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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 883 records · Page 49Linked to original sources

Biological control of lymphokine function.

Lymphokine-dependent reactions are subject to various kinds of biological control. These are most readily studied under conditions in which such reactions are suppressed by systemic administration of a relatively large dose of antigen. This effect is known as desensitization of delayed-type hypersensitivity and mimics the state of clinical anergy seen in various granulomatous and lymphoproliferative diseases. Experiments on this type of immune unresponsiveness have revealed that the suppression is due to several lymphokine-dependent mechanisms. Thus, a large amount of circulating lymphokines generated and released at the initial stage of desensitization may be responsible for the general suppression of hypersensitivity reactions through both the loss of mediator gradients from one tissue to another and the preemption of effector cells. In a subsequent step, monocytes and/or macrophages activated by these lymphokines release arachidonic acid metabolites including prostaglandin (PG) E1 and PGE2, which inhibit both the production and the activities of lymphokines. Lymphokines are also suggested as being capable of directly inducing suppressor cells for lymphokine production, thus exerting a feedback inhibition. These lymphokine-dependent multiple suppression mechanisms are important for regulatory processes in cell-mediated immunity.

Animals↗

Hemophiliac knee: rehabilitation techniques.

Hemophilia is an inherited bleeding disorder which produces its greatest morbidity in the musculoskeletal system. This article reviews current rehabilitation techniques for the hemophiliac knee--including restrictions of physical activity, external support, and corrective orthotic devices--reports our experience using aggressive strengthening techniques in 2 children, and compares the effectiveness of the 2 methods. It is the impression of the authors that strengthening, rather than immobilization, can bring about increased range of motion, increased strength, and decreased bleeding frequency.

Adolescent↗

Enhancement of calcium uptake and phosphatidylinositol turnover by epidermal growth factor in A-431 cells.

Epidermal growth factor (EGF) stimulates the incorporation of 32Pi and [3H]inositol into phosphatidylinositol (5-10-fold) in A-431 cells. EGF also stimulates the incorporation of 32Pi into phosphatidic acid (up to 10-fold). These effects are attributed to an acceleration of the turnover of phosphatidylinositol as a consequence of the binding of EGF to its membrane receptor. The extent of the phosphatidylinositol response to EGF parallels the extent of hormone binding. The phosphatidylinositol response to EGF appears to be dependent on an influx of calcium since (a) external calcium is required for the enhancement of phosphatidylinositol turnover, (2) the accumulation of 45Ca by A-431 cells is stimulated by EGF, (3) blockage of calcium influx with LaCl3 inhibits stimulation of phosphatidylinositol turnover, and (4) calcium influx via ionophore A23187 is sufficient to stimulate phosphatidylinositol turnover. Since the binding, internalization, and degradation of 125I-labeled EGF in A-431 cells are unaffected by the omission of calcium from the medium, external calcium and phosphatidylinositol turnover are not necessary for the internalization and degradation of the EGF-receptor complex.

Biological Transport, Active↗

Receptor binding and antinociceptive properties of phencyclidine opiate-like derivatives.

The relative potencies of a new series of phencyclidine (PCP) analogs for the displacement of [3H] morphine binding from rat brain homogenates are well correlated with the relative antinociceptive potencies in the test of writhing induced by acetic acid (0.6%). One group of compounds exerts a completely naloxone-reversible analgesic effect, while the effects of a second group are partially reversed by naxolone. These findings and the structural differences between the two groups suggest that their analgesic is mediated through different opiate receptors.

Analgesics↗

Purified EGF receptor-kinase interacts specifically with antibodies to Rous sarcoma virus transforming protein.

Transformation by several RNA tumour viruses seems to be mediated by virally coded protein kinases which specifically phosphorylate tyrosine. A tyrosine-specific protein kinase also seems to be involved in the mitogenic action of epidermal growth factor (EGF). This EGF-stimulated kinase activity is closely associated with the EGF receptor, with which it copurifies during EGF-affinity chromatography. Because both the virus- and EGF-stimulated tyrosine kinases may be involved in stimulation of cell growth, and because the viral kinases may be antigenically related to normal cell proteins, we examined the interaction of antibodies to viral tyrosine kinases with the affinity-purified EGF receptor-kinase preparation. We report here that the receptor-kinase specifically phosphorylates antibodies directed against the transforming protein kinase pp60src of Rous sarcoma virus. However, none of these antibodies, including those which cross-react with the normal cellular homologue of pp60src (pp60sarc), precipitate the receptor-kinase. These results suggest that the EGF receptor-kinase is related to, but probably not identical with, pp60sarc.

Antibodies, Neoplasm↗

Lower esophageal sphincter pressure as an index of gastroesophageal acid reflux.

The purpose of this study was to determine the relationship of lower esophageal sphincter (LES) pressure and the volume of acid placed into the stomach required to induce gastroesophageal reflux in man. LES pressure was recorded continuously and by station pull-through by three radially oriented catheters in both symptomatic and asymptomatic subjects during the graded infusions of 0.1 N HCl acid into the stomach. Symptomatic subjects had a mean LES pressure of 7.5 +/- 0.7 mm Hg and refluxed at a volume of 140.0 +/- 21.0 ml. Fifty-five percent of asymptomatic subjects refluxed at a mean volume of 380.0 +/- 24.7 ml, and had a mean LES pressure of 13.8 +/- 0.4 mm Hg. Asymptomatic nonrefluxers at a volume of 500 ml of 0.1 N HCl acid had a mean LES pressure of 18.9 +/- 1.1 mm Hg. The mean LES pressure and acid volumes showed statistical significance between the three groups (P less than 0.01). There was an excellent overall correlation between LES pressure and acid volume required to produce reflux in all subjects (r = 0.91, P less than 0.001). Following reflux, asymptomatic but not symptomatic subjects showed a significance increase in LES pressure. These studies suggest that: (1) LES pressure does provide an accurate index of the gastroesophageal antireflux mechanism, provided that acid volume is considered; and (2) asymptomatic subjects showing acid reflux have higher LES pressures, reflux at higher volumes, and develop an LES contractile response after the reflux episode.

Esophagogastric Junction↗

Distinct classes of substance P receptors revealed by a comparison of the activities of substance P and some of its segments.

The contracting potency of Substance P and of its C-terminal fragments was studied using four isolated preparations of smooth muscle. The Substance P receptors in the four muscles studied can be differentiated on the basis of their interactions with Substance P and its C-terminal fragments. On the guinea pig ileum, the potency of Substance P is equal to that of the C-terminal octa- and heptapeptide segments and in the rat ileum the potency of Substance P is equal to that of the C-terminal octapeptide and even higher than that of the heptapeptide. In contrast, on the cow pupillary sphincter and guinea pig urinary bladder, Substance P is markedly less potent that the C-terminal octa-, hepta- and hexapeptides. These results suggest the existence of different classes of Substance P receptors and indicate that the N-terminal sequence may be important in regulating Substance P activity.

Animals↗

Successful treatment of achalasia in childhood by pneumatic dilatation.

Ten consecutive patients (ages 10 to 17) with achalasia of the esophagus diagnosed by radiographic, manometric, and endoscopic criteria were treated by forceful dilatations of the lower esophageal sphincter. A good to excellent response was seen in eight of the ten patients, manifested by disappearance of vomiting, improvement in dysphagia, and weight gain. A decrease in resting gastroesophageal sphincter pressure was documented in four patients tested. Short-term complications of fever or chest pain were seen following three of 18 procedures; however, barium swallow was negative for perforation and symptoms resolved spontaneously without treatment. Our findings suggest that pneumatic dilatation may produce similar results as surgical esophagomyotomy (Heller procedure) without the immediate operative morbidity, cost, and potential long-term effects.

Adolescent↗

New analgesic drugs derived from phencyclidine.

Several esters of 1-(1-phenylcyclohexyl)-4-piperidinol (3), 1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol (10) and its propionate (11), and 1-(1-phenylcyclohexyl)-4-phenylpiperidine (13) were prepared and characterized. The new compounds, which are derived from phencyclidine, exerted analgesic activity in mice. The most potent is 10, which is twice as active as morphine. The antinociceptive activity of 10, 11, and 13 could be well correlated with their potency in the mouse vas deferens bioassay, and both were completely reversed by naloxone.

Analgesics↗

Rapid rounding of human epidermoid carcinoma cells A-431 induced by epidermal growth factor.

Epidermal growth factor (EGF) induces rapid rounding of A-431 human epidermoid carcinoma cells in Ca(++)-free medium. Cell rounding is not induced by a variety of other polypeptide hormones, antiserum to cell membranes, local anesthetics, colchicine, cytochalasin B, or cyclic nucleotides. However, trypsin, like EGF, induces rounding of A- 431 cells in the absence of Ca(++). Both trypsin- and EGF-induced rounding are temperature dependent, appear to be energy dependent, and are inhibited by cytochalasins, suggesting that the active participation of microfilaments in cell rounding. However, a medium transfer experiment suggests that EGF-induced rounding is not attributable to secretion of a protease, and a number of serine protease inhibitors have no effect on the EGF-induced rounding process. Cell rounding is not attributable to the slight stimulation by EGF of the release of Ca(++) that is observed in the Ca(++)-free medium, as stimulation of such release by the ionophore A23187 neither induces cell rounding nor blocks EGF-induced rounding. Cells that have rounded up after treatment with EGF or trypsin spread out upon addition of Ca(++) to the medium, even in the continuing presence of EGF or typsin. Like the cell-rounding process, the cell-spreading process is temperature dependent, appears to be energy dependent, and is inhibited by cytochalasin B. Thus, EGF does not destroy the ability of the cell to spread; rather, in the presence of the EGF (or trypsin), cell spreading and the maintenance of the flattened state become dependent on external Ca(++). Because untreated cells remain flattened in the absence of Ca(++), the data suggest that EGF may disrupt Ca(++)-independent mechanisms of adhesion normally present in A-431 cells.

Adenosine Triphosphate↗