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Biomedical subjects

A Fein

Publications and source records attributed to A Fein.

At least 109 records · Page 6Linked to original sources

Transplacental kanamycin ototoxicity in the guinea pig.

The effect of kanamycin on the cochlear sensory epithelium of albino guinea pig fetuses was studied histologically following the administration of 200 or 400 mg/kg body weight kanamycin sulfate to the pregnant mothers for 8 consecutive days at different stages of gestation. Surface view analysis of Corti's organ revealed slight damage following treatment in the middle trimester of gestation and marked damage due to treatment in the last trimester. The pattern of hair cell loss induced during and after the functional differentiation of the cochlea resembled the pattern of ototoxic lesions in the adult ear. The assumed mechanisms for induction of teratogenesis by kanamycin in the fetal organ of Corti are discussed.

Animals↗

Quantitative pressure injection of picoliter volumes into Limulus ventral photoreceptors.

Many pharmacological probes must be applied to the interior of cells to produce their effects. Ideally, a method for injecting such materials should be simple, rapid, and independent of the chemical properties of the material to be injected. In addition, one might desire to confirm immediately that an injection occurred and to estimate the volume injected shortly thereafter. We report that these conditions are fulfilled when the injection of materials from micropipettes by pressure pulses is confirmed by visualization of injection-induced disturbances in cells viewed on a video monitor. Volumes of aqueous droplets subsequently injected into a nearby oil pool may be used to estimate the volumes injected into cells. We have obtained a calibration curve for these quantitative estimates of injected volumes by injecting radioactively labeled sulfate into Limulus photoreceptor cells. We find that the estimates are accurate within a range covering one order of magnitude. We assess the sources of systematic and random errors in making these estimates.

Animals↗

Spatial localization of bleaching adaptation in isolated vertebrate rod photoreceptors.

Bleaching of a large fraction of the rhodopsin in isolated rod outer segments results in an irreversible desensitization of the rod. This desensitization is referred to as bleaching adaptation. The logarithm of the sensitivity of the rod during bleaching adaptation has been found by a number of workers to be linearly related to the concentration of unbleached rhodopsin. We have measured the desensitization due to bleaching adaptation produced by a spatially confined stimulus and found that its effects are highly local. The space constant for the spread of desensitization was less than 4 microns. The small apparent spread of desensitization beyond the bleached regions probably can be accounted for by defocusing and light scatter. Thus, the involvement of a freely diffusible transmitter in bleaching adaptation does not appear to be required.

Adaptation, Physiological↗

Chemical excitation of Limulus photoreceptors. I. Phosphatase inhibitors induce discrete-wave production in the dark.

Molybdate, tungstate, fluoride, vanadate, and GTP-gamma-S [guanosine-5'-0-(3-thiotriphosphate)] were injected into Limulus ventral photoreceptors by ionophoresis from microelectrodes. All of these drugs induce discrete waves of depolarization similar in waveform to, but smaller in amplitude than, those normally elicited by dim light. As for light-evoked waves, the amplitude of drug-induced waves decreases with light adaptation. For the compounds examined so far (fluoride, vanadate, GTP-gamma-S), the drug-induced waves share a reversal potential with light-induced discrete waves at about +15 mV. The induction of discrete waves by fluoride, vanadate, and molybdate was found to be reversible, whereas the induction of waves by GTP-gamma-S was not. Unlike fluoride and vanadate, which induce waves when added to the bath, molybdate appears to be ineffective when applied extracellularly. Because of the similarity of the drug-induced waves to light-induced discrete waves, we conclude that the drug-induced waves arise from a process similar or perhaps identical to visual excitation of the photoreceptor. However, the smaller size of drug-induced waves suggests that they arise at a stage of phototransduction subsequent to the isomerization of rhodopsin. On the basis of the chemical properties and action of the drugs, we suggest that discrete waves may arise through the activation of a GTP-binding protein.

Animals↗

Chemical excitation of Limulus photoreceptors. II. Vanadate, GTP-gamma-S, and fluoride prolong excitation evoked by dim flashes of light.

We treated Limulus ventral photoreceptors with the phosphatase inhibitors fluoride, vanadate, and GTP-gamma-S [guanosine-5'0-(3-thiotriphosphate)] under various conditions of illumination and external calcium concentrations. In the dark in low-calcium (1 mM) artificial seawater (ASW), fluoride-induced discrete waves cluster together in time. Under these conditions, the intervals between waves were found to be correlated, and there were excess short intervals beyond the number expected from an exponential interval distribution. To assess the effects of the inhibitors on the light response, we stimulated ventral receptors with a series of dim flashes and averaged the current response under voltage clamp. In ASW, vanadate and GTP-gamma-S prolong the decay of the averaged response to dim test flashes, but prolongation does not always accompany the induction of discrete waves in the dark. Prolongation induced by vanadate in normal-calcium (10 mM) ASW was enhanced in low-calcium (1 mM Ca2+) ASW. Many individual response records suggest that prolongation results from extra discrete waves late in the light response, whereas others reveal long-lasting complex waveforms that cannot easily be resolved into discrete waves. The apparent effect of the inhibitors on the light response is to allow a single photoactivated rhodopsin molecule to produce multiple discrete waves and complex long-lasting events. We suggest that both prolongation of the light response and clustering of waves in the dark result from inhibition of a step in the pathway of visual transduction, in which GTP hydrolysis normally helps to turn off the production of both light-evoked and spontaneous waves.

Animals↗

Concanavalin A agglutinability and immunoadherent properties of rat blastocyst.

Preimplantation rat blastocysts were examined in vitro for concanavalin A agglutinability and antigenic properties on the 5th day of development after flushing and after 24 h in culture, following regional differentiation. Differences were found between the two trophoblastic cell populations with regard to cell membrane receptors to concanavalin A. Immunoadherence hemagglutination tests show that the early trophoblast possesses antigenic properties, which are similarly present in the mural and polar cells of the early preimplantation blastocyst. With later differentiation in vitro, differences can be found between the two trophoblastic cell populations with regard to detectable surface antigens.

Agglutination Tests↗

Immunologic measurement of elastin-derived peptides in human serum.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and usually significant impairment of lung function has occurred before the disease is diagnosed. It is likely that destruction of the elastic fiber is a prerequisite for the development of the disease, and it is possible that immunologic identification in the serum of peptides derived from lung elastin degradation might be an effective approach to the early detection and monitoring of the disease. We prepared antibodies to peptides derived from human lung parenchymal elastin and used these antibodies in an enzyme-linked immunosorbant assay to quantitate elastin-derived peptides in the serum of 39 normal control nonsmokers, 33 smokers with normal lung function, and 40 patients with COPD. On average, statistically significant higher levels of elastin-derived peptides were found in the normal smokers and COPD patients compared to the controls. Further work with larger numbers of subjects is necessary to determine whether such a test is effective in identifying those individuals who are at risk of developing COPD.

Antibodies↗

Plasma and serum concentrations of DNA in pulmonary thromboembolism.

The value of circulating DNA concentrations in the diagnosis of pulmonary embolism (PE) was assessed in 68 consecutive patients, of which 36 (Group 1) had clinical symptoms suggesting PE. The diagnosis of PE was established in 13 patients on the basis of pulmonary angiography (PA) (8 patients) and high probability ventilation-perfusion lung scanning (VPS) (5 patients). Pulmonary embolism was ruled out in 23 patients (by PA, 9 patients; by VPS, 14 patients). We found abnormally high DNA concentrations in 26 of the 36 patients (72%) with suggested PE, but there was no significant differences between patients with and patients without PE (p less than 0.05). The results were compared with the DNA concentrations in the remaining 32 patients (16 medical and 16 surgical cases) who had no clinical evidence of PE (Group 2). Increased DNA concentrations were found in 21 of these (66%). There was no significant difference in mean DNA concentrations between Group 1 and Group 2 (p less than 0.05). We conclude that pulmonary angiography and high probability ventilation-perfusion scanning remain the most reliable methods for the diagnosis of PE.

Adrenal Cortex Hormones↗

Observations on some immune properties of preimplantation rat blastocysts.

Rat blastocysts after 3, 24 or 72 hours in culture, were exposed to antiserum against rat embryo and mouse placenta in the presence of complement. The concomitant exposure damaged the trophoblastic cells and the inner cell mass. Differences were not observed in the nature and strength of the damage between blastocysts with or without zona pellucida. When the cultured blastocysts were exposed first to antisera and only later to complement, the damage seemed to be selective. In the 3 and 24 hour cultured blastocysts, only the trophoblastic cells were destroyed but not the inner cell mass. In the 72 hour cultures, the damage was inflicted to all cells including the inner cell mass, exposed after spreading of trophoblastic cells. The anti-rat embryo serum and the anti-mouse placenta serum had similar effects in low dilutions. In high dilution, the anti-rat embryo serum was more potent. Isolated inner cell masses were cultured up to 72 hours but did not attach to the dish nor spread. Nevertheless, the cells survived, proliferated and differentiated into an outer layer of seemingly endodermal cells.

Animals↗

Excitation of Limulus photoreceptors by vanadate and by a hydrolysis-resistant analog of guanosine triphosphate.

Discrete voltage fluctuations that occur spontaneously or in response to dim lights can be recorded from the ventral photoreceptors of Limulus. The injection of vanadate or the hydrolysis-resistant analog of guanosine triphosphate, GTP-gamma-S, into ventral photoreceptors induces the production of discrete waves in the dark. The chemically induced discrete waves are similar to those induced by light. Ventral photoreceptors may contain a guanyl nucleotide binding protein whose activation by vanadate or GTP-gamma-S induces the discrete waves.

Action Potentials↗

Diamide, a sulfhydryl reagent, modifies the light response of Limulus ventral photoreceptors.

Responses to light were recorded intracellularly from Limulus ventral photoreceptors during the application of diamide, a sulfhydryl oxidizing agent. At diamide concentrations of over 0.5 mM there was a brief phase of increased response followed by a marked decrease. Diamide also prolonged the response latency, and in several cases increased the frequency of spontaneous discrete waves. At concentrations of 0.25 mM and below, the response only increased. Although the underlying mechanisms of these effects are not understood, these findings may be significant for the understanding of transduction in photoreceptors.

Action Potentials↗

Effect of major burns on alveolar-epithelial permeability in rabbits.

To evaluate the effect of major surface burns on pulmonary epithelial permeability, the authors studied 8 rabbits. After a 60-min baseline period, a 40% body surface area burn was inflicted. Permeability was assessed by following the rate of passage of 2 radiolabeled tracers from alveoli to arterial blood (125I antipyrene, 51Cr EDTA) and correlated with dynamic compliance, airflow resistance, blood pressure, heart rate, and arterial blood gases. Although dynamic compliance and the pH declined and airflow resistance increased (p less than 0.05), there was no significant change in permeability or P(A-a)O2. The authors conclude that extensive surface burns produce alterations in pulmonary mechanics and arterial pH which are not associated with increased alveolar epithelial permeability.

Animals↗

Renal damage following transplantations of heterologous placental tissue.

Immunological interrelations between placenta and kidney have become a matter of interest with regard to the pathogenesis of preeclampsia. Kidney morphology of Lewis rats was studied following repeated transplantations of heterologous or syngeneic placental tissue. In most of the heterologous placenta-recipient animals, diffuse severe glomerular lesions were found, similar to those seen in women with preeclampsia. In the strongly responding recipients, endothelial cell swelling, narrowing of capillary lumina and proliferation of mesangial matrix were observed. Patchy areas of fluorescence associated with dense IgG deposition, as well as fibrin deposits demonstrated in the affected glomeruli, were correlated with histologic changes. The use of syngeneic placenta as a transplant did not cause histological or immunohistological changes. These findings support the view that differences in histocompatibility antigens between mother and fetus may be involved in the pathogenesis of the nephropathy in preeclampsia.

Animals↗

Pulmonary embolism in the patient with chronic obstructive pulmonary disease. A diagnostic dilemma.

It is often difficult to distinguish pulmonary embolism from worsening underlying disease in the setting of severe chronic obstructive lung disease. We describe three patients with severe COPD and angiographically documented pulmonary embolus to stress that standard clinical and radioisotopic studies were of little value in establishing a diagnosis. All patients had acute increases in alveolar ventilation immediately following the embolus with a reduction in previously elevated levels of PaCO2, as well as hypoxemia. Such changes in arterial blood gases in the patient with severe COPD should suggest pulmonary embolus rather than increased obstruction.

Aged↗

Effect of high molecular levan on implantation and embryonic development in mice.

Pregnant Balb C mice were treated daily with levan beginning on either the first or the ninth day of pregnancy. Damage to embryos appeared on the eighth day in mice treated from the first day. In the second group, the damage was apparent two to four days after the levan treatment was begun. In both groups the damaged and dead embryos were found side by side with apparently normal conceptuses. The damage seems to have been caused by lesions to the trophoblast since it only occurred after implantation and placentation, and it appeared to be different from the antitumoral or the graft-rejection delaying effects of levan.

Animals↗