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M Meyers

Publications and source records attributed to M Meyers.

72 records · Page 4Linked to original sources
PubMed1981

Steroid D-ring glucuronides: characterization of a new class of cholestatic agents in the rat.

Estriol-17 beta(beta-D-glucuronide) (E317G), estriol-16 alpha(beta-D-glucuronide) (E316G) and testosterone-17 beta(beta-D-glucuronide) (TG) produced an immediate, reversible and dose-dependent inhibition of bile flow after their i.v. administration in the rat. Within 15 to 30 min of their administration, bile flow was inhibited by 50% at doses of 13.2, 20.0 and 31.6 mumol/kg of E317G, TG and E316G, respectively. A plot of the logarithm of the dose of each agent vs. the maximal percentage of inhibition of bile flow yielded straight lines which were parallel. E317G, TG and E316G were 0.68, 0.40 and 0.29 times as potent, respectively, as estradiol-17 beta(beta-D-glucuronide), a previously identified cholestatic steroid glucuronide. Maximal inhibition of bile acid secretory rate was similar to that of bile flow for all three agents. Calculation of the bile acid vs. bile flow regression lines indicated substantial inhibition of bile acid independent flow by E317G and TG but only slight inhibition by E316G. In contrast, estriol-3(beta-D-glucuronide) at doses of 11 and 33 mumol/kg increased bile flow. After an i.v. dose (44 mumol/kg) of [3H]E316G, 53% of the dose was recovered in the bile in 3 hr. Unchanged [3H]E316G and a minor metabolite tentatively identified as [3H]estriol-3-sulfate-16 alpha(beta-D-glucuronide) were the predominant compounds recovered in the bile. These data present evidence for a new class of cholestatic compounds, the steroid D-ring glucuronides, and suggest a means by which endogenous or exogenous steroids may produce hepatobiliary dysfunction.

Animals↗
PubMed1980

Identification of the quinone species in cyanide-sensitive and cyanide-insensitive mitochondria of Moniliella tomentosa.

Moniliella tomentosa was investigated for the presence of different quinones that might be involved in the cyanide-sensitive and/or cyanide-insensitive electron-transport pathways. The naturally occurring quinone in Moniliella tomentosa was found to be ubiquinone-45. Other quinone species could not be detected. The concentration of ubiquinone-45 in mitochondria is not related to the presence or absence of the alternative oxidase activity.

Chromatography, Thin Layer↗
PubMed1980

Morphological and biochemical studies on the development of cholinergic properties in cultured sympathetic neurons. I. Correlative changes in choline acetyltransferase and synaptic vesicle cytochemistry.

Under certain culture conditions, neonatal rat superior cervical ganglion neurons display not only a number of expected adrenergic characteristics but, paradoxically, also certain cholinergic functions such as the development of hexamethonium-sensitive synaptic contacts and accumulation of choline acetyltransferase (ChAc). The purpose of this study was to determine whether the entire population of cultured neurons was aquiring cholinergic capabilities, or whether this phenomenon was restricted to a subpopulation. After 1--6 and 8 wk in culture, neurons were fixed in KMnO4 after incubation in norepinephrine and prepared for electron microscopy analysis of synaptic vesicle content to determine whether vesicles were dense cored or clear. ChAc, acetylcholinesterase (AChE), and DOPA-decarboxylase (DDC) activities were assayed in sister cultures. In the period from 1 to 8 wk in culture, the average ChAc activity per neuron increased 1,100-fold, and the DDC and AChE activities increased 20- and 30-fold, respectively. After 1 wk in culture, 48 of 50 synaptic boutons contained predominantly dense-cored vesicles, but by 8 wk the synaptic vesicle population was predominantly of the clear type. At intermediate times, the vesicle population in many boutons was mixed. The morphology of the synaptic contacts on neuronal surfaces was that characteristic of autonomic systems, with no definite clustering of the vesicles adjacent to the area of contact. Increased vesicle size correlated with increasing age in culture and the presence of a dense core. Considering these data along with available physiological studies, we conclude that these cultures contain one population of neurons that is initially adrenergic. Over time, under conditions of this culture system, this population develops cholinergic mechanisms. That a neuron may, at a given time, express both cholinergic and adrenergic mechanisms is suggested by the approximately equal numbers of clear and dense-cored vesicles in the boutons found at the intermediate times.

Acetylcholinesterase↗
PubMed1980

Characterization of cholestasis induced by estradiol-17 beta-D-glucuronide in the rat.

Estradiol-17 beta-D-glucuronide induced an immediate, profound and reversible inhibition of bile flow after its i.v. administration in the rat. The degree of cholestasis was dose-dependent in the range of 8.5 to 21 mumol/kg i.v. A dose of 11 mumol/kg i.v. inhibited bile flow and bile acid secretory rate 65 to 70% within 15 to 30 min of its administration; bile flow and bile acid secretion had returned to near control values within 3 hr. Linear regression analysis of the relationship between bile flow and bile acid secretion indicated a substantial decrease in bile acid independent flow. In contrast, neither estradiol-17 beta, estradiol-3-glucuronide nor estradiol-3-sulfate-17 beta-D-glucuronide at an equimolar dose had any inhibitory effect on these parameters. After a dose of [3H]estradiol-17 beta-D-glucuronide, 79% of the administered radioactivity was excreted in the bile in 3 hr. Estradiol-3-sulfate-17 beta-D-glucuronide was tentatively identified as the predominant biliary metabolite with estradiol-17 beta-D-glucuronide also present in substantial amounts. These data indicate that estradiol-17 beta-D-glucuronide is toxicologically active and suggest the possibility that this estrogen metabolite may induce hepatic pathology in vivo.

Animals↗
PubMed1979

Chromosomal radiosensitivity of ataxia telangiectasia cells at different cell cycle stages.

X-ray induced chromosomal aberrations in peripheral blood lymphocytes as well as in skin fibroblasts from ataxia telangiectasia patients, and from normal individuals were studied. At all stages of cell cycles-namely G0, G1, and G2, more aberrations were induced in AT cells than in normal cells. In addition, AT cells were sensitive to induction of chromosomal aberrations by tritium beta rays from incorporated radioactive thymidine. Possible reasons for the increased sensitivity of AT cells for induction of chromosomal aberrations by ionizing radiations are discussed.

Ataxia Telangiectasia↗
PubMed1976

Induction of vitellogenin synthesis by estrogen in avian liver: relationship between level of vitellogenin mRNA and vitellogenin synthesis.

We have investigated the estrogen-mediated induction of vitellogenin synthesis in rooster liver. We compared the concentrations of vitellogenin messenger RNA (mRNA) in the liver with the concentrations of vitellogenin in the sera of roosters that had recieved various treatments with estrogen. We found no vitellogenin mRNA in the livers of the unstimulated roosters. An initial injection of estrogen was attended by de novo synthesis of vitellogenin mRNA in the liver and accumulation of vitellogenin in the serum. When vitellogenin was no longer present in the serum or liver (the "post-estrogen-serum-negative" state), the liver was found to contain appreciable amounts of vitellogenin mRNA. This mRNA was of the same size as that found in the liver of the rooster actively synthesizing vitellogenin in response to estrogen. Whereas vitellogenin mRNA was in large polysomes in the livers of the roosters actively synthesizing vitellogenin, the vitellogenin mRNA in the liver of the post-estrogen-serum-negative rooster was not associated with polysomes. The possible relevance of these findings to the fact that the rooster responds differently to a primary stimulation with estrogen than to subsequent stimulations is discussed.

Animals↗
PubMed1975

Vitellogenin synthesis in the avian liver. Vitellogenin is the precursor of the egg yolk phosphoproteins.

Administration of estrogen to roosters induces the synthesis of egg yolk phosphoproteins in the liver. We have demonstrated that these proteins are synthesized in the form of a large precursor, vitellogenin, and that vitellogenin is the only phosphoprotein found in the plasma of the estrogen-treated rooster. Vitellogenin is cleaved to form the egg yolk phosphoproteins, lipovitellin, and phosvitin. We have purified vitellogenin to hemogeneity by two methods: chromatography on diethylaminoethyl-52-cellulose and affinity chromatography on an antibody-Sepharose column. Antibodies were elicited in rabbits and sheep by immunization with vitellogenin and lipovitellin, and these antibodies were purified by affinity chromatography on antigen-Sepharose columns. We found that phosvitin was not immunogenic in its native form or in any of the large variety of modified forms we have tested. We have determined the molecular weights of native and denatured vitellogenin and have examined the immunological relationship between vitellogenin and lipovitellin. On the basis of these studies, together with data from phosphate analyses, we suggest that avian vitellogenin is composed of two polypeptides, each of which has a molecular weight of approximately 240,000 and contains within it lipovitellin and two phosvitins.

Animals↗
PubMed1975

Effect of estrogen on gene expression: purification of vitellogenin messenger RNA.

We report initial studies on estrogen-mediated regulation of egg yolk protein synthesis in the rooster. Egg yolk proteins are normally synthesized as a large precursor, vitellogenin, in the liver of the laying hen; roosters synthesize vitellogenin only when treated with estrogen. Polysomal RNA from the liver of estrogen-treated roosters was translated in a reticulocyte cell-free system, and the newly synthesized proteins were identified by a highly specific and sensitive indirect immunoprecipitation reaction. The messenger RNA that specifies vitellogenin has been purified more than 800-fold from rooster liver polysomal RNA by a combination of methods, including immunoprecipitation of polysomes and chromatography of RNA on poly(U)-Sepharose.

Animals↗
PubMed1975

Specific binding of the first enzyme for histidine biosynthesis to the DNA of histidine operon.

Studies were done to examine direct binding of the first enzyme of the histidine biosynthetic pathway (phosphoribosyltransferase) to 32P-labeled phi80dhis DNA and competition of this binding by unlabeled homologous DNA and by various preparations of unlabeled heterologous DNA, including that from a defective phi80 bacteriophage carrying the histidine operon with a deletion of part of its operator region. Our findings show that phosphoribosyltransferase binds specifically to site in or near the regulatory region of the histidine operon. The stability of the complex formed by interaction of the enzyme with the DNA was markedly decreased by the substrates of the enzyme and was slightly increased by the allosteric inhibitor, histidine. These findings are consistent with previous data that indicate that phosphoribosyltransferase plays a role in regulating expression of the histidine operon.

ATP Phosphoribosyltransferase↗
PubMed1975

trans-Recessive mutation in the first structural gene of the histidine operon that results in constitutive expression of the operon.

The first enzyme for histidine biosynthesis, encoded in the hisG gene, is involved in regulation of expression of the histidine operon in Salmonella typhimurium. The studies reported here concern the question of how expression of the histidine operon is affected by a mutation in the hisG gene that alters the allosteric site of the first enzyme for histidine biosynthesis, rendering the enzyme completely resistant to inhibition by histidine. The intracellular concentrations of the enzymes encoded in the histidine operon in a strain carrying such a mutation on an episome and missing the chromosomal hisG gene are three- to fourfold higher than in a strain carrying a wild-type hisG gene on the episome. The histidine operon on such a strain fails to derepress in response to histidine limitation and fails to repress in response to excess histidine. Furthermore, utilizing other merodiploid strains, we demonstrate that the wild-type hisG gene is trans dominant to the mutant allele with respect to this regulatory phenomenon. Examination of the regulation of the histidine operon in strains carrying the feedback-resistant mutation in an episome and hisT and hisW mutations in the chromosome showed that the hisG regulatory mutation is epistatic to the hisT and hisW mutations. These data provide additional evidence that the first enzyme for histidine biosynthesis is involved in autogenous regulation of expression of the histidine operon.

ATP Phosphoribosyltransferase↗
PubMed1973

A cis-trans test of the effect of the first enzyme for histidine biosynthesis on regulation of the histidine operon.

Previous studies showed that when triazolalanine was added to a derepressed culture of a histidine auxotroph, repression of the histidine operon occurred as though histidine had been added (6). However, when triazolalanine was added to a derepressed culture of a strain with a mutation in the first gene of the histidine operon which rendered the first enzyme for histidine biosynthesis resistant to inhibition by histidine, repression did not occur. The studies reported here represent a cis/trans test of this effect of mutations to feedback resistance. Using specially constructed merodiploid strains, we were able to show that the wild-type allele is dominant to the mutant (feedback resistant) allele and that the effect operates in trans. We conclude that the enzyme encoded by the first gene of the histidine operon exerts its regulatory effect on the operon not by acting locally at its site of synthesis, but by acting as a freely diffusible protein.

Alanine↗
PubMed1973

Deletion mapping and orientation of the histidine operon of Escherichia coli on a transducing bacteriophage.

The defective prophage phi80ilambdac(I)857dhis has been mapped through both marker rescue and deletion analysis. Deletions have been isolated which put residual his genes close to trp genes. Analysis of these deletions shows that the histidine operon on the prophage is oriented clockwise as on the bacterial chromosome, thus opposite to the orientation of the trp operon. The presence of the his promoter-operator region is inferred by the ability of the prophage-carrying strain to derepress sequentially under conditions in which the histidine concentration is limiting. In addition to his, the gnd gene is also present on the prophage and is located between his and trp operons. The bacterial genes are inserted in the right arm of the prophage and substitute for all of the late function genes, except for the first three. These data indicate that the "sense" strand for transcription of the his operon in vivo must be the "R" strand.

Chromosome Mapping↗
PubMed1972

Specificity of interaction between the first enzyme for histidine biosynthesis and aminoacylated histidine transfer ribonucleic acid.

The specificity of the interaction between phosphoribosyltransferase and partially purified preparations of various species of transfer ribonucleic acid (tRNA) was investigated with the use of a filter binding assay. The enzyme showed a higher affinity for histidyl-tRNA than for arginyl- or glutamyl-tRNA. Competition experiments revealed that the enzyme does not distinguish between the aminoacylated and deacylated forms of arginine tRNA or glutamic acid tRNA, since all the binding of the aminoacylated tRNA could be inhibited by deacylated tRNA. The enzyme does, however, distinguish between the aminoacylated and deacylated forms of histidine tRNA. Approximately 70% of the binding of aminoacylated histidine tRNA is specific, since only 30% of the binding could be inhibited by deacylated tRNA. The possibility that the regulatory role of phosphoribosyltransferase is carried out as a complex with histidyl-tRNA is consistent with these data.

Acylation↗