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M T Williams

Publications and source records attributed to M T Williams.

At least 55 records · Page 3Linked to original sources
PubMed1980

Correlation of cyclic AMP and cyclic GMP accumulation and steroidogenesis during stimulation of bovine luteal cells with luteinizing hormone.

The relationship between LH-induced steroidogenesis and the production of cyclic AMP and cyclic GMP was studied as a function of LH dose and time in isolated luteal cells from pregnant cows. Submaximal steroidogenic concentrations of LH caused a transient but significant rise in cyclic AMP that peaked after incubation for 5 min. A consequent rise in progesterone occurred at 30 min even though cyclic AMP had returned to the basal level at that time. Higher steroidogenic doses of LH elicited a maximum increase of cyclic AMP at 5 min and this was sustained for up to 1 h; the related progesterone production was significantly raised at 15 min and reached a maximum plateau at 30 min. The corresponding levels of cyclic GMP did not appear to be altered by any of the LH concentrations used. The present study has provided direct evidence that even at very low doses of LH, cyclic AMP plays an intermediary role in the stimulation of steroidogenesis in a mixed population of cells isolated from the bovine corpus luteum. Cyclic GMP, on the other hand, did not appear to play a role in the action of LH on the same population of luteal cells.

Animals↗
PubMed1979

Inhibition of human chorionic gonadotropin-induced progesterone synthesis by estradiol in isolated human luteal cells.

The purpose of this study was to determine whether estrogens exerted a direct inhibitory effect on progesterone synthesis in isolated human luteal cells in vitro. It was found that hCG stimulated progesterone synthesis by luteal cells, obtained from corpora lutea of the menstrual cycle, whereas cells isolated from corpora lutea of pregnancy were unresponsive to exogenous hCG. Estradiol markedly inhibited (P less than 0.001) this hCG effect in luteal cells of the menstrual cycle, and this inhibition was dose dependent. Estradiol did not block the stimulation of cAMP accumulated by hCG in the luteal cells of the cycle but did inhibit the stimulatory effect of dibutyryl cAMP on progesterone synthesis. These data suggest that estrogens may directly cause functional luteolysis in the human and that its site of action may be after the accumulation of cAMP.

Chorionic Gonadotropin↗
PubMed1978

Estradiol inhibition of luteinizing hormone-stimulated progesterone synthesis in isolated bovine luteal cells.

The effects of several steroid hormones on progesterone synthesis and cAMP accumulation in isolated bovine corpora luteal cells were investigated in an attempt to determine if any of the steroids would affect the basal level of these processes or their response to gonadotropin. Isolated bovine corpora luteal cells responded to LH with a significant (P less than 0.05) increase in progesterone synthesis and cAMP accumulation when incubated at 37 C for up to 1 h. Exogenous cAMP and analogs of cAMP also significantly stimulated steroidogenesis in these incubated cells. Stimulation of progesterone synthesis by 1 microgram/ml LH was significantly suppressed (P less than 0.05) in the presence of 5--10 microgram/ml estradiol. This inhibition appeared to be largely specific for 17beta-estradiol, in that other steroids such as estrone, estriol, 17alpha-estradiol, cortisol, and dihydrotestosterone were not inhibitory. Testosterone was found to be inhibitory, but it is uncertain if this effect was due to the androgen itself or to its conversion to estradiol. Estradiol did not affect the increase in endogenous cAMP caused by LH in these cells, but did inhibit the effect of exogenous dibutyryl cAMP on progesterone synthesis. The magnitude of this inhibition of the effect of dibutyryl cAMP was not, however, equal to the estradiol inhibition of the stimulation of progesterone synthesis by LH. These data indicate that estradiol, a possible physiological luteolytic agent, has a direct inhibitory action on the corpus luteum and produces its suppression by blocking the stimulatory effect of LH at a step after cAMP.

Animals↗
PubMed1977

Temperate Bacillus subtilis bacteriophage phi 3T: chromosomal attachment site and comparison with temperate bacteriophages phi 105 and SPO2.

The temperate Bacillus subtilis bacteriophage phi 3T contains within its genome a locus, designated thyP3, that encodes for a protein with thymidylate synthetase activity. Bacteriophage phi 3T is different from the two previously characterized temperate phages, phi 105 and SPO2, in: heteroimmunity, response to bacteriophage antisera, endonuclease digestion pattern, induction in the presence of 6-(p-hydroxyphenylazo)-uracil, and effect on the lytic cycle of bacteriophage phi 1. The mean burst size of phi 3T is 56. The dose response curve with bacteriophage phi 3T DNA is linear for transfection and transformation to the Thy+ phenotype. The inserted prophage has been mapped by PBS1 transduction; it is between chromosomal markers ilvA8 and gltA in the terminus of the chromosome. Thus thyP3 maps at a site separate from, but between, the bacterial markers thyA and thyB when thyP3 is in the prophage state.

Bacillus subtilis↗
PubMed1977

Investigation of the rate-determining microsomal reaction of cholesterol biosynthesis from lanosterol in Morris hepatomas and liver.

Previously, we reported that the properties or microsomal 4-methyl sterol demethylase isolated from liver and Morris hepatomas 5123C and 7777 are grossly similar. The individual enzymic steps of this multicomponent system have now been studied, and the rate-determining step has been determined and shown to be identical for liver and these hepatomas. The rates of microsomal oxidative attacks of the 4alpha-methyl, 4alpha-hydroxymethyl, and 4-aldehydic groups are similar for microsomes prepared from rat liver and hepatoma 7777. The rates of mixed-function oxidative attack appear to increase in the order;--CH3 less than --CH2OH less than --CHO. Furthermore, the hepatic and hepatoma NAD-dependent decarboxylase, which catalyzes the reaction following the three oxidative attacks is similar in properties and velocity. The fifth step, an NADPH-dependent reduction of the 3 ketosteroid that is produced by decarboxylation, is also similar. For both tissues, the latter two reactions, under in vitro conditions, proceed at rates that exceed the initial oxidative process. Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors. When the rate-determining reaction of both liver and hepatoma 7777 microsomes is assayed at different temperatures, the same activation energies and the same characteristic breaks in the arrhenius plots are observed. Thus, for both liver and hepatoma, both the nature and the site of rate determination in this multienzymic system must be similar. Since the microsomal enzymes of liver nad hepatoma appear to be catalytically similar and rate determination appears to be similar, too, the characteristic lact of response of tumor microsomes to treatments in vivo that alter host liver microsomal demethylation activity suggests that the insensitivity of these tumors to dietary cholesterol should not be ascribed to alterations in the catalytic proteins. Evidence in this report suggests that the postmicrosomal supernatant fraction of both liver and hepatoma contains a cytosolic protein that may participate in the regulation of the rate-determining attack of 4alpha-methyl sterol substrates. Thus, either qualitative or quantitative differences between the postmicrosomal supernatant fractions obtained from liver and heptomas may account for the observed differences in rates of cholesterol biosynthesis.

Animals↗
PubMed1976

Characterization of microsomal methyl sterol demethylase in two Morris hepatomas.

Previously, we reported that the rate of metabolism of methyl sterol intermediates of cholesterol biosynthesis by broken-cell preparations of Morriss hepatoma 7777 is very slow, whereas the intact tumors are known to synthesize cholesterol quite efficiently. Active preparations have now been obtained by substitution of pyrophosphate for phosphate buffer. Although substitution of pyrophosphate buffer markedly enhances microsomal methyl sterol demethylation rates 3- to 4-fold in hepatoma 7777, other microsomal enzymes and electron carriers in either liver or a more slowly growing hepatoma appear to be unaffected by pyrophosphate. Several properties of the active microsomal methyl sterol demethylase have now been compared for control rat liver, host liver, tumor 7777, and tumor 5123C. Conditions necessary for the assay of initial velocities of enzymic reactions in the tumor microsomes have been established with respect to the amount of protein, time-course, concentrations of cofactors and substrate, pH, and other variables. The K'm and the responses to the variables studied above are very similar for methyl sterol demethylase of microsomes isolated from control liver, host liver, tumor 5123C, and tumor 7777. The multienzymic demethylase in the various preparations has been found to be inhibited similarly by in vitro additions of cyanide, cytochrome c, and bile salts. Thus, the enzymes of the microsomal-bound 4-methyl sterol demethylase of cholesterol biosynthesis appear to be very similar in liver and these 2 Morris hepatomas. When xenobiotic inducers of microsomal oxidases, such as phenobarbital and methylcholanthrene, are administered to normal and tumor-bearing rats, elevated rates of methyl sterol demethylation are observed with isolated liver microsomes obtained from both normal and tumor-bearing rats. Similar increases are not observed in the tumors. Furthermore, daily administration of an intestinal bile acid sequestrant elevates hepatic methyl sterol demethylase, but statistically significant changes were not observed in tumors 7777 and 5123C. Since the enzymes of methyl sterol demethylase appear to be grossly similar in liver and these hepatomas, regulation of the activity of the multienzymic system contained in the tumors may be altered. On the other hand, these agents in vivo simply may not affect liver and the hepatomas similarly, due to a lack of uptake of the foreign substances by the tumor that has been transplanted to the thighs.

Animals↗
PubMed1974

Characterization of temperate bacteriophages of Bacillus subtilis by the restriction endonuclease EcoRI: evidence for three different temperate bacteriophages.

Temperate bacteriophages of Bacillus subtilis were characterized according to host range and digestion of the bacteriophage genome by endonuclease EcoRI. The three bacteriophages, phi3T, SPO2, and phi105, were all heteroimmune, and the DNA digests showed dissimilar patterns by agarose-ethidium bromide gel electrophoresis.

Bacillus subtilis↗
PubMedDate not supplied

Self-efficacy and motivation for controlling drinking and drinking/driving: an investigation of changes across a driving under the influence (DUI) intervention program and of recidivism prediction.

Measures of (a) self-efficacy and (b) motivation to change (stage) for controlling drinking and drinking/driving were examined at the beginning and the end of a four-week intervention in a sample of 670 Driving Under the Influence (DUI) offenders in a court-mandated program. Hypotheses regarding stability of stage classifications over the course of intervention, and the relation between stage classification, stage scores, self-efficacy, and DUI recidivism were examined. Based on results of an earlier study it was expected that most offenders would be classified into the action stage at entry and that classifications would tend to remain stable from pretest to posttest. Action was the most frequent stage classification in both drinking and drinking/driving domains at both test periods, with precontemplation being the least frequent classification. When tracked over the four weeks, stage classifications for drinking and drinking/driving were stable for 74 to 89% of offenders in the two domains, respectively. As predicted, higher action and self-efficacy scores were related to lower recidivism, and action scores in the drinking/driving domain were the best early recidivism predictors among a predictor set that included traditional recidivism indicators. Drinking contemplators (i.e., those with the highest stage score on the contemplation scale) had higher recidivism rates than other drinking stage classifications. Implications for DUI intervention programs are discussed.

Adult↗
PubMedDate not supplied

The distribution of radiolabeled corticotropin-releasing factor in pregnant rats: an investigation of placental transfer to the fetuses.

Stress during gestation can have serious consequences on the development of the fetus. Many of these effects appear to be mediated by hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing factor (CRF), released by the hypothalamus during times of stress serves to activate release of pituitary hormones and is also present in low levels in rat plasma. Moreover, the uterus contains significant quantities of CRF at implantation sites, probably from local sources. Therefore, the possibility exists that CRF may cross the placenta and activate the fetal HPA axis. However, the ability of CRF to cross the placenta has not been demonstrated. In the present study, pregnant rats were administered radiolabeled CRF intraperitoneally, and the distribution of the labeled product was determined in the fetuses and various maternal organs. High levels of activity were observed in the pregnant female's uterus, adrenals, heart and the placentae, but only background levels of activity were detected in the maternal brain. Very low levels of activity were observed in the fetuses, indicating that the transfer of CRF across the placenta is greatly restricted. These findings suggest that maternal CRF has little or no direct effect on the developing fetus during gestational stress.

Analysis of Variance↗
PubMedDate not supplied

Effects of prenatal cocaine on Morris and Barnes maze tests of spatial learning and memory in the offspring of C57BL/6J mice.

Cocaine was administered to gravid C57BL/6J mice on embryonic days E8-18 at doses of either 17.5 or 20 mg/kg x 2 per day; controls received equal volumes of vehicle. The two cocaine dose groups were indistinguishable in their effects on maternal weight gain, offspring survival or body weight; therefore, the two groups were combined. Offspring were assessed as adults in straight channel swimming, cued and spatial reference-memory and working memory versions of the Morris water maze (MWM), and in the Barnes spatial maze to escape from a light, tone and fan. Cocaine offspring had shorter latencies in the straight channel and increased cumulative distance from the platform and path length in the spatial version of the Morris maze, but only when the platform size was reduced, not under standard platform conditions. In the working memory test, cocaine offspring showed deficits in acquisition and, following random trials, on relearning during a final test phase. In the Barnes maze, cocaine offspring were delayed in utilizing more efficient search strategies and took longer to find the goal. Taken together, the data suggest that prenatal cocaine induces modest but significant long-term alterations in both reference and working memory-based spatial learning and memory.

Animals↗
PubMedDate not supplied

Preweaning treatment with methamphetamine induces increases in both corticosterone and ACTH in rats.

Treatment with methamphetamine (MA) on postnatal days P11-20 induces adult spatial learning and memory deficits without affecting monoamine levels in various brain regions. In this study, we examined the pituitary and adrenal response of animals administered MA four times daily on P11, P11-15, or from P11 to P20. Corticosterone (CORT) and adrenocorticotropin hormone (ACTH) levels were assessed over a 1-hour period following MA exposure. On P11, MA produced marked elevations of both CORT and ACTH; this is during the stress hyporesponsive period (SHRP). On P15 and P20, the maximal effect of MA on CORT titers was observed at 30 min, with lower, but still significantly increased, levels at 60 min compared to controls. Males receiving MA on P15 had higher levels of ACTH than did control males, while no differences were noted among females. On P20, MA treatment resulted in higher levels of ACTH relative to vehicle-injected controls, but levels were not different from controls that were only weighed at each drug administration. MA treatment inhibited body, but not brain weight gain, resulting in hippocampal weights that were heavier in the MA-treated animals when expressed as a percent of body weight. The elevations of adrenal steroids by MA, during late phases of hippocampal neurogenesis, may contribute to neuronal alterations that are later manifested in deficits of learning and memory.

Adrenocorticotropic Hormone↗