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S Cohen

Publications and source records attributed to S Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1979

Plasmodium knowlesi in the marmoset (Callithrix jacchus).

Common marmosets were shown to be susceptible to Plasmodium knowlesi malaria. The morphology of the parasite was indistinguishable from the observed in the natural host (Macaca fascicularis) and the common laboratory model (Macaca mulatta). A differential susceptibility to P. knowlesi was observed in the 8 marmosets studied. Multiplication rates of parasites were variable over 24 h periods. Five animals died of a fulminating infection within 12--17 days after challenge. Three animals recovered spontaneously from infection and were subsequently resistant to challenge with homologous and heterologous variants and strains of P. knowlesi. This resistance was maintained for intervals up to 100 days between challenge infections.

Animals↗
PubMed1979

Differential solubilities in subregions of the membrane: a nonsteric mechanism of drug specificity.

We studied the effect of four volatile anesthetics and convulsants on the GABA- and glutamate-induced conductance change in crab muscle. The intensity of drug action correlated with the solubility parameter (delta) values of the four drugs. Thus, the higher that value was for a given drug, the stronger was its effect on the glutamate response but the weaker was it on the response to gamma-aminobutyric acid (GABA). We suggest that different gating molecules are housed in specific subregions of the membrane, each characterized by a particular value of the solubility parameter. The differential distribution of drugs in these subregions may be a nonsteric mechanism for drug specificity.

Anesthetics↗
PubMed1979

Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor.

Previous studies using a biologically active 1:1 conjugate of EGF and ferritin (F-EGF) have traced the binding and internalization of the hormone molecules. In the present report, we develop ultrastructural criteria for identification of the F-EGF.receptor complex, and, thereby, enable utilization of the F-EGF as an indirect marker to localize the receptor for this peptide hormone. The ferritin cores of bound F-EGF are situated 4-6 nm from the extracellular surface of the membrane. When cells were incubated for up to 30 min at 37 degrees C, this characteristic spatial relationship was observed in all uptake stages (surface clustering, endocytosis, and incorporation into multivesicular bodies), indicating that the hormone.receptor complex remains intact through these steps. However, when incubation was continued for periods sufficient to allow hormone degradation (30-60 min), pools of free ferritin were observed in lysosomes. In the presence of various amine inhibitors of hormone degradation, internalization and multivesicular body incorporation proceeded, but hormone.receptor degradation was blocked as evidenced by preservation of the ferritin-membrane relationship; i.e., no pools of free ferritin were seen after 60 min. These data provide morphological support for the hypothesis that down-regulation of surface receptors involves internalization of intact hormone.receptor complexes. In addition, we have developed a method for viewing the surface of intact cells en face, allowing closer scrutiny of the clustering of F-EGF.receptor complexes in the plane of the membrane prior to internalization. The particles in the F-EGF clusters observed by this method are spaced at 12 nm center-to-center, serving to set upper limits on the packing dimensions of the EGF.receptor complex.

Animals↗
PubMed1979

Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431.

We have prepared a conjugate of epidermal growth factor (EGF) and ferritin that retains substantial binding affinity for cell receptors and is biologically active. Glutaraldehyde-activated EGF was covalently linked to ferritin to produce a conjugate that contained EGF and ferritin in a 1:1 molar ratio. The conjugate was separated from free ferritin by affinity chromatography using antibodies to EGF. Monolayers of human epithelioid carcinoma cells (A-431) were incubated with EGF:ferritin at 4 degrees C and processed for transmission electron microscopy. Under these conditions, approximately 6 X 10(5) molecules of EGF:ferritin bound to the plasma membrane of each cell. In the presence of excess native EGF, the number of bound ferritin particles was reduced by 99%, indicating that EGF:ferritin binds specifically to cellular EGF receptors. At 37 degrees C, cell-bound EGF:ferritin rapidly redistributed in the plane of the plasma membrane to form small groups that were subsequently internalized into pinocytic vesicles. By 2.5 min at 37 degrees C, 32% of the cell-bound EGF:ferritin was localized in vesicles. After 2.5 min, there was a decrease in the proportion of conjugate in vesicles with a concomitant accumulation of EGF:ferritin in multivesicular bodies. By 30 min, 84% of the conjugate was located in structures morphologically identified as multivesicular bodies or lysosomes. These results are consistent with other morphological and biochemical studies utilizing 125I-EGF and fluorescein-conjugated EGF.

Carcinoma, Squamous Cell↗
PubMed1979

Rapid induction of morphological changes in human carcinoma cells A-431 by epidermal growth factors.

The morphological effects of epidermal growth factor (EGF) on human carcinoma cells A-431 have been examined by scanning electron microscopy. These flat polygonal cells normally exhibit only small membrane folds, but show extensive ruffling and extension of filopodia within 5 min of exposure to EGF at 37 degrees C. This ruffling activity is transient, subsiding within another 5--15 min, but several other changes in surface morphology follow. Within the first hour of exposure to the hormone, the cell surface becomes exceedingly smooth and the nuclei seem to protrude above the plane of the otherwise thin monolayer, giving the cells a "fried egg" appearance. Cells at the edges of colonies gradually retract from the substrate, leading to reorganization, by 12 h, of the monolayer into multilayered colonies. EGF thus induces both rapid and long-term alterations in the morphology of these epidermoid cells.

Carcinoma, Squamous Cell↗
PubMed1979

Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor.

Horseradish peroxidase (HRP) uptake was used to measure fluid-phase pinocytosis in monolayers of human epithelioid carcinoma cells (A-431). Histochemistry confirmed that cell-associated HRP was restricted to intracellular vesicles. Biochemical methods showed that HRP uptake in control cultures was directly proportional to the duration of exposure. The addition of low concentrations of epidermal growth factor (EGF) to the incubation media produced a 10-fold increase in the initial rate of pinocytosis. The EGF effect was rapid (within 30 s) but transient; the rate of pinocytosis returned to control levels within 15 min. Metabolic inhibitors reduced the EGF-stimulated rate of pinocytosis by greater than 90%. A conjugate of EGF and ferritin (F:EGF) was used to simultaneously compare the intracellular locations of EGF and HRP. Much of F:EGF was internalized in approximately 100-nm vesicles, while most of the HRP was located in much larger vesicles (range 0.1--1.2 micrometer) which also contained F:EGF. The tumor-promoter 12-0-tetradecanoyl-phorbol-13-acetate, which shares several biological activities with EGF, was also effective in stimulating an increase in the rate of pinocytosis.

Animals↗
PubMed1979

Regulation of lymphokine function.

Although we have focused on desensitization as an experimental model, the findings obtained suggest mechanisms by which physiological control of cell-mediated immunity is attained. Thus, such regulation may occur either at the stage of expression of lymphokine activity or at the level of lymphokine production itself. The former may involve unique suppressor molecules, but as indicated above may be due to the inflammatory lymphokines themselves. The latter appears to involve suppressor systems similar to those operative in antibody formation. Over and above any specific model for regulation, the findings presented here suggest that local fluctuations in lymphokine distribution can modulate immunologically induced inflammatory responses, either through alterations in chemotactic gradients, or by other mechanisms as yet unknown.

Animals↗
PubMed1979

Modulation of protein A formation in Staphylococcus aureus by genetic determinants for methicillin resistance.

Many methicillin-resistant (Mec(r)) strains of Staphylococcus aureus either produce no protein A or secrete it extracellularly (S. Winblad and C. Ericson, Acta Pathol. Microbiol. Scand. Sect. B 81:150-156, 1973). We found that methicillin resistance and protein A production were apparently lost coordinately from the natively Mec(r) strain A676. Restoration of the genetic determinant for methicillin resistance (mec) by transduction or transformation restored protein A production. In two other Mec(r) strains, loss of mec was accompanied by marked reduction in protein A formation. Genetic transfer of mec to derivatives of S. aureus 8325 affected protein A formation differently with different mec determinants. Those derived from strain A676 and two other Mec(r) strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereas mec from two more Mec(r) strains increased its protein A content. This "mec-effect," i.e., stimulation or inhibition of protein A formation dependent on the combination of host strain and mec determinant, was reduced in methicillin-susceptible (Mec(s)) mutants produced by ethyl methane sulfonate treatment of Mec(r) strains. The mec-effect reappeared in spontaneous revertants to methicillin resistance. Phenotypic reduction of methicillin resistance in Mec(r) strains grown at 44 degrees C was accompanied by reduction of the mec-effect on protein A, but it had no effect on protein A formation in Mec(s) strains. Two independent mutants of strain 8325 produced large amounts of protein A at rates that were unaffected by growth at 44 degrees C or by the introduction of mec determinants.

Genes↗
PubMed1979

Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.

Action Potentials↗
PubMed1979

Comparison of proximal and distal colonic muscle of the rabbit.

Mechanical length-tension properties and response to neurohumoral agents were compared for proximal and distal colonic muscle. Resting tension during stretch, acetylcholine-stimulated tension, and the total tension were determined. Proximal circular muscle developed a maximum total tension of 0.96 +/- 0.18 kg/cm2 (mean +/- SE) compared to 0.86 +/- 0.06 kg/cm2 for the distal colon (P greater than 0.05). Resting tension was 0.33 +/- 0.03 kg/cm2 for the proximal colon and 0.05 +/- 0.01 kg/cm2 for the distal colon at the length of optimal acetylcholine-stimulated tension (Lo) (P less than 0.01). Longitudinal muscle showed a similar difference for the proximal and distal colon. The high resting tension in the proximal colonic muscle was reduced by nitroprusside or calcium-free Krebs with EGTA. Dose-response curves to acetylcholine, histamine, phenylephrine, and isoproterenol were similar for the muscle of either part of the colon. Gastrin or cholecystokinin had no effect on the muscle. In summary, the circular or longitudinal muscles of the proximal and distal colon have different length-tension properties but only minimal differences in response to neurohumoral agents.

Acetylcholine↗
PubMed1979

Modulation of lower esophageal sphincter relaxation in the opossum.

The relationship of lower esophageal sphincter (LES) relaxation and sphincter pressure was studied in the basal state and after neurohumoral stimulation in the anesthetized opossum. LES relaxation was induced by electrical vagal stimulation, balloon distension, and swallowing, whereas LES pressure was increased by infusions of gastrin I, histamine, phenylephrine, or bethanechol. Each agent was selected to give an approximately twofold increase in LES pressure, at the highest dosage. The lower dosage gave a submaximal increase in LES pressure. Neither gastrin nor histamine modified sphincter relaxation as induced by vagal stimulation, esophageal distension, or swallowing. Phenylephrine or bethanechol made the LES less sensitive to vagal stimulation or esophageal distension without reducing maximal LES relaxation. Only bethanechol significantly decreased sphincter relaxation in response to swallowing (P less than 0.05). The results of this study suggest that LES relaxation is not a fixed response simply dependent on the inhibitory stimulus or the resting tonic level of LES pressure, but may be modulated by both alpha-adrenergic and cholinergic drugs.

Animals↗
PubMed1979

Sympathetic control of lower esophageal sphincter function in the cat. Action of direct cervical and splanchnic nerve stimulation.

The purpose of this study was to determine the effect of direct stimulation of the sympathetic nerves on the lower esophageal sphincter (LES) in the anesthetized cat. Neither unilateral nor bilateral cervical sympathectomy, or splanchnicectomy significantly modified basal LES pressure in animals with intact vagi, or animals having undergone bilateral cervical vagotomy. Electrical stimulation of the cut, peripheral, cervical sympathetic trunk increased mean arterial blood pressure, but had no effect on LES pressure or LES relaxation as induced by vagal stimulation. Stimulation of the central end of the cervical sympathetic trunk had no effect on LES pressure. Stimulation of the central end of the cut splanchnic nerve produced a decrease in LES pressure with a maximal response of 69.1+/-16.0% (mean+/-SEM). This inhibitory response was not modified by either propranolol or bilateral cervical vagotomy. Stimulation of the peripheral end of the cut, greater splanchnic nerve gave an increase in LES pressure with a maximal response of 38.2+/-7.19 mm Hg. Guanethidine, in the presence or absence of the adrenal glands, significantly augmented this excitatory response. This response was also slightly increased by phentolamine alone at 10 V, 1 Hz, but was not altered by propranolol. The excitatory response was completely antagonized by atropine or by trimethaphan camsylate. Stimulation of the peripheral end of the splanchnic nerve inhibited LES relaxation as induced by vagal stimulation. The results of this study suggest that: (a) the LES in the cat is not affected by either central or peripheral stimulation of the cervical sympathetic trunk; (b) the central portion of the splanchnic nerve carries an afferent inhibitory response to the LES through yet unknown pathways; (c) the peripheral splanchnic nerve carries an atropine-sensitive excitatory response to the LES; and (d) the splanchnic nerves may modulate LES relaxation as induced by vagal stimulation.

Adrenalectomy↗
PubMed1979

Localization and chemical characterization of Plasmodium knowlesi schizont antigens.

The identification of malarial antigens that induce protective immunity could provide a rational basis for developing an effective antimalarial vaccine as well as specific serodiagnostic tests indicative of clinical immune status. Since protective immunity is probably induced by stage-dependent rather than stage-independent antigens, the antigenic composition of different stages of Plasmodium knowlesi has been compared, and a limited chemical characterization undertaken. This information should provide some insight into the types of preparative procedure appropriate for the purification of functionally important malarial antigens.

Animals↗