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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 847 records · Page 47Linked to original sources
PubMed1983

The effect of charge on the renal distribution of ferritin.

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.

Animals↗
PubMed1983

Spike-associated and spike-independent esophageal contractions in patients with symptomatic diffuse esophageal spasm.

We report the electrical correlates of esophageal and lower esophageal sphincter contraction in humans using a bipolar ring electrode assembly mounted on a catheter. No spike activity was seen in the resting state in the esophagus or lower esophageal sphincter. Swallowing induced both electrical spike activity and contractile activity in both areas. The delay in the proximal and distal esophagus from swallowing to the onset of electrical activity was 0.3 +/- 0.1 s and 3.3 +/- 0.2 s, respectively, and from swallowing to the onset of contractile activity the time was 1.9 +/- 0.1 s and 5.2 +/- 0.2 s. respectively. The rate of propagation of electrical activity was constant throughout the esophageal body while contractile activity was propagated more rapidly in the middle third of the esophagus. Spike activity preceded the peak of esophageal contractions in 100% of swallows. Lower esophageal sphincter relaxation was initiated without spike activity, but the postswallow lower esophageal sphincter contraction was preceded by spike activity in 100% of cases. Basal lower esophageal sphincter pressure was maintained in the absence of spike activity. Spontaneous esophageal contractions, seen in patients with symptomatic diffuse esophageal spasm, were spike-independent in 70% of cases. Prolonged repetitive contractions, once initiated, were also spike-independent. Thus, with the use of intraluminal ring electrodes, we suggest that the human esophagus and lower esophageal sphincter are capable of generating both spike-dependent and spike-independent contractions. The latter may be prominent in patients with esophageal motor disorders.

Biomechanical Phenomena↗
PubMed1983

Specialty choices and board certifications of 'fifth pathway' graduates.

We studied the specialty choices and board certification status of 258 graduates over a ten-year period of a single "fifth pathway" program. Not including obstetrics and gynecology as a primary care specialty, 54% of our graduates chose primary care specialties. Including obstetrics and gynecology, the number increased to 63%. Thirty-five of 158 graduates through 1978 are specialty board certified and another 49 are board eligible. We believe that our program has fulfilled the need of assisting Americans studying medicine abroad, primarily in Mexico, to overcome their clinical deficits and become integrated into the mainstream of American medicine. The future role of fifth pathway programs must be reevaluated in light of the 1980 Graduate Medical Education National Advisory Committee report, which concluded that by 1990, there will be an overabundance of physicians in the United States.

Career Choice↗
PubMed1982

The muscarinic cholinergic receptors in the posterior hypothalamus of hypertensive and normotensive rats.

The density of [3H]quinuclidin-3-yl benzilate ([3H]QNB) binding sites in the posterior hypothalamus was determined in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats at the ages of 1, 3, 11 and 50 weeks. In SHR, even at the early age of 1 week which is prehypertensive, the values obtained were 1.5 times greater than those of age-matched WKY rats. The values of the equilibrium dissociation constant (KD) did not differ between SHR and WKY rats of the same age. In the pons medulla, however, the density of [3H]QNB binding sites was not different between the two strains of rats of matching age. Isolation-induced hypertension in adult Wistar rats and an increase in the density of [3H]QNB binding sites in the posterior hypothalamus were observed to arise concomitantly. A hypothesis is offered whereby a relative increase in ACh receptor sites in the posterior hypothalamus is a primary cause of hypertension in the models considered.

Animals↗
PubMed1982

Histiocytic lymphoma and malignant angioendotheliomatosis: one disease or two?

The case history of a patient with diffuse histiocytic lymphoma and skin lesions characteristic of malignant angioendotheliomatosis is reported. The patient initially responded to aggressive chemotherapy but quickly had a relapse, CNS disease developed, and the patient died one year after diagnosis. Microscopic, ultrastructural, and surface membrane studies showed that the intravascular tumor cells were not of endothelial origin. The morphologic similarity of the malignant intravascular cells and peripheral blood cells, as well as the demonstration of surface membrane immunoglobulin on malignant blood cells suggested that, in some cases, unusual features of malignant lymphoma may be confused with malignant angioendotheliomatosis.

Diagnosis, Differential↗
PubMed1982

Adenosine-induced slow ionic currents in the Xenopus oocyte.

Adenosine and its 5'-phosphorylated congeners evoke specific membrane-mediated responses in excitable tissues. Available data suggest that inhibition of the target cell occurs due to hyperpolarization, and in some preparations a compound effect of ATP (excitation and inhibition) has been found. However, the ionic mechanism of the purinergic-mediated response has not been studied by standard intracellular voltage-clamping techniques. Recently, we have discovered purinergic receptors in the Xenopus oocyte, a well defined giant cell amenable to rigorous electrophysiological and biochemical studies. We report here that in these cells, adenosine-induced slow membrane responses consisted of an early depolarizing (D) transient current carried by Cl ions, followed by a steady hyperpolarizing (H) current involving K+ ions. The relative potency sequence for the D current was ATP congruent to ADP greater than AMP congruent to adenosine; this order was reversed for the H current.

Adenosine↗
PubMed1982

Phosphotyrosyl-protein phosphatase of TCRC-2 cells.

Homogenization of TCRC-2 cells yielded a phosphotyrosyl-protein phosphatase with a specific activity approximately 10-=fold higher in particulate than in soluble fractions. Over 90% of the phosphotyrosyl-protein phosphatase associated with the particles was solubilized with 1.0% Nonidet P-40. Chromatography of the detergent-solubilized particulate fraction on either wheat germ lectin-Sepharose or histone-Sepharose columns separated two major components of phosphatase activity. One peak (eluted with 200 mM NaCl from histone-Sepharose or with N-acetylglucosamine from the lectin column) contained both phosphotyrosyl- and phosphoseryl-protein phosphatase as well as p-nitrophenyl phosphatase activities. The other peak (eluted with 1.0 M NaCl from histone-Sepharose or not bound to the lectin column) contained essentially only phosphoseryl-protein phosphatase activity. Various agents (EDTA, p-nitrophenyl phosphate, fluoride) showed considerable differences in their ability to inhibit the two phosphatase fractions; of these, the most potent and selective inhibitor was orthovanadate. At micromolar concentrations, vanadate inhibited the fraction containing phosphotyrosyl-protein phosphatase and failed to inhibit the fraction containing only phosphoseryl-protein phosphatase activity. These data show that the particulate forms of phosphotyrosyl-protein phosphatase and p-nitrophenyl phosphatase represent the activities of very similar or identical proteins.

Chromatography, Affinity↗
PubMed1982

Affinity labeling of the protein kinase associated with the epidermal growth factor receptor in membrane vesicles from A431 cells.

Epidermal growth factor (EGF), a mitogenic polypeptide hormone, stimulates the phosphorylation of certain endogenous proteins in membrane preparations derived from A431 cells, a human tumor cell line. Membrane vesicles prepared from A431 cells were reacted with 5'-p-fluorosulfonylbenzoyl adenosine (5'-p-FSO2BzAdo). Reaction of the vesicles with 5'-p-FSO2BzAdo results in a time-dependent inhibition of EGF-stimulable protein kinase activity which parallels an increase in incorporation into the vesicles of the 5'-p-sulfonylbenzoyl-[8-14C]adenosine moiety from 5'-p-FSO2Bz[14C]Ado. The primary bands labeled have Mr = 170,000 and 150,000. Labeling of these bands by 5'-p-FSO2Bz[14C]Ado is inhibited by incubation of the membrane vesicles with adenyl-5'-yl imidodiphosphate, an ATP analog. Inactivation of the kinase with N-ethylmaleimide or by heating results in a sharply decreased labeling of the proteins with Mr = 170,000 and 150,000. Proteins of these molecular weights have previously been identified in these cells as the EGF receptor and a degradation product of the receptor. These experiments provide chemical evidence that the EGF receptor and the EGF-stimulable kinase are the same protein.

Adenosine↗
PubMed1982

A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles.

A method is presented for the preparation of a "native" epidermal growth factor (EGF) receptor-kinase complex of molecular weight 170,000 from A-431 cells. Although this receptor complex is capable of binding EGF, noncovalently, in quantities similar to the previously isolated 150,000 complex (Cohen, S., Carpenter, G., and King, L., Jr. (1980) J. Biol. Chem. 255, 4834-4842), the 170,000 preparation has 5 to 10 times the intrinsic kinase activity (autophosphorylation). However, the 170,000 kinase activity toward other proteins is lower than that of the 150,000 preparation. Both the 170,000 and 150,000 kinase activities are enhanced by EGF. The 170,000 and 150,000 proteins are also capable of forming covalent linkages to 125I-EGF, and each is precipitated by antisera directed against the 170,000 protein. We suggest the 150,000 protein is a proteolytic degradation product of the 170,000 protein. The EGF-enhanced kinase activity of the 170,000 preparation remains associated with the 125I-EGF-binding activity following EGF affinity chromatography, electrophoresis in nondenaturing gels, or immunoprecipitation with antisera directed against the sodium dodecyl sulfate (SDS) gel-purified 170,000 protein. These results indicate that the receptor, kinase, and substrate domains are linked, possibly covalently.

Animals↗
PubMed1982

Migration inhibition of endothelial cells by lymphokine-containing supernatants.

Many of the reactions of cellular immunity are mediated by soluble lymphocyte-derived factors (lymphokines). One important category of lymphokine action involves effects on cell motility. These effects have been described mainly with respect to inflammatory cells. In this report, we describe the ability of a lymphocyte product to inhibit the migration of endothelial cells in a system in vitro. The responsible factor is distinct from a previously described mediator that inhibits the migration of tumor cells. The ability of lymphocytes to influence the migration properties of endothelial cells is consistent with data of others showing a relation between the immune system and processes involving neovascularization.

Cell Line↗
PubMed1982

Effect of an oral beta2-adrenergic agonist on lower esophageal sphincter pressure in normals and in patients with achalasia.

The effect of the beta2-adrenergic agonist, carbuterol, was studied on the lower esophageal sphincter (LES) pressure in normals and in patients with achalasia. In normals, the mean LES pressure decreased from 23.1 +/- 6.2 mm Hg (mean +/- SEM) to 16.0 +/- 5.0 mm Hg at a 4.0-mg dose of carbuterol (P less than 0.05). In patients with achalasia, the mean LES pressure decreased from 50.1 +/- 5.1 mm Hg to 22.7 +/- 2.4 mm Hg after a 4.0-mg dose of carbuterol (P less than 0.01). The duration of action following oral administration exceeded 90 min. These studies indicate that the LES in man has beta2-adrenergic receptors that mediate a reduction in pressure. The magnitude of LES pressure reduction in patients with achalasia suggests that this drug may be of therapeutic benefit.

Administration, Oral↗
PubMed1982

Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver.

We have purified the epidermal growth factor (EGF) receptor/protein kinase from the livers of normal mice by affinity chromatography. The biochemical properties of the liver receptor are very similar to those of the EGF receptor previously prepared from the human tumor cell line A-431 [Cohen, S., Ushiro, H., Stoscheck, C. & Chinkers, M. (1982) J. Biol. Chem. 257, 1523-1531]. The liver receptor for EGF is a glycoprotein of Mr 170,000. It binds 125I-labeled EGF and possesses an EGF-stimulable protein kinase activity specific for tyrosine residues. Both autophosphorylation and kinase activity toward exogenous substrates are demonstrable. The EGF receptor purified from normal mouse liver is antigenically related to the receptor purified from human A-431 cells.

Animals↗
PubMed1982

Co-localization of 125I-epidermal growth factor and ferritin-low density lipoprotein in coated pits: a quantitative electron microscopic study in normal and mutant human fibroblasts.

Low density lipoprotein (LDL) and epidermal growth factor (EGF) bind to receptors on the surface of human fibroblasts and are internalized in coated vesicles. Each of the ligands has been studied separately by electron microscopy in human fibroblasts using ferritin-LDL as one visual probe and 125I-EGF as a second visual probe. A mutant strain of human fibroblasts (J.D.) has been described in which LDL does not localize to coated pits and hence is not internalized. Because LDL and EGF do not compete with each other for binding, in the current studies we coincubated the two ligands with normal and mutant cells to visualize their cellular fates. In normal fibroblasts ferritin-LDL and 125I-EGF both bound preferentially to coated pits at 4 degrees C and both ligands were internalized into endocytotic vesicles and lysosomes. Quantitative studies in normal cells showed that 75% of the coated pits and vesicles that contained 125I-EGF also contained ferritin-LDL, indicating that both ligands enter the cell through the same endocytotic vesicles. In the LDL internalization-mutant J.D. cells, ferritin-LDL did not localize in coated pits and was not internalized, but 125I-EGF bound to coated pits and was internalized just as in normal fibroblasts.

Cell Line↗