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Biomedical subjects

N R Sinclair

Publications and source records attributed to N R Sinclair.

At least 55 records · Page 3Linked to original sources
PubMed1986

Immune response after gastric bypass and weight loss.

The immune response of 22 morbidly obese patients was measured before and 6 months after gastric bypass. In-vivo skin testing was carried out using five recall antigens. In-vitro response assessed the ability of isolated lymphocytes to take up radioactive thymidine after culture with the same antigens. The mean (+/- SD) preoperative weight of the patients of 122 +/- 14 kg declined by 33.5 +/- 8 kg after 6 months. The number of positive skin tests increased from a mean (+/- SEM) of 1.8 +/- 0.17 to 2.1 +/- 0.17 (p = 0.2). Mean (+/- SEM) induration of the skin-test response assessed at 24 hours after antigen injection increased from 4.7 +/- 0.6 mm to 5.5 +/- 0.6 mm (p = 0.35) and at 48 hours from 5.4 +/- 0.7 mm to 6.9 +/- 0.9 mm (p = 0.05). One patient who was anergic before gastroplasty responded normally 6 months later after substantial weight loss. In-vitro response, expressed as a stimulation index (+/- SEM), increased from 4.71 +/- 0.65 to 7.95 +/- 1.56 (p = 0.06) for the average of all antigens and from 12.85 +/- 2.05 to 15.79 +/- 2.84 (p = 0.2) for the largest response. The authors conclude that the response to test antigens in vitro and in vivo is not reduced significantly 6 months after gastric bypass and profound weight loss. Patients with severe vomiting, rapid weight loss or sepsis may respond differently and require individual assessment.

Adult↗
PubMed1985

Inhibition of human in vivo cytotoxic T lymphocyte generation by cyclosporine following organ transplantation.

The effect of cyclosporine (CsA) on the in vivo cell-mediated immune response to donor antigens was examined sequentially following cadaveric renal transplantation in both immunologically naive and specifically sensitized allograft recipients. Cytotoxic T lymphocytes (CTL) exhibiting preferential specificity for donor antigens were detected in the peripheral blood of all patients receiving azathioprine (AZA) immunosuppression by two weeks posttransplant, disappearing progressively over the first three months with clinical quiescence. In contrast, the generation of donor-reactive CTL was significantly diminished in incidence (P = 0.05) and in magnitude (P = 0.004) in subjects receiving CsA. CTL were detected in only 36% of patients by two weeks posttransplant, and were not detectable in any CsA-treated patient after the sixth posttransplant week. The ability of CsA to inhibit clonal reexpansion of CTL was examined both in vitro and in vivo in subjects exhibiting prior sensitization to donor antigens. In vitro, CsA caused a dose-dependent inhibition of accelerated (72-hr MLC) CTL generation following restimulation with donor spleen cells, which was quantitatively identical to that in parallel cultures using responder PBL from non-sensitized individuals. In vivo, CsA produced a rapid disappearance of circulating CTL posttransplant in patients who exhibited specific cell-mediated sensitization to the graft donor, as evidenced by the presence of circulating donor-reactive CTL prior to transplantation. In contrast, in patients receiving AZA there was a rapid increase in donor-reactive CTL in the peripheral blood following transplantation. CTL persisted for six weeks or longer, and two of four patients lost the graft to irreversible acute rejection within the first four weeks.

Azathioprine↗
PubMed1981

Immunological and pharmacological monitoring in the clinical use of cyclosporin A.

Immunological reactivity to donor antigens and serum concentrations of cyclosporin A were monitored in six patients after renal transplantation. At concentrations of 0.1--1.0 microgram/ml cyclosporin A prevented both donor-specific immune reactivity and clinical rejection during the early post-transplant course. Measurement of cyclosporin A levels and immunological indices allowed individual adjustment of the dosage so as to give excellent early graft function with few adverse effects.

Cyclosporins↗
PubMed1979

Monitoring of rejection.

Rejection in non-identical pairs is both antibody- and cell-mediated. Measurements of CDC and LMC specific for the donor can be useful clinical tools in confirming rejection, detecting periods of likely rejection, and helping to predict responses to therapy. In particular, the LMC assay appears to have excellent temporal correlations with graft status. Rejection in the HLA-identical sibling transplant is directed against a non-MHC antigen, is cell-mediated, and can be typed for using CTL.

Antibodies↗
PubMed1979

Antibody-mediated immunosuppression of a cytotoxic cell response not involving a simple antigen-masking mechanism.

An in vitro cytotoxic cell response against alloantigens was inhibited by antibody directed against the alloantigens and also by anti-trinitrophenyl antibody provided that the allogeneic stimulator cells were modified with trinitrophenyl. Inhibition of an anti-allogeneic cytotoxic cell response against trinitrophenyl-coupled allogeneic stimulator cells by anti-trinitrophenyl antibody is dependent upon the intact Fc portion of inhibitory antibody. The magnitude of the difference between intact and F(ab')2 anti-trinitrophenyl antibody in immunosuppressive activity suggests that the Fc portion emits negative signals rather than simply adding to a steric hindrance effect.

Animals↗
PubMed1978

Histocompatibility antigens as markers of abnormal iron metabolism in idiopathic hemochromatosis.

To determine the frequency of HLA histocompatibility antigens in persons with idiopathic hemochromatosis and their usefulness as genetic markers of the disease, HLA typing for the A, B and C loci was carried out. HLA-A3 was found in 61% of 18 unrelated individuals with idiopathic hemochromatosis compared with 25% of 253 randomly chosen control subjects (P less than 0.001), and HLA-B7 was found in 50% and 22% respectively (P less than 0.025). Eighty-six members of seven families with idiopathic hemochromatosis were screened for abnormalities in iron metabolism with tests for serum iron concentration, transferrin saturation, serum ferritin concentration and iron content of the hepatocytes. Of the 14 persons selected for liver biopsy because of abnormalities detected by these tests, 8 had increased amounts of stainable iron in the hepatocytes. Body iron overload was subsequently demonstrated in six of the seven, who had undergone repeated phlebotomy. In sibships having one member with hemochromatosis, only 1 of 22 members had two haplotypes in common with the proband, whereas in sibships having more than 1 member with the disease 4 of 5 affected members had two haplotypes in common. HLA typing in families with hemochromatosis may provide a means of identifying persons at risk of acquiring the disease.

Epitopes↗
PubMed1978

Beneficial effect of operation-day blood-transfusions on human renal-allograft survival.

In 56 patients 1-year renal-graft survival was significantly better (71% vs 40%) in those who had received blood before operation, confirming previous observations. In addition, transfusion on the day of operation proved to have been beneficial, both in those previously transfused (82% vs 64%) and in those never previously transfused (71% vs 28%). Irrespective of pretransplant transfusion, 1-year graft survival was significantly better (79% vs 44%) in those transfused on the day of operation.

Blood Transfusion↗