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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 793 records · Page 44Linked to original sources

Evidence for an opiate-mediated pyloric sphincter reflex.

The purpose of this study was to determine the mechanism by which the feline pylorus contracts in response to duodenal acidification. Simultaneous intraluminal pressures and serosal electrical activity were recorded from the antrum, pylorus, and duodenum of the anesthetized cat. The pylorus demonstrated a narrow zone of tonically increased pressure. Duodenal but not antral acidification increased the frequency and amplitude of phasic spike-associated pyloric contractions (P less than 0.001). This response was antagonized by tetrodotoxin, intraluminal (ethyl aminobenzoate), or naloxone. Bilateral cervical vagotomy, atropine, phentolamine, propranolol, cinanserine, diphenhydramine, or cimetidine had no effect on the pyloric response to duodenal acidification. Duodenal spike activity was also increased by duodenal acidification but was antagonized by atropine and not by naloxone. Leucine- or methionine-enkephalin intra-arterially produced dose-dependent increases in phasic pyloric contractions. The EDmax for leucin-enkephalin was 1.0 microgram/kg. The enkephalins inhibited duodenal spike activity in a dose-dependent fashion. These studies suggest that the pyloric spike-associated, high-amplitude phasic contractions in response to duodenal acidification involve local neural pathways that may be mediated through an opioid peptide. The pyloric response to duodenal acidification is distinguished from that of the duodenum, which is cholinergic.

Acid-Base Equilibrium↗

A lower esophageal sphincter reflex involving substance P.

The purpose of this study was to determine the mechanism by which distal esophageal acidification increases lower esophageal sphincter (LES) pressure in the anesthetized cat. Intraluminal pressures and myoelectric activity were recorded using fixed, localized manometric catheters and serosal bipolar silver-silver chloride electrodes. The increase in LES pressure (27.1 +/- 4.9 mmHg) and spike activity (133.8 +/- 22.6 spikes/min) following distal esophageal acidification were greater than after saline (P less than 0.001). These responses were abolished by either tetrodotoxin (intravenously) or intraluminal ethyl aminobenzoate. The responses were not antagonized by bilateral cervical vagotomy or by atropine, hexamethonium, phentolamine, propranolol, diphenhydramine, cimetidine, cinanserin, naloxone, haloperidol, or proglumide. Tachyphylaxis to substance P abolished the LES pressure and spike responses to exogenous substance P and to distal esophageal acidification but had no effect on the LES responses to phenylephrine (25.0 micrograms/kg iv) or pentagastrin (0.5 microgram/kg iv). The putative substance P antagonist [D-Pro2,D-Trp7,9]substance P was a partial antagonist and a weak agonist on the LES. Large doses of [D-Pro2,D-TRP7,9]substance P (200.0 micrograms/kg iv) gave a 61.3 +/- 19.3% inhibition of the LES pressure response to acid (P less than 0.05). Intravenous tetrodotoxin partially antagonized the LES response to substance P (10.0 micrograms/kg iv). These studies suggest that the increases in LES pressure and spike activity following distal esophageal acidification occur through a spike-associated enteric neural reflex that involves substance P as a neurotransmitter.

Action Potentials↗

Malignant mesothelioma of the tunica vaginalis testis.

Eighteen patients with malignant mesothelioma of the tunica vaginalis testis have been previously reported. These and the six patients reported here are reviewed for natural history and response to treatment. This tumor should be considered in men of any age with scrotal masses that include a hydrocele. Staging procedures should include computerized tomography scanning of the chest and abdomen. Inguinal orchiectomy appears to be the optimal primary surgical approach. Intraabdominal disease found at diagnostic laparotomy may be effectively treated by surgery and/or abdominal radiotherapy. Clinical features such as a long asymptomatic interval from initial presentation to clinical recurrence were observed and are also worthy of emphasis. Thus, serial follow-up is advised. Upon recurrence, treatment remains unsatisfactory but some responsiveness to chemotherapy has been noted. Doxorubicin-containing regimens were administered to five patients with measurable pulmonary nodules resulting in two partial regressions by standard criteria.

Adult↗

The hallucinogens and the inhalants.

The hallucinogenic drugs represent a recurrent outbreak pattern with each generation or two seeming to rediscover their ego-dissolving effects. The inhalants produce a short-lived intoxication with certain volatile solvents affecting specific organ systems.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

The role of cytoplasmic intermediates in IL 2-induced T cell growth.

In previous studies we showed that PHA-stimulated human peripheral blood lymphocytes contain an extractable cytoplasmic protein that is capable of inducing DNA synthesis in isolated quiescent nuclei. This factor, which we have called ADR (for activator of DNA replication), appears to represent an endogenous intracellular mitogen, or cytoplasmic transducer of extracellular mitogenic signals. In light of the known role of IL 2 in PHA-induced T cell mitogenesis, we continued these studies to investigate whether ADR may be involved in the mechanism of action of IL 2. Results from both dose-response and time-response studies strongly suggest a functional role for ADR in IL 2 mediated T cell growth. Furthermore, the absence of ADR in dexamethasone-treated, PHA-stimulated cells suggests that the induction of ADR is not an early event in T cell activation associated with the expression of IL 2 receptors; rather, the induction of ADR appears to be a later event resulting directly or indirectly from the binding of IL 2 to IL 2-responsive cells. In sum, our findings suggest a pathway for T cell growth in which extracellular exogenous mitogenic signals are transmitted to the nucleus first through an extracellular endogenous growth factor (IL 2) and finally through an intracellular, endogenous molecule (ADR) that acts at the level of the nucleus itself.

Blood Proteins↗

Retinal manifestations of acquired immunodeficiency syndrome (AIDS). Report of a case.

The syndrome of acquired immunodeficiency (AIDS) has previously been described. Originally thought to affect homosexuals and drug abusers exclusively, the disorder has also been observed in women associated with drug abuse, hemophiliacs, Haitians and, rarely, in heterosexual men. Several hundred cases have been reported in the United States whereas only a small number have been reported elsewhere. We report the first case of AIDS in Israel in a heterosexual male who developed the opportunistic infections of esophageal candidiasis and pneumocystis caranii pneumonia as well as the ischemic retinopathy which has come to be associated with the syndrome.

Acquired Immunodeficiency Syndrome↗

Drugs in the workplace.

Many corporations are making concerted efforts to reduce the growing costs of on-the-job intoxication by the use of preemployment urine screening and breath alcohol testing, in addition to the more traditional histories and physical examinations. The worker who is accident prone, frequently ill, demonstrates poor work performance, or who seems to be under the influence of a mind-altering drug is examined for possible drug toxicity. Disciplinary action must be equitable and with the concurrence of the union. The advantages and problems associated with the chemical testing procedure and the safeguards to the individual and the corporation are discussed.

Administrative Personnel↗

Comparison of airway responses following tracheal or esophageal acidification in the cat.

To determine a possible mechanism for the association between gastroesophageal reflux and obstructive pulmonary disease, we quantitatively compared the short latent airway response after acid infusion into the trachea or esophagus in 13 anesthetized adult cats. Total lung resistance was calculated from synchronous measurements of air flow and intrapleural pressure differences from those at end expiratory level. Tracheal infusion of as little as 0.05 ml of 0.2 N HCl evoked an average 4.65-fold increase in total lung resistance from baseline in all animals tested (p less than 0.005). Intratracheal saline had no effect. The response to intratracheal acid infusion was rapidly adapting, pH dependent, and vagally mediated. Infusion of a much larger volume of 10 ml of 0.2 N HCl into the esophagus produced an average 1.47-fold increase in total lung resistance from baseline (p less than 0.05). No change was seen with intraesophageal saline. In contrast to intratracheal acid infusion, a clearly significant increase in resistance was seen in only 8 of 13 animals tested after intraesophageal acidification. When it occurred, the response was sustained for at least 60 s after acid infusion. The magnitude of the response was not augmented by the presence of severe esophagitis. These studies strengthen the concept that reflex pathways in the trachea and esophagus may explain a causal relationship between gastroesophageal reflux and obstructive pulmonary diseases. The results support the view that microaspiration into the trachea is a much more likely mechanism for bronchospasm associated with gastroesophageal reflux than simple acid reflux into the esophagus.

Airway Resistance↗

[Uni- and bidimensional echocardiography in the etiologic diagnosis of precordial pain].

The distinction between precordial pain of cardiac origin and pain of extra-cardiac origin is a daily problem. We wanted to study the value of echocardiography in this difficult diagnostic problem. In a series of 148 patients admitted to the unit in 1982 for chest pain. 104 were investigated by echocardiography and coronary angiography. In 36 per cent of patients, the echocardiogram was normal and was unable to predict the presence or absence of coronary artery disease. Further investigations seem to be justified in these cases. In 57 per cent of cases, the echocardiogram was abnormal, suggestive of a cardiac cause for the pain. The demonstration of a disorder of segmental kinetics in the left ventricle is suggestive of coronary artery disease, which is detected 82 per cent of cases and is a good indication for coronary angiography. The other abnormalities detected, mitral valve prolapse, hypertrophic cardiomyopathy and dilated cardiomyopathy are rarely associated with coronary artery disease, which was found in 0, 13 and 14 per cent of cases, respectively. Initially, these abnormalities may be sufficient to explain the symptomatology. Pericardial detachments are associated with coronary artery lesions in 50 per cent of cases and should be very carefully monitored.

Adult↗

Intracytoplasmic signals for DNA replication in lymphocyte proliferation.

Cytoplasmic extracts prepared from continuously proliferating lymphoblastoid cells, as well as mitogen-activated normal lymphocytes, contain a protein or proteins (ADR) capable of inducing DNA synthesis in isolated quiescent nuclei. Lymphocytes obtained from aged donors with depressed proliferative responses have normal levels of ADR, but depressed nuclear responses to exogenous ADR, suggesting a nuclear defect in these cells. In no instance could an effect of ADR on intact cells be demonstrated. Moreover, it is not released into the extracellular milieu by cells that contain it. These observations suggest that it serves as an intracellular mitogenic signal in replicating cells. Thus, it may be an important intermediate in the pathway leading from cell membrane activation to nuclear activation.

Animals↗

Desensitization. IV: Permeability changes during active and passive desensitization.

The systemic injection of large amounts of specific antigen (active desensitization) or exogenous lymphokine-containing preparations (passive desensitization) leads to a state of anergy or hyporesponsiveness with respect to cellular immunity without effect on antibody production. In the present study, we show that desensitization is associated with the suppression of permeability alterations at the skin reaction site. This effect is not confined to delayed hypersensitivity responses; it is observed in antibody-mediated and nonimmunologically induced reactions as well. Thus, although the mechanism of desensitization involves the cellular rather than the humoral limb of the immune response, it is possible for the expression of a variety of inflammatory responses to be modified during this state.

Animals↗

Studies of hematoporphyrin and hematoporphyrin derivative equilibria in heterogeneous systems. Porphyrin-liposome binding and porphyrin aqueous dimerization.

Two processes of porphyrins in heterogeneous systems containing aqueous and membrane phases have been studied with hematoporphyrin and hematoporphyrin derivative: Dimerization equilibrium in the aqueous phases and porphyrin-membrane binding equilibrium using liposomes as models for biological membranes. The interrelationship of aqueous aggregations and membrane binding was probed and the porphyrin aggregation state in the membrane, at equilibrium, was assessed. Fluorimetric techniques were employed. The dimerization equilibrium constants, at neutral pH and 37 degrees C were found to be 2.8 X 10(5) M-1 and 1.9 X 10(6) M-1 for hematoporphyrin and its derivative, respectively. Over a porphyrin concentration range going from monomer-dominant to dimer-dominant systems, we have found that only monomers are bound to the membrane. The respective monomer-liposome binding constants, found to be independent of the initial monomer/dimer distribution in the aqueous phase, were determined to be 1.6 X 10(3) M-1 and 4.1 X 10(3) M-1 at neutral pH and 37 degrees C for hematoporphyrin and its derivative, respectively. The monomer-liposome interaction was found to perurb the initial monomer/dimer distribution in the aqueous phase, so that the monomers residing at equilibrium in the membrane originate from both monomers and dimers in the aqueous phase.

Chemical Phenomena↗

Characterization of the interaction of 5'-p-fluorosulfonylbenzoyl adenosine with the epidermal growth factor receptor/protein kinase in A431 cell membranes.

Treatment of membrane vesicles from A431 cells, a human epidermoid carcinoma line, with the affinity label 5'-p-fluorosulfonylbenzoyl [8-14C]adenosine (5'-p-FSO2Bz[14C]Ado) results in an inhibition of the epidermal growth factor (EGF)-stimulable protein kinase and in the modification of proteins having the same molecular weight (Mr = 170,000 and 150,000) as the receptor for EGF (Buhrow, S. A., Cohen, S., and Staros, J. V. (1982) J. Biol. Chem. 257, 4019-4022). Modification of the vesicles with 5'-p-FSO2BzAdo inhibits not only the EGF-stimulated phosphorylation of endogenous membrane proteins but also the EGF-stimulated phosphorylation of an exogenous synthetic tyrosine-containing peptide substrate. This indicates that the EGF-stimulable protein kinase is modified by 5'-p-FSO2BzAdo at a site affecting catalytic activity. Membrane vesicles were treated with 5'-p-FSO2Bz-[14C]Ado to affinity label the kinase, then the EGF receptor was purified by affinity chromatography on immobilized EGF. The EGF receptor thus purified contains the 5'-p-SO2Bz[14C]Ado moiety. These data strongly support our hypothesis that the EGF receptor and EGF-stimulable kinase are two parts of the same polypeptide chain.

Adenosine↗