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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 307 records · Page 17Linked to original sources
PubMed1983

Corticosteroid binder IB: a model of glucocorticoid receptor diversity.

Corticosteroid binder IB is a glucocorticoid receptor present in rat liver, kidney cortex and proximal colon. It is characterized by a lower molecular weight than the traditional and widely distributed glucocorticoid receptor II. The two receptors also differ in charge, affinity towards various steroids and potency of binding to DNA, nuclei and homodeoxypolymers. The in vivo and in vitro production of binder IB is not affected by protease inhibitors, nor can IB be produced by RNase digestion or proteolytic cleavage of binder II or its precursor molecule. The presumptive physiological role of corticosteroid binder IB and the implied biological significance of receptor diversity are discussed.

Animals↗
PubMed1982

Inhibition of serine proteases by steroids.

Proteolysis of 14C-labeled globin, as well as the hydrolysis of the specific substrate benzoyl tyrosine ethyl ester, by purified bovine chymotrypsin was found to be inhibited by several steroid hormones. The inhibition of chymotrypsin by the steroids was of a competitive nature, with Ki values of 9.9 x 10(-5) M for triamcinolone (9-fluoro-11 beta, 16 alpha, 17,21-tetrahydroxy-1,4-pregnadiene-3,20-dione), 1.6 x 10(-4) M for cortisol (11 beta, 17 alpha, 21-trihydroxypregn-4-ene-3,20-dione), 3.7 x 10(-4) M for testosterone (17 beta-hydroxy-4-androsten-3-one), 5.0 x 10(-4) M for dexamethasone (9-fluoro-11 beta, 17,21-trihydroxy-16 alpha-methyl-1,4-pregnadiene-3,20-dione) and 1.0 x 10(-4) M for epicortisol (11 alpha, 17,21-trihydroxy-4-pregnene-3,20-dione). The activity of purified bovine trypsin on its specific substrate, TAME (tosyl arginine methyl ester), also showed a similar pattern of inhibition by steroids. Both chymotrypsin and trypsin were found to bind 3H-labeled dexamethasone and cortisol. This binding was markedly inhibited by the general protease inhibitor, PMSF (phenylmethanesulfonyl fluoride), whereas the chymotrypsin-specific inhibitor, TPCK (L-[1-tosyl-amido-2-phenyl]ethylchloromethyl ketone), inhibited only the steroid binding to chymotrypsin but not to trypsin. These observations indicate that serine proteases recognize steroid hormones in a fashion similar to the recognition of their specific substrates and that the steroids inhibit activity of these enzymes at their binding sites.

Animals↗
PubMed1982

Protease and protease inhibitory activity in pregnant and postpartum involuting uterus.

The presence of two distinct proteolytic activities in the rat uterus was confirmed with 14C-labeled globin used as a sensitive protein substrate and following release of label into the trichloroacetic acid-soluble supernatant fraction. Protease I is a cytoplasmic acid protease while protease II is associated with the pellet fraction, can be extracted by 0.6 M sodium chloride, and is active at pH 7.0. Protease I activity is low during pregnancy and markedly increases at term achieving maximal activity at day 3 post partum with a subsequent decline to preterm activity values. Lactation did not affect the uterine protease I activity. Protease II activity is not significantly different during pregnancy, at term, and post partum. The presence of an inhibitor of protease I was suggested by a decrease in enzyme activity with an increased cytosolic protein concentration. The inhibitor also lessened bovine trypsin activity but had no effect on protease II. Although its inhibitory potency on trypsin fluctuated during the various uterine physiologic stages, these changes appeared to be statistically insignificant. Human uterine samples were also found to contain the two protease activities with similar changes in protease I post partum. It is suggested that, both in the rat and in man, uterine involution post partum is associated with a marked increase in activity of acid cytosolic protease, while a particulate neutral protease and a soluble inhibitor of trypsin, which are also present in uterine cells, do not appear to play a significant role in the dissolution of uterine tissues after parturition.

Animals↗
PubMed1982

Marker X syndrome in an oriental family with probable transmission by a normal male.

We report an oriental family with sex-linked mental retardation, macroorchidism, and a marker or fragile site on the X chromosome--mar(X)(q28). The three affected males resemble clinically most previously reported affected Caucasians. The marker was present in four female 40-70 years old, including one with normal intelligence. Transmission of the disorder appears to have taken place through a clinically normal male to his grandson.

Adolescent↗
PubMed1982

Ammonia uptake by skeletal muscle in the hyperammonaemic rat.

A two-stage surgical occlusion of the portal vein was employed to produce hyperammonaemia in the rat. The procedure resulted in a significant rise of arterial blood ammonia level from 70 . 5 +/- 6 . 5 mumol/l (mean +/- SEM, n = 10) to 214 . 0 +/- 37 . 7 mumol/l and in a rise of venous blood ammonia from 65 . 0 +/- 9 . 4 mumol/l to 122 . 2 +/- 7 . 4 mumol/l during the first day following the complete vein occlusion. A marked increase of the arteriovenous difference of ammonia concentration from virtually zero in sham-operated controls to 72 +/- 9 (n = 8) mumol/l in rats 1 day after the surgical manipulation suggested uptake of ammonia by skeletal muscle. Rat muscle glutamine synthetase activity increased from 0 . 46 +/- 0 . 06 u/mg (n = 7) in controls to 2 . 7 +/- 0 . 3 u/mg (n = 7) on the fourth day following portal vein ligation, and muscle branched chain amino acids aminotransferase increased from 0 . 2 +/- 0 . 05 u/mg in controls to 0 . 96 +/- 0 . 1 u/mg (n = 7) during the first day of ligation. Glutamine dehydrogenase and aspartate aminotransferase activities were not affected by the surgical procedure. These observations suggest that ammonia trapping in skeletal muscle is coupled to glutamine formation via amination of glutamic acid. This conclusion was further supported by the finding that ammonia uptake correlated (r = 0 . 92) with enhanced release of glutamine from muscle and that treatment with methionine sulfoximine, a potent inhibitor of glutamine synthetase, changed the arteriovenous difference of glutamine from -0 . 92 +/- 0 . 01 mmol/l in ligated animals (net release) to +0 . 12 +/- 0 . 01 mmol/l (net uptake) in ligated and inhibitor-treated animals. Similarly, the inhibitor also abolished the arterio-venous difference of ammonia. Thus, the animal model of hyperammonaemia and the muscle enzyme assays reveal that skeletal muscle is involved in the regulation of blood ammonia level by conversion of ammonia, via glutamic acid, to glutamine.

Ammonia↗
PubMed1982

Intracellular protease activity in glucocorticoid-mediated thymolysis.

The effect of dexamethasone on rat thymus protease activity was tested by following hydrolysis of 14C-labeled globin. Most of the proteolytic activity was located in the cytoplasmic fraction obtained from either whole thymus homogenates or isolated thymic lymphocytes. The protease showed an acid pH optimum and was inhibited by pepstatin and leupeptin. The particulate fractions exhibited only a negligible proteolytic activity throughout the pH range tested. The administration of dexamethasone (9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione; 1 mg/kg, ip) to adrenalectomized castrated rats caused a marked increase in the acid protease activity assayed in the cytosol of whole thymus or thymic lymphocytes, with no change in the particular enzyme activity. The sensitivity of the cytosolic enzyme to several protease inhibitors was unchanged after glucocorticoid treatment. Minimal effective dexamethasone doses for thymic involution and increases in protease activity were 0.01 and 0.1 mg/kg BW, respectively. The half-maximal thymolytic effect was obtained at 0.05 mg/kg dexamethasone, while the half-maximal effect on the protease was observed only at 0.30 mg/kg dexamethasone. In contrast, in vitro exposure of isolated thymic lymphocytes to 8.3 X 10(-6) M dexamethasone failed to affect the acid protease activity in the cytosol, but produced a marked time-dependent cytolytic response. These observations suggest that glucocorticoid-induced cytolysis in rat thymic lymphocytes is not mediated by a direct effect of the hormone on endogenous proteases.

Adrenalectomy↗
PubMed1982

Changes in proteolytic activities of human leukemic promyelocytes (HL-60 cells) during maturation.

Proteolytic activity was measured in human leukemic promyelocytic cell line (HL-60) grown in culture, before and after the addition of agents which promote differentiation. The 36000 X g soluble fraction of the cells degraded [14C]globin with maximal activity at pH 3.6, while the insoluble fraction had a pH optimum at 8.0. This pattern did not change upon differentiation. The acid protease activity of the soluble fraction increased following differentiation. After 4 days in the presence of dimethyl sulfoxide, the differentiated cells exhibited 4-fold higher specific activity as compared with 4 day-old control cells. In contrast, the alkaline activity of the insoluble fraction of the differentiated cells was 4-fold lower than that of the undifferentiated cells. It is suggested that the changes in enzyme activities may serve the new functions acquired by the mature granulocytes.

Aspartic Acid Endopeptidases↗
PubMed1982

Expression of the marker (X) (q28) in lymphoblastoid cell lines.

The marker(X)(q28) chromosome associated with one type of X-linked mental retardation has been demonstrated in lymphoblastoid cell lines established from affected individuals. The mar(x) can reliably and repeatedly be seen by the addition of FUdR to the cultures for 24 hrs prior to harvest. This simple technique provides an excellent in vitro experimental test system for investigation of the mar(X).

Cell Line↗
PubMed1982

[Thalamic tumors in children. A study of 38 cases (author's transl)].

The main clinical, evolutive and therapeutic features of thalamic tumors are reviewed in 38 children. Signs of increased intracranial pressure (76% of the cases) and of controlateral hemiparesis of varying degree (76% of the cases) were the main clinical symptoms. CT-scan is the best means of investigation. Therapeutic protocols that seem to obtain the best results consist of radiotherapy (between 45 and 55 grays) associated with shunting, when intracranial hypertension results from obstruction of an interventricular foramen by the tumor. Surgery is contra-indicated in most tumors in this area.

Adolescent↗
PubMed1982

Protease inhibitor activity in rat skeletal muscle.

The cytosol fraction obtained by homogenization of rat gastrocnemius muscle inhibited the activities of rat alkaline myofibrillar protease, bovine trypsin and bovine chymotrypsin. The inhibition of the three proteolytic enzymes by muscle cytosol changed differentially during ageing, fasting and following administration of glucocorticoid hormone. The inhibition exerted by the cytosol on the three proteases was also differentially affected by precipitation with trichloracetic acid, heat, dialysis and molecular sieve chromatography. It is suggested that the intracellular protease inhibitor(s) are involved in the regulation of muscle protein degradation.

Aging↗
PubMed1982

[Changes in some ventilation and respiration parameters in patients with chronic obstructive lung disease in prospective longitudinal study].

The changes of several parameters of ventilation and respiration in 104 men taken into prospective longitudinal observation were analysed. All men in average 53.3 years old at the time of first examination were suffering from chronic obstructive lung diseases. The time between last and first examination amounted to 52 months in average. During this period the functional state did not change in one third of all patients; in the other two thirds the condition has impaired and 19 (18.3%) among 104 had died. The functional parameters evaluated showed a statistically significant decrease of FEV1 (71 ml in average every year) and of pulmonary diffusion capacity for CO by the steady state and single breath methods whereas the changes of airway resistance being insignificant in these cases. The results give rise to the statement that progression of the disease would occur in the area of peripheral airways and alveoli.

Adult↗
PubMed1981

Results of combined chemosurgical therapy for pulmonary metastases.

The authors study the results of the combined surgery and postoperative chemotherapy, for treatment of pulmonary metastases. At Léon-Bérard Center, 50 patients have been operated on since 1963. The sites and histologies of the primitive cancers are varied, corresponding to 12 epidermoid cancers, 12 adenocarcinomas, 10 osteogenic sarcomas, 1 Ewing's tumor, 3 malignant melanomas, 6 testicular tumors, and 4 others. The total survival rate is 30% in 4 years. The prognosis is influenced by different factors, which are studied. It depends on the histology of the primitive cancer and the type of the pulmonary excision. It is suggested that postoperative chemotherapy improves the results. It appears that the longer the free interval is between the treatment of the primitive cancer and the discovery of the pulmonary metastasis, the better the prognosis. The correlation between the time lapse of the free interval and the survey after pulmonary excision is studied. The conclusions of the authors are: The association of surgery and chemotherapy improves the results and enforces the indications for surgical excision of pulmonary metastases.

Adenocarcinoma↗