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Biomedical subjects

H Gershman

Publications and source records attributed to H Gershman.

At least 19 recordsLinked to original sources

Prehospital pulse oximetry: useful or misused?

STUDY OBJECTIVE: This study evaluated the ability of emergency medical technicians (EMT-As) and emergency medical technicians-paramedics (EMT-Ps) to use pulse oximetry measurements in determining patient oxygen requirements. DESIGN: Prospective case series. SETTING: Cleveland emergency medical services (EMS) system. TYPE OF PARTICIPANTS: Five hundred thirty-two consecutive patients transported to Cleveland area hospitals by the Cleveland EMS system; no exclusions. INTERVENTIONS: EMT-Ps and EMT-As predicted patients' supplemental oxygen requirements based on clinical assessment. Pulse oximetry was performed while patients were breathing room air (RA SpO2). Treatment intervention, including oxygen supplementation and medication given, oxygen saturation after intervention, and oxygen saturation on arrival at the hospital, was also recorded. Therapy guided by the patient's initial RA SpO2 was reviewed to determine the appropriateness of oxygen therapy. RESULTS: Data were analyzed using the chi 2 test and correlation analysis. Eleven percent (59) of patients transported by Cleveland EMS had an initial RA SpO2 of less than 91%. Advanced life support units increased oxygen supplementation on all desaturated patients, whereas basic life support units failed to make appropriate increases in FIO2 in 20% (two) of desaturated patients (P less than .0001). Sixty percent (164) of patients transported by EMT-Ps and 62% (162) of patients transported by EMT-As had an initial RA SpO2 of 97% or greater. EMT-Ps gave supplemental oxygen therapy to all but 7% (11) of these already well-saturated patients, and EMT-As gave supplemental oxygen to all but 6% (nine) of these patients. EMT-Ps administered a higher FIO2 than they had predicted clinically necessary to 2% (four) of patients with an initial RA SpO2 of 97% of greater, whereas EMT-As gave a higher FIO2 than initially predicted to 16% (25) of such patients (P less than .0001). CONCLUSION: EMT-Ps were more likely to appropriately base oxygen therapy on oximetry measurements than were EMT-As. Both groups failed to decrease supplemental oxygen in patients with high explicit protocols for EMS systems contemplating the use of oximetry to guide oxygen therapy. Our results further suggest that pulse oximetry could be used to avoid unnecessary oxygen therapy on a significant number of patients transported by EMS systems because they are already well saturated on room air.

Cost Control↗

A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma.

STUDY OBJECTIVE: To determine whether treatment of acute asthma with repeated doses of nebulized albuterol leads to greater bronchodilation and lower hospital admission rate than treatment with nebulized isoetharine. DESIGN: Randomized, double-blinded, controlled trial of albuterol and isoetharine. TYPE OF PARTICIPANTS: Patients between 18 and 50 years old presenting with acute asthma. Patients were excluded if they had a history of sensitivity to the study drugs, had congestive heart failure or chronic-obstructive pulmonary disease, or were unable to perform spirometry. One hundred three patients were entered into the study. INTERVENTIONS: All patients received oxygen and methylprednisolone in addition to administration of either isoetharine or albuterol. The nebulized aerosol was given at hourly intervals for a total of three doses. MEASUREMENTS AND MAIN RESULTS: Spirometry was performed before treatment and again at 90 and 180 minutes. Initial forced expiratory volume at one minute (FEV1) was 38.1% of predicted normal for the albuterol group and 36.0% of predicted normal for the isoetharine group. At 180 minutes, FEV1 was 55.6% of predicted normal for the albuterol group and 57.1% of predicted for the isoetharine group (NS). Twenty-eight percent of the albuterol group required admission compared with 26% of the isoetharine group (NS). There was no difference in occurrence of side effects between the two groups. CONCLUSION: Repeated doses of albuterol do not lead to a greater improvement in pulmonary function or a lower hospital admission rate than treatment with isoetharine.

Adolescent↗

Hirudin insensitive thrombin-stimulated platelet release.

It has been previously proposed that platelet stimulation may involve two platelet-thrombin complexes: an initial platelet-thrombin complex (P-T) which is converted to an activated platelet-thrombin complex (P*-T). By using the release of radioactive serotonin as a measure of thrombin stimulation, we have demonstrated that under appropriate conditions, a hirudin sensitive and a hirudin insensitive complex can be differentiated. At short platelet-thrombin preincubation times (0-2 minutes) at 4 degrees C, in a buffer containing 18.7 mM phosphate, added hirudin almost completely inhibited the release of radioactive serotonin obtained upon subsequent warming to 37 degrees C (only the hirudin sensitive complex exists). If platelets were preincubated with thrombin for longer periods of time (30 minutes), hirudin became less effective in inhibiting the release obtained upon subsequent warming to 37 degrees C. The same results were obtained whether or not the platelets were washed after incubation at 4 degrees C and before warming to 37 degrees C. We postulate that this change in hirudin sensitivity may reflect a slow conversion of the first platelet-thrombin complex (P-T) to an activated platelet-thrombin complex (P*-T) which can undergo release upon warming. This transition appears to be much faster in acetatetris buffer since at short platelet-thrombin incubation times at 4 degrees C, added hirudin had little or no effect on the release obtained upon warming to 37 degrees C. The difference in the ability of hirudin to inhibit thrombin-induced release in the two buffers was shown to depend upon the presence of phosphate and on variations in ionic strength, and not due to a change in the inhibition constant (Ki) for hirudin.

Animals↗

Control of cell mobility by cyclic AMP.

Cyclic AMP concentrations have been measured in a number of different cell types under a variety of culture conditions in an attempt to define the relationship between the endogenous concentration of cyclic AMP and cell mobility. In previous work it was shown that agents that increase the intracellular concentration of cyclic AMP can effectively suppress cell movement. In Balb/c 3T3 cells, which have a very low mobility in cellular aggregates, the intracellular concentration of cyclic AMP was elevated only transiently soon after the formation of the three-dimensional cell masses. In contrast, in the highly mobile virally transformed counterpart of Balb/c 3T3 cells, called SVT-2, the concentration of cyclic AMP was relatively low soon after the cell masses were formed, but later rose to a level that was higher than that in Balb/c 3T3 cells. Using NIL B cells, SV40-transformed NIL B cells, and several lines of tumour cells derived from NIL B cells, it was found that the average intracellular concentration of cyclic AMP did not vary significantly from one population of cells to another. Finally, the intracellular concentration of cyclic AMP was measured in chick embryo ventricle cells. The mobility of these cells had previously been found to decrease as embryonic development progressed; furthermore, it had been shown that dibutyryl cyclic AMP plus theophylline produced nearly complete inhibition of their movement in cell masses. In the series of experiments reported here we found that the endogenous concentration of cyclic AMP in aggregates and fragments of chick embryo ventricle cells decreases as development proceeds; these data are consistent with preliminary experiments reported by other investigators. In a separate set of experiments, the intracellular concentration of cyclic AMP was measured in cells that had been cultured in a medium containing 1.2 mM-dibutyryl cyclic AMP plus 1.0 mM-theophylline. This drug treatment has previously been shown to inhibit the movement of cells both in aggregates and in monolayers; it also produces striking effects on cell shape and ultrastructure. In aggregates of chick embryo ventricle cells, treatment with these drugs resulted in increases in the intracellular concentrations of cyclic AMP from approximately 10 picomol/mg protein to approximately 500 picomol/mg protein. In Balb/c 3T3 and SVT-2 cells this treatment increased cyclic AMP concentrations from 3.7 to 160 and from 6.4 to 470 picomol/mg protein, respectively.

Animals↗

Mycoplasma-induced BALB/c 3T3 collagenase is a mammalian enzyme.

A collagenase previously reported to accumulate in the medium of cultures of BALB/c 3T3 cells on infection with Mycoplasma orale [Kluve, Merrick, Stanbridge & Gershman (1981) Nature (London) 292, 855-857] was partially purified and characterized. With regard to purification properties, activation, sensitivity to inhibitors and relative molecular mass the enzyme was similar to previously reported vertebrate collagenases, but could not be unequivocally distinguished from bacterial collagenases. With regard to substrate-specificity and reaction products, however, the collagenase was typical of vertebrate collagenases and distinct from bacterial collagenases. Specifically, the enzyme displayed a preference for type III collagen and type I collagen, a somewhat decreased ability to degrade type II collagen, and a very limited ability to degrade type IV collagen. The initial products of the action of the collagenase on type I collagen were characterized as fragments one-quarter and three-quarters of the length of the intact collagen molecule. Because the properties of the collagenase produced by cultures of mycoplasma-infected BALB/c 3T3 cells are those of a mammalian-type (vertebrate-type) enzyme, we have concluded that the collagenase is a product of the mouse (BALB/c 3T3) genome, and is not produced by the mycoplasma. Therefore it appears that infection of BALB/c 3T3 mouse fibroblasts with Mycoplasma orale induces the mouse cells to produce and secrete collagenase.

Animals↗

The stress of coming out.

To conclude, (1) although homosexuality has been recognized for hundreds of years, we still do not understand it completely. (2) This paper places emphasis on the process of individuation and gender-identity that takes place very early in childhood as the cause of homosexuality. (3) If the process is not completed properly, the individual's gender-identity will deviate from that of the vast majority of people. Homosexuality is, therefore, considered by me as a deviation from, rather than a variation of, human sexuality. (4) The degree of neurosis or psychosis associated with homosexuality or heterosexuality is not causal in nature, although the two are intimately intertwined. (5) The stress of coming out varies a great deal in intensity and depends on the degree of integration of the individual and the support given to him by his friends, associates, and family. (6) Although the last decade has brought about a greater acceptance of homosexuality than ever before, sufficient prejudice, ignorance, and fear remain to keep many homosexuals "in the closet." (7) Even today the disclosure of one's homosexuality threatens the individual with the loss of so many important aspects of his life, such as his job, his friends, and even his family, that there is little wonder that coming out of the closet poses such problems for so many homosexuals.

Anxiety↗

Platelet stimulation by antifibronectin antibodies requires the Fc region of antibody.

Anti-human fibronectin antibodies produced in a goat or in rabbits stimulate the release of serotonin from washed or gelatin/Sepharose-treated human platelets in a dose-dependent manner. This finding led us to propose that fibronectin on the platelet plasma membrane might serve as a collagen receptor on these cells [Bensusan, H. B., Koh, T. L., Henry, K. G., Murray, B. A. & Culp, L. A. (1978) Proc. Natl. Acad. Sci. USA 75, 5864-5868]. To determine whether direct interaction of the antibody with platelet membrane fibronectin was responsible for this stimulation, we prepared proteolytic fragments of the antifibronectin antibodies. Purified F(ab')2 fragments had a greatly diminished ability to elicit degranulation, and rabbit F(ab')2 fragments were totally ineffective in this regard. Preimmune IgG from these sources was capable of inhibiting antibody-induced serotonin release in a dose-dependent manner. Purified antibody Fc fragments also inhibited this stimulation in doses stoichiometrically equivalent to the inhibition seen with preimmune IgG. These results suggest that (i) platelet stimulation elicited by anti-human fibronectin antibody is mediated by the platelet Fc receptor and therefore is likely to be dependent on antigen-antibody complex formation and (ii) fibronectin on the platelet surface may not be the primary receptor for platelet adherence to collagen.

Antigen-Antibody Complex↗

Gonadotrophin, testosterone and prolactin interrelationships in cadmium-treated rats.

We have investigated the long-term effect of a single subcutaneous injection of cadmium chloride on plasma testosterone and gonadotrophin levels and the prolactin response to the dopaminergic antagonist metoclopramide in the rat. Twelve days after treatment with cadmium there was testicular necrosis, associated with a decrease in testosterone concentration and atrophy of the accessory sexual glands. By 185 days, partial recovery of the accessory sexual glands indicated by Leydig cell regeneration and a slight rise in testosterone levels had occurred. There was, however, persistent damage to the germinal epithelium. Concentrations of LH increased eightfold above controls by day 12, remained raised until 60 days and then decreased to threefold above controls at 280 days. In contrast, FSH levels reached a maximum between 60 and 130 days and remained persistently raised. The peak prolactin response to metoclopramide in cadmium-treated rats was depressed 12 days after cadmium administration and levels remained low at 19 and 75 days. Normal prolactin responses to metoclopramide were obtained 130 days after cadmium treatment using 1:0 mg metoclopramide/kg or 280 days after treatment using 0.25 mg/kg. When control and cadmium-treated rats were castrated at 280 days and then given metoclopramide 10 days later, the prolactin response was significantly reduced. It is concluded that the impaired prolactin response to metoclopramide in cadmium-treated rats is reversible. Prolactin returns to normal in parallel with regeneration of the Leydig cells, partial restoration of the accessory sex organ weight, slight increase in plasma testosterone and decrease in LH levels. These results suggest that testosterone is not solely responsible for the maintenance of normal prolactin secretion in the male rat.

Animals↗

Transitory effects of glucose starvation on the synthesis of dolichol-linked oligosaccharides in mammalian cells.

The distribution of lipid-linked oligosaccharide intermediates in cultured mammalian cells has been studied under conditions of glucose deprivation. It was found that at low to moderate cell densities within 20 min of glucose starvation, the major species of lipid-linked oligosaccharide shifted from mainly a single species containing three glucose, nine mannose, and two N-acetylglucosamine residues to a pattern dominated by two species containing either five mannose and two N-acetylglucosamine residues or two mannose and two N-acetylglucosamine residues. At high cell densities, this effect was not evident. Continued glucose starvation at low density resulted in a second shift in distribution in which the proportions of these two species decreased and that of the original major species (Glc3Man9GlcNAc2) increased. Addition of glucose or mannose, but not pyruvate, glutamine, galactose, inositol, or glycine, prevented the shift to the Man5GlcNAc2 and Man2GlcNAc2 species. The intermediates that accumulate during glucose starvation were identified by their elution position on gel filtration columns, sensitivity to digestion with alpha-mannosidase, resistance to digestion with endo-beta-N-acetylglucosaminidase H, and by the products of Smith degradation. These data suggest that a regulatory point in the lipid-linked oligosaccharide synthetic pathway exists at the reaction in which Man5GlcNAc2-P-P-dolichol is converted to Man6GlcNAc2-P-P-dolichol.

Animals↗

Cell cycle parameters of 3T3 cells cultured as aggregates.

BALB/c3T3 cells cultured as aggregates were examined by two independent techniques to determine whether or not cells accumulated at a specific point in the cell cycle, and if so to determine the point at which they accumulate. Replating cells onto dishes followed by pulse labeling with [3H]thymidine and autoradiography indicated that aggregate-cultured cells were in the same phase of the cell cycle as cells cultured as confluent monolayers. Flow microfluorometry confirmed that 75% of the aggregate-maintained cells were arrested in G(0) or G(1), with 25% distributed throughout the rest of the cell cycle. Labeling and mitotic indices of cells in aggregates were also consistent with about 20 to 25% of the cells being in S + G(2) = M phases of the cell cycle at any time.

Animals↗

Ketone-body metabolism in glioma and neuroblastoma cells.

We have examined the metabolism of ketone bodies in neuroblastoma C1300 and glioma C6 cells, two established lines of neural origin. The three ketone body-metabolizing enzymes are present in cells of both lines in the relative proportions normally found in brain (D-3-hydroxybutyrate dehydrogenase less than acetoacetyl-CoA thiolase less than 3-ketoacid CoA-transferase), the activities of the first two are higher in glioma cells than in neuroblastoma, and that of the third is 2-fold higher in neuroblastoma cells than in glioma cells. The specific activity of 3-ketoacid CoA-transferase (EC 2.8.3.5) in both cell lines increased as the cultures achieved confluence, then decreased. Ketone bodies and especially acetoacetate are preferred substrates for synthesis of neural lipids in cells of both lines. The incorporation of glucose carbon into lipids is significantly reduced in cells of both lines in the presence of ketone bodies. Addition of acetoacetate but not DL-3-hydroxybutyrate to the culture medium resulted in a significant increase in the activity of 3-ketoacid CoA-transferase and also in the rate of acetoacetate oxidation in neuroblastoma cells but not glioma cells. These findings indicate that specific differences exist in the capacity of these two cell lines to metabolize ketone bodies and also that substrate-level regulation of the ketone body-metabolizing pathway exists. These two lines therefore provide a potentially useful system in which the mechanisms of regulation of these enzymes may be examined.

3-Hydroxybutyric Acid↗

Dibutyryl cyclic AMP suppresses mobility of embryonic chick heart cells in aggregates.

The intermixing of chick embryonic heart ventricle cells was studied in cellular aggregates as a function of embryonic age of the cells. Cell mobility, as measured by intermixing of radiolabelled and unlabelled cells, was high in cells derived from young embryos: 5.36 +/- 1.05 cell diameters per 2.5 days for 6-day-old heart ventricle cells. During development, mobility steadily declined to 1.56 +/- 0.24 cell diameters per 2.5 days for 18-day old cells. Treatment of aggregates with 1.0 mM theophylline plus 1.2 mM dibutyryl cyclic AMP resulted in greatly decreased mobility, particularly in aggregates of the more mobile younger cells. Depending on the embryonic age of the heart ventricle cells, this treatment reduced mobility by 45.3 to 89.4%. These data are consistent with an age-dependent decrease in intrinsic mobility superimposed upon a contact-paralysis mediated inhibition of movement present in solid tissues. In addition, the sensitivity of heart ventricle cells to inhibition by agents that increase intracellular cyclic AMP levels suggest that this is another possible inhibitory mechanism, although its physiological significance has not been established.

Aging↗