The association between chronic cannabis use and cognitive functions.
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Biomedical subjects
Publications and source records attributed to R Ray.
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The psychosocial effects of chronic heavy use of cannabis were studied in a rural population of males in north India. The user group comprised thirty persons who had been taking only cannabis at least 11 times a month over a period of five years or more. The controls were fifty subjects selected from among the general population to which the users belonged. The controls had not been using any drugs. The subjects had similar age distribution, occupation, socioeconomic status, and educational background. Psychosocial adaptation was assessed by enquiries into such areas as self-aspiration, present occupation, occupational satisfaction, marital status, marital relationships, sexual behaviour, self-reported deviant behaviour, and future planning for children. On no variable were the present users found to be different from the non-user control group.
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In a prospective study carried out on a cohort of 17,942 women belonging to the Kaiser Foundation Health Plan and living in suburban communities of the San Francisco Bay Area, a positive association was found between the incidence of cervical carcinoma and total duration of oral contraceptive use. The association was established while controlling for the effects of age, education, and selected infections. The association persists when incident cases of dysplasia are added to those of carcinoma. A further study, in which covariates relating to sexual behavior will also be taken into account, is in progress.
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Four neurotoxins that activate the action potential Na+ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin, a specific inhibitor of the action potential Na+ current, inhibits activation by each of these toxins in a noncompetitive manner (KI=4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ionophore: two regulatory components which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin. The dissociation constant for scorpion toxin binding is increased 10-fold by depolarization of the cells with K+, suggesting that the scorpion toxin binding site is located on a voltage-sensitive regulatory component of the ionophore.
Depolarization of neuroblastoma cells causes a 70-fold increase in the apparent dissociation constant KD for scorpion toxin enhancement of activation of the action potential Na+ ionophore by veratridine and a large increase in the rate of reversal of scorpion toxin action. Depolarization also inhibits binding of 125I-labeled scorpion toxin to a small number of saturable binding sites on electrically excitable neuroblastoma cells and increases the rate of dissociation of scorpion toxin from these sites. The results suggest that scorpion toxin binds to a regulatory component of the action potential Na+ ionophore whose conformation changes on depolarization.
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One of the mechanisms of the skin blistering effect (vesication) of sulfur mustard (bis-(2-chloroethyl)sulfide, HD) is believed to be via the stimulation of specific protease(s) at the dermal-epidermal junction. Cultured normal human epidermal keratinocytes (NHEK) were used as a model to study and characterize protease stimulated by the mustards 2-chloroethyl ethyl sulfide (CEES), 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride (nitrogen mustard, HN(2)) and HD. The results obtained using a chromozym (TRY) peptide substrate protease assay revealed the optimum mustard concentrations and time for protease stimulation to be about 200 microM (CEES), 100 microM (HN(2)) and 100 microM (HD) and 16 h. The mustard-stimulated protease was membrane bound and was inhibited by adding a Ca(2+) chelator (either 2 mM EGTA (ethylene glycol-bis(amino ethyl ether) N,N,N',N' tetraacetic acid) or 50 microM BAPTA AM (1,2-bis(z-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxy methyl ester) alone or in combination), a serine protease inhibitor diisopropyl fluoro-phosphate (DFP, 1 mM), or a protein synthesis inhibitor cycloheximide (35 microM) in the extracellular medium. These results suggest that mustard toxicity may involve the stimulation of trypsin/chymotrypsin-like serine protease, dependent on Ca(2+) and new protein synthesis. Protein purification by gel exclusion and hydrophobic chromatography produced a 70-80 kDa protease, which had an amino acid sequence homologous with a mammalian-type bacterial serine endopeptidase. Based on this information, research is in progress to identify the protease stimulated by HD in NHEK and to determine whether its inhibitors are useful as prospective antivesicant drugs.
The clinical and hematological characteristics of ten children with myelodysplastic syndromes diagnosed and followed up over a 3 year period are presented. All of them had anemia and a low platelet count whilst the white blood cell count was variable. Presentation with bilateral proptosis and acute febrile neutrophilic dermatosis (Sweet's syndrome) were unique features observed in one case each. None of these cases could afford specific therapy and thus serve to illustrate the natural history of the disease in pediatric practice.
The synthesis of 1 alpha,25-dihydroxyvitamin D3-3 beta-[N-(4-azido-2-nitro-[2,6-3H] phenyl)]glycinate, a radiolabeled photoaffinity analog of 1,25-dihydroxyvitamin D3, is described.
Clinical efficacy of buprenorphine in controlling withdrawal symptoms was compared against clonidine among 44 opiate dependent males. Subjective and objective withdrawal symptoms were assessed by withdrawal rating scales daily for 10 days. The subjects were randomly assigned to fixed dose schedule of either buprenorphine (0.6-1.2 mg per day, sublingually) or clonidine (0.3-0.9 mg per day, oral) for 10 days. Buprenorphine was found superior to clonidine in alleviating most of the subjective and objective opiate withdrawal symptoms. Subjective symptoms declined earlier among the subjects receiving buprenorphine. No untoward side-effects of buprenorphine were noticed.