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Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 325 records · Page 18Linked to original sources
PubMed1983

Long-term incompatible kidney survival in outbred higher primates without chronic immunosuppression.

Transplantation between non-identical humans has been limited by the requirement for chronic immunosuppression (CI). This study demonstrates in a nonhuman primate model that long-term acceptance of incompatible kidney allografts can be achieved without the use of CI. Following incompatible kidney transplantation, rhesus monkey recipients were given a 5-day course of clinical rabbit antithymocyte globulin (RATG). On day 12, unfractionated donor bone marrow (BM) was infused intravenously. Recipients were monitored for T-cell levels and T-cell subset levels with monoclonal antibodies and for responses in one way MLR. Graft survival in untreated control animals was 9.2 +/- 2.8 days. In six animals given RATG only, all died of rejection at a mean 35.8 +/- 5.7 days. Of five animals given RATG and donor BM (mean 2.5 RhLA mismatches, mean MLC 12.7), four are alive at 150 days, 248 days, 342 days, and 401 days (median 248 days). The ATG-BM infused group showed a prolonged imbalance of their OKT4/OKT8 cell ratio and cellular suppression of MLR responsiveness. The long-term survival obtained in these outbred primates is apparently due to a synergistic immunoregulatory effect induced by the RATG and donor BM. The model described is apparently the first report of long-term survival of outbred higher primates without CI and may represent a technique for producing tolerance without CI in the human.

Animals↗
PubMed1983

A prostaglandin-dependent immunoregulatory mechanism activated by in vivo administration of antithymocyte globulin.

The mechanism responsible for the profound and enduring immunosuppressive action of antithymocyte globulin (ATG) is not well understood. In a primate model, we found that a 5-day rabbit ATG (RATG treatment course activates a prostaglandin (PG)-dependent suppressor cell mechanism that persists for several months. Groups of normal rhesus monkey skin allograft recipients, kidney allograft recipients, or nontransplant control animals received either RATG or no immunosuppression. The peripheral blood mononuclear cell (PBMC) population was longitudinally monitored for (1) percentage of total T cells, helper cells, and suppressor/cytotoxic T cell subsets with the monoclonal antibodies Leu-5, OKT4, and CKT8, respectively, and (2) phytohemagglutinin (PHA)-induced lymphocyte proliferative responses (LPR). The nonimmunosuppressed control groups showed no significant changes in any of these parameters. In contrast, PBMCs from all RATG-treated monkeys developed a persistent imbalance in the ratio of OKT4+ and OKT8+ subsets. Their PBMCs became unresponsive to PHA and remained unresponsive (less than 20% of control level) for at least 3 months, although total T cell counts recovered within 2 to 3 weeks after cessation of RATG. Addition of PG synthetase inhibitors indomethacin. RO-20-5720, and tolmetin caused a significant, dose-dependent recovery of LPR that was completely inhibited by exogenous PGE2 at 1 X 10(-8) M. PBMCs from RATG-treated monkeys caused a dose-dependent suppression of the normal PHA response, and this suppressor cell activity was blocked by indomethacin. PHA responses of nonimmunosuppressed control groups were not increased significantly in the presence of PG synthetase inhibitors, were less sensitive to suppression by PGE2, and did not exhibit suppressor cell activity. These data suggest that the prolonged depression in LPR after RATG treatment is due to an active PG-dependent suppressor cell mechanism and provide a new concept to explain the immunosuppressive action of RATG.

Animals↗
PubMed1983

Ureteric obstruction after dacron vascular replacement.

Ureteric obstruction is a recognised complication of aortic bifurcation grafting where the graft material is in close proximity to the ureter as it crosses the common iliac vessels. We have assessed the value of routine postoperative urography in (1) a retrospective 6-year study of ruptured aortic aneurysm repair (11 patients reviewed) and (2) a prospective 18-month study of all patients receiving intra-abdominal dacron grafts (24 assessable patients) in a district general hospital. Renal function was normal in all cases and only 1 ureter was shown at urography to be minimally dilated but not significantly obstructed out of 32 'at risk' ureters in 18 patients in the 2 studies. This complication is uncommon, and no particular advantage can be demonstrated in positioning the ureters either behind or in front of the graft limbs. There is no place for routine urography which should be reserved for the patient with symptoms of ureteric obstruction.

Aged↗
PubMed1982

Prediction of 90Sr body burdens and radiation dose in Anaktuvuk Pass Alaska Eskimos due to fallout.

Strontium-90 concentrations in skeletons of Eskimo residents of Anaktuvuk Pass. Alaska during 1954-79 were predicted from two models based on (1) Sr kinetics in human bond and (2) estimated annual 90Sr ingestion rates via caribou meat. Predicted skeletal burdens of adult Eskimos gradually increased through 1961 and then rapidly achieved maximal values during 1964-66, reflecting fallout 90Sr levels in caribou meat which contributed 80-97% of dietary 90Sr intake. Concentrations of 90Sr in male Eskimo bone samples were similar using either model. Predicted values in vertebrae of adult Eskimo males were slightly lower than values reported in New York City adults until 1980 and subsequently declined by 9% per yr, while samples from adults in New York City and San Francisco declined by 6 and 5%, respectively. Predicted skeletal burdens in Anaktuvuk Pass residents born in 1954 and 1959 achieved maxima in 1971 and 1974, respectively; concentration in children born in 1964 were still increasing in 1979 but had achieved a lower level than older age cohorts. Estimated radiation dose rates to adult skeletons during 1964-66 were 13-15 mrad/yr based on predicted vertebrae 90Sr concentrations. Those dose rates were less than or equal to 1% of recommended ICRP limits for general populations.

Adolescent↗
PubMed1982

Suppressor cells in rhesus monkeys treated with antithymocyte globulin.

Treatment of rhesus monkey skin allograft recipients with a brief course of rabbit antithymocyte globulin (ATG) produces an enduring immunosuppressive effect on the cellular immune system. Despite early recovery of circulating T cells, in vitro mitogen-induced lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) remain abnormally depressed for months. In this study we show that depressed mitogen-induced lymphoproliferative responses in these animals are attributable to regulatory effects of adherent PBMCs. Removal of the adherent fraction of PBMCs on Sephadex G-10 produced a significant restoration of the mitogen-induced lymphoproliferative responses in ATG-treated monkeys. Addition of the prostaglandin synthetase inhibitor indomethacin to cultures of unfractionated PBMCs from these animals also caused a significant recovery of the lymphoproliferative response. Indomethacin did not enhance the response of control animals or the response of the nonadherent PBMC fraction of ATG-treated animals. These data suggest that a prostaglandin-dependent mechanism is involved in the suppressive action of the adherent cells. PBMCs from ATG-treated monkeys cocultured with normal cryopreserved autologous cells induced a dose-dependent suppression in the response to both concanavalin A (Con A) and phytohemagglutinin (PHA). The suppressive activity depended upon the adherent cell fraction and was found to be resistant to low-dose gamma irradiation. These data indicate that administration of rabbit ATG induces nonspecific suppressor cells in the rhesus monkey. Preliminary characterization studies suggest the involvement of suppressor monocytes. The possible role of this suppressor cell system in the immunosuppressive action of rabbit ATG is discussed.

Animals↗
PubMed1982

A trial of prophylactic mexiletine in home coronary care.

A double blind randomised study was undertaken comparing the effects of oral mexiletine and placebo given by general practitioners at home in the early stages of suspected acute myocardial infarction, and continued for six weeks. The study comprised 216 patients. In 59 the diagnosis of acute myocardial infarction was not confirmed. Of the 72 patients with confirmed myocardial infarction treated with mexiletine, 11 (15.3%) died, compared with 19 (22.4%) of the 85 patients given the placebo, and significantly fewer of the former compared with the latter had frequent ventricular ectopics or ventricular tachycardia recorded on 24 hour electrocardiograms. Numbers of patients transferred to hospital or withdrawn from the trial because of arrhythmia or heart failure were similar in the two treated groups. Ten (13.9%) of the patients taking mexiletine had the drug withdrawn because of side effects attributed to it, compared with three (3.5%) of the group taking the placebo. A further five patients (all on mexiletine) also had treatment withdrawn because of side effects but infarction was not later confirmed. The results indicate that oral mexiletine can be given safely to patients with suspected myocardial infarction at home by their general practitioners in the absence of a positive electrocardiographic diagnosis. The frequency of ventricular tachycardia is significantly reduced; but there is no evidence of reduced mortality.

Aged↗
PubMed1981

Correction of the anomalous electrophoretic behavior of ribonuclease A.

Ribonuclease A behaves anomalously on polyacrylamide gel electrophoresis at acid pH. The distance traveled by the protein is a function of the amount of enzyme added at the lower range of detectable activity (10 pg to 100 ng). Addition of myoglobin (1 mg/ml) abolishes the anomaly. The observations are consistent with the known affinity of RNase for anions. Caution is warranted in the interpretation of apparent electrophoretic variants of RNase observed at low concentrations of enzyme.

Animals↗
PubMed1981

Isozymes of ribonuclease in human serum and urine. I. Methodology and a survey of a control population.

Methods are presented for the electrophoretic analysis of ribonuclease (RNase) enzymes in human serum and urine. Protocols for sample treatment, electrophoresis, and the RNase zymogram technique are described. With the application of these methods, RNase from serum and urine was separated into components differing on the basis of charge (charge isomers or "isozymes"), but not differing with respect to hydrolyzable sialic acid residues. Preliminary characterization of the electrophoretically separated components showed that some of the RNase species have different properties (pH optima and substrate preference). The major urine RNase isozymes appeared to be distinct from the major serum RNase isozymes. A survey of a control population indicated that the major serum and urine RNase enzymes are not genetically polymorphic.

Electrophoresis, Polyacrylamide Gel↗
PubMed1981

Isozymes of ribonuclease in human serum and urine. II. A survey of patients with cystic fibrosis.

A comparison of serum and urine RNase isozymes from CF patients, heterozygotes, and control subjects demonstrated that the major RNase isozymes are not abnormal in CF. Some preliminary evidence indicated that RNase activity of the pancreatic extracts administered to CF patients may appear in the urine and result in a slightly different urine isozyme pattern. In addition, the mean serum RNase activities of the CF patients and heterozygotes were significantly greater than the mean activity of the controls, but there was much overlap in values between the groups.

Animals↗