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Biomedical subjects

E Rubin

Publications and source records attributed to E Rubin.

At least 217 records · Page 12Linked to original sources
PubMed1982

Chronic ethanol ingestion increases calcium uptake and resistance to molecular disordering by ethanol in liver microsomes.

Calcium uptake and molecular ordering were studied in hepatic microsomes from rats treated chronically with ethanol and were compared with the effects of ethanol in vitro. Calcium uptake was increased by 30% in microsomes from ethanol-fed animals, the Vmax being increased and the Km remaining unchanged. In Arrhenius plots of calcium uptake, the transition temperature in the 25-30 degrees C range was higher by 1.5 degrees C in microsomes from ethanol-fed rats. Chronic ethanol administration resulted in more rigid microsomal membranes, as evidenced by EPR spectra of the spin probe 5-doxylstearic acid. In a plot of the order parameter, S, as a function of temperature, microsomes from ethanol-fed rats showed a discontinuity at a higher temperature than those from controls (29.9 versus 24.2 degrees C). Ethanol, in vitro, inhibited microsomal calcium uptake in both preparations. However, the degree of inhibition was greater in controls. The rate of calcium uptake by microsomes from ethanol-treated animals in the presence of 100 mM ethanol was the same as those from controls in the absence of ethanol. In vitro, increasing concentrations of ethanol progressively decreased molecular ordering of control microsomes, whereas little change was noted in microsomes after chronic ethanol treatment.

Adenosine Triphosphate↗
PubMed1982

Alcohol and the heart: theoretical considerations.

It is now well established that consumption of ethyl alcohol, both acute and chronic, exerts deleterious effects on the heart. Evidence is presented that the initial event that precipitates both acute and chronic changes reflects the physical effects of alcohol on membrane phospholipids and perhaps proteins. The presence of alcohol increases membrane fluidity, a condition that leads to an adaptive change in the phospholipid composition of the membranes, with resultant greater rigidity of the membranes. The effects of alcohol on the lipid bilayer of the plasma membrane, when combined with other nonspecific insults, may lead to a drastic increase in calcium permeability; the resulting calcium influx may cause cell necrosis and initiate irreversibly cardiomyopathy. It is likely that changes in membrane fluidity also exert profound effects on enzyme and transport activities of membrane-bound proteins. In addition, alcohol may interact directly with the hydrophobic regions of proteins. Such interactions may play an important role not only in membrane-bound proteins, but also in alcohol-induced changes in contractile proteins of the heart. It is suggested that, in general, the effects of alcohol are similar to those of other anesthetic agents, and that the elucidation of the pathogenesis of alcoholic cardiomyopathy may require a deeper understanding of the physical interaction among alcohol, phospholipids, and proteins.

Animals↗
PubMed1982

The biology of viral hepatitis.

Dramatic advances in the understanding of the pathogenesis, pathophysiology, prevention, and treatment of the major viral diseases of the liver have been made. Hepatitis B and A viruses have been identified, with specific diagnostic serologic assays commercially available for these infections. The diagnosis of non-A, non-B hepatitis is currently made by exclusion. Morphological alterations in viral hepatitis are similar, regardless of the etiologic agent. Chronic viral hepatitis may be associated with hepatitis B and non-A, non-B, but not with hepatitis A. Persistent infection with hepatitis B virus is associated with an increased incidence of primary hepatocellular carcinoma. Viruses similar to the hepatitis B virus cause the same spectrum of liver disease in certain animals. With the development of a vaccine against hepatitis B virus infection, it may be possible to prevent a large proportion of worldwide chronic liver disease, as well as primary hepatocellular carcinoma.

Animals↗
PubMed1982

Ethanol-induced injury and adaptation in biological membranes.

Ethanol intoxication, both acute and chronic, exerts profound effects on the protein and lipid constituents of biological membranes, which reflect damage and adaptation. Changes in mitochondrial structure are accompanied by specific decreases in components of the electron transport chain, an effect probably related to decreased mitochondrial protein synthesis. Ethanol in vitro reduces the transition temperatures of membrane-bound enzyme activities and decreases the order parameter, as measured by electron paramagnetic resonance. By contrast, both are increased after chronic ethanol administration, and membranes from rats chronically treated with ethanol are highly resistant to disordering by ethanol. This adaptation to the acute fluidizing effect of ethanol may be attributed to an increased saturation of mitochondrial phospholipids, particularly cardiolipin. The increased rigidity of mitochondrial and synaptosomal membranes leads to conspicuously reduced binding of ethanol and of the general anesthetic halothane in preparations from chronically treated animals, a finding that may explain tolerance to ethanol and cross-tolerance to anesthetics. Ethanol also affects the plasma membrane, as demonstrated by a decrease in amino acid transport by hepatocytes. Moreover, the addition of physiological concentrations of ethanol to nonlethal concentrations of membrane-active hepatotoxins produces necrosis of hepatocytes, apparently by augmenting the permeability of the plasma membrane to calcium. Inasmuch as the human liver es exposed to numerous membrane-active agents, e.g., viruses, products of intestinal bacteria, and xenobiotics, this finding may explain the sudden onset of hepatic necrosis in individuals who have abused alcohol for many years. The data suggest that initially ethanol increases the fluidity of all biological membranes. This effect, if continued chronically, is balanced by a change in the lipid composition of the membranes, which increases their rigidity and makes them resistant to disordering by ethanol (homeoviscous adaptation). The increased rigidity reduces the binding of ethanol and other compounds, but also impairs a variety of membrane-bound functions. The combination of ethanol and membrane-active toxins can lead to cell necrosis, a mechanism that may explain cell death not only in the liver, but also in organs that do not metabolize ethanol, such as the heart, pancreas, and brain.

Adenosine Triphosphate↗
PubMed1981

Tolerance and cross-tolerance in chronic alcoholics: reduced membrane binding of ethanol and other drugs.

Membrane binding of ethanol, anesthetics, and hydrophobic molecules in brain synaptosomes and liver mitochondria from rats is conspicuously reduced after long-term consumption of ethanol. The membranes are resistant to structural disordering by both ethanol and halothane. Tolerance, cross-tolerance, and dependence in chronic alcoholics may in part result from membrane alterations that inhibit the binding of ethanol and other drugs.

Alcoholism↗
PubMed1981

Molecular alterations in the respiratory chain of rat liver after chronic ethanol consumption.

Mitochondria, submitochondrial particles, and hepatocytes prepared from the livers of rats treated chronically with ethanol (36% calories, 40 days) exhibited significant alterations in the content of specific respiratory chain components. As measured by heme absorbance, the amounts of substrate-reducible cytochromes aa3 and b were each decreased about 50%, while the amount of cytochromes c plus c1 was unchanged after chronic ethanol treatment. The amounts of extractable flavin and ubiquinone associated with the respiratory chain were also unaltered. The effects of an altered cytochrome ratio on electron transport were studied by measurements of the aerobic reduction levels of the cytochromes during steady state respiration using submitochondrial particles. The aerobic reduction patterns observed after chronic ethanol treatment reflected the differential alterations in amounts of respiratory chain components present in the membranes, as well as the intrinsic kinetic characteristics of respiratory. The most notable change was observed during ascorbate oxidation, in which case cytochrome c was maintained at a higher level of steady state reduction. The results suggest that at the level of the electron transport chain itself, the lower respiratory rates found after chronic ethanol treatment arise, at least in part, from specific alterations in the content of particular electron transfer chain carriers, but that different alterations limit the rate of respiration with different substrates.

Animals↗
PubMed1981

Alcohol-dependent liver cell necrosis in vitro: a new model.

In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

Animals↗
PubMed1981

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

Using the spin probe 5-doxylstearic acid, we studied the structural perturbations of rat liver mitochondrial membranes produced by exposure to ethanol in vitro and by chronic ethanol feeding. The addition of ethanol in vitro to mitochondria from control animals appears to "fluidize" the membranes, as evidenced by a pronounced decrease in the order parameter. By contrast, in membranes from rats fed ethanol chronically, there was no effect on the order parameter. This resistance of the mitochondrial membranes from chronically intoxicated animals to the fluidizing effect of ethanol probably results from a change in the composition of the phospholipids, because the same differential response to ethanol was observed upon using vesicles of mitochondrial phospholipids extracted from control and chronically treated rats. In the presence of 0.025--0.1 M ethanol, a range that prevails in the blood of chronic alcoholics, the order parameter of mitochondrial membranes from rats fed ethanol was comparable to that of control membranes without ethanol in vitro. Analysis of extracted mitochondrial phospholipids showed that the cardiolipin from ethanol-fed animals had fatty acyl residues that are more saturated than those of controls. These findings point to the underlying molecular mechanism of our previous observation that mitochondria from chronic alcoholic rats are more resistant to uncoupling by ethanol at physiological temperature [Rottenberg, H., Robertson, D. E. & Rubin, E. (1980) Lab. Invest. 42, 318--326]. We suggest that an adaptive change in the phospholipid composition leads to structural alterations, which result in increased resistance to disruption of mitochondrial membranes by ethanol. These changes in lipid composition and structure may explain many, if not all, of the mitochondrial abnormalities that have been previously reported to result from chronic ethanol intoxication.

Alcoholism↗
PubMed1981

Atypical pulmonary malaria.

Three atypical cases of pulmonary malaria are presented and discussed. Radiologically, they were manifested by very subtle thickening of interlobular septae or by more overt interstitial edema and pleural effusion. They were all relatively mild and cleared completely on antimalarial drugs. This is in contrast to most reported cases which were severe and fatal. This resultant widening of the clinical and radiologic spectrum of pulmonary malaria leads to the conclusion that such a complication is likely more common than previously recognized. The radiologist can suggest the correct diagnosis by being aware of its many manifestations and by having a high index of suspicion.

Adult↗
PubMed1980

Disruption of optic fibre growth following eye rotation in Xenopus laevis embryos.

Eye rotation is an experimental paradigm used to study axial specification of the amphibian retina and its connections to the tectum. Jacobson reported that the naso-temporal and dorso-ventral axes are determined sequentially and independently between Nieuwkoop-Faber (NF) stages 28 and 32 in Xenopus. Others claim however, that both retinal axes are determined much earlier and not independently in Xenopus and Rana. We now find that in Xenopus this operation can disturb the exit of optic fibres from the retina with the severity of disruption depending on the time of surgery. Eyes rotated 180 degrees at NF stage 26-27, before any fibres develop, form aberrant retinal fascicle patterns in which the first optic fibres to differentiate (pioneer fibres), failing to exit from the eye, are deflected into circling instead of radial trajectories. Optic fibres appearing later follow these early misguided axons, creating circular bundles. Eyes rotated later (NF 32-34), after optic fibres differentiate, develop normal but inverted patterns because radial fascicles in the retina at the time of operation accurately guide all newly arising fibres to the optic nerve head. This stage-dependent sensitivity of retinal fascicle development must be considered when interpreting the results of rotation experiments.

Age Factors↗
PubMed1980

Segmental organization of sympathetic preganglionic neurons in the mammalian spinal cord.

We have used retrograde transport of horseradish peroxidase to determine the distribution of the preganglionic cell bodies whose axons join particular rami of the thoracic spinal cord in a series of guinea pigs, and in a small number of hamsters and cats. In contrast to other recent studies, our results show that the neurons sending axons to a ramus are confined to a single segment at the corresponding spinal level. This segmental organization supports the idea that the rostro-caudal position of preganglionic cell bodies is one determinant of selective synapse formation between preganglionic axons and sympathetic ganglion cells.

Adrenergic Fibers↗
PubMed1980

Characterization of iron-sulfur clusters in rat liver submitochondrial particles by electron paramagnetic resonance spectroscopy. Alterations produced by chronic ethanol consumption.

Iron-sulfur clusters present in rat liver submitochondrial particles were characterized by ESR at temperatures between 30 and 5.5 K combined with potentiometric titrations. The spectral and thermodynamic characteristics of the iron-sulfur clusters were generally similar to those previously reported for pigeon or bovine heart submitochondrial particles. Clusters N-1a, N-1b, N-2, N-3 and N-4 of NADH dehydrogenase had midpoint oxidation-reduction potentials at pH 7.5 of -425, -265, -85, -240 and -260 mV, respectively. Clusters S-1 and S-3 of succinate dehydrogenase had midpoint potentials of 0 and +65 mV, respectively. The iron-sulfur cluster of electron-transferring flavo-protein-ubiquinone oxidoreductase exhibited the gz signal at g = 2.08 and had a midpoint potential of +30 mV. This signal was relatively prominent in rat liver compared to pigeon or bovine heart. Submitochondrial particles from rats chronically treated with ethanol (36% of total calories, 40 days) showed decreases of 20-30+% in amplitudes of signals due to clusters N-2, N-3 and N-4 compared to those from pair-fed control rats. Signals from clusters N-1b, S-1, S-3 and electron-transferring flavoprotein-ubiquinone oxidoreductase were unaffected. Microwave power-saturation behavior was similar for both submitochondrial particle preparations, suggesting that the lower signal amplitudes reflected a lower content of these particular clusters. NADH dehydrogenase activity was significantly decreased (46%), whilst succinate dehydrogenase activity was elevated (25%), following chronic ethanol consumption. The results indicate that chronic ethanol treatment leads to an alteration of the structure and function of the NADH dehydrogenase segment of the electron transfer chain. This alteration is one of the factors contributing to the lower respiration rates observed following chronic ethanol administration.

Animals↗
PubMed1980

Ontogeny of the retina and optic nerve in Xenopus laevis. I. Stages in the early development of the retina.

A staging series for retinal histogenesis is described for Xenopus laevis. It is based on scanning EM studies of intact eyes and serial section analysis of silver-stained preparations. Retinal development is arbitrarily divided into twelve stages (I--XII) based on distinct morphological and histological changes. In general, four different phases of retinal development can be identified: an embryonic phase of rapid histogenesis (Nieuwkoop-Faber stages 21--39) and onset of visual function; a second or functional phase completed by stage 52 is a period of growth, synaptogenesis, and the organization of visual function; a third phase ending at metamorphic climax (NF57) when mature function is achieved and binocular vision begins; and a final mature phase at the end of metamorphosis, when road and cones are adult size and the visuotectal projection extends over the entire tectum. Ten of the twelve developmental stages are assigned to the first phase since this is the period of intense morphogenesis and differentiation.

Acetylcholine↗