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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 487 records · Page 27Linked to original sources
PubMed1990

Percutaneous absorption of physostigmine: optimization of delivery from a binary solvent by thermodynamic control.

A series of binary vehicles was used to deliver physostigmine across dermatomed human skin. The vehicles consisted of isopropyl myristate (IPM) and isopropyl alcohol (IPA) mixed in various volume fractions. The kinetics of penetration is conveniently considered as the sum total of two contributing effects: a "push" process resulting from the excess free energy (delta EG) of the penetrant in the donor vehicle, and a "pull" process resulting from the effect of IPA and IPM on the skin barrier. The inverse ratio of the solubility of the drug in a given vehicle to that in pure IPA was used to estimate the relative delta EG, hence the relative "push" effect. The solubility of physostigmine was highest in pure IPA (delta = 11.5), lowest in pure IPM (delta = 8.5), and intermediate in their various mixtures. But the permeability coefficient (Kp) of physostigmine was highest when delivered from a 1:9 (v/v) solution of IPA:IPM and a calculated delta y = 8.8. A further increase in the volume fraction of IPA caused an opposite decrease in the Kp values of physostigmine. The "steady-state" flux (Jss) of IPA from the same vehicle was lowest at a volume fraction of 1:9 and highest at one of 1:1 IPA:IPM. Thus, the maximal physostigmine penetration enhancing effect of IPA occurs at the lowest flux of IPA found in the present series. This indicates that the "pull" process ascribed to the presence of IPA in the barrier membrane is not important enough to outweigh the decrease in delta EG of physostigmine following an increase in the volume fraction of IPA in the donor vehicle, or that an excess of IPA in the barrier is not conducive to further enhancement of physostigmine diffusivity across the barrier. Optimized percutaneous delivery of physostigmine is possible by thermodynamic control of the penetration process.

1-Propanol↗
PubMed1990

Praziquantel treatment of porcine brain and muscle Taenia solium cysticercosis. 1. Radiological, physiological and histopathological studies.

Porcine Taenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.

Animals↗
PubMed1990

Infection of tomato by the tomato yellow leaf curl virus: susceptibility to infection, symptom development, and accumulation of viral DNA.

Symptom development in tomato plants following whitefly-mediated inoculation with tomato yellow leaf curl virus (TYLCV) was related to the occurrence of viral DNA using a specific DNA probe. Although disease symptoms were first observed 15 days post-inoculation, viral DNA could be detected 7 days earlier. TYLCV-DNA concentrations reached an optimum 4 days before symptoms appeared. The highest concentrations of TYLCV-DNA were found in rapidly growing tissues (shoot apex, young leaves, roots) and in the stems; the lowest concentrations were found in the older leaves and cotyledons. Plants were also inoculated on specific sites. Young leaves and apices were the best targets for virus inoculation. In these tissues, the viral DNA replicated at the site of inoculation and was transported first to the roots, then to the shoot apex and to the neighboring leaves and the flowers. Inoculation through the oldest leaves was inefficient.

DNA Probes↗
PubMed1990

The frequency of the delta F508 mutation on cystic fibrosis chromosomes in Israeli families: correlation to CF haplotypes in Jewish communities and Arabs.

We have analysed the distribution of the delta F508 mutation and the haplotypes of cystic fibrosis (CF) bearing chromosomes among the Israeli CF population. The population was classified according to its ethnic origin and included 3 groups, Ashkenazi Jews, Sephardic/Oriental Jews and Arabs. Haplotype B (KM19 allele 2, XV2c allele 1) was found to be the predominant haplotype in all groups but in each of them the haplotype distribution was different. The delta F508 mutation was present in all groups and accounts for 32% of the CF mutations. It was mainly associated with the B haplotype but only one third of the CF chromosomes with this haplotype carry the delta F508 mutation.

Chromosome Deletion↗
PubMed1990

A cytoplasmic activator of DNA replication is involved in signal transduction in antigen-specific T cell lines.

Cytoplasmic extracts prepared from T cell lines undergoing antigen-specific, interleukin-2 (IL-2)-dependent proliferation were tested for their ability to induce DNA synthesis in isolated, quiescent nuclei. A tetanus toxoid (TET)-specific T cell line, established from peripheral blood of a normal human volunteer, was stimulated in the presence of relevant antigen and 1 unit/ml IL-2. Cytoplasmic extracts prepared from these cells were capable of inducing DNA synthesis in isolated, quiescent nuclei. The ability of cytoplasmic extracts to induce DNA synthesis in isolated, quiescent nuclei. The ability of cytoplasmic extracts to induce DNA synthesis in isolated nuclei correlated positively with the degree of proliferation induced in these cells. In contrast, incubation of this T cell line in the absence of antigen failed to induce proliferation and cytoplasmic extracts prepared from these cells induced little to no DNA synthesis in isolated, quiescent nuclei. The factor present in the cytoplasm of T cells stimulated with relevant antigen in the presence of IL-2 is similar, if not identical, to a factor which we have previously demonstrated in cytoplasmic extracts prepared from transformed lymphoblastoid cell lines and from mitogenically stimulated normal human peripheral blood mononuclear cells. This factor, which we have called activator of DNA replication (ADR) is a heat-labile protein, and is inactivated by treatment with protease inhibitors, including aprotinin. The ability of cytoplasmic extracts from T cells undergoing antigen-specific, IL-2-dependent proliferation to induce DNA synthesis in isolated, quiescent nuclei was markedly inhibited in the presence of aprotinin, providing strong evidence that a cytoplasmic activator of DNA replication, ADR, is involved in the signal transduction process for antigen-specific, IL-2-dependent T cell proliferation. ADR may represent a common intracellular mediator of DNA synthesis in activated and transformed lymphocytes.

Aprotinin↗
PubMed1990

Desensitization of delayed-type hypersensitivity in mice: possible involvement of interleukin 2-dependent regulatory mechanisms in desensitized mice.

The systemic injection of high doses of antigen into a previously immunized animal results in a state of transient anergy with respect to cell-mediated immune responses. This phenomenon is known as desensitization. The results presented here demonstrated that serum interleukin 2 (IL-2) activity was found transiently in desensitized mice at early stage (3 hr after the challenge). Subsequently, these mice could not develop in vivo (footpad swelling) and in vitro (lymphocyte proliferation) manifestations of cell-mediated immune responses 1 day after the challenge. Antigen-nonspecific and specific suppression of IL-2 production was observed in desensitized mice. The serum from 3 hr-desensitized mice containing endogenous IL-2 activity showed a marked suppressive effect on IL-2 production. Exposure of lymph node cells to IL-2 was capable of inhibiting IL-2 production in vitro. Additionally, in vivo administration of exogenous IL-2 into preimmunized mice led to the failure of development of footpad responses to antigen. These results suggest that IL-2-dependent regulatory mechanisms of T cell-mediated immune responses play an important role in the immunosuppression of desensitized mice.

Animals↗
PubMed1990

Antipsychotic effect of milieu in the acute treatment of schizophrenia.

We studied 35 patients meeting DSM-III criteria for schizophrenia, paranoid or undifferentiated type, chronic with acute exacerbation. All were treated in hospital, 13 on a psychiatric intensive care unit, and 22 on an open ward. The former unit is a more structured and less stimulating one. We found those patients treated on that ward to show greater improvement in BPRS ratings during the first 2 days of hospitalization compared to the open-ward group, despite similar doses of medication being utilized. Additionally, this improvement was noted to occur among BPRS items comprising a psychotic subscale.

Acute Disease↗
PubMed1990

Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.

Alertness is a vital function, and medications that do not impair this vital function are clinically desirable in terms of safety. In a comparative study to measure daytime alertness objectively, 60 men and women in good health were assigned to receive either cetirizine, 5 mg, 10 mg, or 20 mg, hydroxyzine, 25 mg, or placebo in a randomized, double-blind, parallel-group design. Subjects slept in the laboratory for 2 consecutive nights to facilitate adaptation. During the second night, the subjects' sleep patterns were recorded by electroencephalogram (EEG), electrooculogram, and chin electromyogram. After the second night, subjects were awakened at 7:30 AM and given a single dose of the assigned treatment. Multiple Sleep Latency Tests (standardized 20-minute opportunities to fall asleep in bed while EEG and eye movements are recorded) were given every 2 hours. Subjects who received cetirizine did not differ from control subjects given placebo in any measure of daytime alertness. Subjects who received hydroxyzine were significantly more sedated than were control subjects given placebo for about 4 hours after treatment. The data from this study provide evidence that cetirizine does not differ from placebo with respect to alertness. The usefulness of the specific and sensitive standardized electroencephalogram, compared with alternative assessments of daytime alertness, is discussed.

Adult↗
PubMed1990

Partner behaviors that support quitting smoking.

One month after their quit date, 221 Ss completed a shortened Partner Interaction Questionnaire (PIQ) in which they reported the frequency of 10 positive and 10 negative behaviors performed by a spouse or romantic partner in response to their quitting attempt. A subset, using the same instrument, reported expectations of support prior to quitting. The ratio of received positive/negative behaviors was a consistently better predictor of abstinence than were the frequencies of either positive or negative behavior alone, with higher ratios associated with abstinence. In addition, partners were less interactive than expected but performed more positive behaviors than expected. The overall pattern of results suggests that the context of a relationship mediates the impact of specific supportive or nonsupportive behaviors. Psychometrics for the 20-item PIQ are presented.

Adult↗
PubMed1990

Perceived stress, quitting smoking, and smoking relapse.

Assessed perceptions of stress prior to quitting and at 1, 3, and 6 months following quit date. Self-reported smoking status was augmented by a bogus pipeline procedure at each interview, and abstinence at 6 months was verified by carbon monoxide and saliva cotinine. The analyses provide strong evidence for a relation between changes in stress levels and changes in smoking status. Those who failed to quit smoking for more than 24 hr maintained a relatively high and consistent level of stress over the entire 6-month period. For those remaining continuously abstinent over the course of the study, stress decreased as duration of abstinence increased. Increases in stress with relapse were found across all three panel lags (prequit to 1 month, 1 to 3 months, and 3 to 6 months), and decreases in stress with quitting were found across the two lags where that comparison was possible. The possibility that the relation between smoking and stress is bidirectional is discussed as a possible interpretation of the results.

Adult↗
PubMed1990

Induction of a cytoplasmic activator of DNA synthesis in lymphocytes is mediated through a membrane-associated protein kinase.

We have shown previously that cytoplasmic extracts from actively dividing lymphoid cells are capable of inducing DNA synthesis in isolated nuclei. One of the factors involved in this activity, ADR, appears to be a greater than 90 kDa heat-labile protease. Cytoplasmic extracts prepared from nonproliferating lymphocytes express little to no ADR activity. However, ADR activity can be generated in these extracts by brief exposure to a membrane-enriched fraction of spontaneously proliferating, leukemic human T lymphoblastoid (MOLT-4) cells. This suggests that ADR activity is present in the resting cytoplasm in an inactive or precursor form. This in vitro generation of ADR activity can be inhibited in a dose-dependent manner by the isoquinolinesulfonamide derivative, H-7 (1-(5-isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride), an inhibitor of both cyclic adenosine monophosphate (cAMP)-dependent protein kinases and protein kinase C (PKC). However, more specific inhibitors of cAMP-dependent protein kinases, including N-[( 2-methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8) and N-(2-gua-nidinoethyl)-5-isoquinolinesulfonamide (HA-1004), had little to no effect on the in vitro generation of ADR activity. Furthermore, membranes from MOLT-4 cells depleted of PKC by long-term exposure (24 h) to phorbol esters and calcium ionophores were unable to induce ADR activity in resting peripheral blood lymphocytes extracts. The results of these studies suggest 1) ADR activity is present in resting cell cytoplasm in an inactive or precursor form; and 2) ADR activity can be induced in this resting cytoplasm through a mechanism involving a membrane-associated protein kinase, possibly PKC. The ability of alkaline phosphatase to deplete the activity of preformed ADR suggests the possibility that ADR itself is phosphoprotein.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Distinct muscarinic receptor subtypes differentially modulate acetylcholine release from corticocerebral synaptosomes.

The effect of McN-A-343 and oxotremorine on acetylcholine (ACh) release and choline (Ch) transport was studied in corticocerebral synaptosomes of the guinea pig. The synaptosomes were preloaded with [3H]Ch after treatment with the irreversible cholinesterase inhibitor, diisopropyl fluorophosphate, and then tested for their ability to release isotope-labeled ACh and Ch in the presence and absence of these agents. The kinetics of release were determined at the resting state (basal release) and in the presence of 50 mM K+. Under either condition, McN-A-343 enhanced the release of isotope-labeled ACh, whereas oxotremorine inhibited the K(+)-evoked release but had no effect on the basal release. The enhancing effect of McN-A-343 on basal ACh release was fully blocked by the selective M1 muscarinic antagonist, pirenzepine (100 nM). In contrast to its enhancing effect on ACh release, McN-A-343 potently inhibited Ch efflux as well as Ch influx. These effects were not blocked by atropine, a nonselective muscarinic antagonist. Oxotremorine had no effect on Ch transport. Binding studies showed that McN-A-343 was 3.6-fold more potent in displacing radiolabeled quinuclidinyl benzilate from cerebral cortex muscarinic receptors (mostly M1 subtype) than from cerebellar receptors (mostly M2 subtype), whereas oxotremorine was 2.6-fold more potent in the cerebellum. The displacements of radio-labeled pirenzepine and cis-dioxolane confirmed the M1 subtype preference of McN-A-343 and the M2 subtype preference of oxotremorine.(ABSTRACT TRUNCATED AT 250 WORDS)

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1990

Weight gain associated with clozapine.

Six of seven patients treated with clozapine gained 6-69 lb. Because of clozapine's anticipated availability in the United States, clinicians should be aware of this possible side effect, which, to the authors' knowledge, has not been reported previously.

Adult↗
PubMed1990

Effects of two fluoride dentifrices containing triclosan and a copolymer on calculus formation.

A 12-week, double-blind, parallel and unsupervised clinical study was conducted to compare the effects on supragingival calculus formation of two dentifrices containing triclosan (Irgacare MP) and a copolymer of methoxyethylene and maleic acid (Gantrez) as compared to a placebo dentifrice. All 147 adult male and female subjects completed the study. Subjects were stratified into three balanced groups on the basis of their Volpe-Manhold index calculus scores as obtained from a 3-month pre-test period using a placebo dentifrice. After a complete oral prophylaxis, subjects were assigned to the use of either the placebo dentifrice, a dentifrice containing 0.3% triclosan and 2.0% of a copolymer in a 0.243% sodium fluoride silica base, or a dentifrice containing 0.3% triclosan and 2.0% of a coplymer in a 0.76% sodium monofluorophosphate alumina base. Subjects, after brushing with their assigned dentifrice and soft-bristled toothbrush for 12 weeks, were evaluated by the examining dentist for supragingival calculus formation using the Volpe-Manhold assessment method. These examinations showed that the dentifrice containing 0.3% triclosan/2.0% copolymer in a 0.243% sodium fluoride silica base reduced supragingival calculus deposits by 23.12% and the dentifrice containing 0.3% triclosan/2.0% copolymer in a 0.76% sodium monofluorophosphate alumina base reduced supragingival calculus deposits by 26.15%. Both of these reductions in supragingival calculus were compared to the placebo dentifrice and were statistically significant at the 99% level of confidence.

Adult↗