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M Buscema

Publications and source records attributed to M Buscema.

44 records · Page 3Linked to original sources
PubMed1989

Retrovirus-like sequences in Graves' disease: implications for human autoimmunity.

On Southern blotting of DNA extracted from thyroid glands of five patients with Graves' disease, two probes (720 bp and 942 bp) for gag human immunodeficiency virus type 1 (HIV-1) gave a positive hybridisation signal in all samples tested. DNAs from peripheral blood mononuclear cells hybridised with the 720 bp gag HIV-1 probe in three of the five patients, none of whom had antibodies to HIV-1. Negative results were obtained with DNA from normal thyroid glands, thyroid neoplasms, various unrelated normal tissues, and virus-infected human cell lines. The intensity of the signal and the pattern of bands observed with the DNA of Graves' patients were heterogeneous and, in general, were not the same in the thyroid glands and peripheral blood mononuclear cells of individual patients. Similarly, no correlation was found between the positive hybridisation signals and other genetic and immunological indices or the duration of anti-thyroid drug treatment at the time the patients were investigated. The findings suggest the presence of a novel retrovirus, and the retrovirus-like sequences seem to be closely associated with thyroid autoimmunity.

Adolescent↗
PubMed1989

Inappropriate expression of HLA class II molecules in endocrine epithelial cells: the phenomenon, the new experimental data and comparison with animal models.

Physiologically, HLA Class II molecules are primarily expressed on immunoregulatory cells. In recent years, it has been shown that tissues affected by autoimmunity, including beta cells of 'diabetic' pancreases, 'inappropriately' express these glycoproteins. Cytokines are potent Class II inducers on a variety of cells but they exert a heterogenous effect when incubated with different human endocrine cells, i.e. thyroid cells are readily inducible, beta cells are much more resistant. The fine modulation of Class II expression by cytokines has been extensively studied and recent information on their action on endocrine cells is reported here. The possibility that distinct environmental factors from those postulated until now may be responsible for triggering the inappropriate expression of MHC molecules in epithelial cells in vivo is also emphasized. Despite several similarities between human Type I diabetes and spontaneous animal models of the disease, major differences still exist. Transgenic models have now been produced. However, even if they offer interesting new insights, they have not so far provided the decisive answer to explain the pathogenesis of human autoimmune diseases.

Animals↗
PubMed1989

Influence of tumor necrosis factor-alpha on the modulation by interferon-gamma of HLA class II molecules in human thyroid cells and its effect on interferon-gamma binding.

Cytokines are important modulators of immunological reactions, but it has been postulated that they might act on other unrelated epithelial cells. We studied the effects of recombinant interferon-gamma (rIFN gamma) and recombinant tumor necrosis factor-alpha (rTNF alpha) on normal human thyroid cells. We found that the combination of these two cytokines enhanced HLA class II molecule expression on these cells compared with the effect of rIFN gamma alone. This was proven by both immunofluorescence as well as a more sensitive and quantitative RIA. rTNF alpha alone had no effect on HLA class II molecule induction on the same thyrocytes, suggesting a synergistic rather than an additive action in combination with rIFN gamma. The addition of 600 U/ml rTNF alpha to low dose rIFN gamma (10 U/mL) enhanced class II expression by 50%, as quantified by RIA. We also demonstrated that normal thyrocytes possess distinct receptors for the two cytokines and that rTNF alpha probably augments IFN gamma binding, since it increased when the cells were first incubated with rTNF alpha. This increased binding provides an explanation for the synergistic action of rTNF alpha in enhancing class II molecule expression by rIFN gamma. We conclude that the presence of receptors for these cytokines on human thyroid cells gives a direct demonstration of their potential biological action on cells normally not involved in the immunological circuit. The phenomenon might also explain their direct or indirect involvement in vivo, such as in influencing inappropriate HLA class II molecule expression in epithelial cells affected by autoimmunity.

Binding Sites↗
PubMed1988

Metformin enhances certain insulin actions in cultured rat hepatoma cells.

The effect of the oral antidiabetic agent metformin on insulin regulation of glycogen metabolism, tyrosine-aminotransferase activity, and [1-14C]aminoisobutyric acid uptake was studied in H4IIE cultured rat hepatoma cells. Metformin enhanced both basal (from 0.213 +/- 0.016 to 0.262 +/- 0.024 nmol/mg protein, p less than 0.01) and insulin stimulated [3H] glucose incorporation into glycogen in a time-dependent and dose-dependent manner. A small effect of metformin was seen at 1 mumol/l, and its greatest effects were obtained at 10 mumol/l. At the same concentrations, metformin did not influence basal tyrosine-aminotransferase activity but it potentiated insulin stimulated tyrosine-aminotransferase activity (+29.2 +/- 1.4%, p less than 0.01) and prevented the loss of tyrosine-aminotransferase responsiveness to insulin in H4IIE cells desensitised by a previous exposure to insulin. In contrast, metformin had no effect on basal or insulin-stimulated [1-14C]aminoisobutyric acid uptake. Over the concentrations of metformin that enhanced insulin action in H4IIE cells, the drug had no significant effect on insulin binding to its receptor. These studies suggest, therefore, that metformin may influence cellular metabolism by potentiating certain insulin actions through mechanisms that may be beyond insulin receptor binding.

Aminoisobutyric Acids↗
PubMed1987

Direct effects of biguanides on glucose utilization in vitro.

The effect of the biguanides metformin and phenformin on glucose utilization in isolated cells was studied with IM-9 human lymphocytes. Both agents stimulated glucose consumption from the incubation media. Detectable effects of metformin were seen at 33 mumol/L and detectable effects of phenformin were seen at 1.7 mumol/L. Both agents, at similar concentrations, also stimulated [3H] 2-deoxy-D-glucose uptake. Studies with phenformin indicated that biguanides increase the Vmax of uptake without changing the Km. In contrast to the biguanides, IM-9 cells insulin did not influence either glucose consumption or [3H] 2-deoxy-D-glucose uptake. These data provide evidence, therefore, that biguanides may directly influence the cellular utilization of glucose.

Blood Glucose↗
PubMedDate not supplied

Toward an integrative approach in the analysis of dependency problems.

This article takes some preliminary steps towards an integrated analysis of dependency problems e.g., long-term tranquillizer use, alcohol dependence, problematic use of narcotics. It argues for the need to outline important theoretical, epistemological, and methodological prerequisites in the analysis of the complex dynamic developmental processes involved in dependency problems. The dynamic process leading to dependence can be studied by the aid of an artificial science neural network approach in combination with a mixed method strategy including a clarification of a combination of different epistemological positions. It is intended that the empirical output of this complex strategy will provide a starting point for a new theoretical analysis which, in turn, will lead to new and more relevant input variables in the neural network approach that will help us to extend our knowledge of the dynamic processes leading to dependency.

Comorbidity↗