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Biomedical subjects

N Sherman

Publications and source records attributed to N Sherman.

26 records · Page 2Linked to original sources
PubMed1986

Somatostatin inhibits fusion of pituitary secretion vesicles with the plasma membranes.

Somatostatin has been found to inhibit secretion vesicle fusion with the iodinated (125-I) inside-out plasma membrane vesicles (both were isolated from the anterior pituitaries). This effect of somatostatin was specific and dose-dependent (half-maximal effect at 10(-9) M). Calmodulin (10 microM), but not cyclic AMP, enhanced the fusion process between the two organelles and somatostatin inhibited calmodulin-stimulated fusion. These observations suggest that one facet of somatostatin action on hormone secretion may be its inhibition of secretion vesicle fusion with the plasma membrane.

Animals↗
PubMed1986

Somatostatin receptors are biologically active before they are inserted into the plasma membrane.

We have examined the biological activity of intracellular somatostatin (SRIF) receptors in cultured rat anterior pituitary cells. We used digitonin-permeabilized cells to introduce free SRIF intracellularly and chloroquine-treated cells to promote intracellular accumulation of SRIF via a receptor-mediated pathway. At a concentration of 0.001%, digitonin (3-min incubation at 37 C) allowed [125I]SRIF to enter the cells without affecting cell viability. Autoradiography of [125I]SRIF demonstrated its association with secretion vesicles (28%), nuclei (25%), and other intracellular organelles. An acid wash technique that removes cell surface-bound ligand revealed that both digitonin-permeabilized cells and chloroquine-treated cells accumulated approximately twice as much intracellular SRIF as did control cells. The biological activities of intracellular SRIF accumulated via two different pathways, receptor mediated and through digitonin-produced pores in the plasma membrane, were different. In chloroquine-treated cells, the accumulation of intracellular SRIF did not result in its additional biological effect. SRIF inhibited GH-releasing factor-induced GH release from 578 +/- 12 to 168 +/- 9 ng/10(6) cells X 30 min, which did not differ from the control value. Cells incubated with digitonin demonstrated normal basal (160 +/- 9 ng/10(6) cells X 30 min) and GH-releasing factor-stimulated GH release (564 +/- 11 ng/10(6) cells X 30 min). However, the inhibitory action of SRIF in these cells was approximately 30% greater (98 +/- 8 ng/10(6) cells X 30 min) than that in either control or chloroquine-treated cells, suggesting that SRIF freely admitted intracellularly produces additional biological activity. These observations confirm the presence of the intracellular receptors and suggest that these receptors exist in a biologically active form.

Animals↗
PubMed1985

Internalization and cellular processing of somatostatin in primary culture of rat anterior pituitary cells.

Somatostatin (SRIF) binding, internalization, and intracellular processing in primary culture of anterior pituitary cells have been studied using somatostatin coupled to an electron-opaque marker, colloidal gold. Initially, after 2 min of incubation (37 C), gold-conjugated SRIF is localized on the cell surface, with 38% of the marker being found around microvilli, 10% at the junction of secretion vesicles with the plasma membrane, and 51% distributed over the remaining areas of the cell membrane. There was no internalization of SRIF at this time. After 20 min of incubation, distribution of the cell-surface bound hormone was similar to that at 2 min (40.6% at microvilli, 12% at the junction with the secretion vesicle, and 47.4% over the rest of the plasma membrane). However, 12% of the electron-opaque markers were found intracellularly in association with coated vesicles, intermediate-sized vesicles, lysosomes, and Golgi structures. SRIF did not enter pituitary cells at 4 C. To study the role of coated vesicles in internalization of SRIF, we have measured somatostatin binding to isolated coated vesicles before and after various treatments and sonication. SRIF binding to sonicated vesicles (3.46 +/- 0.36 fmol/micrograms protein), was much greater than to intact ones (0.75 +/- 0.16 fmol/micrograms protein), suggesting intraluminal localization of SRIF receptors in the coated vesicles. Approximately 80% of SRIF-binding sites were recovered on the intraluminal surface of the coated vesicles. The results of these experiments suggest that internalization of SRIF is a time- and temperature-dependent process. Within the cell, SRIF is routed to either lysosomes or the Golgi apparatus. Coated vesicles participate in intracellular translocation of SRIF-receptor complexes. It appears that the receptor for SRIF being internalized is located on the intraluminal surface of the coated vesicle.

Animals↗
PubMedDate not supplied

Moderate alcohol consumption during pregnancy and the incidence of fetal malformations: a meta-analysis.

To determine whether there is an association between moderate alcohol consumption in the first trimester of pregnancy and increased risk of fetal malformations, we conducted a literature search using Medline (1966-present), PsycLit (1974-1995), and EMBASE (1988-1995). The following inclusion criteria were used to select the studies to be evaluated: 1) pregnant women; 2) moderate alcohol consumption (> 2 drinks/week to 2 drinks/day); 3) case-control or cohort studies; 4) presence of an abstainer group (0 to 2 drinks/wk); 5) outcome measures include major or minor malformations; 6) papers published in the English language. The exclusion criteria were: 1) studies in which moderate alcohol consumption could not be confirmed; 2) case reports, and editorials. The Methods section of each study was examined independently by two blinded investigators with a third investigator settling any disagreement. The number of malformations in the abstainer and moderate alcohol consuming groups in two by two tables. Out of 24 studies which met the inclusion criteria, only seven had extractable data. The included studies evaluated 130,810 pregnancy outcomes, with 24,007 in the moderate alcohol group and 106,803 in the control group. An overall Mantel-Haenszel odds ratio showed that the relative risk for fetal malformations was 1.01 with 95% confidence limits of 0.94 to 1.08 and a chi-square for homogeneity of 8.26 (p = 0.220). Quality of the studies did not correlate with their showing negative or positive association. Moderate alcohol consumption during the first trimester of pregnancy is not associated with increased risk of fetal malformations.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Comparison of finasteride and alpha-blockers as independent risk factors for erectile dysfunction.

There are insufficient data on the effects of alpha-blockers and finasteride on erectile function in men who have other risk factors for erectile dysfunction (ED). This study was conducted to compare the relative effects of these medications on ED in men who may be on other medications or have other risk factors for ED. Patients attending urology and primary care clinics were asked to complete an IRB-approved questionnaire that combined the validated Sexual Health Inventory for Men (SHIM) and a detailed medical history. A total of 123 patients completed the questionnaire. The age range was 28-88 years (mean: 68 years). Eighty-one per cent of patients had SHIM scores <21, indicating some degree of ED. The average SHIM scores in a population of patients with similar age and risk factors who had been on finasteride or alpha-blockers indicated the presence of ED but did not reveal a significant difference between the two groups. The scores were no different from an age-matched group of patients who were not on either medication, demonstrating the relatively greater importance of various other risk factors for ED. There was an inverse linear relationship between the number of ED risk factors and SHIM scores. There does not appear to be a significant difference between alpha-blockers and finasteride as independent risk factors for ED. Age and other risk factors (heart disease, diabetes, hypertension, smoking, and hypercholesterolaemia) tend to have a much stronger influence on the severity of ED as assessed by SHIM scores.

Adrenergic alpha-Antagonists↗