Search PubMed⌕ Search

Biomedical subjects

R White

Publications and source records attributed to R White.

At least 685 records · Page 38Linked to original sources
PubMed1983

Ultrastructural modifications during the metabolism of metronidazole by Trypanosoma cruzi.

Trypanosoma cruzi epimastigotes incubated in the presence of [14C] metronidazole are capable of a rapid uptake of the drug as shown by timecourse experiments and by autoradiography of the cells. The drug is metabolized to a more polar compound which has the chromatographic behavior of 2-methyl-5-nitroimidazole-1-yl-acetic acid. Mass spectral analysis of the metabolite shows diagnostic mass values (185, 184, 126) which are compatible with the 2-methyl-5-nitroimidazole-1-yl-acetic acid derivative. Flavone dramatically increases the production of the metabolite both in control and cells pretreated with phenobarbital. The cells show the presence of vesicles whose number is not significantly increased by phenobarbital. Metronidazole, on the other hand, significantly increases the number of vesicles in both control and cells grown in phenobarbital. The vesicles do not contain acid phosphatase and/or polyphosphates. It is concluded that the vesicles may correspond to a marked proliferation of the endoplasmic reticulum. A secondary effect of flavone is the proliferation of the mitochondrial membranes.

Acid Phosphatase↗
PubMed1983

A test of the role of two oncogenes in inherited predisposition to colon cancer.

Inheritance of mutationally altered oncogenes could predispose individuals to the development of specific tumors and account for familial tumor phenotypes. Using adjacent DNA sequence polymorphisms as genetic markers, we have examined two oncogenes, the Kirsten ras2, isolated from a human colon cancer cell line, and the Harvey ras1, isolated from a human bladder cancer cell line, for their role in the genetic etiology of inherited colon cancer in Gardner syndrome. Both oncogene loci have been shown to be unlinked to the Gardner syndrome locus and are, therefore, eliminated as candidates for the Gardner syndrome gene.

Base Sequence↗
PubMed1982

Prostatic steroid binding protein: organisation of C1 and C2 genes.

Prostatic steroid binding protein, whose expression is stimulated by androgens, consists of two subunits: one containing the polypeptides C1 and C3 and the other containing C2 and C3. We have characterised genomic clones containing the C1 and C2 genes by restriction enzyme analysis and DNA sequencing. Both genes are 3.2 Kb, have similar exon/intron arrangements and share considerable DNA sequence homologies in their coding regions, intervening sequences and 5' upstream DNA sequence which suggests that they have probably arisen from the duplication of an ancestral gene. The 5' termini of C1 and C2 mRNA have been mapped; the sequence TATAAA appears 30 nucleotides upstream but a CAAT-like sequence at -60 - -80 is absent. Finally, homologous human genes have not been detected.

Androgen-Binding Protein↗
PubMed1982

Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes.

Use of a 4.5-kilobase-pair (kb) segment of single-copy DNA from a human genomic library as a hybridization probe of genomic human DNAs revealed allelic Taq I restriction fragments 10.6, 11.8, and 14.6 kb long. Among 12 unrelated individuals, all 6 males exhibited the 14.6-kb fragment in addition to one of the other fragments. Three of the females displayed 10.6- and 11.8-kb fragments, and the other three displayed only one fragment length; none had the 14.6-kb fragment. Hybridization of this probe to Taq I-digested DNAs from human-rodent hybrid cell lines (which have partial complements of human chromosomes) demonstrated segregation of the 14.6-kb fragment with the human Y chromosome and segregation of the 10.6- and 11.8-kb fragments with the human X chromosome. Furthermore, hybridization of this probe to Taq I-digested DNAs from 48 members of a single kindred revealed Y-linked inheritance of the 14.6-kb fragment and X-linked inheritance of the 10.6- and 11.8-kb fragments. These experiments demonstrate homology between single-copy sequences on the human X and Y chromosomes.

Alleles↗
PubMed1982

Evidence for in vivo internalization of human leukocyte elastase by alveolar macrophages.

Cell lysates from cultured human alveolar macrophages contain detectable amounts of an elastinolytic enzyme. Although particulate elastin was solubilized only after prolonged incubations, lysates readily hydrolyzed T-OC-alanyl-p-nitrophenol-ester. Hydrolysis of the latter substrate was inhibited by the leukocyte elastase site-specific inhibitor, N-ac-(ala)4-chloromethyl ketone. In addition, radioimmunoelectrophoresis of concentrated alveolar macrophage lysates, previously incubated with 3H diisopropyl-phosphofluoridate (DFP), revealed the presence of DFP binding material that comigrated with inactivated human leukocyte elastase. Human leukocyte elastase can cause lung lesions resembling pulmonary emphysema in experimental animals; therefore, the clearance of this enzyme by alveolar macrophages may represent a significant route for the removal of this potentially pathogenic enzyme from the lung.

Cells, Cultured↗
PubMed1982

Effect of thyroid status on ouabain binding to the human lymphocyte.

Lymphocyte Na-K ATPase was evaluated as an index of thyroid status in man. Lymphocytes from 24 untreated hypothyroid patients and 11 hyperthyroid subjects were sampled in parallel with normal lymphocytes, and Na-K ATPase activity was assessed by measurements of ouabain binding to a plasma membrane fraction or to whole cells. In both systems, ouabain bound saturably and specifically, resulting in linear Scatchard plots. Normal lymphocyte plasma membranes bound 2.30 +/- 0.16 pmol ouabain/mg protein (mean +/- SEM; n = 11), with a Kd of 68 +/- 12 nM. Intact normal lymphocytes bound 3.24 +/- 0.30 pmol ouabain/10(7) cells (n = 14), representing 189,000 sites/cell. In hypothyroidism, ouabain binding, when compared with normal cells sampled on the same day, was reduced by 22.0 +/- 5.3% (n = 11; P less than 0.001) in plasma membranes and by 29.1 +/- 3.5% (n = 14) in whole lymphocytes (P less than 0.001), but there was no significant change in the Kd in the membrane fraction. In 6 subjects, the decrease in ouabain binding to lymphocytes was reversed by thyroid hormone replacement. Red cells from hypothyroid subjects showed normal ouabain binding. Ouabain binding to hyperthyroid plasma membranes (2.42 +/- 0.18 pmol/mg protein) was not significantly different from normal. The results in hypothyroid subjects are consistent with the hypothesis that lymphocyte Na-K ATPase is regulated by thyroid hormones. However, lymphocyte Na-K ATPase does not increase in parallel with elevated thyroid hormone levels in hyperthyroidism. The mechanisms underlying these observations remain to be clarified.

Adult↗
PubMed1982

Assignment of first random restriction fragment length polymorphism (RFLP) locus ((D14S1) to a region of human chromosome 14.

A locus responsible for a restriction fragment length polymorphism (RFLP) has been identified by hybridization of Eco RI fragments to the random human DNA sequence in recombinant plasmid pAW101. We have examined DNA extracted from 20 human X Chinese hamster somatic cell hybrids for the presence of sequences homologous to the human insert in pAW101. The hybrids were derived from six different human donors, five of whom were heterozygous, producing two bands on Southern transfers. The presence of homologous sequences in the hybrids correlated exclusively with the presence of human chromosome 14. Three hybrids contained chromosome 14 in a frequency of greater than one per cell and were positive for two alleles. Two hybrids contained only the distal half of the long arm of 14 as part of a translocation and were still positive. These results assign the first highly polymorphic random RFPL locus (D14S1) to region q21 leads to qter of chromosome 14.

Animals↗
PubMed1981

The specificity of macrophage elastase on the insulin B-chain.

The specificity of macrophage elastase obtained from mouse peritoneal exudative macrophages was determined in the hydrolysis of the oxidized insulin B-chain. This elastase hydrolysed two bonds, namely Ala-Leu and Tyr-Leu. The rate of hydrolysis of the latter was two to three times greater than that of the former. The hexapeptide Glu-Ala-Leu-Tyr-Leu-Val, obtained by cleavage of the insulin B-chain, was not hydrolysed by macrophage elastase. When EDTA was present, proteolysis of the B-chain was not observed. The macrophage elastase is therefore different from the neutrophil elastase in specificity and mechanism.

Animals↗