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Biomedical subjects

S Middleton

Publications and source records attributed to S Middleton.

17 recordsLinked to original sources
PubMed1991

Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans.

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.

Analysis of Variance↗
PubMed1991

[Francisco Hoffmann, pioneer of physiological research in Chile].

Francisco Hoffmann MD became a Professor of Physiology at the University of Chile School of Medicine in 1934. After postgraduate studies in Germany he came back to Chile in 1931 when he began proposing the creation of an Institute of Physiology. This became a reality in 1936. He was a proponent of full time job and of greater participation of students in the learning process. The main research interest of the Institute was centered on thyroid function and its relation to the nervous and circulatory systems. Professor Hoffmann was made a corresponding member of the Royal and the Spanish Academies of Medicine. In 1960 he retired from the Institute to help develop an Anthropology Center leaving many of his disciples to continue his work in physiology.

Chile↗
PubMed1990

Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture.

In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis.

Autoantibodies↗
PubMed1990

Bone pain as the presenting manifestation of secondary syphilis.

A 31 year old fireman presented with acute pain and tenderness in both shins and forearms. Radiographs were normal but bone scintigraphy showed widespread increased isotope uptake. Serology was consistent with a diagnosis of secondary syphilis, and the patient's symptoms resolved completely six weeks after a course of penicillin.

Adult↗
PubMed1987

Production of factor VIII deficient plasma by immunodepletion using three monoclonal antibodies.

Factor VIII deficient plasma was made from pooled, HIV antibody and hepatitis B antigen screened, normal human plasma by cryoprecipitation and immuno-depletion, using three different monoclonal antibodies bound to Sepharose columns, in series. These monoclonal antibodies are specific respectively for von Willebrand factor, factor VIII heavy chain and factor VIII light chain. The immunodepleted plasma contained less than 0.002 u/ml factor VIII coagulation activity (VIII:C) less than 0.0001 u/ml von Willebrand factor antigen and 1-2 g/l fibrinogen, while the levels of other clotting factors were unchanged. This immunodepleted plasma was compared with commercial factor VIII deficient plasma obtained from a severe haemophilia A patient as substrate in the one-stage factor VIII assay. Plasmas obtained from 20 normal subjects and 28 patients with von Willebrand's disease or haemophilia A were assayed for VIII:C using the two substrates. The results were very highly correlated (r = 0.96). The columns have high capacity and can be regenerated at least 10 times. Large-scale production of a substrate for factor VIII assays free of virus contamination is now feasible.

Antibodies, Monoclonal↗
PubMed1985

The effect of carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes.

Thyroid autoantibody synthesis was investigated in cultures of lymphocytes isolated from several sources, including thyroid and lymph nodes from patients with hyperthyroid Graves' disease treated preoperatively with carbimazole or propranolol. The ability of thyroid lymphocytes to secrete immunoglobulins, including thyroid microsomal or thyroglobulin autoantibodies, was markedly reduced in lymphocyte suspensions obtained from patients treated with carbimazole compared with suspensions from patients treated with propranolol. This effect (which was greater in individuals treated with carbimazole for longer periods) was attributable to a significant reduction in the number of viable lymphocytes present after the 14-day culture interval. In contrast, the type of preoperative therapy had little effect on cultures of lymphocytes obtained from lymph nodes draining the thyroid. Although it is not yet clear whether carbimazole exerts its effects in vivo by direct immunosuppression or indirectly by altering the thyroid microenvironment, our observations indicate that the fall in serum levels of thyroid autoantibodies that occurs during carbimazole therapy is related to an effect of the drug on lymphocytes within the thyroid.

Antibody Formation↗
PubMed1976

Removal of hepatitis B surface antigen (HBsAg) from plasma fractions.

Endogenous or deliberately added hepatitis B antigen was removed and concentrated for assay from albumin, and from coagulation factor II, VII, IX, and X concentrates as model plasma fractions. The concentrates carry considerable risk of causing hepatitis in transfused patients. The amount of antigen remaining in the fraction was estimated to be less than 1/10,000 of that detectable by the Ausria II radioimmunoassay and 1/100 of that found to be infectious when highly contaminated human sera were diluted and injected in chimpanzees. Batch fractionation methods with polyethylene glycol were used. The yield of albumin was 96 per cent and of the coagulation factors about 90 per cent.

Blood Proteins↗
PubMed1975

In vitro spontaneous thrombin generation in human factor-IX concentrates.

A series of in vitro studies designed to ascertain the potential in vivo thrombogenicity of human factor IX-containing concentrates is described. Using concentrates obtained from several different Centres the fibrinogen clotting time with some preparations was less than 6 h and/or the recalcification time of normal plasma was shortened. In some preparations, however, the plasma recalcification time was lengthened. Further studies revealed that all diluted factor-IX concentrates generated thrombin after recalcification, and that the rate of thrombin generation appeared to be characteristic of a particular preparation. This characteristic has been designated the TGt50, which is the incubation period in minutes, after recalcification, required to obtain a 50 s clotting time of a fibrinogen substrate. The TGt50 was found to correlate most strongly with recalcification time of celite exhausted plasma (P less than 0.001), but no correlation was observed between it and the immunological antithrombin III or factor-VIII antigen levels. Evidence is presented which suggests that the thrombin generation test and recalcification time of celite exhausted plasma may represent suitable in vitro quality control assays for factor-IX concentrates.

Blood Coagulation↗