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Biomedical subjects

E Rubin

Publications and source records attributed to E Rubin.

At least 235 records · Page 13Linked to original sources

Ontogeny of the retina and optic nerve in Xenopus laevis. II. Ontogeny of the optic fiber pattern in the retina.

The ontogeny of optic fiber patterns within the Xenopus laevis retina has been studied in silver-stained serial sections and whole mounts. Ganglion cell axons ("pioneers") appear much earlier than previously recognized, at Nieuwkoop-Faber ('56) Stage 28. Fibers fasciculate into bundles as they arise in the retina and reach the chiasma by NF Stage 32. Because the retina grows in rings at its margins, ganglion cell axons differentiate at the periphery and join the nearest fiber bundles (fascicles) to reach the optical disc. A radial fascicle pattern develops by Stage X (Grant et al., '80) within the optic fiber layer of the retina and acts as a template of pathways that lead all later appearing fibers out of the retina. Since the retina grows asymmetrically along its dorso-ventral axis, the fascicle pattern develops asymmetrically, with dorsal quadrant fascicles forming an arcuate pattern in contrast to shorter, thicker ventral quadrant fascicles. The growth pattern of the retina and the "principle" of fiber following suggest that "positional information" is acquired by ganglion cells according to a system of polar coordinates (MacDonald, '77). A radial distance "r" from the center is determined temporarily by ganglion cell birthday and an angular value "theta" is given by the angular position of the fascicle followed by its axons to the optical disc. Wedges of ganglion cells send their axons into a common fascicle which retains its integrity as it leaves the retina at the optic disc. This pattern of optic fiber development suggests a model for retino-topic ordering of the optic fiber projection in Xenopus, with the fascicle acting as the "pattern-forming unit of connectivity."

Animals↗

The temperature dependence of respiration and ATPase in rat liver mitochondria is altered by ethanol.

We studied hepatic mitochondria to determine the effects of ethanol in vitro and of chronic ethanol consumption on the temperature dependence (10 degrees-45 degrees C) of a) substrate oxidation, and b) ATP hydrolysis, with or without CCCP. Arrhenius plots showed the characteristic breaks around 20 degrees C both for electron transport and ATP hydrolysis with high energy of activation at low temperature and low energy of activation at high temperature. Ethanol, in vitro, generally lowered the energy of activation at high temperature and shifted the break in the Arrhenius plots to lower temperatures suggesting an increase in membrane fluidity. At 40 degrees C and above ethanol accelerated electron transport and greatly stimulated ATPase activity. In mitochondria from ethanol-fed rats, Arrhenius plots showed a shift in the breaks to a higher temperature, a finding which suggests a change in membrane structure, possibly associated with decreased fluidity. This may be an adaption of the mitochondrial membranes to counter the effect of ethanol on membrane structure.

Adenosine Triphosphatases↗

Effects of chronic ethanol consumption on the respiratory chain of rat liver submitochondrial particles.

Studies of hepatic submitochondrial particles, which provide an experimental system allowing direct measurements of electron transfer independent of substrate transport reactions, showed that chronic ethanol ingestion (36% calories, 40 days) lowered the specific respiratory rates associated with substrate oxidation. NADH oxidase activity was decreased about 40%, succinoxidase was decreased 25%, and oxidation in ascorbate mediated by phenazine methosulfate was decreased 20%. The content of dithionite-reducible cytochrome aa3 was decreased 38%, while that of cytochrome b was decreased 8%, and that of cytochromes c + c1 was decreased 14%. Steady state kinetic measurements indicated that the turnover number of cytochrome oxidase was unchanged, about 15 s-1 under uncoupled conditions with NADH as substrate. When electron flux to cytochrome c was maximal, cytochrome c was maintained in a more highly reduced state relative to cytochrome aa3 in submitochondrial particles from the ethanol-treated rat compared to those from the control rat. This finding is consistent with the greater decrease in cytochrome aa3 content relative to that of cytochrome c. The results indicate that the diminished content of cytochrome oxidase is one of the factors responsible for the lower respiration rates caused by chronic ethanol consumption.

Alcoholism↗

Iatrogenic hepatic injury.

Liver injury produced by therapeutic drugs is common, and has been increasing in incidence. Drug induced injury can mimic almost all varieties of liver disease. These conditions include cholestasis, steatosis, granulomas, acute and chronic hepatitis, cirrhosis, vascular disorders, and tumors. When confronted with a patient suffering from liver disease, it is imperative for the physician to obtain an accurate history of drug administration.

Adenoma↗

Cardiovascular effects of alcohol.

Epidemiologic studies suggest that moderate consumption of alcohol provides some degree of protection against ischemic heart disease. On the other hand, cerebrovascular accidents and overall mortality are increased at all levels of alcohol intake. Thus, it is inappropriate to advise abstainers to begin to drink alcoholic beverages as a protective measure for coronary artery disease. Acute ingestion of large amounts of alcohol leads to a negative inotropic effect on the myocardium, together with inhibition of a variety of biochemical reactions in subcellular organelles of the heart. Chronic alcoholism is associated with the development of a congestive cardiomyopathy (alcoholic cardiomyopathy), which is independent of vitamin B1 deficiency or other nutritional deficits.

Alcohol Drinking↗

Pulmonary alveolar proteinosis: relationship to silicosis and pulmonary infection.

Pulmonary alveolar proteinosis is a rare disease with varied radiographic and clinical manifestations. Thirteen patients are presented and the role of pulmonary lavage in management is illustrated. Six patients had associated diseases such as nocardiosis, leukemia, and silicosis. The broad spectrum of relationships found in alveolar proteinosis suggests that it represents one mechanism by which the lung responds to a variety of insults.

Adolescent↗

Effects of ethanol on amino acid uptake by rat liver cells.

The effects of ethanol on amino acid uptake were investigated in primary cultures of parenchymal cells isolated from adult rat liver. Sodium-dependent and energy-requiring amino acid transport was studied by measuring the uptake of the nonmetabolizable acid, alpha-amino isobutyric acid (AIB). Ethanol (80 to 100 mM) inhibits both basal and insulin-stimulated AIB uptake, measured after 21 hours of exposure to ethanol. Both the initial rate and cumulative uptake of AIB are inhibited. Although inhibition of basal uptake may involve an effect on more than one system for amino acid transport, the inhibition of insulin-stimulated AIB uptake suggests a major effect on the "A" system. The inhibition is dependent on the concentration of ethanol and results in an increase in Km, but no change in Vmax. Blocking the metabolism of ethanol by pyrazole does not prevent the inhibition of AIB uptake. Under these conditions, the presence of ethanol, rather than its metabolism, appears to inhibit amino acid transport. Inhibition of amino acid transport by ethanol may play a role in the ethanol-induced interference with hepatic gluconeogenesis and protein synthesis.

Adenosine Triphosphate↗

Six years' experience with screening of a diethylstilbestrol-exposed population.

The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.

Adenocarcinoma↗

Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions.

Thiourea and diethylthiourea, two compounds which react with hydroxyl radicals, inhibited NADPH-dependent microsomal oxidation of ethanol and 1-butanol. Inhibition by both compounds was more effective in the presence of the catalase inhibitor, azide. Inhibition by thiourea was noncompetitive with respect to ethanol in the absence of azide but was competitive in the presence of azide. Urea, a compound which does not react with hydroxyl radicals or H2O2, was without effect. Thiourea had no effect on NADH- and NADH-cytochrome c reductase, NADPH oxidase, and NADH- and NADPH-dependent oxygen uptake. Thiourea inhibited the activities of aniline hydroxylase and aminopyrine demethylase. Thiourea, but no other hydroxyl radical scavengers, e.g., dimethyl sulfoxide, mannitol, and benzoate, reacted directly with H202 and decreased H2O2 accumulation in the presence of azide. Therefore the actions of thiourea are complex because it can react with both hydroxyl radicals and H2O2. Differences between the actions of thiourea and those previously reported for dimethyl sulfoxide, mannitol, and benzoate, e.g., effects on drug metabolism, effectiveness of inhibition in the absence of azide, or kinetics of the inhibition, probably reflect the fact that thiourea reacts directly with H2O2 whereas the other agents do not. The current results remain consistent with the concept that microsomal oxidation of alcohols involves interactions of the alcohols with hydroxyl radicals generated from microsomal electron transfer.

Aminopyrine N-Demethylase↗

5'-Nucleotidase levels in normal and virus-transformed cells: implications for cellular aging in vitro.

5'-Nucleotidase activity in the postnuclear supernatant of normal and SV-40 virus-transformed human embryonic lung, chick embryo, and mouse embryo fibroblasts, WI-38, IMR-90, VA-13, CEF, 3T3, and SV3T3 cells was measured. In IMR-90 and CEF cells, both of which have a limited lifespan in vitro, 5'-nucleotidase activity increased 6- and 20-fold, respectively, with increasing population doublings. However, VA-13 cells, a permanent cell line, showed no increase in this enzyme activity with progressive population doublings. 5'-Nucleotidase activity was not detectable in two other permanent cell lines, 3T3 and SV3T3 cells. Of the six cell lines tested, the conspicuous enhancement in 5'-nucleotidase activity with increasing population doublings was observed only in normal cell lines and was absent in transformed cell lines. These observations suggest a molecular mechanism which may play a role in aging of normal cells in vitro and which may involve catabolism of nucleic acids.

Adenosine Monophosphate↗

The effects of ethanol and acetaldehyde on the products of protein synthesis by liver mitochondria.

Ethanol and acetaldehyde, alone or in combination, at physiologic concentrations, significantly inhibit mitochondrial protein synthesis in vitro. Mitochondria from rats chronically fed ethanol also display a reduced rate of mitochondrial protein synthesis in vitro. This effect is further aggravated by addition of ethanol to the incubation medium. Sodium dodecyl sulfate-gel electrophoresis of mitochondria fractionated with acetic acid-lubrol, which were incubated in the presence of ethanol or acetaldehyde, revealed a modest over-all decrease in labeling. However, a polypeptide fraction in the molecular weight range of 36,000 to 40,000 was conspicuously decreased. This range includes subunits of cytochrome oxidase, cytochrome b, and ATPase. Liver mitochondria from rats fed ethanol chronically showed a comparable decrease in the 36,000- to 40,000-molecular weight peak after incubation with radioactive leucine in vitro and fractionation with acetic acid-lubrol. Similar results were obtained when mitochondrial protein synthesis was determined in vivo in chronically treated rats. The data suggest that chronic ethanol consumption interferes with mitochondrial membrane biogenesis and that several products are more sensitive to this effect than others.

Acetaldehyde↗

The caudal ganglion of the leech, with particular reference to homologues of segmental touch receptors.

The caudal ganglion of the leech, which provides sensory and motor innervation to the posterior sucker, represents the fusion of seven embryonic segmental ganglia. Although fused, each of the seven contributing ganglia ("subganglia") of the caudal ganglion can be distinguished morphologically and functionally. The roots from each subganglion carry the axons of mechanoreceptors homologous to "touch" cells found in the segmental ganglia and the subesophageal compound ganglion. The receptive fields supplied by the touch cells of the caudal ganglion are uniquely arranged and reveal the modified segmentation of the circular posterior sucker. Extensive overlap of sensory innervation occurs between adjacent segments of the sucker, beyond the overlap characteristic of the homologous cells of body segments. It thus appears that the touch receptors of the caudal ganglion are less restricted than receptors of the segmental ganglia with regard to their territories of innervation. The caudal ganglion has additional unique properties that establish it as a distinct integrative center of the leech CNS.

Animals↗