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S Cohen

Publications and source records attributed to S Cohen.

At least 613 records · Page 34Linked to original sources
PubMed1987

Further characterization of the slow muscarinic responses in Xenopus oocytes.

In immature follicular oocytes of the frog Xenopus laevis, application of muscarinic agonists evokes a complex response consisting of a fast and a slow Cl currents (the dominant responses), Cl current fluctuations, and a less prominent slow K current. The characteristics of the slow ACh-evoked potassium current were studied using the two-electrode voltage clamp method, and compared to those of the ACh-evoked Cl currents. In experiments designed to study the K current response separately, without the interference of ACh-evoked Cl currents, the holding potential was set close or equal to Cl equilibrium potential (measured as the reversal potential of the ACh-evoked Cl current). The Cl current responses were studied in cells that had negligible K current response. The dose-response curve of the potassium response followed classical Michaelis-Menten kinetics. The dose-response characteristics of the slow ACh-evoked Cl current displayed a positive cooperativity of at least 3. In spite of this difference, kinetic analysis revealed that these two responses, as well as the fast Cl current response that was characterized earlier (Dascal and Landau 1982), had almost identical apparent equilibrium dissociation constants (0.29-0.39 microM), suggesting involvement of a single receptor class. Both K and Cl currents were reduced (to 32-56% of control) by millimolar concentrations of phosphodiesterase (PDE) inhibitors, theophylline and isobutylmethylxanthine. Elevation of extracellular Ca concentration from 1 to 10 mM doubled the K current; depletion of external Ca caused a partial inhibition of this response. The K current was potentiated by 0.1 microM 4-phorbol 12,13-dibutyrate (PDBu).(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1987

Esophageal chest pain. Value of high-dose provocative testing with edrophonium chloride in patients with normal esophageal manometries.

The unequivocal diagnosis of esophageal chest pain requires the demonstration of simultaneous manometric changes and chest pain. Numerous provocative agents have been used to enhance the diagnostic value of esophageal manometry. Our aims were to: evaluate consecutively a large group of patients with proven noncardiac chest pain and normal baseline manometric studies, using edrophonium chloride, 10 mg, and determine the value of provocative testing in clinical practice. One hundred twenty patients with normal standard baseline esophageal manometries were studied using blinded testing with edrophonium chloride and followed clinically by questionnaire. A positive response of both chest pain and manometric changes was observed in 34%, a negative response in 49%, and an indeterminate response in 17% of patients. Baseline manometric features, including high-amplitude contractions, did not predict the response to edrophonium chloride. Following edrophonium chloride administration, the change in amplitude, duration, and number of repetitive contractions from baseline was significantly greater in positive responders. Edrophonium decreased the velocity of propagated contractions in positive responders (P less than 0.05), but not in nonresponders. Response to edrophonium chloride could not be predicted by patient age, sex, or clinical symptomatology. Seventy percent of patients in both groups had symptoms indistinguishable from ischemic heart disease. After making a specific diagnosis of esophageal chest pain, patients showed a marked clinical improvement, with a significant decrease in physical limitation, emergency room visits, hospital and CCU admissions, and in further cardiac testing. We conclude that provocative testing with edrophonium chloride will make it possible to definitively implicate the esophagus in over 30% of patients with normal baseline manometric findings and noncardiac chest pain.

Adult↗
PubMed1987

Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma.

Gastroesophageal reflux is well documented in scleroderma, but the complications of Barrett's metaplasia and adenocarcinoma are not well described. The records of 75 patients with scleroderma seen over a four-year period at the Hospital of the University of Pennsylvania were retrospectively reviewed to determine the prevalence of Barrett's metaplasia and adenocarcinoma of the esophagus and to identify clinical, manometric, laboratory, or radiographic criteria that might predict the presence of these lesions. Twenty-four of these patients underwent endoscopy. In this group, the prevalence of Barrett's metaplasia was 37 percent (nine patients) and adenocarcinoma was also present in two of these patients. The patients with and without Barrett's metaplasia were similar in age (range, 22 to 64 compared with 28 to 79, respectively), sex (six of nine compared with 12 of 15 female, respectively), frequency of esophageal motility disorders, presence of proximal skin involvement, digital ulceration, and pulmonary involvement as measured by diffusion capacity. Barrett's metaplasia was diagnosed on the basis of double-contrast esophagographic results in only one of eight patients with Barrett's metaplasia so-studied. Patients with Barrett's metaplasia tended to have longer duration of heartburn (90 +/- 40 months compared with 11 +/- 35 months) and dysphagia (39 +/- 22 months compared with 7 +/- 3 months). Patients with Barrett's metaplasia also tended to have greater impairment of lower esophageal sphincter pressure either at end-expiration (4.0 +/- 2.1 compared with 6.1 +/- 1.8 mm Hg) or mid-respiration (13.0 +/- 3.0 compared with 16.9 +/- 2.5 mm Hg). Using chi-square analysis, however, none of these differences reached statistical significance. Discrimination did occur on the basis of the presence of the CREST (calcinosis, Raynaud's phenomenon, esophageal manifestations of scleroderma, sclerodactyly, and telangiectasis) variant (55 percent compared with 7 percent, p less than 0.01), a duration of dysphagia of more than five months (p less than 0.03), and mid-respiratory lower esophageal sphincter pressure of less than 10 mm Hg (p less than 0.05). It is suggested that: Barrett's metaplasia of the esophagus occurs in one third of patients with scleroderma; clinical, manometric, laboratory, and radiographic features are poor predictors of the presence of Barrett's metaplasia; patients with CREST syndrome, prolonged dysphagia, or a very low lower esophageal sphincter pressure may have an increased risk for the development of metaplasia; patients with scleroderma and Barrett's metaplasia have an increased risk of complications such as stricture or adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1987

Thymic epithelium in vitro. III. Cytokine production by a thymic epithelial subset.

We have previously shown that two populations of thymic epithelium can be separated in culture on the basis of their differential growth rates and their adherence to the culture substratum, and maintained as long-term, morphologically distinct cell cultures, TECs and TECL. We have also described the effects of supernatants from the small epithelial cell (TESs) on the proliferative responses of thymocytes cocultured with mitogen and TESs over a 72-hr period. We now describe the effects in thymic epithelial supernatants (TESL) of soluble factors produced by TECL (the large epithelial cell) on thymocytes costimulated with mitogen and compare their effects to those derived from TECs. Both TESL and TESs suppress optimally stimulated thymocytes and enhance the proliferative responses of suboptimally stimulated thymocytes over a 72-hr period. The suppressive activities produced by TECL and TECs appear distinct, based upon markedly different molecular weights, but have similar sensitivities to heat treatment. The enhancing activities are of similar molecular weight, but have different sensitivities to heat treatment. In addition, TECL synthesize four- to fivefold less PGE2 than TECs. These results provide additional distinctions between the two cell types, and taken in conjunction with data on the anatomic distribution of similar cells, suggest that although they have similar functional effects in vitro, they may prove to have separable roles in vivo.

Animals↗
PubMed1987

Inhibition of nuclear DNA synthesis by an autoantibody to proliferating cell nuclear antigen/cyclin.

Proliferating cell nuclear antigen (PCNA) is expressed in the nuclei of proliferating cells, but is not detected in resting cells. The kinetics of PCNA expression suggest that it is associated with a phase preceding active DNA synthesis. DNA synthesis is under cytoplasmic control, and there is a cytoplasmic protein, ADR (activator of DNA replication), that induces DNA synthesis in isolated quiescent nuclei. We now report that a human antibody preparation monospecific for PCNA, but not two monoclonal antibodies directed against different epitopes on PCNA, can inhibit the ability of ADR to induce DNA synthesis in isolated quiescent nuclei. This effect is not due to inhibition of DNA polymerase alpha activity. Thus, the anti-PCNA antibody exerts its effect either by directly influencing the initial interaction of ADR with the nucleus, or by inhibiting subsequent synthetic events.

Antigen-Antibody Reactions↗
PubMed1987

Thymic epithelium in vitro. IV. Regulation of growth and mediator production by epidermal growth factor.

The regulation of thymic epithelial cell function has been examined using pure cultures of morphologically distinct thymic epithelial cells and the ubiquitous hormone epidermal growth factor (EGF). Small thymic epithelial cells, TECS, had receptors for EGF with high affinity, Kd = 1.2 X 10(-9) M, and exhibited increased DNA synthesis and increased RNA synthesis upon stimulation with EGF. In addition, incubation of TECS monolayers with EGF resulted in enhanced production of prostaglandin E2. In contrast, large thymic epithelial cells, TECL, did not express receptors for EGF and demonstrated no biological response to the hormone. These results suggest the possibility that intrathymic regulation of lymphoid cells may occur via the action of "nonimmunologic" mediators on thymic epithelial cells. They further suggest the more general possibility that immunologic and nonimmunologic hormonal systems may be linked via intersecting cellular pathways.

Animals↗
PubMed1987

Properties of the feline pyloric sphincter in vitro.

The purpose of this study was to determine the intrinsic functions of the feline pylorus in vitro. The myoelectric and pressure characteristics of the intact pylorus, antrum, and duodenum, free of extrinsic hormonal or neural influences, were studied in an in vitro bath that allowed separation of the bathing medium surrounding the different bowel segments. Basal recordings revealed a zone of tonic high pressure of 28.4 +/- 3.5 mmHg (mean +/- SEM) at the pylorus. The basal slow wave frequencies in the pylorus and duodenum were 2.8 +/- 1.4 and 12.6 +/- 0.6 cycles/min, respectively. Spontaneous action potential-associated phasic contractions of the pylorus were noted in 38% of preparations. Enteric nerve stimulation with direct electric current (10 Hz, 1 ms, 10-50 V) applied proximal to the pylorus gave relaxation of the pylorus at the lower voltages and rebound excitation at higher voltages. Electrical stimulation distal to the pylorus yielded phasic contractile pyloric response during the entire stimulus. The duodenal instillation of 0.5 N HCl produced action potential-associated phasic contractions of the pylorus and duodenum but not the antrum. Pyloric responses to electrical stimulation or acidification were abolished by tetrodotoxin (10(-5) M). Bethanechol (10(-6) M) or substance P (10(-7) M) produced a contractile response at the site of stimulation but this response was not transmitted to include adjacent bowel segments. These studies suggest that the pyloric sphincter with its intrinsic reflex properties can be studied in vitro.

Action Potentials↗
PubMed1987

Efficacy of ipecac-induced emesis, orogastric lavage, and activated charcoal for acute drug overdose.

The efficacy of ipecac-induced emesis, large-bore orogastric lavage, and activated charcoal as gastrointestinal decontamination procedures after acute drug overdose is unknown. Using an ampicillin overdose model, these three procedures were compared with one another and to a control ingestion in ten human volunteers. Serial serum ampicillin levels were used to compute the areas under the concentration vs time curves (AUC) for each study. The reductions of ampicillin absorption compared to control were as follows: orogastric lavage 32% (NS), ipecac-induced emesis 38% (P less than .01), and activated charcoal 57% (P less than .01). This model examines each intervention in a mutually exclusive fashion. It supports activated charcoal administration as the primary gastrointestinal decontamination procedure after acute drug overdose.

Acute Disease↗
PubMed1987

Induction of DNA synthesis in isolated nuclei by cytoplasmic factors: inhibition by protease inhibitors.

Cytoplasmic extracts from spontaneously proliferating and mitogen-activated lymphoid cells contain a protein factor called ADR (activator of DNA replication) that induces DNA synthesis in isolated quiescent nuclei. ADR-containing preparations have proteolytic activity, as indicated by their ability to degrade fibrin in a plasminogen-independent and plasminogen-dependent manner. In addition, aprotinin, a nonspecific protease inhibitor, abrogates ADR-induced DNA synthesis in a dose-dependent fashion. Preincubation studies demonstrated that the effect of aprotinin is not due to its suppressive effects on the nuclei themselves. Other protease inhibitors such as leupeptin, p-aminobenzamidine, and N-alpha-tosyllysine chloromethyl ketone are also inhibitory, but soybean trypsin inhibitor is without effect. ADR activity can be removed from active extracts by adsorption with aprotinin-conjugated agarose beads and can be recovered by elution with an acetate buffer (pH 5). These findings are consistent with the interpretation that the initiation of DNA synthesis in resting nuclei may be protease dependent and, further, that the cytoplasmic stimulatory factor we have called ADR may be a protease itself.

Animals↗
PubMed1987

Cytoplasmic [Ca2+] and intracellular pH in lymphocytes. Role of membrane potential and volume-activated Na+/H+ exchange.

The effect of elevating cytoplasmic Ca2+ [( Ca2+]i) on the intracellular pH (pHi) of thymic lymphocytes was investigated. In Na+-containing media, treatment of the cells with ionomycin, a divalent cation ionophore, induced a moderate cytoplasmic alkalinization. In the presence of amiloride or in Na+-free media, an acidification was observed. This acidification is at least partly due to H+ (equivalent) uptake in response to membrane hyperpolarization since: it was enhanced by pretreatment with conductive protonophores, it could be mimicked by valinomycin, and it was decreased by depolarization with K+ or gramicidin. In addition, activation of metabolic H+ production also contributes to the acidification. The alkalinization is due to Na+/H+ exchange inasmuch as it is Na+ dependent, amiloride sensitive, and accompanied by H+ efflux and net Na+ gain. A shift in the pHi dependence underlies the activation of the antiport. The effect of [Ca2+]i on Na+/H+ exchange was not associated with redistribution of protein kinase C and was also observed in cells previously depleted of this enzyme. Treatment with ionomycin induced significant cell shrinking. Prevention of shrinking largely eliminated the activation of the antiport. Moreover, a comparable shrinking produced by hypertonic media also activated the antiport. It is concluded that stimulation of Na+/H+ exchange by elevation of [Ca2+]i is due, at least in part, to cell shrinking and does not require stimulation of protein kinase C.

Animals↗
PubMed1987

The effect of nonsteroidal antiinflammatory drugs on upper gastrointestinal tract symptoms and mucosal integrity.

Gastrointestinal side effects are the most common adverse reactions to the use of nonsteroidal anti-inflammatory drugs (NSAIDs), but their true incidence is controversial. Studies have shown an approximate 20% incidence of upper gastrointestinal symptoms in patients using aspirin and a 10% incidence in patients using some other NSAIDs, such as ibuprofen. Because symptom assessment is subjective and may correlate poorly with objective evidence of gastroduodenal injury, studies of endoscopic and fecal blood loss have been used to assess mucosal injury. Whereas high doses of aspirin may produce overt mucosal injury in a majority of patients and normal volunteers, ibuprofen causes significantly less qualitative and quantitative damage in a dose-dependent manner. Daily doses of 1,200 mg of ibuprofen may produce endoscopic injury and fecal blood losses similar to placebo. Although epidemiologic evidence shows a strong correlation of daily aspirin use to gastric ulcer and upper gastrointestinal hemorrhage, other NSAIDs have not been definitively linked to these lesions; no epidemiologic study has established NSAIDs as a cause of duodenal ulcer or gastric lesions when given in low doses. NSAIDs, particularly ibuprofen, in low doses can be considered to have low gastroduodenal toxicity.

Animals↗
PubMed1987

Preliminary survey of family abuse of children served by United Cerebral Palsy centers.

Two preliminary surveys were performed of children under six years of age to determine: whether handicapping conditions may have occurred as a result of abuse, and the incidence of abuse among children who already had disabilities. The first group of children were in preschool programs operated by United Cerebral Palsy affiliates and the second group were in respite care programs operated by such affiliates. 42 preschool programs with 2771 children and 14 respite care programs with 435 children responded to the survey questionnaire. The results suggest a high incidence of abuse among handicapped children in preschool programs, but a lower incidence in respite care programs. There is a need for greater awareness and reporting of abuse in programs for young handicapped children.

Accidents↗
PubMed1987

Changing patterns of dental caries in Ethiopian adolescents who immigrated to Israel.

The aim of this investigation was to explore changes in caries prevalence and gingival health in adolescents who immigrated from Ethiopia to Israel, experiencing an abrupt cultural transition. Fifty adolescents, aged 15-17, born in Ethiopia, and 196 adolescents born in Israel were examined. All were pupils of a boarding school, sharing the same living conditions and eating schedules. The results showed a nearly sixfold difference in caries prevalence between the Ethiopian and the Israeli group (1.5/9.6). No differences could be seen clinically between the Ethiopians who immigrated more than 1 yr ago and those who arrived within the last year. Radiographically, a significant difference was found between the two Ethiopian subgroups. Those who arrived more than 1 yr ago had nearly three times more initial caries. Total interproximal caries scores for the Israeli group, Ethiopians who arrived more than 1 yr ago, and newly arrived Ethiopians were 6.9, 5.7 and 2.1 respectively. Oral hygiene was poorer in the Ethiopian group than in the Israeli group; little difference was found in gingival health. Change in dietary habits, more meals per day and more frequent consumption of fermentable carbohydrates, could have been the cause of the change in caries rate.

Adolescent↗