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Biomedical subjects

R J Monnat

Publications and source records attributed to R J Monnat.

44 records · Page 3Linked to original sources
PubMed1986

Nucleotide sequence identity of mitochondrial DNA from different human tissues.

Recombinant DNA techniques have been used to search for mitochondrial (mt) nucleotide (nt) sequence differences between human tissues within an individual. mtDNA isolated from brain, heart, liver, kidney, and skeletal muscle of two different individuals was cleaved with SacI and XbaI, and then cloned in bacteriophage M13. Partial nt sequence determination of 121 independently isolated recombinant M13 clones containing either the cytochrome oxidase subunit III gene or the D-loop region of human mtDNA revealed base substitution differences between individuals, and between each individual and the published human mtDNA sequence. A majority of these base substitutions were transitions. No systematic nt sequence differences were identified between tissues within an individual, however. These results suggest that mtDNA sequence alterations do not accompany organogenesis, and that somatic mutations do not accumulate in the mtDNA of different human tissues to a level of greater than one nt substitution per molecule.

Base Sequence↗
PubMed1985

Nucleotide sequence preservation of human mitochondrial DNA.

Recombinant DNA techniques have been used to quantitate the amount of nucleotide sequence divergence in the mitochondrial DNA population of individual normal humans. Mitochondrial DNA was isolated from the peripheral blood lymphocytes of five normal humans and cloned in M13 mp11; 49 kilobases of nucleotide sequence information was obtained from 248 independently isolated clones from the five normal donors. Both between- and within-individual differences were identified. Between-individual differences were identified in approximately 1/200 nucleotides. In contrast, only one within-individual difference was identified in 49 kilobases of nucleotide sequence information. This high degree of mitochondrial nucleotide sequence homogeneity in human somatic cells is in marked contrast to the rapid evolutionary divergence of human mitochondrial DNA and suggests the existence of mechanisms for the concerted preservation of mammalian mitochondrial DNA sequences in single organisms.

Adult↗
PubMed1985

Nucleotide sequence preservation of human leukemic mitochondrial DNA.

Nucleotide sequence variation in mitochondrial DNA isolated from human leukemic cells has been analyzed by recombinant DNA techniques. Three hundred eighty-seven independent recombinant DNA clones, each containing one of three defined segments of mitochondrial DNA isolated from the neoplastic cells of four leukemic patients, were analyzed. Partial nucleotide sequence determination of the 387 clones yielded a total of 81.7 kilobases of nucleotide sequence information. The only evidence of within-individual nucleotide sequence divergence consisted of three clones containing deletions of one or two nucleotides in one mitochondrial DNA region. These clones were three of 113 independent clones isolated from a patient with acute lymphocytic leukemia. The low level of nucleotide sequence divergence in the mitochondrial DNA population of neoplastic cells from individual leukemic patients suggests that a mechanism or mechanisms exist that limit the development of nucleotide sequence divergence in mammalian mitochondrial DNA. The results further suggest that this mechanism does not appear to be abrogated by neoplastic transformation in leukemic patients.

Adolescent↗
PubMed1983

Mechanisms of neoplastic transformation.

This paper introduces a series of invited essays on current controversies in basic cancer research. The initial group of essays focuses on the detection and interpretation of molecular and cellular changes suspected to be of importance in the cause and pathogenesis of cancer. There are two formats: (i) differing viewpoints are presented in parallel, or (ii) the author(s) evaluate a hypothesis in light of available data. Each type of paper aims to critically evaluate current hypotheses and supporting data, while avoiding pronouncements on validity. Recent advances in molecular biology now permit us to consider genes as chemical entities. Individual genes can be isolated, cloned to produce multiple copies, sequenced, and assayed for biological function. This new molecular technology is being applied to fundamental questions in cancer research. The controversies resulting from these pioneering studies are the topics of the initial papers in this series. Forthcoming essays will concern the mechanism(s) of tumor promotion; a search for cancer genes by DNA transfection; the role of DNA rearrangements as initiating events in carcinogenesis; the O6 position of guanine as a critical target of carcinogens; and metals as mutagens and carcinogens.

Animals↗
PubMed1978

Aluminum induced pulmonary granulomatosis.

The association of aluminum dusts and pulmonary fibrosis with emphysema in workers in the aluminum processing and manufacturing industries is well established. The early and minimal reactions of the lungs to the aluminum dusts are not known. This report presents the first case of pulmonary granulomatosis associated with aluminum inhalation. The occupational history of this patient was thoroughly examined, and the aluminum was identified by electron probe microanalysis of the lung biopsy specimen. The granulomatous response in this patient was similar to that observed in rabbits following aluminum dust inhalation. Hypersensitivity or individual idiosyncrasy may play a role in the development of the pulmonary granulomas following exposure to aluminum.

Adult↗
PubMedDate not supplied

Cell fusion corrects the 4-nitroquinoline 1-oxide sensitivity of Werner syndrome fibroblast cell lines.

We have shown that Werner syndrome (WRN) fibroblast cell lines are unusually sensitive to the DNA-damaging agent 4-nitroquinoline 1-oxide (4NQO), though not to gamma radiation or to hydrogen peroxide. The fusion of 4NQO-sensitive WRN and 4NQO-resistant control fibroblast cell lines generated proliferating WRN x control cell hybrids that expressed WRN protein and were 4NQO-resistant. These results establish the recessive nature of 4NQO sensitivity in WRN cell lines and provide a cellular assay for WRN protein function.

4-Nitroquinoline-1-oxide↗