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Biomedical subjects

M S Roginsky

Publications and source records attributed to M S Roginsky.

At least 19 recordsLinked to original sources

Phorbol ester, prolactin, and relaxin cause translocation of protein kinase C from cytosol to membranes in human endometrial cells.

Incubation of endometrial cells with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2, 5, 10 and 30 min decreased cytosolic protein kinase C (PKC) activity to 80%, 68%, 66%, and 72% of the control values, while membrane-associated PKC increased to 116%, 168%, 154% and 134% of the control values, respectively. Long-term incubation of cells with TPA resulted in a loss in total PKC activity. Treatment of secretory endometrial cells with prolactin (100 ng/ml) decreased cytosolic PKC to 64% (10 min) and 72% (20 min) while membrane PKC increased to 133% (10 min) and 158% (20 min) compared to control values. Relaxin (100 ng/ml) also caused translocation of PKC in secretory endometrium. Neither hormone induced PKC translocation in proliferative endometrium. In intact endometrial cells TPA stimulated the phosphorylation of an 80 kDa protein. Cytosolic protein phosphorylation in the presence of EGTA resulted in phosphorylation of proteins of 68 kDa and 19 kDa which was increased by prolactin. Upon activation by calcium and phosphatidylserine, PKC phosphorylated a protein of 39 kDa, and prolactin did not further enhance its phosphorylation. The present results indicate that TPA induces an intracellular translocation and down-regulation of PKC. The translocation of PKC by prolactin and relaxin suggests an involvement of this enzyme in the action of these hormones in human endometrium.

Biological Transport

Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans.

The effects of several neurotransmitter amino acids on pituitary hormone secretion were examined in normal humans. Oral administration of 10 g of glutamic acid stimulated the secretion of prolactin (PRL) and cortisol to approximately twice baseline values, with no effect on GH, TSH or LH. Aspartic acid (10 g), taurine (5 g), and cysteine (5 or 10 g) had no consistent effect on any hormone measured, although the lack of effect of aspartic acid may relate to the modest increments in serum concentration achieved. Glutamic acid may be an important modulator of PRL and ACTH secretion in humans.

Adrenocorticotropic Hormone

Significance of serum level of 25-hydroxycholecalciferol in gastrointestinal disease.

The serum 25-OHCC concentration was measured in 151 patients in order to evaluate the potential use of this determination in the management of gastrointestinal disorders. Patients with functional bowel disease had lower serum mean 25-OHCC levels than normals. The results were divided into normal (greater than 21 ng/ml), low normal (12-21 ng/ml), and low levels (less than 21 ng/ml). Two thirds of patients with malabsorption had low serum 25-OHCC. Most patients following jejunoileal bypass surgery for morbid obesity had low levels despite supplemental oral calciferol therapy. In patients with chronic liver disease, cholestasis more than parenchymal cell disease appeared responsible for low serum 25-OHCC levels. Measurement of serum 25-OHCC may be an ancillary screening test for fat malabsorption and in patients with intraluminal bile salt deficiency. Furthermore, repeated measurements may be useful in monitoring therapy with vitamin D products in patients with chronic malabsorption and cholestasis.

Cholestasis

Serum thyroid hormones changes in patients undergoing Caesarean section under general or regional anaesthesia.

The effects of anaesthesia on serum thyroid hormones were studied in 32 pregnant young women undergoing Caesarean section at term. Eighteen patients received general anaesthesia and 14 lumbar extradural blockade. Maternal serum concentrations of thyrotrophin (TSH), thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) were measured using radioimmunoassay at 0, delivery and 24 h. There were no significant changes in TSH in the two groups. T4 concentrations decreased significantly at 24 h in the general anaesthesia group but regional anaesthesia produced a significant decrease only at the time of delivery. T3 concentrations decreased with both techniques. Reverse T3 increased markedly with general anaesthesia only at 24 h.

Anesthesia, Epidural

Effect of human chorionic gonadotrophin on adenylate cyclase activity and testosterone content in rat testicular mitochondria.

The adneylate cyclase activity and the concentration of testosterone in testicular mitochondria from immature rats were measured after administration of human chorionic gonadotrophin (HCG) or dibutyryl cyclic AMP in vivo or in vitro. Intratesticular injection of HCG produced an increase in adenylate cyclase activity which preceded the rise in the level of testosterone, whereas addition of the trophic hormone in vitro resulted simultaneous increases. Administration of dibutyryl cyclic AMP in vivo enhanced the testosterone content of the mitochondria. However, the cyclic nucleotide added in vitro at concentrations up to 5 mmol/l had no effect. Cycloheximide injected intraperitoneally before the administration of HCG abolished the stimulatory effect of the trophic hormone on the level of testosterone in the mitochondria, whereas chloramphenicol had no effect. These results, although they confirm the role of cyclic AMP as an intermediate in the stimulatory effect of HCG on the concentration of testosterone in rat testis, do not support a role for mitochondrial adenylate cyclase in this action. A protein regulator(s) formed extramitochondrially appears to be involved in the stimulatory effect of gonadotrophins on steroidogenesis.

Adenylyl Cyclases

Amniotic fluid adenosine 3',5' - monophosphate in prostaglandin-induced midtrimester abortions.

Cyclic adenosine 3'5-monophosphate (cAMP) was serially measured in the amniotic fluid (AF) of 9 patients undergoing midtrimester abortions induced by intraamniotic prostaglandins. The results demonstrate an increase in AF cAMP ranging from 2- to 7-fold within the 6 hours of observation. The fetal heart tones were closely monitored by a Doppler instrument and the time from injection of abortifacient to fetal demise (IDT) and to fetal expulsion (IAT) was accurately recorded. No correlation between the rate of AF cAMP increase and IDT or IAT could be demonstrated. The concentration of cAMP in amniotic fluid obtained from patients with fetal demise in utero was lower than that found in AF of fetuses of corresponding gestational age where the fetus was alive. The significance of AF cAMP as a potential indicator of fetal distress is discussed.

Abortion, Induced

Erythrocyte 2,3-diphosphoglycerate in normal and hypertensive gravid women and their newborn infants.

Red blood cell 2,3-diphosphoglycerate (2,3-DPG) levels were studied in 227 normal gravid women in all stages of pregnancy, active labor, and early post partum. An increase to peak levels was observed at 19 to 22 weeks followed by a gradual fall toward normal. During labor and early post partum, 2,3-DPG again rose significantly above levels observed at term. Serial 2,3-DPG values through the third trimester, labor, and postpartum period in 11 hypertensive mothers and 20 normal gravid control subjects and their newborn infants were studied. Maternal 2,3-DPG levels were significantly higher in the hypertensive mothers when compared to control mothers at similar gestational stages. However, no difference in 2,3-DPG levels was observed when newborn infants of hypertensive mothers were compared with those of normal control subjects.

Adolescent

Changes in body chemical composition with age measured by total-body neutron activation.

Total-body levels of calcium and phosphorus (reflecting skeletal mass) and total-body levels of potassium (reflecting muscle mass) were measured by neutron activation analysis in 39 men and 40 women ages 30-90 yr. In order to intercompare the total body calcium (TBCa) values in a heterogeneous population, such as this, it was necessary to normalize the data for skeletal size. The normalization consisted of dividing the absolute calcium level by the predicted calcium level for each individual matched to a set of critical parameters. The parameter used in the computation of normal values were age, sex, muscle mass, i.e., total body potassium (TBK) and height. For the calcium data of the women, it was necessary to add an age correction factor after the age of 55 yr. The calcium ratio(mean ratio of the predicted to measured TBCa) in men was 1.000 +/- 7.8% and in women 0.996 +/- 7.1%. The TBCa of normal males and females can thus be predicted to +/- 13% (at the 90% confidence level). An exception to this was found in males (70-90 yr) who exhibited a mean calcium ratio greater than 1.13. The derivative of TBCa with time was determined for this population of men and women by taking into account the dependency of calcium on three time dependent variables, height, TBK, and an explicit age correction factor in the case of the women. The mean rate of loss of TBCa in women was 0.37% and 1.1% per year before and after menopause (50 yr). In the males, the average rate of loss of TBCa was 0.7% per year after 50 yr of age. The pattern of total body phosphorus (TBP) loss with age paralleled that of TBCa as the ratio of TBP/TBCa was rather constant with age. The constancy of the ratio suggests that the mineral composition of bone does not change significantly with age. The rate of loss of TBK with age was also related directly to that of TBCa. The mean ratio of TBK/TBCa was 9.9 in females and 8.0 in males and this ratio remained relatively constant from 30-70 yr. Thus, the mechanism responsible for the loss of bone with age, whether nutritional deficiency or decreased gonadal function and physical activity may also be responsible for the loss of muscle mass with age.

Adult

Microcirculation in diabetes mellitus: a study of gingival biopsies.

Gingival biopsy specimens from 24 diabetic patients, six obese persons, and six controls were studied statistically and morphologically to detect vascular basement membrane changes using a proposed classification of microvessels. Statistically significant basement membrane thickening is seen in all diabetic groups in most true capillaries and vessels proximal to them, especially in terminal arterioles and metarterioles, although the degree and extent of the changes vary among different clinical groups and vessel types. The basement membrane thickening is characterized by increased amorphous, granular, and fibrillary material with occasional scattered collagenous fibrils. Although nonspecific, basement membrane thickening in microvessels at, and especially proximal to, the level of true capillaries is intimately related to diabetes. Gingival biopsy may possibly be used as an adjunct in the diagnosis of diabetes.

Adult

Metastatic adrenal cortical carcinoma. Documented cure with combined chemotherapy.

In 1966, we published the case report of a patient with adrenal carcinoma and wide spread metatasis who, after treatment with mitotane (o,p-DDD) and fluorouracil, developed Addison disease accompanied by a clinical remission. The patient's unexpected death from an unrelated cause now allows us to verify what to our knowledge is the first cure of metastatic adrenal carcinoma by chemotherapy.

Adolescent