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Biomedical subjects

R M Coles

Publications and source records attributed to R M Coles.

9 recordsLinked to original sources

Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1.

The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.

Animals↗

Herpes simplex virus type 1-specific cytotoxic T-lymphocyte arming occurs within lymph nodes draining the site of cutaneous infection.

Various studies have shown that major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL) can be isolated from lymph nodes draining sites of cutaneous infection with herpes simplex virus type 1 (HSV-1). Invariably, detection of this cytolytic activity appeared to require some level of in vitro culture of the isolated lymph node cells, usually for 3 days, in the absence of exogenous viral antigen. This in vitro "resting" period was thought to represent the phase during which committed CD8(+) T cells become "armed" killers after leaving the lymph nodes and prior to their entry into infected tissue as effector CTL. In this study we reexamined the issue of CTL appearance in the HSV-1 immune response and found that cytolytic activity can be isolated directly from draining lymph nodes, although at levels considerably below those found after in vitro culture. By using T-cell receptor elements that represent effective markers for class I-restricted T cells specific for an immunodominant glycoprotein B (gB) determinant from HSV-1, we show that the increase in cytotoxicity apparent after in vitro culture closely mirrors the expansion of gB-specific CTL during the same period. Taken together, our results suggest that HSV-1-specific CTL priming does not appear to require any level of cytolytic machinery arming outside the lymph node compartment despite the absence of any detectable infection within that site.

Animals↗

HM Dockyard, Devonport: 1947 mortality study.

To investigate the effect of occupational exposure to asbestos on mortality, names of all 6292 men born on or after 1 January 1910 and employed as industrial workers in the RN Dockyard, Devonport on 1 January 1947 were submitted to the Office of Population Censuses and Surveys for tracing. Follow-up continued until the end of 1978: over 99% were traced; 3% emigrated; and there were 1043 (17%) deaths. On the basis of the mortality in England and Wales for each five years of age and each five calendar years, the standardized mortality ratio (SMR) was 96. Adjusting the rates for the lower mortality in south-west England, the SMR was 104. No relation was found between SMR and date of birth, and there was only a very slight excess among those more heavily exposed to asbestos. Thirty-one men died with mesothelioma and a further 14 with asbestosis or pulmonary fibrosis. The circulatory disease death rate was slightly raised (SMR = 118), but no more than might have been expected for manual workers. Asbestos-related deaths accounted for at least 4% of all deaths, but probably not many more.

Aged↗

Chronic leukaemia.

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Antineoplastic Agents↗

Mesothelioma risks in a naval dockyard.

There have been 108 deaths from mesothelioma of the pleura or peritoneum in Plymouth and the immediate neighborhood as of mid-1978. Ninety-six deaths have been associated with work at the Devonport Dockyard, 53 of which represented men employed at the dockyard in 1966. Occupational mesothelioma rates were similar to those recorded in London asbestos textile workers. Above average rates in this study were observed in laggers, boilermakers, painters, welders and burners, and shipwrights. In addition to mesothelioma in other men with neighborhood exposure at work, cases have occurred in men whose only exposure has been to the environment within the walls of the dockyard, outside ships and workshops where asbestos has been handled. No case has been seen in indoor office workers. There is no evidence of any increase in risk to the population of Plymouth outside the dockyard.

Adolescent↗