Stimulatory effects of prostaglandin e-1 on rat anterior pituitary cyclic AMP and luteinizing hormone release.
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Biomedical subjects
Publications and source records attributed to M C Wilson.
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Wilson, Melba Carr (Brown University, Providence, R.I.), James L. Farmer, and Frank Rothman. Thymidylate synthesis and aminopterin resistance in Bacillus subtilis. J. Bacteriol. 92:186-196. 1966.-The thymine-requirement of Bacillus subtilis 168 thy results from mutation in two unlinked genes (i.e., genetic loci) designated thyA and thyB. The thyB gene is located between the met and ile markers. Both thyA(+)thyB and thyA thyB(+) strains are phenotypically thy(+). ThyA(+)thyB strains resemble the wild type in their sensitivity to aminopterin, poor incorporation of exogenous thymine into deoxyribonucleic acid (DNA), and high level of thymidylate synthetase activity in crude extracts. ThyA thyB(+) strains are resistant to aminopterin in the presence of thymine, incorporate exogenous thymine into DNA, and have no detectable thymidylate synthetase activity. Experiments designed to elucidate the role of the thyB gene indicate that it specifies an alternate pathway of thymidylate synthesis, similar to thymidylate synthetase but requiring a cofactor other than tetrahydrofolate. The mechanism of selection of thymine-requiring mutants by aminopterin is revealed by these results.
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Previous investigations have demonstrated the ability of atropine and chlorpromazine pretreatment to increase intravenous cocaine self-administration in rhesus monkeys. These results were interpreted as resulting from either an antagonism of cocaine's reinforcing effect or an effect of cocaine which may interfere with its self-administration. The generality of the postulated drug antagonism was tested in monkeys exhibiting stable FR10 food-reinforced behavior. Intramuscular pretreatment with 0.25-4.0 mg/kg of chlorpromazine significantly depressed this behavior as did pretreatment with 0.25-2.0 mg/kg of atropine. These same dosages had been shown to increase cocaine self-administration. Fifteen-minute influsions of cocaine (1.0-10 mg/kg), which began 15 min after session onset, also resulted in a depression of food reinforced behavior. When chlorpromazine pretreatment and cocaine infusion were combined, the decrement in food reinforced responding was lessened. However, when cocaine infusion and atropine pretreatment occurred concurrently, the depression in responding was increased. These data indicate that chlorpromazine may nonspecifically antagonize the behavioral effects of cocaine; whereas, atropine may enhance these effects.
The current study involves an investigation of the possible neurotransmitter systems involved in the ability of exogenously administered sincalide (cholecystokinin octapeptide, CCK-8) to suppress feeding. Male rats previously trained to obtain food either during a daily 3-hr session, or conditioned to obtain food pellets on a fixed-ratio or fixed-interval schedule of reinforcement, were treated IP with CCK-8, following pretreatment with representative drugs of several pharmacological classes. Pretreatment with phenoxybenzamine, tolazoline, yohimbine, morphine, haloperidol or picrotoxin reduced the efficacy of CCK-8. However, pretreatment with naloxone or clonidine potentiated the suppressant action of CCK-8 on feeding. Propranolol, diphenhydramine, cimetidine, atropine, d-amphetamine, fenfluramine or diazepam pretreatment either had no effect or no consistent action in altering the activity of CCK-8. The ability of CCK-8 to suppress feeding was not altered by subacute treatment with the anorectics, d-amphetamine or fenfluramine, using a regimen known to induce tolerance. These data indicate that CCK-8 exerts a different mechanism of action than that of fenfluramine or d-amphetamine, and furthermore, that noradrenergic, dopaminergic, GABAergic or endogenous opioid systems either mediate or can modify the effect of CCK-8 on feeding.
Medical practitioners often have difficulty in assessing the presence or severity of diabetic retinopathy. The tourniquet test is a method of assessing diabetic capillary fragility that has been felt to reliably correlate with background and proliferative diabetic retinopathy. We studied 100 consecutive diabetic patients and 50 age-matched controls in a masked fashion, using fundus photographs and fluorescein angiography to correlate the amount of capillary fragility with the presence and severity of background and proliferative diabetic retinopathy. Although the severity of diabetic capillary fragility did correlate with the presence and severity of diabetic retinopathy (p less than 0.001), this test was not as good an indicator of diabetic retinopathy as were other risk factors such as duration of diabetes (p much less than 0.001). The tourniquet test is unreliable in predicting the presence or severity of diabetic retinopathy because of its high false negative response rate.
Male Swiss mice, 20-25 g, were utilized to assess the effects of dermal and oral administration of the pyrethroid insecticide formulations Pydrin (30% fenvalerate) and Ambush (25.6% permethrin). Animals were subjected to a conditioned taste aversion procedure using a normally preferred 0.3% saccharin solution. Subjects were allowed 30 min access to a drinking syringe containing the saccharin solution, followed immediately by the administration of the pyrethroid or control solution. Pydrin (0.3, 3.0, or 30 mg/kg orally; 60, 600, or 1800 mg/kg dermally) and Ambush (0.5, 5.0, or 50 mg/kg orally; 30, or 300 mg/kg dermally) produced significant (p less than 0.05) reductions in the percent saccharin consumed. Total fluid intake, however, was not significantly altered by any of the treatments. The effect of the insecticides on both grouped and individual activity was also assessed in 20-25 g male Swiss mice. Activity measurements were taken over the 4-hr time period immediately following the administration of the pyrethroid or control solution. Pydrin (30 mg/kg orally; 600 and 1800 mg/kg dermally) and Ambush (50 mg/kg orally; 300 mg/kg dermally) significantly (p less than 0.05) increased activity in both grouped and individually tested mice. When subjects were individually tested, significant increases were seen in non-ambulatory, but not in ambulatory activity. The results of this work indicate that administration of the commercially available preparations of Pydrin and Ambush in mice at doses that do not induce the tremor and choreoathetosis-salivation syndromes usually associated with pyrethroid insecticides may result in behavioral changes.