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Biomedical subjects

J H Clark

Publications and source records attributed to J H Clark.

At least 235 records · Page 13Linked to original sources
PubMed1978

Role of estrogen receptor binding and transcriptional activity in the stimulation of hyperestrogenism and nuclear bodies.

The effects of estradiol and nafoxidine on nuclear estrogen receptor binding, RNA polymerase activities, and uterine ultrastructure were studied. Animals were either injected with estradiol, implanted with estradiol/paraffin pellets, or injected with nafoxidine. Animals treated with nafoxidine or estradiol implants showed sustained long-term nuclear retention of estrogen receptor and increased nuclear RNA polymerase activities for up to 72 hr. A single injection of estradiol caused initial increases in these variables which returned to control levels by 24 hr after hormone treatment. Uterine tissue was examined by light and electron microscopy 72 hr after hormone treatments. Uteri from eith estradiol-implanted or nafoxidine-treated animals showed markedly increased hypertrophy of the luminal epithelial cells. Nuclei in sections of the uteri of these hyperestrogenized animals displayed a large number and wide array of nuclear bodies composed of a filamentous capsule and granular cores. We conclude that hyperestrogenization, a condition that eventually results in abnormal cell growth, is correlated with increased and sustained nuclear binding of the estrogen receptor, increased and sustained RNA polymerase activity, and the appearance of nuclear bodies.

Animals↗
PubMed1978

Stoichiometric translocation of the rat uterine progesterone receptor.

In several previous studies nuclear accumulation of the progesterone receptor was significantly lower than the quantity depleted from the cytosol one h after progesterone injection. The results presented herein indicate that this apparent lack of stoichiometry is due to loss of detectable receptor from the nucleus during the nuclear washes and after the assay incubation. This decrease in measured receptor results both from solubilization of the receptor-progesterone complex into the supernatant and from dissociation of [3H] ligand from the receptor. Conversely, no significant quantities of receptor were detected in the mitochondrial/microsomal fraction, preincubation nuclear washes, second ethanol extraction of the nuclear pellet, and soluene digest of the extracted pellet. Thin layer chromatography of the radioactive ligand bound to the nuclear receptor after in vitro exchange confirmed that virtually all the specific binding was due to [3H] progesterone, in spite of a 30% conversion to other metabolites in the incubation fluid.

Animals↗
PubMed1978

Enhanced biotransformation of theophylline in marihuana and tobacco smokers.

Single oral doses of theophylline were administered to 7 chronic marihuana smokers, to 7 chronic users of both marihuana and tobacco, and to 43 appropriate control subjects. Theophylline was cleared from the blood more rapidly in both marihuana and tobacco smokers with a mean increase in total clearance from 52 ml/kg/hr in nonsmokers to 74 ml/kg/hr in subjects who smoked either material alone. There was an additive increase in clearance to 93 ml/kg/hr in those who smoked both substances. Concern over enhanced metabolism of other drugs is probably warranted in tobacco and cannabis smokers.

Adult↗
PubMed1977

Milk production, nitrogen utilization and glucose synthesis in lactating cows infused postruminally with sodium caseinate and glucose.

Four lactating Holstein cows were used in a 4 X 4 Latin Square design to determine the effects of postruminally administering sodium caseinate and/or glucose on milk production, milk composition, nitrogen utilization, amino acid utilization by the lactating mammary gland and glucose turnover rate. An 8.5% increase in milk yield and a 13.3% increase in milk protein production were obtained during infusion of sodium caseinate. No significant production responses were attributed to abomasal infusion of glucose. Arterial concentrations of most essential amino acids were increased during infusion of sodium caseinate. Uptake of phenylalanine, methionine and lysine by the mammary gland most closely paralleled their output in milk. The relative concentrations of methionine, lysine and phenylalanine in arterial plasma were considerably less than their concentrations in milk which resulted in a large percentage extraction of these amino acids by the mammary gland. If the availability of essential amino acids to the mammary gland, per se, was limiting the synthesis of milk protein, methionine, lysine and phenylalanine may have been the three amino acids most limiting. Measurements of glucose entry rate showed a trend toward increased glucose flux when either glucose, sodium caseinate or glucose plus sodium caseinate were infused abomasally. The similarity in glucose entry rates obtained during infusion of glucose and sodium caseinate suggest that the increase in milk production was not due totally to increased glucose flux resulting from sodium caseinate infusion.

Amino Acids↗
PubMed1977

Nuclear binding and retention of the receptor estrogen complex: relation to the agonistic and antagonistic properties of estriol.

The relationship between nuclear retention or residency or receptor estrogen complexes and the agonistic and antagonistic properties of estriol was examined. Cytoplasmic estrogen receptor (Rc) and uterine weight were measured 24 and 48 h after treatment with estradiol (E2), estriol (E3), or or both hormones (E2 and E3). Levels of Rc were elevated in all groups at either time. Since levels of Rc were above control in each case, Rc does not appear to be the limiting factor in the antagonistic effect of estriol. Therefore, the effect of these steroids on translocation and retention of nuclear receptor estrogen complexes (RnE) was examined. Rats were injectd as above and RnE measured by 3[H] estradiol exchange 1, 3, and 6 h after injection. All treatments cause equal translocation of receptor of the nuclear compartment. However, by 6 h the quantity of Rn present in E2 treated animals was significantly above controls while that in E2 + E3 animals was intermediate. E3 alone failed to cause significant nuclear retention of Rn. These patterns of retention correlate with the weight and cytoplasmic receptor responses above and suggest that the short nuclear residency time of RnE3 complexes relates to the antagonism of E3. To test this, these estrogens were administered via paraffin pellets to maintain blood levels of each hormone. Levels of Rn were elevated 24 and 48 h after implant with no significant differences between treatment groups. Likewise, there were no differences in the growth response. Uterine weights were highly stimulated in all three cases (300% above control). These results indicate that E3 acts as an estrogen antagonist when injected as a bolus because of the short nuclear retention time of RnE3 complexes. However, when E3 is present continuously and RnE3 is elevated and maintained, E3 is a potent estrogen without antagonistic properties.

Animals↗
PubMed1977

Effect of ionic strength on charcoal adsorption assays of receptor-estradiol complexes.

The effect of increasing ionic strength on the efficacy of the charcoal adsorption assay for estrogen receptors has been examined. Cytosol prepared from immature rat uteri was exposed to variable concentrations of KCl and the saturable or "specific" binding of [3H]estradiol was measured by charcoal and hydroxylapatite adsorption, gel filtration, and/or density gradient centrifugation using excess diethylstilbestrol to correct for non-saturable or "non-specific" binding. As the concentration of KCl was increased, the number of estradiol binding sites as measured via charcoal adsorption decreased in proportion to the conversion of receptor from a low salt (8S) to a high salt (4S) complex. This "stripping" of [3H]estradiol from the 4S receptor species was both time- and charcoal concentration-dependent. It is concluded that the charcoal adsorption procedure quantitatively assesses the binding of [3H]estradiol to low salt, 8S receptor species but is not the assay of choice for salt-extracted or salt-treated receptors in view of the potential for artifactually low estimates of receptor number. Low values for receptor number under high salt conditions may result from exposure of the binding site of the estrogen receptor to charcoal.

Animals↗
PubMed1977

Valine, leucine, and isoleucine metabolism by lactating bovine mammary tissue.

Valine, leucine, and isoleucine were extracted by the lactating bovine mammary gland in excess of outputs in milk protein. Carbon-14 uniformly labeled L-valine, L-leucine or L-isoleucine were catabolized when incubated in vitro with lactating bovine mammary tissue slices. The pathways of degradation of these amino acids by mammary tissue appear to be those common to other tissues. These amino acids represent a potential source of energy to the mammary gland as well as a source of carbon and alpha-amino nitrogen for synthesis of nonessential amino acids.

Acetates↗
PubMed1977

The management of severe preeclampsia and eclampsia with intravenous diazoxide.

Twelve patients with either severe preeclampsia (9) or eclampsia (3) were treated with intravenous diazoxide, 300-mg bolus, for the reduction of diastolic blood pressure (less than or equal 110 torr) after the usual and customary measures had been initiated to include parenteral MgSO4 and diazepam. Diazoxide precipitously decreased both systolic and diastolic blood pressure proportionately (35-50%); the nadir was invariably reached in 5-15 minutes. Diastolic pressure never fell below 50 torr, and mean arterial pressure always exceeded 70 torr. Oliguria was not apparent. The vasodepressor response was fairly persistent for 4 hours in all but 3 patients; 2 of these received a second 300-mg dose. Significant changes in fetal heart activity (bradycardia, dysrhythmia) were observed in only 1 patient. Labor was immediately ablated in all patients, but could be restimulated with oxytocin. All pregnancies were terminated within 7 hours (mean, 3.7 hours), seven of them by cesarean section. Eleven newborns did well. We conclude that the immediate reduction in maternal arterial blood pressure is without apparent hazard to the mother as well as the fetus.

Adolescent↗