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Biomedical subjects

E Robey

Publications and source records attributed to E Robey.

26 records · Page 2Linked to original sources

Selective events in T cell development.

Somatic rearrangement of the genes encoding antigen receptors allows the mammalian immune system to produce receptors that can recognize virtually any foreign protein. This rearrangement process also generates nonfunctional antigen receptors as well as receptors that can recognize self-proteins. During thymic development, T cells go through a testing process which ensures that cells expressing useless or harmful antigen receptors do not mature. The selection of T cells in the thymus consists of several components driven by distinct recognition events that have distinct consequences for the cell. T cell selection appears to begin before the rearrangement process is complete. Evidence is emerging that T cells have a developmental checkpoint to make sure that the antigen receptor beta gene is successfully rearranged before development can proceed. This checkpoint also appears to be linked to the regulation of rearrangement and mechanisms to ensure that each cell expresses only one antigen receptor (allelic exclusion). After a T cell has successfully rearranged and expressed both its alpha and beta antigen receptor genes, a second phase of selection occurs. During this phase, T cells with self-reactive antigen receptors are eliminated by negative selection, and T cells that can recognize foreign peptides bound to polymorphic self-MHC molecules are selected to mature (positive selection. How these seemingly incompatible forms of selection both occur is a subject of considerable interest. Positive selection is linked also to the choice between the CD4 helper lineage and the CD8 cytotoxic T cell lineage; the mechanisms by which these two events are linked is an ongoing area of investigation.

Animals↗

Expression of CD4 in transgenic mice alters the specificity of CD8 cells for allogeneic major histocompatibility complex.

We have generated a transgenic mouse line in which a CD4 transgene is expressed on a significant fraction of the mature CD8+ lymphocytes but is not expressed in the thymus. This provides an opportunity to examine the functional consequences of CD4 expression in a population of class I-selected CD8+ lymphocytes. CD8+ lymphocytes expressing the CD4 transgene proliferate in response to allogeneic class I and class II major histocompatibility complex, whereas CD8+ cells from control animals proliferate only to allogeneic class I gene products. These observations suggest that the ability of a T-cell population to react with class II allogeneic major histocompatibility complex is determined by the presence of CD4.

Animals↗

Tolerance and immune regulation.

Understanding of both the phenomenon of immunological tolerance and the mechanisms by which it is achieved is rapidly advancing, as was evident from a recent meeting. This report summarizes key developments in both T- and B-cell biology.

Animals↗

Infection of brain cells by diverse human immunodeficiency virus isolates: role of CD4 as receptor.

Cell lines originally derived from malignant tumours of the brain were infected by diverse human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) isolates. By surface immunofluorescence it was shown that susceptible cells did not bear the CD4 antigen. They were also non-permissive for the formation of plaques by vesicular stomatitis virus pseudotypes and did not form syncytia with HIV-producing cells. Virus production was of low titre, and reverse transcriptase and the p24 antigen were consistently undetectable in the culture supernatants. Output virus could be detected by cocultivation with a sensitive T cell line, C8166, by the culture of supernatant medium with T cells and by detection of proviral HIV DNA after amplification. A higher multiplicity of input virus was required to establish a brain cell infection than was required for T lymphocytes or monocytes. Some HIV-susceptible brain cells contained mRNA for CD4 but infection was not blocked by anti-CD4 antibodies. Apparently HIV infection of these cells does not involve CD4 as the cellular receptor.

Antibodies, Viral↗

Fractional diffusion-limited component of reactions catalyzed by acetylcholinesterase.

The values of kcat/Km for the reactions of four substrates, p-nitrophenyl acetate (PNPA), propionyl-beta-methylthiocholine (PrMSCh), 3,3-dimethylbutyl thioacetate (DBTA), and acetylthiocholine (AcSCh), with acetylcholinesterase were determined as a function of increasing viscosity (eta rel) in sucrose-containing and in glycerol-containing buffers. Glycerol, or possibly some contaminant of it, was found to be a nonspecific inhibitor and sucrose a nonspecific activator of the enzyme as reflected in the dependence of kcat/Km values measured for PNPA and PrMSCh upon the concentration of these reagents. The rates of reactions of these two substrates, the first neutral and the second cationic, are chemically limited rather than diffusion limited, and they thus serve as quantitative controls or internal standards to monitor the effects of the viscosogens on the enzyme, which are not related to diffusion. The additional effect on kcat/Km over the controls observed for the rapidly reacting substrates AcSCh (cationic) and DBTA (neutral) serves as a measure of the extent to which these values of kcat/Km measure diffusion-controlled processes. The reaction rate of DBTA with the enzyme is 24% diffusion controlled as measured in glycerol-containing buffers and 16-20% as determined in sucrose-containing buffers, while that for AcSCh is 100% (in glycerol) and 24-40% (in sucrose) diffusion controlled.

Acetylcholinesterase↗

Blunt transection of the pancrease treated by distal pancreatectomy, splenic salvage and hyperalimentation. Four cases and review of the literature.

The increasing awareness among surgeons of overwhelming postsplenectomy sepsis has led to new and innovative procedures to save the spleen. In pancreatic transection injuries (Type II)26 the classical treatment has been distal pancreatectomy and splenectomy. The opportunity to treat several patients with pancreatic transections sustained during blunt abdominal trauma lead to the review of the literature on the subject. Particular attention was paid to treatment of these injuries during distal pancreatectomy with splenic salvage, appropriate drainage, and hyperalimentation. Associated complications were likewise investigated and reviewed.

Adolescent↗

A survey of the haematological, nutritional and biochemical state of the rural elderly with particular reference to vitamin C.

A survey of the rural elderly has been carried out to determine basic haematological and biochemical data, and to establish a pattern of living for this 'well' population. The blood parameters related to diet, such as haemoglobin, folate, cholesterol, vitamin C etc., show considerable changes with increasing age in the male but little significant change in the female. The vitamin C status for both sexes compares favourably with that reported by other workers studying the urban elderly. The biochemical and haematological data derived provide a normal range with which the 'sick' elderly can be compared. The subjects were generally active and independent in spite of (or because of) a somewhat Spartan existence.

Adolescent↗