Biomedical subjects
Publications and source records attributed to S Cohen.
The neuromuscular disorders of the bowel, lacking defined structural abnormalities, have been poorly understood and too often misclassified as psychosomatic. With advancing technology, however, we are gaining increasing evidence of specific abnormalities in the gastrointestinal neuromuscular apparatus. Some specific therapies have already been developed for restoring function.
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Sera from 7 patients with pemphigus vulgaris and both mouse and rabbit antisera against bovine epidermal desmosomes contained antibodies that bound to cell surface components of the spinous layer of bovine epidermis. The antidesmosomal sera showed significant binding to purified desmosomal proteins in an enzyme-linked immunosorbent assay (ELISA). Two of 7 pemphigus sera bound to desmosomal protein-coated microtiter plates at low dilution titers. Two of 6 normal human sera also bound to desmosomal protein-coated microtiter plates at titers comparable to those of the pemphigus sera. Indirect immunofluorescent labeling of frozen sections of monkey esophagus revealed striking differences in the distribution of pemphigus antigens and desmosomal constituents. Pemphigus antisera produced rather uniform fluorescence around the borders of spinous cells of the esophageal epithelium, while anti-desmosomal antibodies bound in a punctate pattern. Anti-desmosomal antibodies labeled cells of the basal layer in a strongly punctate pattern. Only 1 pemphigus serum appreciably labeled basal cells. Two of 3 anti-desmosomal antisera bound avidly in the upper differentiating layers of the epithelium. Pemphigus antibodies did not. Pemphigus sera that reacted with desmosomal proteins in ELISA were absorbed by affinity chromatography on immobilized desmosomal proteins. This treatment did not alter the immunofluorescent labeling patterns produced by these sera. From these results we conclude that the pemphigus autoantibodies studied here bind to epithelial cell surface antigens which are distinguishable from the structural components of desmosomes.
We have previously reported the transfer of gentamicin resistance (Gmr) plasmids in a mixed culture inter- and intraspecifically between strains of Staphylococcus aureus and Staphylococcus epidermidis isolated at Michael Reese Hospital (Jaffe et al., Antimicrob. Agents Chemother. 21:773-779, 1982). We have now shown that representatives of these plasmids were transferred between apparently nonlysogenic strains of S. aureus either in mixed culture in broth or by filter-mating on agar medium. The mechanism of transfer appeared to be conjugation. A transferable Gmr plasmid (pSH8) mobilized or cotransferred a tetracycline R-plasmid and a chloramphenicol R-plasmid that were not independently transferable. The transfer of Gmr plasmids was accompanied by a high incidence of deletion mutations with varied loss of plasmid resistance determinants and, with some mutants, loss of the ability to effect self-transfer. Restriction endonuclease digestion of pSH8 and its deletion mutants made it possible to assign the property of self-transfer to a specific segment of the pSH8 genome and provided the basis for a physical and genetic map of that plasmid. Similar Gmr plasmids from S. aureus strains isolated in locations remote from Michael Reese Hospital had resistance determinants and transfer properties comparable to those of pSH8. Our observations provide evidence for the conjugal transfer of some staphylococcal plasmids, apparently independent of the presence of phage. This mechanism may be of significance in the intra- and interspecific dissemination of resistance to aminoglycosides and other antibiotics in Staphylococcus spp.
Control of lipogenesis by glucagon and cyclic nucleotide derivatives was examined in freshly isolated hepatocytes. [14C]Acetate was incorporated at a linear rate for 2 h into cellular lipids and for at least 6 h into medium lipids. About 80% of the incorporated label was recovered in fatty acids. Incorporation of [1-14C]acetate and 3H2O into cellular and medium lipids was inhibited by glucagon (K50 = 8 X 10(-10) M), dibutyryladenosine 3':5'-cyclic monophosphate (K50 = 7.5 X 10(-8) M), and guanosine 3':5'-cyclic monophosphate and its dibutyryl and 8-bromo derivatives, each with K50 = 2.9 X 10(-6) M. Glucagon (10 nM) reduced incorporation of [14C]acetate and 3H2O into fatty acid by 73 and 52%, respectively, and into cholesterol by 24 and 10%, respectively. When added together to hepatocytes at submaximally inhibitory concentrations, dibutyryl cAMP and dibutyryl cGMP exerted additive effects. However, maximal inhibitory concentrations of both produced the same effect as the addition of either nucleotide alone. Thus, this preparation of rat hepatocytes responded to physiological concentrations of glucagon and low concentrations of dibutyryl cAMP. Cyclic guanosine derivatives inhibited lipogenesis, but 100 times greater concentration was required when compared with dibutyryl cAMP. Dibutyryl cAMP and dibutyryl cGMP did not act synergistically.
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The effects of 5-hydroxytryptamine (5-HT) on the feline ileum and ileocecal sphincter (ICS) were studied in vivo using simultaneous myoelectric and pressure recordings. Both inhibitory and excitatory responses were seen in the ileum and ICS, with the inhibitory response being seen with lower doses of 5-HT (EDmax for inhibition was 5.0 micrograms/kg and EDmax for contractile response was 80.0 micrograms/kg). The inhibitory and excitatory responses were antagonized separately by different 5-HT antagonists. Methysergide inhibited the ICS relaxation response only, whereas cinanserin inhibited the ICS contractile response. Neither effect was inhibited by tetrodotoxin, suggesting that 5-HT acts directly on the smooth muscle at at least two separate receptors. In addition, methysergide alone resulted in a usually tonic increase (8.6 +/- 0.6 mmHg) in basal ICS pressure (P less than 0.05) without an ileal effect, and tetrodotoxin alone induced phasic ileal and ICS contractions (delta ICS = 7.3 +/- 1.5 mmHg). These data suggest the action of at least two inhibitory neurons tonically at the ICS.
A questionnaire addressing itself to the necessity of psychiatric training in gender specific issues and therapists' attitudes towards women in treatment was answered by almost half the total number of residents in psychiatric programs across Canada in the spring of 1980. Although the majority felt that training in gender specific psychology was a necessity, our survey indicated only a small proportion of Canadian programs (2 out of the 16 psychiatric schools) have incorporated this into their present curricula. An overview of the survey showed residents to agree with the following attitudes regarding women in therapy: 1) women's conflicts should be considered in the framework of their developmental life cycle and reproductive issues; 2) women do not present the same conflicts, goals and values as men; 3) therapy should help women to become more autonomous and assertive in the home and at work; and 4) women's primary goal should not necessarily be seen as that of caregivers and homemakers. Further, the residents expressed the beliefs that sex role ideology could interfere with therapy and that the "traditional hierarchy of power" should not be replicated between therapist and patient.
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The fat component of the meal is the major stimulant of the gastrocolonic response. The aim of this study was to characterize the mechanism of the gastrocolonic response after eating fat in healthy human volunteers. A bipolar clip electrode recorded spike activity (SP) from the distal colon. An immediate increase in colonic spike activity occurred after eating a fat meal (18.0 +/- 3.0 SP/30 min) (p less than 0.02). Spike activity remained elevated for 90 min after eating the fat meal (18.6 +/- 2.7 SP/30 min) (p less than 0.01). The intravenous infusion of naloxone or atropine inhibited the fat-induced increase in colonic motility. Cholecystokinin is a candidate mediator of the fat-stimulated gastrocolonic response. The intravenous infusion of the octapeptide of cholecystokinin (20 ng/kg . h) stimulated an increase in distal colonic spike activity (16.0 +/- 3.7 SP/30 min) (p less than 0.025). Intravenous atropine did not affect stimulation of colonic motility by the octapeptide of cholecystokinin. Continuous infusion of naloxone, however, did inhibit stimulation of colonic spike activity by the octapeptide of cholecystokinin. There was no cross-reactivity between opiate or muscarinic receptors. These data suggest (a) fat stimulation of the gastro-colonic response required a muscarinic and opiate receptor, and (b) octapeptide of cholecystokinin can stimulate colonic motility, but it is not the major mediator of the gastrocolonic response.
The intraperitoneal injection of antigen into delayed hypersensitive animals or of preformed lymphokines into unimmunized animals can lead to changes in the distribution and content of inflammatory cells within the peritoneal cavity. If a preexisting macrophage-rich exudate is present, then these challenges will lead to a diminution of the number of macrophages recoverable (macrophage disappearance reaction, MDR). If the peritoneal cavity has been unprepared, then the same stimuli will lead to an increase in the number of macrophages (macrophage appearance reaction, MAR). The existence of opposite effects that can be produced at a given site by the same stimuli provides insights into the multiple interactions involved in biologic reactions mediated by complex mixtures of mediators. Such factors include, in addition to the reaction site itself and the kinds of mediators present, both qualitative and quantitative aspects of the target cell population.
The presence of thymulin (formerly called Facteur Thymique Sérique, FTS) in cultured human thymic epithelial cells was studied using a monoclonal anti-thymulin antibody in an immunofluorescence technique. The percentage of thymulin-containing cells increases gradually as a function of time, from 10% at day 4 to 90% at day 14. Furthermore, this increase can be prevented by the addition of thymulin in the culture medium. These data suggest a feedback control of thymulin secretion by thymic epithelial cells.
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Desensitization with respect to cellular immunity can be achieved by the systemic administration of large doses of antigen. We have demonstrated two patterns of reactivity during the desensitized state. Early in desensitization, the animal is hyporesponsive to both antigen and preformed lymphokine (skin reactive factor, SRF). In the later period, the animal can respond normally to preformed lymphokine while remaining poorly responsive to antigen. In addition, when inflammatory cells (macrophages and neutrophils) from desensitized animals are examined, those obtained early show diminished reactivity to a variety of chemotactic stimuli. Their capacity to so respond recovers later, during a period in which the state of desensitization persists. We have also found that nonspecific desensitization can be inhibited by L-fucose, an agent known to suppress lymphokine-dependent reactions. These observations, in conjunction with previous reports of serum lymphokine activity early in desensitization, are consistent with a two-stage mechanism for desensitization.
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The authors, taking the opportunity of an epidemiological study, submit the results of 12 day hospitals functioning, having a similar administrative structure, receiving an homogeneous train of clients but distributed on different points of the national territory and having a different functional organization. They draw conclusions from it, on the day hospital definition, the interest of defining scientific evaluation systems, for a better assessment of the therapeutic functioning, the place and importance of this type of medical service for the evolution of actions in the field of mental health.
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