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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 901 records · Page 50Linked to original sources

Adverse effects of marijuana: selected issues.

I have selected two areas of concern about cannabis that have emerged because new patterns of usage are perceptible over the past few years. In the case of pulmonary pathology there is good reason to suspect that long term use can result in inflammatory or neoplastic changes, particularly when the lung has a double burden of dealing with both tobacco and cannabis smoke. With reference to chronic substantial cannabis use and its impact on brain function, the definitive studies are yet to be done. If clinical impressions are meaningful, some people, especially young people, can sustain temporary and perhaps permanent impairment of nonintoxicated mental performance.

Adolescent↗

Myoelectric properties of the cat ileocecal sphincter.

Myoelectric activity and intraluminal pressures were recorded simultaneously from the ileum, ileocecal sphincter (ICS), and proximal colon in chloralose-anesthetized cats. Slow-wave activity, seen at all areas, showed coupling of frequency in the distal ileum and ICS. ICS spike activity was both isolated and associated with ileal or colonic spike activity and correlated with phasic contractions (r = 0.86; P less than 0.01). Ileal distensions caused ICS relaxation and decreased spike activity 33.8% of the time. Colonic distensions caused contraction and increased spike activity 46.9% of the time. Migrating action-potential complexes (MAPC) induced by castor oil, ricinoleic acid, or cholecystokinin propagated to the ICS and through to the colon significantly more frequently than ileal non-MAPC (P less than 0.05). Both spike potential-dependent and spike potential-independent mechanisms were involved in ICS contraction. Bethanechol increased spike activity and phasic and tonic contractions. Phenylephrine, despite loss of spike activity in all leads, caused tonic contraction of the ICS. Isoproterenol caused loss of spike activity and decreased ICS pressure. Thus, ICS myoelectric activity appears to be important in determining sphincter function during neurohumoral and mechanical stimulation, with ICS contractions occurring through both a phasic spike-related mechanism and a tonic mechanism without spike activity.

Action Potentials↗

Properties of the cat ileocecal sphincter muscle.

The purpose of this study was to determine the length-tension properties and the response to neurohumoral agents of the feline ileocecal sphincter (ICS) circular smooth muscle in vitro. The ICS muscle during stretch maintained a higher resting tension at lower degrees of stretch than did the adjacent ileum and colon. Sodium nitroprusside (10(-3) M) or calcium-free Krebs solution with EGTA (5.0 mM) reduced the resting tension of ICS muscle by 15.8 +/- 2.1 and 19.1 +/- 2.5%, respectively. The ICS response to KCl depolarization was lower (0.37 +/- 0.03 kg/cm2) than colonic muscle (0.55 +/- 0.06 kg/cm2) oe ileal muscle (0.51 +/- 0.04 kg/cm2) (P less than 0.05). However, in response to acetylcholine, ICS muscle tension was minimal (0.06 +/- 0.02 kg/cm2) was compared with the colon (0.49 +/- 0.05 kg/cm2) or ileum (0.53 +/- 0.05 kg/cm2) (P less than 0.01). The ICS muscle contracted in response to phenylephrine, whereas other muscles were inhibited. Secretin, gastrin, glucagon, and cholecystokinin failed to act on the ICS muscle while other muscles did respond. These studies suggest that ICS muscle differs from adjacent ileal and colonic circular muscle in that a) in response to stretch it develops a high resting tension that is relatively resistant to calcium withdrawal, and b) it also shows quantitative and qualitative differences in response to neurohumoral agents.

Acetylcholine↗

Marijuana legalization: solution or dissolution.

What is being suggested as the most feasible course now is a standfast position on the legal front; an aggressive, directed research program planned to answer the critical questions about marijuana; and a discouragement policy for adolescents. Legalization is not seen as a tenable solution for many reasons, and it is one that may be irreversible and regretted.

Adolescent↗

Abnormal colonic motility in progressive systemic sclerosis.

Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.

Adult↗

In vitro contraction of the pupillary sphincter by substance P and its stable analogs.

The effects of substance P and substance P analogs have been studied quantitatively by use of an isolated preparation of bovine pupillary sphincter muscle. Substance P contracts the pupillary sphincter in a dose-dependent manner with a value for median effective dose (ED50) of 1.0 X 10(-6) M. The effects of substance P result from its interaction with a specific receptor in the pupillary sphincter. These results strengthen the view that substance P is involved in the oculopupillary reflex.

Animals↗

Epidermal growth factor-receptor-protein kinase interactions.

Membranes prepared from A-431 human epidermoid carcinoma cells retained the ability to bind 125I-labeled epidermal growth factor (EGF) in a specific manner. In the presence of [gamma-32]ATP and Mn2+ or Mg2+, this membrane preparation was capable of phosphorylating specific endogenous membrane proteins, as well as exogenously added histone. The binding of EGF to membranes in vitro resulted in a several-fold stimulation of the phosphorylation reaction. The phosphorylation reaction was not dependent on cyclic AMP or cyclic GMP. These findings suggest that one of the biochemical consequences of the binding of EGF to membranes is a rapid activation of a cyclic AMP-independent phosphorylating system. The activation of the membrane-associated protein kinase by EGF appears to be a reversible phenomenon. The membrane preparation could be solubilized by a number of non-ionic detergents with the retention of both 125I-labeled EGF binding activity and EGF-enhanced phosphorylation of specific membrane proteins. The solubilized membrane preparation was purified by affinity chromatography. The purified preparation retained both EGF-binding activity and EGF-enhanced phosphorylation activity. Analysis of the affinity-purified preparation by SDS gel electrophoresis indicated the presence of one major protein band of molecular weight 150,000 and several trace bands. The evidence suggests that the major 150,000 protein band is the receptor for EGF and is a substrate of the phosphorylation reaction. The co-purification of EGF-binding activity and EGF-stimulated phosphorylation activity suggests an inherent close relationship. The EGF-stimulated phosphorylation reaction appears to be specific for tyrosine residues and in this regard resembles the src protein kinase.

Carcinoma, Squamous Cell↗

T and B-cell activation by mitogenic factor generated from antigen-stimulated lymphocytes.

Guinea-pig mitogenic factor(s) were found capable of stimulating both normal T and B cells. Preliminary physicochemical characterization could not dissociate the mitogenic factors for respective cell populations. Furthermore, both immune T and B cells could produce mitogenic factors upon stimulation with antigen in contrast to some other lymphokines which are known to be produced only by immune T cells. While T-cell-derived mitogenic factor was active on both allogenic T and B cells, it was only mitogenic to syngeneic B cells and not to syngeneic T cells. B-cell-derived factor, on the other hand, could stimulate both T and B cells either of syngeneic or allogeneic origin.

Animals↗

Regulation of lymphokine-dependent reactions.

The experimental findings described here represent an initial approach toward a study of the mechanisms involved in the regulation and control of lymphokine activity. Work on experimental desensitization as well as clinical studies in lymphoproliferative disorders and sarcoidosis suggest that such control can be both at the stage of lymphokine production and at the stage in which lymphokine activity is being expressed. Interestingly, lymphokines themselves, when present systemically, can interfere with the induction of lymphokine-dependent delayed hypersensitivity reactions, both via preemption mechanisms and by abolition of essential mediator gradients.

Animals↗

Effect of bethanechol or vagal nerve stimulation on ileocecal sphincter pressure in the cat.

Ileocecal sphincter pressure was studied in the cat, using an open-tipped perfused catheter system. Ileocecal sphincter pressure was measured under basal conditions and in response to bethanechol or direct vagal nerve electrical stimulation. The pressure was 26.1 +/- 5.0 mmHg basally, and was unaltered by section of either or both cervical vagi (p less than 0.05). Peripheral cervical vagal stimulation gave a 9.1 +/- 1.1 mmHg increase in ileocecal sphincter pressure (p less than 0.05) but central stimulation had no effect on ileocecal sphincter pressure. The ileocecal sphincter response to peripheral vagal nerve stimulation was antagonized completely by propranolol or phentolamine. Bethanechol gave a dose-response increase in ileocecal sphincter pressure with a maximal response of 18.0 +/- 2.9 mmHg at 50.0 microgram/kg (p less than 0.01). The ileocecal sphincter relaxed with ileal distension and contracted with colonic distension. These studies indicate that (a) the ileocecal sphincter shows an excitatory response to vagal stimulation and cholinergic agonists; (b) basal ileocecal sphincter pressure is independent of the vagi; (c) ileocecal sphincter inhibition can be initiated by ileal distension but not by vagal stimulation.

Animals↗

Provocation of esophageal pain by ergonovine or edrophonium.

Ten patients with anginal symptoms and ergonovine-induced chest pain without coronary artery spasm had esophageal manometry with provocative pharmacologic testing. Increased amplitude of esophageal contractions on baseline manometry (68.2 +/- 10.3 mmHg) was the only characteristic discriminating these patients from normals (40.9 +/- 6.3 mmHg) and from patients with esophageal motility disorders (39.6 +/- 7.5 mmHg). The administration of ergonovine or edrophonium provoked typical chest pain in association with high amplitude, long duration, and repetitive esophageal contractions in all 10 patients. Patients with esophageal motor disorders showed a similar, but less marked esophageal response with pain infrequently produced. Normals showed no response to ergonovine, and a minimal response to edrophonium, but without chest pain. Clinical features of patients with ergonovine-induced chest pain could not distinguish them from patients with coronary artery disease; esophageal symptoms were infrequent and mild. These studies suggest that certain patients with chest pain of esophageal origin may be identified only by provocative testing during esophageal manometry. However, these provocative drugs may also induce coronary artery spasm and should not be used during routine clinical manometry.

Adult↗

Use of hydrogen gas (H2) analysis to assess intestinal absorption. Studies in normal rats and in rats infected with the nematode, Nippostrongylus brasiliensis.

The in vitro and in vivo production of hydrogen gas (H2) from various carbohydrates or proteins has been examined in normal rats and in rats infected with the nematode Nippostrongylus brasiliensis. Normal rat fecal homogenates were capable of producing H2 in vitro from glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate. Direct injection of glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate into the cecum of normal rats resulted in approximately twice as much H2 production in vivo than when these same carbohydrates or proteins were administered to the normal rats by gavage. Partial small intestinal villous atrophy was produced by infecting rats with the nematode N. brasiliensis. Impaired small intestinal cell function and evidence of malabsorption in the nematode-infected rats included: (a) decreased activity of intestinal cell lactase (-43%), sucrase (-33%), and alkaline phosphatase (-46%); (b) decreased gut sac uptake of 3-O-(methyl-3H]-D-glucose (-21%) or 1-[carboxyl-14C]-aminocyclopentane-1-carboxylic acid (-28%); and (c) increased (+ 64%-561%) 14CO2 production after D-[U-14C]xylose administration. These rats produced approximately twice as much H2 after gavage administration of glucose, sucrose, xylose, bovine serum albumin, or casein hydrolysate compared with normal rats. The present study suggests that H2 analysis may be useful in the evaluation of small intestinal malabsorption states in rats.

Animals↗