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Biomedical subjects

M R Alderson

Publications and source records attributed to M R Alderson.

At least 73 records · Page 4Linked to original sources
PubMed1987

T-independent activation of single B cells: an orderly analysis of overlapping stages in the activation pathway.

This review has three chief purposes. It describes a microculture system in which single, hapten-specific B lymphocytes can be microscopically observed, cultured and assayed for antibody production in isolation and thus are the unequivocal target of ligands present in the culture fluid. It defines the respective roles of antigens and cytokines acting singly or in combination in the four discernible phases of the immunoproliferative cascade, namely activation, clonal expansion, IgM antibody secretion and isotype switching. It then argues that this precise stepwise analysis can yield useful information concerning important immunological situations, such as experimentally induced immunological tolerance or the effects of constitutive expression of the c-myc oncogene. Evidence is presented that initial activation of the resting B cell in "T-independent" triggering can be achieved either by attachment of a molecule that has B-cell stimulatory properties, such as FLU-LPS or FLU-polymerized flagellin (FLU-POL) or by the lymphokine interleukin 4 (IL-4). IL-4 + FLU-POL is somewhat more effective than either agent alone. IL-4 alone or, better, FLU-POL + IL-4 can stimulate clonal proliferation of the B cell, but FLU-POL alone does not achieve this. Moreover, IL-4 or FLU-POL + IL-4 lead to very little antibody formation. None of IL-1, IL-2 or IL-5 acting alone causes either activation or proliferation. IgM antibody formation is stimulated most strongly by FLU-POL + IL-5, somewhat less strongly by FLU-POL + IL-1 + IL-2 and rather weakly with antigen plus only one of the latter cytokines. The cloning efficiency in the single cell system, and the median clone size can be markedly enhanced by the addition of small numbers of fibroblast or other filler cells to the cultures. While filler cell-free clones do not progress to the stage of isotype switching, filler cell-supported ones can do so in up to 30% of cases. The only cloned lymphokine which has so far been found to promote such switching is IL-4, and the fact that it is at least as powerful as a T-cell supernatant may mean that it is the only agent active in this particular system. However, the detailed pattern of secreted isotypes is different from that seen when MHC-restricted, carrier-specific T cells act on hapten-specific B cells. Hapten-specific B cells from animals rendered neonatally tolerant to FLU-HGG exhibit anergy in the single cell system.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibody-Producing Cells↗
PubMed1986

The effect of ultraviolet radiation on humoral immune responses to T-dependent antigens.

Multiple exposures to broadband ultraviolet (uv) radiation resulted in alterations in the ability of BALB/c mice to produce antibodies to the T-dependent antigens ovalbumin and sheep erythrocytes following intraperitoneal, intradermal, and intravenous inoculation. A number of differences were observed in the influence of uv radiation on the specific cells producing antibody, as opposed to pure serological analyses. While both enhancement and reduction of the humoral response occurred, the experiments have suggested that the alterations in antibody responses following uv irradiation appear to be dependent on the nature of the antigen, the route of antigen administration, and the sometimes transient nature of the responses. The intradermal route of antigen inoculation was under the greatest influence of uv radiation.

Animals↗
PubMed1986

Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases.

In the latter part of a large hospital case-control study of the relationship of type of cigarette smoked to risk of various smoking-associated diseases, patients answered questions on the smoking habits of their first spouse and on the extent of passive smoke exposure at home, at work, during travel and during leisure. In an extension of this study an attempt was made to obtain smoking habit data directly from the spouses of all lifelong non-smoking lung cancer cases and of two lifelong non-smoking matched controls for each case. The attempt was made regardless of whether the patients had answered passive smoking questions in hospital or not. Amongst lifelong non-smokers, passive smoking was not associated with any significant increase in risk of lung cancer, chronic bronchitis, ischaemic heart disease or stroke in any analysis. Limitations of past studies on passive smoking are discussed and the need for further research underlined. From all the available evidence, it appears that any effect of passive smoke on risk of any of the major diseases that have been associated with active smoking is at most small, and may not exist at all.

Adult↗
PubMed1986

The occupational risks of alcoholism.

The occupations of 6,596 psychiatric admissions with alcoholism were analyzed and their admission rates compared with occupational death rates due to cirrhosis of the liver. Two thirds of occupations with high admission rates had correspondingly high cirrhosis death rates but a dozen occupations had low admission rates and high liver cirrhosis death rates, suggesting a degree of heavy drinking which is not treated. Low-risk occupations are identified and their characteristics discussed.

Adolescent↗
PubMed1985

Risks of lung cancer, chronic bronchitis, ischaemic heart disease, and stroke in relation to type of cigarette smoked.

In a case control study of over 12 000 inpatients aged 35-74, risk of lung cancer, chronic bronchitis, and, particularly in those aged 35-54, ischaemic heart disease was positively associated with the number of manufactured cigarettes smoked daily and was negatively associated with long term giving up. Risk of stroke was not clearly related to smoking. Among manufactured cigarette smokers, lung cancer risk tended to be lowest in those who had always smoked filter cigarettes. This pattern was, however, evident only in men who additionally smoked pipes, cigars or handrolled cigarettes and in women, not being seen in men who smoked only manufactured cigarettes. Risk of lung cancer was not clearly related to time of switch to filter cigarettes. A markedly lower risk of chronic bronchitis was seen in men, but not women, who smoked filter rather than plain cigarettes. Heart disease risk did not vary by type of cigarette smoked 10 years before admission, but, compared with those who had never smoked filter cigarettes, those who had ever smoked filter cigarettes had a higher risk in men and a lower risk in younger women. Compared with the general population, markedly more controls were ex-smokers, suggesting incipient disease, whether or not smoking related, may alter smoking habits, thus affecting the interpretability of the findings. Control smokers were also relatively much more likely to report smoking plain cigarettes than expected. This comparison, not made in other studies relating risk to type of cigarette smoked, indicates that great care must be taken in verifying validity of reported smoking habits. While our findings are compatible with other evidence that risk of lung cancer and chronic bronchitis is probably reduced by switching from plain to filter cigarettes, they underline the difficulties in obtaining valid evidence from epidemiological studies.

Adult↗
PubMed1984

Death certification in cancer of the breast.

The cause of death entered on the death certificates of 193 patients originally diagnosed as having cancer of the breast was compared with information obtained from clinical records, cancer registry records, and necropsy findings to determine the accuracy of death certification and the proportion of patients who, though dying from another cause, still had overt signs of cancer of the breast. It was found that the overall error in certifying cause of death as breast cancer was small, being an underestimate of about 4%. About a third of patients with breast cancer dying from other causes had overt signs of breast cancer at the time of death.

Aged↗
PubMed1984

Pilot study of revised stillbirth and neonatal death certificates.

Draft revised stillbirth and early infant death certificates were sent with a short questionnaire to certifying doctors for 206 stillbirths and 198 neonatal deaths for which death certificates had been received in the Office of Population Censuses and Surveys over a three week period in 1982. The new certificates complied with the recommendations of the World Health Organisation and asked for details of the cause of death, including separate sections for maternal and fetal conditions. Replies were received for 163 stillbirths and 151 neonatal deaths. Questionnaires were examined clerically and answers and comments analysed. Draft certificates were processed by computer to examine any differences between the causes of death given on the new forms and information given on the original certificates. This testing suggested that revised certificates are acceptable. Extension of the early infant death certificate to cover all neonatal deaths does not seem to create problems and should provide information on the association between maternal conditions and deaths occurring in the second to fourth weeks of life. If the full potential of the new certificates is to be realised, attention needs to be given to the detailed layout of the forms and clearer notes of guidance. Certifiers need to be encouraged to give appropriate details of any obstetric problems.

Attitude of Health Personnel↗
PubMed1983

Epidemiological survey of oil distribution centres in Britain.

A mortality study of workers employed for at least one year between 1 January 1950 and 31 December 1975 at oil distribution centres from three oil companies in Britain has been carried out. Ninety nine per cent of the population were successfully traced to determine their vital status at 31 December 1975. The mortality observed in the study population was compared with that which would be expected from the mortality rates for all the male population of England and Wales. The overall mortality observed was considerably lower than expected on this basis as was the mortality from stroke, hypertensive disease, bronchitis, and pneumonia. The observed number of deaths from all neoplasms was also much less than expected as were the observed deaths from lung cancer. The observed deaths from ischaemic heart disease approximately equalled those expected overall and in each of the companies, however, and there was no evidence of a "healthy worker effect" for this disease group. The ratio of observed over expected deaths from ischaemic heart disease tended to decrease with increasing age at death, and for most of the job groups overall, the observed and expected deaths were about the same. Raised mortality patterns from ischaemic heart disease were found in several subgroups of the population of one company. Mortality from myelofibrosis and diseases of the lymphatic and haematopoietic tissue was slightly raised overall. Only myelofibrosis showed an overall excess but raised mortality was found in subgroups of the population defined by company, job, and length of service in several of the other neoplasms making up this disease group. The numbers of deaths from these causes were all small, making it difficult to exclude chance effects. Further work would be required to ascertain whether these results are due to an occupational factor and if so to identify the physical or chemical nature of the risk.

Accidents, Traffic↗
PubMed1983

Epidemiological survey of maintenance workers in London Transport Executive bus garages and Chiswick Works.

A mortality study of maintenance men employed for at least one year between 1 January 1967 and 31 December 1975 at 71 London Transport bus garages and Chiswick Works has been carried out. Over 97% of the population were successfully traced to determine their vital status at 31 December 1975. The mortality observed in the study population was compared with that which would be expected from the mortality rates for the all male population of England and Wales. The mortality of the study population from all causes was much lower than expected on this basis, as was the mortality from cerebrovascular disease, ischaemic heart disease, and bronchitis. Mortality from all neoplasms was slightly less than expected overall and especially in the younger age groups. The observed deaths from cancer of the lung were approximately the same as those expected on the basis of national rates. Nevertheless, a deficit of observed deaths from lung cancer was obtained after adjusting for the higher mortality from this disease in Greater London. Raised mortality was found in subgroups of the population for several malignant disease groups but these were almost all based on small numbers of deaths, making it difficult to exclude chance effects. Both the number of men and deaths in the study were limited and the follow up time was also short. Considerable extension of the study to include more men and increase the follow up time would be required for any definite mortality patterns to emerge.

Bronchitis↗
PubMed1981

A case-control study to investigate the association between exposure to benzene and deaths from leukaemia in oil refinery workers.

All deaths with a mention of leukaemia on the death certificate, in men employed over a period of 25 years of 8 oil refineries in the U.K. were identified. The potential benzene exposure of these cases was compared with that of two sets of controls selected from the total refinery population. One set of controls was matched for refinery and year of birth, the other set was matched for refinery, year of birth nd length of service. No information was available on measurement of benzene in the work environment but a job history was obtained from refinery personnel records for all cases and controls. This was used to allocate each man to a benzene exposure level of "low", "medium", or "high". There was no overall excess of deaths from leukaemia when compared with the expectation from national rates. There was also no excess of cytological types of leukaemia which have been shown to be particularly associated with benzene exposure. However, the risk for those men with medium or high exposure relative to the risk for those with low benzene exposure approached a significance (P=0.05) when length of service was taken into account. If there were an increased risk of leukaemia due to benzene exposure, it could have only been one that affected a very small proportion of men within the refinery workforce.

Benzene↗
PubMed1981

Health of workmen in the chromate-producing industry in Britain.

In a follow-up study of 2715 men who had worked for at least one year at the three chromate-producing factories in Britain between 1948 and 1977 only 298 were lost to follow-up, and the average number of person-years in the study was 16.3. One hundred and sixteen deaths from lung cancer occurred in these men, with only 48.0 expected (O/E = 2.4; p less than 0.001). For men employed at the factory, which is still in operation, the relative risk of lung cancer has decreased from over 3.0 before plant modification to about 1.8 in those who have worked only since plant modification. A multivariate analysis was used in an attempt to unravel the overlapping influence of duration of employment, length of follow-up, plant modification, factory, age at entry to work, and estimated degree of chromate exposure. The major dependent factor appeared to be duration of employment; in addition the analysis suggested that modifications in the plant and work environment had been associated with an appreciable reduction of the excess risk from lung cancer.

Adult↗
PubMed1981

An epidemiological survey of eight oil refineries in Britain.

A mortality study of workers employed for at least one year between 1 January 1950 and 31 December 1975 at eight oil refineries in Britain has been carried out. Over 99% of the population were successfully traced to determine their vital status at 31 December 1975. The mortality observed in the study population was compared with that which would be expected from the mortality rates for the all male population of England and Wales, and Scotland, with adjustment for regional variation in mortality for the English and Welsh refineries. The overall mortality observed was considerably lower than that expected on this basis, as was the mortality from heart disease, stroke, bronchitis, and pneumonia. The observed number of deaths from all neoplasms was also very much less than expected, a result almost entirely due to a large deficit of observed deaths from lung cancer. Raised mortality patterns were found in several refineries for cancers of the oesophagus, stomach, intestines, and rectum, although no location was consistently high for all these causes of death. Different year-of-entry cohorts and job groups were also affected. In general, mortality from these causes increased as length of service and interval from starting work increased. There were also significantly more observed deaths than expected from cancer of the nasal cavities and sinus, and melanoma. Further work is required to ascertain whether these are due to an occupational factor and, if so, to identify the physical or chemical nature of the risk.

Aged↗