DEFECT IN FOWLS

THE Agricultural Research Council’s Poultry ResearchCentre at Edinburgh maintains inbred lines of poultry,among which a number of unexpected lesions have

emerged. One with a good deal of intrinsic interest, andsome prospects of significance for human medicine, is theventricular septal defect described by Siller.3 288 caseshave been seen in the six Brown Leghorn strains affected,and in one strain 84% of birds were affected. A few ofthese were closed defects, and most were small, but abouta third were substantial defects similar in degree to theaverage human case of maladie de Roger. Allowing for thedifferences in anatomy between the avian and themammalian heart (not very great in the area concerned),the lesions, which are admirably illustrated, seem in allbut one rescect closelv similar to the familiar human