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Biomedical subjects

D Jacobson

Publications and source records attributed to D Jacobson.

At least 37 records · Page 2Linked to original sources

Mechanism involved in the mobilization of neutrophil calcium by 5-hydroxyeicosatetraenoate.

5-Hydroxyeicosatetraenoate (5-HETE), like leukotriene B4 and platelet-activating factor, stimulated human polymorphonuclear neutrophils to mobilize intracellular calcium. The three compounds acted through mechanisms that were inhibited by pertussis toxin, cholera toxin, and PMA. Each agonist, furthermore, desensitized (or down-regulated) the neutrophil's calcium mobilization response to a second challenge with the same agonist. However, 5-HETE and leukotriene B4 had little or no activity in cross-desensitizing neutrophil responses to each other or to platelet-activating factor. Furthermore, 5-HETE interfered minimally or not at all with the binding of radiolabeled leukotriene B4 and platelet-activating factor to their respective receptors on neutrophils. Thus, 5-HETE mobilizes neutrophil calcium by a mechanism different from those used by leukotriene B4 and platelet-activating factor. This mechanism appears to involve specific 5-HETE receptors that couple to pertussis toxin-inhibitable, GTP-binding proteins.

Calcium

Models of stress and meanings of unemployment: reactions to job loss among technical professionals.

The same potentially stressful event may have different meanings to different individuals. Such variation may be explained by reference to different models of stress. Two such models, one based on the concept of person-environment 'transactions' and the other on that of a 'psychosocial transition,' are applied to studies of reactions to job loss among technical professionals.

Engineering

Optional early retirement as an alternative to involuntary layoffs: some observations on the Israeli experience.

The use of optional early retirement (OER) in Israel is discussed in the context of the tendency to consider forms of voluntary work-force reductions as an alternative to dismissals and layoffs during organizational retrenchment. The pros and cons of OER are assessed from both the organizational and the individual points of view. Although much more palatable than involuntary dismissals, attention is called to the hidden costs of OER in terms of organizational effectiveness, the stigmatizing use of age as a selection criterion, and the unintended effects on individual well-being.

Attitude

Binding and metabolism of platelet-activating factor by human neutrophils.

Human polymorphonuclear neutrophils rapidly incorporated radiolabeled platelet-activating factor, 1-O-[hexadecyl-9, 10-3H2]-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF), and then metabolized it into its sn-2-fatty acyl derivative. Fractionation of radiolabel-pretreated cells over Percoll gradients revealed that virtually all of the intact [3H]PAF was located in nongranule membranes that were enriched with alkaline phosphatase and cell surface glycoproteins. While still membrane associated, the ligand was rapidly converted to its acyl derivative and then more slowly transferred to specific granules and, to a lesser extent, azurophilic granules. In contrast, neutrophils did not metabolize [3H]PAF at 4 degrees C but rather gradually accumulated it in their alkaline phosphatase-enriched membrane subfractions. These same subfractions contained receptors for the ligand, as determined by their capacity to bind [3H]PAF specifically. Binding was readily saturated, partially reversible, and fit a two receptor model; dissociation constant (Kd) values for high and low affinity sites were 0.2 and 500 nM, respectively. Receptors with similar affinities were detected in whole cells. Furthermore, the potencies of several structural analogues in inhibiting binding of [3H]PAF to membranes correlated closely with their respective potencies in stimulating degranulation responses. Finally, quantitative studies suggested all or most of the cell's receptors were membrane associated. We conclude that PAF rapidly enters cellular membranes to bind with specific receptors that trigger function. The intramembranous ligand is also deacetylated, acylated, and then transferred to granules. This metabolism may be sufficiently rapid to limit ligand-receptor binding and distort quantitative analyses of receptors.

Binding, Competitive

Protease-specific suppression of pancreatic exocrine secretion.

The purposes of this study were to (a) evaluate the effect of pancreatic extract administered to patients with chronic pancreatitis and recurrent abdominal pain in a placebo-controlled, double-blind crossover study, (b) investigate the effects of acute intraduodenal pancreatic enzyme perfusion on pancreatic secretion, and (c) assess the effect of chronic, noninterrupted pancreatic extract administration on basal and stimulated pancreatic secretion. These studies demonstrated that pancreatic extract decreases abdominal pain and that intraduodenal perfusion with proteases but not with amylase or lipase suppresses pancreatic exocrine secretion in patients with chronic pancreatitis. Chronic administration of pancreatic extract to patients with chronic pancreatitis decreased both basal and stimulated pancreatic exocrine secretion.

Abdomen

Papular dermatitis of pregnancy.

Papular dermatitis of pregnancy is a rare pruritic eruption of widespread urticarialike papules. The eruption developed in a 31-year-old woman during the third trimester of her second pregnancy. Urine chorionic gonadotropin (UCG) levels were elevated. A biopsy specimen of an involved papule showed spongiosis and a perivascular lymphocytic infiltrate in the superficial dermis. No deposits of IgG, IgM, IgA, or C3 were detected by direct immunofluorescence microscopy of perilesional skin. High doses of systemically administered corticosteroids controlled the disease, but papules developed in increased numbers when the dosage was reduced below 80 mg/day. After parturition, widely scattered papules of similar morphology developed in the patient; these persisted for 11 months despite the absence of retained placental fragments and normal findings from UCG determinations. New papules continued to develop premenstrually, suggesting an influence of normal pituitary gonadotropic hormones or other aggravating humoral factors on the eruption.

Adrenal Cortex Hormones

Rheumatoid arthritis in a Chippewa Band. I. Pilot screening study of disease prevalence.

The Mille Lacs Band of Chippewa Indians in central Minnesota was screened for rheumatoid arthritis, with a 77% completion rate of the reservation census. Rheumatoid arthritis was found in marked excess, namely 6.8% of those evaluated or, minimally, 5.3% of the total band if all persons had been evaluated with no additional cases identified. This relatively closed population thus provides an opportunity to assess genetic and environmental factors of significance in this disease.

Adolescent

Nonenzymatic glycosylation of low density lipoproteins in vitro. Effects on cell-interactive properties.

Atherosclerosis occurs at an accelerated rate in patients with diabetes mellitus. Since some proteins undergo nonenzymatic glycosylation in diabetic patients and because certain chemical modifications of low density lipoproteins produced alterations in their interactions with certain cultured cells, a fact that may be relevant to atherogenesis, we investigated the effect of in vitro glycosylation on cell-related properties of low density lipoproteins. Glycosylation was carried out by incubating LDL (1-10 mg LDL-protein/ml) with glucose (0-100 mM) in 0.5 M phosphate buffer, pH 8.0, at 37 degrees C. The amount of glucose incorporated into LDL after 1-2 wk of incubation was estimated to be in the range of 1-10 mol/mol LDL-protein. Amino acid analysis of glycosylated LDL showed that glucose was covalently bound to lysine residues. In studies with cultured human fibroblasts, glycosylated LDL was internalized and degraded significantly less than control LDL, in proportion to the estimated degree of glycosylation (12% of control for the most extensively glycosylated LDL). Glycosylation of LDL also impaired significantly its ability to stimulate cholesteryl ester synthesis by cultured fibroblasts. Glycosylated LDL did not stimulate cholesteryl ester synthesis in rat peritoneal macrophages. If glycosylation of LDL occurs in diabetic patients, some pathophysiologic consequences related to the increased incidence of atherosclerosis in these patients may result.

Arteriosclerosis

Stereopsis and fixation disparity following prolonged monocular occlusion.

The effects of 12 days of continuous monocular occlusion on the stereoscopic acuity and the magnitude of the fixation disparity associated with a given amount of prism-forced vergence were investigated in six adult subjects with normal binocular vision. After the period of occlusion, all six subjects were able to perceive stereopsis, although four of the six subjects demonstrated a slight but reversible elevation in stereothresholds. The general shape of the fixation disparity curve for a given individual was not altered by occlusion, but changes in the magnitude of the fixation disparity were observed for some subjects.

Adult

Effect of dibutyryl cyclic AMP on gastric secretion and mucosal blood flow.

The effects of dibutyryl cyclic AMP (db cAMP) on gastric secretion and blood flow were determined in studies on anesthetized and conscious dogs. In 6 experiments on animals under chloralose-urethane anesthesia, gastric secretion, gastric mucosal and left gastroepiploic artery blood flows were measured. In 8 experiments on 4 conscious dogs with gastric fistulas and Heidenhain pouches, gastric secretion and gastric mucosal blood flow were measured in both the stomach and pouch. Gastric secretion was stimulated with intravenous histamine at a dose of 80 microgram/kg-hr for 3 hours, in each of the above experiments. In the second hour db cAMP was infused intravenously at a dose of 0.5 mg/kg-min. In all experiments db cAMP increased gastric mucosal blood flow, but only in the first group of dogs was there an increase in gastric acid secretion. It is concluded that db cAMP at the dose employed, had a vasodilator effect on the gastric mucosa, which does not appear to depend upon the secretory response to the drug.

Anesthesia

Ligand-activated T cell growth factor-induced proliferation: absorption of T cell growth factor by activated T cells.

The fate in culture of the T cell growth factor (TCGF), which is required for continued growth of human cultured T cells (CTC) in vitro, was studied. TCGF activity was stable for 7 days at 37 degrees C. However, it was no longer detectable after incubation with actively growing CTC at 37 degrees C for 3 days. This loss of TCGF activity also occurred quite rapidly and was detectable within 1 hr of incubation of 0.3 ml supernatant with 2 to 5 x 10(7) CTC at 23 degrees C. 2 x 10(8) mononuclear peripheral blood leukocytes were not effective in removing TCGF activity, and incubation with similar numbers of cells from B and T cell lines had no effect. Three-day-old concanavalin A and phytohemagglutinin blasts were very reactive with TCGF, so that 10(7) or 2 x 10(7) cells consistently removed TCGF activity. These experiments suggested specific absorption of TCGF by activated T cells, and led us to develop a model of ligand-activated TCGF-induced proliferation of T cells: Ligands induce production of TCGF by T-producer cells and deliver a first signal to the T-responder cells. This causes a receptor for TCGF to appear on T-responder cells. Only then does TCGF deliver the obligatory second signal that is needed to drive the T-responder cells into proliferation.

Absorption

Expectancy theory prediction of the preference to remain employed or to retire.

Vroom's (1964) expectancy theory model was used to predict older workers' choices between continued employment or immediate retirement. It was hypothesized that a person's preference for one of the two alternatives would be a function of the differences between the instrumentality of employment and the instrumentality of retirement for the attainment of outcomes, multiplied by the valence of each outcome, summed over outcomes. To test this, 290 Israeli male workers, aged 57 to 64, were interviewed. Measures included: preference for employment or retirement; valences of 35 outcomes; perceived instrumentalities of employment and retirement. The results supported the hypothesis (R = .40; p less than .01). It is suggested that further research along these lines could equip organizations with a tool for assisting older employees in the transition to retirement or for encouraging those who are still capable of making a significant contribution to remain employed.

Decision Making