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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 379 records · Page 21Linked to original sources

Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding.

The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle. The hormone had, however, no effect on the activity of various enzymes involved in amino acid catabolism in muscle. In nephrosis, another condition of muscle wasting, the level of several muscle amino acids were also reduced to a lesser extent. Cortisol and triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic proteins in muscle. Binding of the labeled hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for glucocorticoids, and that muscle responsiveness involves binding of the active hormones to cytoplasmic receptor sites.

Amino Acids↗

Proliferation characteristics of lymphoid cells of human bone marrow in health and in chronic renal failure.

Proliferation of bone marrow lymphoid cells of 8 healthy subjects and 7 patients with chronic renal insufficiency was compared using the cytophotometric measurement of the DNA content combined with 3H-thymidine labelling in vitro. In renal insufficiency the cells showed a marked decrease of the proliferation activity. This is apparent from the impaired labelling indices and accumulation of diploid and unlabelled cells. The data suggest that the lymphoid cell proliferation is affected by the same pathophysiological mechanism as that leading to impairment of red cell production. By subclassification according to cytoplasmic basophilia, this proliferation disturbance could be related to the basophilic and not to the pale type of lymphoid cells.

Adult↗

Multifocal glioma of the brain. Case report.

A case is presented in which two separate concurrent astrocytomas of the brain in the same patient were successfully operated on. The patient has been followed for 3 years and remains well. The authors believe that the diagnosis of multifocal tumors can be established on clinical grounds when the tumors are remote from each other, and when there has been no recurrence of neoplasm between the lesions after a long follow-up period. It is felt that a more optimistic approach to the treatment of multifocal tumors may yield good results.

Adult↗

[Breast cancer and pregnancy. Apropos of 96 cases followed for 3 and 1/2 years at the Centre Léon Bérard, Lyons].

96 cases where cancer of the breast and pregnancy were associated have been studied at the Léon Bérard Centre of Lyon with a follow-up of at least 3 years. Those patients who had a malignant tumour of the breast, which was treated, and then became pregnant (19 cases) were not made any worse (79 per cent survival in 5 years). This was quite independent of the outcome of the pregnancy. On the other hand, those women (54 cases) in which the cancer was discovered and treated during pregnancy had a far worse prognosis (20 per cent survival in 5 years). This prognosis was made worse by the discovery of the cancer in the third trimester of the pregnancy, and by the presence of lymph node involvement, by termination of pregnancy and by weaning. When malignant tumours were discovered during breast-feeding or weaning (23 cases) the prognosis was equally bad (23 per cent survival in 3 years). The authors discuss the frequency of the association of cancer of the breast and pregnancy, as well as the different factors in the prognosis. They attempt to outline the management that should be carried out in the light of recent publications on this subject.

Abortion, Spontaneous↗

Acrocentric chromosome associations in man.

Heterogeneity among chromosomes was found to be a highly significant source of variation for association proportions, while culture, slide, and observer were negligible sources of variation for association proportions although important for numbers of associations. The consequences of these results for tests of group differences are discussed. It seems evident that each pair of acrocentric chromosomes has its own characteristic probability of entering into association. This is presumably a combination of the probability for each individual member of the pair, a proposition easily tested utilizing acrocentric chromosomes carrying polymorphisms which allow each member of the pair to be individually recognized. A mathematical theory for pairwise satellite association was developed and shown to fit observations on banded chromosomes. While we found very significant heterogeneity among individuals in the frequency with which different chromosomes entered into associations, there was no significant evidence for preferential association between any particular chromosomes, either heterologous or homologous. This finding in our material of apparently random associations between different chromosomes is contrary to claims made by other investigators and should be tested on other material. No correlation was found between the phenotype of the chromosome, as judged by cytogenetic polymorphisms, and its probability of association.

Azure Stains↗

Membrane-bound enzymes. III. Protease activity in leucocytes in relation to erythrocyte membranes.

Protease activity was detected in membranes of human bovine erythrocytes prepared by the conventional procedures which include washing and removal of the "buffy layer". The enzyme was extracted by 0.75 M KCNS or (NH4)2SO4 and was activated by 0.4 to 0.5 M of the same salts. Colored, particulate hide powder-azure, membrane fractions and soluble proteins such as hemoglobin, casein or albumin were susceptible to hydrolysis by the membraneous protease. Partial purification of the enzyme was accomplished through disc-gel electrophoresis on polyacrylamide in the presence of 0.25% positively charged detergents like cetyltrimethylammonium bromide. An alkaline protease (pH 7.4) with properties similar to those of the erythrocyte enzyme was found in leucocytes. The similarity between the properties of the leucocytic and erythrocytic proteases and the correlation of the activity in erythrocyte membranes with content of white cells in these preparations, suggest that enzymatic activities in the contaminating leucocytes are responsible for the activity of membraneous proteases in erythrocytes.

Animals↗

Cortisol binding in rat skeletal muscle.

Studies of the reversible binding of [3H]cortisol by rat gastrocnemius muscle cytoplasm in vitro reveal specific binding in the 27,000 times g supernatant fraction at 0 degrees. The [3H]cortisol-binding molecule had an apparant Kd value of 1.7 times 10-7 M and the number of binding sites was 0.99 pmol per mg of cytosol protein. Only a single class of [3H]cortisol-binding sites could be detected, whose protein nature was suggested by its susceptibility to nagarse. The [3H]cortisol-protein complex sedimented at similar to 4 S in a 5 to 20% sucrose gradient either in the presence or absence of 0.3 M KCl. Binding increased more than 2-fold in adrenalectomized rats and was markedly reduced in the muscle of rats pretreated with cortisol. In contrast to the binding of [3H]dexamethasone and [3H]triamcinolone acetonide to receptor proteins in muscle, no correlation was found between the ability of various steroids to complete wtth [3H]cortisol binding and their glucocorticoid potency: [3H]cortisol binding was inhibited by a 1000-fold higher concentration of unlabeled cortisol and progesterone but not by dexamethasone or triamcinolone acetonide. It is therefore suggested that the [3H]cortisol-binding reaction is not directly involved in the biological effects of all potent glucocorticoids in skeletal muscle. The [3H]cortisol-binding protein in muscle cytosol could not be unequivocally distinguished from rat plasma corticosteroid-binding globulin, because both had similar steroid specificity and temperature stability, were not markedly affected by--SH reagents, and displayed similar sedimentation properties.

Adrenal Glands↗

Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol.

While glucocorticoid hormones act catabolically on skeletal muscle through their binding to glucocorticoid-specific receptors in the cytosol, androgens exert anabolic responses but no androgen-specific binding proteins could be detected in this responsive tissue. However, various nonradioactive androgens were effective in displacing labeled dexamethasone or cortisol from their respective cytoplasmic receptors in muscle, both in vitro and in vivo. The inhibition of glucocorticoid binding by androgens is competitive, and could be observed following a single or repeated administration of the androgens to adrenalectomized-castrated animals. The synthetic androgen fluoxymesterone and the hormone testosterone displayed Ki values of 7.5 X 10(-6) M and 1 X 10(-5) M, respectively, for the inhibition of [3H]dexamethasone binding in muscle cytosol. On the basis of competition experiments it is postulated that interaction of androgens with glucocorticoid receptors prevents the binding of glucocorticoids and might be responsible in part for the anabolic effects of pharmacologic doses of androgens in muscle.

Anabolic Agents↗