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R Taub

Publications and source records attributed to R Taub.

105 records · Page 6Linked to original sources
PubMed1982

Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells.

The consistent appearance of specific chromosomal translocations in human Burkitt lymphomas and murine plasmacytomas has suggested that these translocations might play a role in malignant transformation. Here we show that transformation of these cells is frequently accompanied by the somatic rearrangement of a cellular analogue of an avian retrovirus transforming gene, c-myc. Moreover, we map c-myc to human chromosome 8 band q24, the chromosomal segment involved in the reciprocal Burkitt translocations [t(8;14), t(8;22) and t(2;8)]. In two t(8;14) human Burkitt cell lines, c-myc appears to have been translocated directly into a DNA restriction fragment that also encodes the immunoglobulin mu chain gene. In the case of a specific cloned fragment of DNA derived from a mouse plasmacytoma, we demonstrate directly that c-myc has been translocated into the immunoglobulin alpha switch region. Our data provide a molecular basis for considering the role that specific translocations might play in malignant transformation.

Animals↗
PubMed1975

The effect of cyproheptadine (periactin) on rejection of rat kidney allografts.

The effect of cyproheptadine, a potent platelet deaggregator, was investigated in rats bearing renal allografts. Thirty-three bilaterally nephrectomized LEW rats received orthotopic transplants of a (LEW X BN)F-1 kidney. Fourteen rats were treated with cyproheptadine, 1.5 mg/kg i.m. daily, for 60 days after transplantation; the remaining animals served as controls. The median allograft survival time in the cyproheptadine group was prolonged to 64 days compared to 12 days in the untreated group (P less than 0.005). In the cyproheptadine group the blood urea nitrogen rose to over 150 mg/100 ml 1 week after transplantation, fell to 80-120 mg/100 ml, and then rose steadily from the day after transplantation until the death of the animals. Despite prolonged survival, cyproheptadine-treated animals usually showed the histological findings of acute and chronic renal rejection. Cyproheptadine may be a useful adjunct to immunosuppression in the management of human renal allotransplantation.

Animals↗
PubMedDate not supplied

A variant translocation places the lambda immunoglobulin genes 3' to the c-myc oncogene in Burkitt's lymphoma.

Most translocations that occur in Burkitt's lymphoma involve movement of part of chromosome 8, containing the c-myc gene, from its normal position to the immunoglobulin heavy-chain locus on chromosome 14. The genes are often joined at their 5' ends in opposite transcriptional directions. However, a significant minority of Burkitt translocations involve the light-chain loci on chromosome 2 (kappa) or 22 (lambda). We have characterized one of these from a European-derived cell line (IARC-BL37) that carries an 8;22 translocation. Here the translocation has joined the 5' portion of the lambda light-chain locus to the 3' portion of the c-myc gene at a position about 7 kilobases from the normal c-myc promoters. The translocation is reciprocal and relatively conservative, involving the loss of only 21 base pairs from the site of recombination. This translocation allows us to orient the lambda genes with respect to the centromere of chromosome 22 and to predict the orientation of other translocations involving these chromosomal segments. The 3' translocation is accompanied by an increased level of c-myc transcripts, especially that derived from a normally under-used c-myc promoter.

Burkitt Lymphoma↗
PubMedDate not supplied

Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats.

The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC-reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl-H2B1a, its monosaccharide, and 24-hydroxymethyl-H2B1b.

Adipose Tissue↗
PubMedDate not supplied

Comparative metabolic disposition of ivermectin in fat tissues of cattle, sheep, and rats.

In the study of the metabolic disposition of ivermectin in cattle, sheep, and rats, a group of nonpolar metabolites was detected in the fat tissues of these animals. Upon saponification or esterase treatment, these nonpolar metabolites gave rise to polar products that were similar to the ivermectin metabolites present in the liver. A hypothesis was thus proposed that the polar ivermectin metabolites produced in the liver were esterified and stored in the fat as nonpolar entities, which can be reconverted back to the polar metabolites chemically or enzymatically. To substantiate this hypothesis, the regeneration of polar metabolites from the nonpolar metabolites was studied and hydrolysis products were characterized to establish the basic structure of the alcohol portion of the metabolites. Furthermore, chromatographic comparisons were made between radiolabeled in vivo metabolites and synthetic fatty acid ester samples. These results established the general structural class of the ivermectin nonpolar metabolites and also confirmed the unusual metabolic pathway of ivermectin disposition in fat tissue.

Adipose Tissue↗
PubMedDate not supplied

A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens.

Mitogens evoke many alterations in gene expression in eukaryotic cells. Genes which are activated rapidly and transiently, that are evolutionarily conserved and whose induction is shared by diverse cell types when exposed to different growth stimuli are likely to be of critical importance in transducing mitogenic signals and regulating cellular proliferation. c-myc and c-fos are the only known genes fulfilling these criteria. We report on the molecular cloning of a novel early growth response (egr) gene which also satisfies these conditions. In response to serum, its 3.7 kb mRNA is induced dramatically in mouse fibroblasts reaching a peak level at about 30 minutes that is ten times higher than the maximal value attained by c-fos mRNA. This transcript is induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate and is "superinduced" by serum and cycloheximide together. Importantly, the gene is highly induced by different mitogens in a wide array of cell types: insulin stimulated rat hepatoma cells, adenosine diphosphate treated monkey kidney epithelial cells, and phytohemagglutinin stimulated human peripheral blood lymphocytes. Given the many properties that this gene shares with c-myc and c-fos, it may play a key role in the control of cell growth and perhaps in oncogenesis.

Animals↗
PubMedDate not supplied

The metabolism of avermectins B1a, H2B1a, and H2B1b by liver microsomes.

The avermectins area a new class of structurally related antiparasitic agents isolated from Streptomyces avermitilis. The major polar metabolites isolated from in vitro incubations of [3H]avermectins B1a, H2B1a, and H2B1b with either rat or steer liver microsomes have been isolated and identified as the C24-methyl alcohols of the parent compounds. A smaller quantity of a more polar metabolite has also been identified as the monosaccharide of the C24-methyl alcohols of avermectin H2H1b from rat liver microsomal incubation and avermectin H2B1a from steer liver microsomal incubation. The mass spectra and 300-MHz 1H-NMR spectra permitted assignment of structures to these metabolites. Together these two metabolites represent 50-80% of the total radioactivity more polar than the parent compounds. The metabolite profiles on reverse-phase HPLC demonstrate that the rat and steer are qualitatively similar in the production of these two polar metabolites.

Animals↗
PubMedDate not supplied

The metabolism of avermectin-H2B1a and -H2B1b by pig liver microsomes.

The avermectins are a new class of macrocyclic lactone disaccharide antiparasitic agents derived from Streptomyces avermitilis. On incubation of avermectin-H2B1a and avermectin-H2B1b with pig liver microsomes, a group of metabolites slightly more polar than the parent compounds were generated. Two major metabolites have been isolated and purified by repetitive reversed phase and normal phase HPLC. Their structures were established to be the O-demethylation products of the parent compounds, i.e. 3''-O-desmethyl-H2B1a and 3''-O-desmethyl-H2B1b. The structure assignments were based on spectral results of UV, NMR, fast atom bombardment-mass spectrometry, and chemical derivatization studies including acid hydrolysis as well as fluorogenic reaction. Among the in vitro metabolites, there was only a trace amount of the polar metabolites 24-hydroxymethyl-H2B1a and 24-hydroxymethyl-H2B1b which were the major in vitro metabolites of avermectin-H2B1a and -H2B1b by steer or rat liver microsomes.

Animals↗