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M T Williams

Publications and source records attributed to M T Williams.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of peripherally administered corticotropin-releasing factor (CRF) and a CRF antagonist: does peripheral CRE activity mediate behavior of guinea pig pups during isolation?

Guinea pig pups vocalized and ambulated when first isolated in a test cage; at 1 and 24 hr, levels of these behaviors had waned, and pups frequently exhibited a crouched stance, eye-closing, and piloerection. Injection (s.c.) of corticotropin-releasing factor (CRF) prior to isolation diminished the initial vocalization and locomotor responses and induced pups to exhibit the crouched stance, eye-closing, and piloerection at the beginning of the isolation period. Pretreatment with a CRF-receptor antagonist reversed the behavioral effects of CRF. CRF had no effect on blood pressure. Thus, s.c. CRF produced the same behavioral profile as seen with the passage of time in untreated isolated pups. The behavioral effects appeared to be CRF-receptor-mediated events and were not secondary to hypotension. These results support the hypothesis that during prolonged isolation, high or sustained peripheral CRF activity modulates behavior.

Animals↗
PubMed1992

Effects of centrally administered corticotropin-releasing factor (CRF) and alpha-helical CRF on the vocalizations of isolated guinea pig pups.

Intraventricular corticotropin-releasing factor (CRF) was administered to guinea pig pups both with a freehand injection technique and via indwelling cannula. Behavioral effects depended upon the technique used. The highest dose of CRF (5 micrograms) inhibited the vocalizing of pups in a subsequent isolation test only when CRF was given by freehand injection. The possibility that disturbance attendant to the freehand procedure can account for this difference is discussed. To determine the effect of endogenous CRF in the absence of additional disturbance, the CRF antagonist alpha-helical CRF (ahCRF) was administered with the indwelling cannula procedure. ahCRF enhanced vocalizing during the first 10 min, and enhanced locomotor activity during the last 10 min, of a 30-min isolation test. Overall, the results indicate that endogenous CRF reduces vocalizing and locomotion during social isolation and that under certain injection conditions exogenous CRF can exacerbate the behavioral effect. The results also demonstrate the potential impact of the technique used to administer exogenous CRF. Further, the prevailing view, that CRF mediates stress-related behavioral responses, is supported only if behavioral inhibition, rather than vocalizing or locomotor activity, is viewed as the stress-related response in this situation.

Animals↗
PubMed1992

Cytochrome P450. Mechanisms of action and clinical implications.

The term cytochrome P450 refers to a group of hemoproteins whose Fe(2+)-carbon monoxide complex shows an absorption spectrum with a maximum near 450 nm. There is a broad interest in the P450s because of their significance in a variety of disciplines ranging from medical genetics to inorganic chemistry. Cytochrome P450 enzymes are involved in the metabolism of drugs, carcinogens, steroids, pesticides, hydrocarbons and natural products. The toxicity of many of these products may be modulated, either via replacement or by the various oxidations catalyzed by the cytochrome P450 enzymes. In recent years the roles of cytochrome P450 enzymes in the metabolism of endogenous compounds have been partially elucidated. Physiological compounds such as steroids, fatty acids, prostanoids and other eicosanoids, fat-soluble vitamins and mammalian alkaloids have been shown to be substrates. Aside from their roles in metabolism, certain of these enzymes were found to be involved in the metabolic activation of a variety of chemical carcinogens and possibly in the overall process of chemical carcinogenesis. Studies show that alterations in cytochrome P450 activities toward various substrates have been implicated in diseases which affect human health. The roles are reviewed of the various cytochrome P450 enzymes in the metabolism of substrates which may be associated with clinical disease states.

Animals↗
PubMed1991

Predicting length of stay in long-term treatment for chemically dependent females.

Psychological and demographic variables were analyzed for 136 chemically dependent women treated in a residential therapeutic community. Cocaine users constituted 50% of the sample and were likely to drop out of treatment earlier (p less than .05). Of all the variables studied, only the Beck Depression Inventory scores were significantly higher for clients who terminated treatment prematurely compared to clients who completed treatment. The results point to the need for further research on the role of depression as a predictive factor of retention.

Adult↗
PubMed1988

Liver microsomal inactivation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone as an inhibitor of ribonucleotide reductase.

Studies were carried out to determine the effects of preincubation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ) with hepatic microsomes on the ability of MAIQ to inhibit CDP reductase activity in vitro. An aliquot from the 100,000 x g supernatant fraction from this incubation was used in the CDP reductase assay. MAIQ incubated in the absence of microsomes inhibited CDP reductase activity in a dose-dependent manner. At high MAIQ concentration (5 microM) CDP reductase activity was inhibited 95%. When MAIQ (5 microM) was first incubated in the presence of hepatic microsomes and NADPH, CDP reductase activity was inhibited only 30%. This attenuation of MAIQ inhibition was dependent on time of incubation and microsomal protein concentration and showed an obligatory requirement for NADPH or NADH. Significant attenuation was observed at pyridine nucleotide concentrations as low as 0.1 mM. Heat denaturation of microsomal proteins inactivated their ability to attenuate the MAIQ inhibition. Microsomes prepared from Ehrlich tumor cells were ineffective as inactivators of MAIQ. Results of our studies show that hepatic microsomes contain an enzyme(s) which can inactive MAIQ as an inhibitor of CDP reductase.

Animals↗
PubMed1988

Effects of growth hormone on cytochrome P-450j.

Hypophysectomy of male and female rats resulted in a 5 and 10-fold increase respectively, in cytochrome P-450j as determined by immunoblotting. Treatment of hypophysectomized rats with growth hormone resulted in a decrease in P-450j. Microsomal N-nitrosodimethylamine demethylase activity was increased approximately 23 and 75 per cent in male and female rats respectively, over the activity in microsomes of intact animals. These studies suggest that hypophysectomy results in an increase in cytochrome P-450j and that growth hormone acts as a repressive factor for constitutive P-450j.

Animals↗
PubMed1988

In vivo suppression of stearyl CoA desaturase activity by griseofulvin: evidence against the involvement of lipid peroxidation.

Administration of a diet containing 2.5% (w/w) griseofulvin (GF) resulted in a significant decrease in hepatic microsomal stearyl CoA desaturase activity compared to desaturase activity in microsomes from animals fed a normal rat chow diet. Desaturase activities were 0.66 +/- 0.18 vs 0.16 +/- 0.09 nmoles oleyl CoA formed/min/mg protein for control and GF-fed animals, respectively. Examination of lipid peroxides in microsomes from control and GF-treated rats showed an approximate fivefold higher concentration of lipid peroxides in microsomes from GF-treated rats compared to that from controls. However, when rats were fed a diet containing GF and diphenyl-p-phenylenediamine an inhibitor of lipid peroxidation, stearyl CoA desaturase activity was still similar to that observed with GF alone, even though microsomal lipid peroxides were reduced to nondetectable levels. In vitro stimulation of microsomal lipid peroxidation using ADP-Fe and EDTA-Fe did not result in a significant decrease in desaturase activity. Results of our experiments show that dietary administration of GF results in a marked decrease in stearyl CoA desaturase activity in hepatic microsomes. Although GF feeding stimulates microsomal lipid peroxidation, increase in microsomal peroxidation does not appear to be the mechanism by which GF feeding decreases desaturase activity. GF appears to act by decreasing the terminal desaturase activity.

Animals↗
PubMed1988

Policies and procedures for scheduling student nurses.

A smoothly operating system for student clinical affiliations can save staff time and positively influence recruitment and retention. To ensure a systematic approach to scheduling students, the author shares her approach, policies, and procedures.

Clinical Clerkship↗
PubMed1987

Effects of pregnenolone-16 alpha-carbonitrile on drug metabolizing enzymes in hypophysectomized female rats.

Treatment of intact and hypophysectomized female rats with pregnenolone-16 alpha-carbonitrile (PCN) resulted in a significant increase in hepatic aryl hydrocarbon hydroxylase (AHH) activity. However, the total cytochrome P-450 concentration, as measured by CO difference spectra, was increased to a greater extent in hypophysectomized rats than in intact rats. Total cytochrome P-450 was found to be 0.82 +/- 0.16 vs 2.43 +/- 0.31 nmoles/mg protein for control and PCN-treated hypophysectomized rats, respectively, and 0.68 +/- 0.23 vs 1.28 +/- 0.05 nmoles/mg protein for control and PCN-treated intact rats respectively. The concentration of metyrapone complex in microsomes from intact control and PCN-treated rats was found to be 0.4 +/- 0.11 vs 1.88 +/- 0.23 M respectively. Treatment of hypophysectomized rats with PCN resulted in an approximate 10-fold increase in the concentration of the metyrapone complex (0.42 +/- 0.15 M for control and 4.46 +/- 0.44 M for PCN-treated). Microsomal NADPH and NADPH cytochrome c reductase activities were also altered by PCN-treatment. Aminopyrine demethylase activity was stimulated approximately three-fold by PCN treatment in both intact and hypophysectomized rats. Benzphetamine demethylase activity was not significantly affected by PCN treatment. The results of these studies suggest that the absence of the pituitary gland can markedly influence PCN induction of cytochrome P-450 in the liver in female rats. PCN also differentially affects microsomal mixed-function oxidase activities associated with drug and xenobiotic metabolism.

Aminopyrine N-Demethylase↗
PubMed1986

Stimulation of mouse liver glutathione S-transferase activity in propylthiouracil-treated mice in vivo by tri-iodothyronine.

Female C57Bl/6J mice were given drinking water containing 0.05% propylthiouracil to induce a hypothyroid condition. Mitochondrial glycerol-3-phosphate dehydrogenase activity, used as an index of hypothyroidism, was 57.1 +/- 4.5 and 29.4 +/- 3.8 nmol/min per mg of protein for control and propylthiouracil-treated animals respectively. Administration of tri-iodothyronine resulted in an approx. 4.5-fold increase in dehydrogenase activity in propylthiouracil-treated animals. A dose-dependent increase in hepatic GSH S-transferase activity in propylthiouracil-treated animals was observed at tri-iodothyronine concentrations ranging from 2 to 200 micrograms/100 g body wt. This increase in transferase activity was seen only when 1,2-epoxy-3-(p-nitrophenoxy)propane was used as substrate for the transferase. Transferase activity with 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrate was decreased by tri-iodothyronine. Administration of actinomycin D (75 micrograms/100 g body wt.) inhibited the tri-iodothyronine induction of transferase activity. Results of these studies strongly suggest that tri-iodothyronine administration markedly affected the activities of GSH S-transferase by inducing a specific isoenzyme of GSH S-transferase and suppressing other isoenzymic activities.

Animals↗
PubMed1985

Effects of inhibitors of RNA and protein synthesis on hepatic microsomal cytochrome P-450 concentration in fasted and fed rats.

A number of sex-related differences in the metabolism of drugs, steroids and xenobiotics have been reported in studies on rats. Generally, male rats tend to metabolize these compounds more efficiently than females. In the studies presented here, male and female rats were fasted for 24-48 hr, and the effects of fasting on total hepatic microsomal cytochrome P-450 were examined. Hepatic cytochrome P-450, as determined by CO difference spectra, was increased significantly as a percentage of control in microsomes from fasted female rats when compared to fasted male rats. Cytochrome P-450 concentration increased from 0.57 +/- 0.07 nmole/mg protein to 0.99 +/- 0.08 nmole/mg protein following a 24-hr fast. In male rats, cytochrome P-450 levels were essentially unaffected by the 24-hr fast. Cytochrome b5 concentration was not altered by fasting. When female rats were fasted for 24 hr and refed, cytochrome P-450 levels were not significantly different from cytochrome P-450 levels in continuously fed animals. Treatment of fasted female rats with the protein synthesis inhibitor ethionine, or the RNA synthesis inhibitor actinomycin D, prevented the induction of cytochrome P-450 in the fasting animal. Cytochrome P-450 concentration in fed animals was not affected significantly by either inhibitor. Induction of cytochrome P-450 by phenobarbital (PB) and 3-methylcholanthrene (MC) under fed and fasted conditions was also investigated in male and female rats. Xenobiotic-induced cytochrome P-450 concentration was significantly higher in fasted female hepatic microsomes when compared to microsomes from fed female rats. Fasting did not significantly affect xenobiotic-induced cytochrome P-450 in male rats. Our results suggest that fasting in female rats results in an increase in cytochrome P-450 which is dependent upon synthesis of RNA and protein.

Animals↗
PubMed1985

Effects of pregnant mare serum gonadotrophin and oestradiol benzoate on enzymes associated with xenobiotic metabolism in immature and hypophysectomized female rats.

Treatment of immature (22-day-old) female Sprague-Dawley rats with pregnant mare serum gonadotrophin (PMSG) resulted in a significant increase in hepatic microsomal cytochrome P-450 concentrations when compared with animals treated with 0.9% (w/v) NaCl solution. Cytochrome P-450 concentrations in microsomes from control and PMSG-treated animals were 0.49 +/- 0.07 and 0.78 +/- 0.18 nmol/mg microsomal protein respectively (mean +/- S.D.). When hypophysectomized rats were treated with PMSG no significant difference was observed between saline-treated and PMSG-treated animals (0.84 +/- 0.06 vs 0.88 +/- 0.08 nmol/mg microsomal protein). Cytochrome b5 concentration and NADPH-cytochrome c reductase and ferricyanide reductase activities were not significantly affected by PMSG treatment. Similar results were obtained when immature and hypophysectomized rats were treated with oestradiol benzoate. Hepatic glutathione (GSH) S-transferase activity was significantly stimulated over control values when hypophysectomized or immature animals were treated with PMSG, oestradiol benzoate or 3-methylcholanthrene. Treatment of animals simultaneously with PMSG or oestradiol benzoate and 3-methylcholanthrene resulted in higher transferase activity than did either treatment alone. Oestradiol benzoate or PMSG treatment of immature female rats resulted in an approximate twofold increase in hepatic aryl hydrocarbon hydroxylase (AHH) activity. However, AHH activity in hypophysectomized animals was not significantly increased by PMSG or oestradiol benzoate treatment. It is concluded that PMSG or oestradiol benzoate treatment of immature female rats resulted in increased total cytochrome P-450 concentration and AHH activity in hepatic microsomes. Glutathione S-transferase activity was also stimulated. Neither PMSG nor oestradiol benzoate stimulated cytochrome P-450 levels or AHH activity in hypophysectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗