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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 343 records · Page 19Linked to original sources

Effects of sodium valproate and oxygen on the CD-1 mouse fetus.

This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12. Dams were then exposed continuously to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments during gestation days 5-12, in order to determine if hyperoxic maternal conditions offered a protective environment for the fetus, and conversely, if hypoxia exacerbated teratogenicity. Dams were sacrificed on gestation day 18, and litter and fetal data were collected. It was determined in separate groups under normoxic conditions that the osmotic minipump system maintained VA plasma levels corresponding to human therapeutic levels. Sodium valproate was found to induce developmental toxicity in the CD-1 mouse fetus at human therapeutic drug plasma levels. Fetal weights were reduced, and the number of resorptions, deaths, and hematomas was increased. While hypoxia exacerbated the toxic effect on the fetus, hyperoxia failed to ameliorate the outcome.

Animals↗

Alcohol control policy in Israel 1986-1987: recognizing the need for diverse primary prevention initiatives.

The purpose of this paper is to describe the recent integration of two different preventive models (the 'Distribution of Consumption Model' and the 'Social Science Model'), planned to support each other, in order to reduce per capita alcohol consumption and curb the rise in alcohol-related problems in Israel, to shed light on the Israeli laws regulating alcohol use and on the extent of their enforcement, to illustrate the causes for their enforcement and to discern some indications for future directions. Although the focus on attitudes and practices which lead to excessive drinking, and the efforts to change them through education remain the very core of the entire Israeli preventive program, alcohol itself has been considered to be a source of difficulties. The beginning of law-enforcement concerning its availability among youngsters and drivers has emerged, both as a result of several fatal events and intense pressures of the Israeli Alcoholism Prevention and Treatment Services. The present tasks are to reinforce the emerging trends of enforcement concerning the existing laws, to adopt some new regulations pertaining to alcohol advertising targeted at adolescents, and to continue with the educational messages based on Jewish-Israeli norms.

Alcohol Drinking↗

Bilateral suprascapular nerve entrapment syndrome due to an anomalous transverse scapular ligament.

A rare case is reported of a young woman who suffered from suprascapular nerve entrapment syndrome (SNES) of the right side and two years later developed the same syndrome on the left. At the first operation an anomalous bifid transverse ligament was found and cut. The combination of pressure effect from the congenital defect together with frequent protraction of the shoulder due to her work as a physical education teacher caused triggering of the SNES. The clinical course, electromyographic findings, and differential diagnosis are reported. Cutting of the anomalous ligament on both sides brought relief from pain, weakness, and atrophy of the shoulder muscles, enabling the patient to return to work.

Adult↗

[Effect of Broncho-Vaxom on serum IgE and IgG levels in patients with bronchial asthma and chronic obstructive lung disease. A placebo-controlled double-blind study].

In a double-blind study of 33 patients with bronchial asthma or chronic obstructive pulmonary disease, of whom 17 had proven atopies, the results showed a distinct diminution of the mean IgE level in the atopic patients at the end of 1-month treatment with Broncho-Vaxom, though not attaining statistical significance (trend with p less than 0.10), compared to a slight increase under placebo. Simultaneously the mean IgG level increased slightly in the atopic patients under Broncho-Vaxom and remained stable in the patients under placebo (p less than 0.10). The IgE and IgG values of the non-atopic patients in both treatment groups remained practically unchanged. Considering the small number of patients in each group, and the clear tendency towards a diminution of the IgE level, it may be concluded that the administration of Broncho-Vaxom to atopic patients does not lead to an increased IgE level but, on the contrary, seems rather to favour a decrease.

Adjuvants, Immunologic↗

Alpha 2-adrenergic receptors mediate inhibition of cyclic AMP production in neurons in primary culture.

The actions of adrenergic agents on the intracellular production of cyclic adenosine monophosphate (AMP) was examined in intact cortical and striatal neurons in primary culture, generated from the fetal mouse brain. Exposure of striatal neurons to the beta-adrenergic agonist isoproterenol (10 microM) resulted in a 5-fold increase in intraneuronal cyclic AMP; norepinephrine (100 microM), alone or in combination with isoproterenol, produced only a 3-fold increase in cyclic AMP levels. However, in the presence of yohimbine (10 microM), cyclic AMP productions due to norepinephrine or isoproterenol plus norepinephrine were identical to isoproterenol alone. When striatal or cortical neurons were exposed to pertussis toxin (100 ng/ml) overnight, there was no detectable difference between isoproterenol- and norepinephrine-stimulated cyclic AMP production. These data suggest that alpha 2-adrenergic receptors mediate the attenuation of cyclic AMP production in neurons and do so via the inhibitory guanine nucleotide regulatory protein of adenylate cyclase.

Adenylate Cyclase Toxin↗

F-actin and microtubule suspensions as indeterminate fluids.

The viscosity of F-actin and microtubule suspensions has been measured as a function of shear rate with a Weissenberg rheogoniometer. At shear rates of less than 1.0 per second the viscosity of suspensions of these two structural proteins is inversely proportional to shear rate. These results are consistent with previous in vivo measurements of the viscosity of cytoplasm. This power law implies that shear stress is independent of shear rate; that is, shear stress is a constant at all shear rates less than 1.0 per second. Thus the flow profile of these fluids is indeterminate, or nearly so. This flow property may explain several aspects of intracellular motility in living cells. Possible explanations for this flow property are based on a recent model for semidilute suspensions of rigid rods or a classical friction model for liquid crystals.

Actin Cytoskeleton↗

Somatic point mutations in unrearranged immunoglobulin gene segments encoding the variable region of lambda light chains.

Somatic point mutations are usually found in the coding and flanking regions of functionally and aberrantly rearranged immunoglobulin variable region gene segments. Mutations in the unrearranged V gene segments of myelomas or hybridomas have not been described so far. We have cloned and sequenced unrearranged V lambda gene segments from several cell lines. There were no nucleotide changes in four unrearranged V lambda segments: one V lambda 1 from a lambda 3-producing hybridoma and one V lambda 2 from a lambda 1-producing myeloma (J558) and two V lambda 2 from a kappa-producing myeloma (P3X63). However, we found somatic mutations in the unrearranged V lambda segments from the lambda 2-producing myeloma MOPC315. The unrearranged V lambda 1 gene segment had two mutations in the coding region and the unrearranged V lambda 2 had one mutation in the 3' flanking region. We also cloned and sequenced the unrearranged J lambda and C lambda gene segments of MOPC315 and found no sequence alterations. This is consistent with the notion that the overall mutation rate is not higher in this cell line. Therefore, we suggest that the somatic hypermutation system can use unrearranged V gene segments as substrates. The extensive sequencing required for this work revealed a number of errors in the reported nucleotide sequences of the Ig lambda locus in BALB/c mice.

Animals↗

Human safety study of body lotion containing Kathon CG.

The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

Adolescent↗

Analysis of dose-response curves to methacholine. An approach suitable for population studies.

Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.

Aging↗

Dual action of excitatory amino acids on the metabolism of inositol phosphates in striatal neurons.

Glutamate is able to stimulate inositol phosphate (IP) formation in striatal neurons in primary culture, mainly via an excitatory amino acid receptor of the quisqualate subtype. In the present study we show that carbachol (Carb)-(a cholinergic agonist), but not neurotensin or norepinephrine-induced IP production could be reduced by 40% when measured in the presence of Glu. The inhibition of the Carb response by Glu was dose dependent and reproduced by N-methyl-D-aspartate (NMDA). Quisqualate elicited an additive response with Carb. 2-Amino-5-phosphonovalerate (APV) completely reversed the NMDA-induced inhibition. APV had no significant effect on Glu- or kainate-induced inhibition. Therefore, striatal neurons contain at least three different excitatory amino acid receptors: a quisqualate receptor triggering the stimulation of IP metabolism, and an NMDA and a kainate receptor, both able to decrease the Carb-induced IP formation.

2-Amino-5-phosphonovalerate↗

Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients.

Thyrotropin (TSH) concentrations were measured in 1580 hospitalized patients and 109 normal persons. Using the mean +/- 3 SD limits of the log values for the controls (0.35-6.7 milli-int. units/L), the proportion of abnormal TSH results in the hospitalized patients was 17.2%. TSH was undetectable (less than 0.1 milli-int. unit/L) in 3.1% of patients, suggesting hyperthyroidism, and high (greater than 20 milli-int. units/L) in 1.6%, suggesting hypothyroidism. On follow-up of 329 patients, 62% with abnormal TSH (less than 0.35 or greater than 6.7 milli-int. units/L) and 38% with normal TSH concentrations, only 24% of those with undetectable TSH had thyroid disease: 36% of them were being treated with glucocorticoids and 40% had nonthyroidal illness (NTI). Although half the patients with TSH greater than 20 milli-int. units/L had thyroid disease, 45% of patients had high TSH values associated with NTI. TSH concentrations usually returned towards normal when patients' therapy with glucocorticoids was discontinued or they recovered from NTI. TSH test sensitivity appeared good when the mean +/- 3 SD limits of the reference population were used, i.e., no cases of hyper- or hypothyroidism, as identified by free thyroxin index (FT4I), were missed. However, TSH test specificity was inferior to that of the FT4I test (90.7% vs 92.3%), although specificity could be improved to 97.0% if the wider TSH reference limits of 0.1 to 20 milli-int. units/L were used--limits considered pathological if applied to outpatients. Evidently, different reference intervals for TSH are needed for hospitalized and nonhospitalized patients. We conclude that a "sensitive TSH assay" is not a cost-effective thyroid screening test for hospitalized patients as compared with the FT4I.

Adult↗