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Biomedical subjects

M Bernard

Publications and source records attributed to M Bernard.

At least 181 records · Page 10Linked to original sources

Research in action: self health care and older people.

The Self Health Care in Old Age Project is an experimental health education and promotion programme running in Stoke-on-Trent. England. It is funded jointly by the Beth Johnson Foundation and by the European Economic Community under its Second Programme to Combat Poverty. This paper outlines the Project's four components and focuses, in particular, on the inter-relationship between the developmental and research aspects of the Project.

Aged↗

[The decrease in thyroid hormones in CAPD is not explained either by iodine saturation or by dialysate loss].

Total T4, total T3 and TSH were measured in blood, urine and dialysate of 13 patients on CAPD. Iodine was measured in blood and urine. Free T4 and T3 were measured in blood only. Serum measurements revealed one true hypothyroidism, normal total T4, T3 and TSH for 12 patients, low free T4 and T3 with normal TSH for 9 patients. Iodine was slightly elevated for 3 patients. Urinary T4 and T3 were low. Dialysate T4 and T3 were low (T4 = 13, 6 nmol/24 H). Low free thyroid hormones are not relevant to iodine excess, nor to dialysate losses. Low free thyroid hormones may be considered as an endocrine dysfunction of chronic illnesses.

Adult↗

Cloning and sequencing of pro-alpha 1 (XI) collagen cDNA demonstrates that type XI belongs to the fibrillar class of collagens and reveals that the expression of the gene is not restricted to cartilagenous tissue.

We have isolated several overlapping cDNA clones encoding alpha 1(XI) collagen chains from human and rat cDNA libraries. Together the human cDNAs code for 335 uninterrupted Gly-X-Y triplets, and a 264-amino acid C-propeptide, while the rat cDNAs cover the entire C-propeptide and about a third of the triple-helical domain. Comparison of the human and rodent nucleotide sequences showed a 95% sequence similarity. The identification of the clones as alpha 1(XI) cDNAs was based on the complete identity between the amino acid sequences of three human alpha 1(XI) cyanogen bromide peptides and the cDNA-derived sequence. Examination of and the cDNA-derived amino acid sequence showed a variety of structural features characteristic of fibrillar-forming collagens. In addition, nucleotide sequence analysis of a selected portion of the corresponding human gene revealed the characteristic 54-base pair exon motif. We conclude therefore that pro-alpha 1 (XI) collagen belongs to the group of fibrillar collagen genes. We also suggest that the expression of this gene is not restricted to cartilage, as previously thought, since the cDNA libraries from which the clones were isolated, originated from both cartilagenous and noncartilaginous tissues.

Amino Acid Sequence↗

Complete nucleotide sequence of the region encompassing the first twenty-five exons of the human pro alpha 1(I) collagen gene (COL1A1)

Dysfunctions of the genes coding for the two chains of the human type-I procollagen result in genetic disorders that affect the integrity of bone, ligaments, tendons, and other connective tissues. While the primary amino acid (aa) sequence of one of the two type-I subunits, pro alpha 2(I), has been derived in its entirety from the analysis of overlapping cDNAs, the sequence of the first 247 aa residues of the helical domain of the other polypeptide, pro alpha 1(I), had yet to be determined. To this end, we have sequenced nearly 4 kb of the human pro alpha 1(I) collagen gene and identified twelve open reading frames whose conceptual amino acid translation exhibits 95% homology to the first 247 aa of rat alpha 1(I) chain. Furthermore, with these and other data, some of which previously unpublished, we have derived the complete sequence of the first 7618 bp of the gene. This region comprises the 25 exons encoding the N-terminal pre-propeptide and five of the eight cyanogen-bromide-derived peptides. This information therefore represents a most useful reference for the characterization of molecular defects in individuals affected by various connective tissue disorders.

Amino Acid Sequence↗

Identification of a mutation that causes exon skipping during collagen pre-mRNA splicing in an Ehlers-Danlos syndrome variant.

Recent biochemical studies have shown that the fibroblasts from a patient with Ehlers-Danlos Syndrome Type VIIB produce nearly equal amounts of normal and shortened pro-alpha 2(I) collagen chains (Wirtz, M.K., Glanville, R. W., Steinmann, B., Rao, V. H., and Hollister, D. (1987) J. Biol. Chem. 262, 16376-16385). Compositional and sequencing studies of the abnormal pro-alpha 2(I) chain identified an interstitial deletion of 18 residues corresponding to the N-telopeptide of the collagen molecule. Since this region is encoded by a 54-base pair exon, number 6, the protein defect could have been caused by gene deletion, abnormal pre-mRNA splicing, or both. Here, in order to elucidate the molecular nature of this mutation we have analyzed the sequences of pro-alpha 2(I) collagen cDNA and genomic clones obtained from RNA and DNA of the patient's fibroblasts. Using oligomer-specific cloning we identified a cDNA that contains a 54-base pair deletion corresponding precisely to the sequence of exon 6. Identification of the normal gene was based on the finding of an identical sequence polymorphism in a normal cDNA and in the genomic clone derived from one of the two collagen alleles. The other gene, instead, displayed a base substitution (T to C) in the obligatory GT dinucleotide of the 5' splice-site sequence of intron 6. Analysis of nearly 100 base pairs immediately 5' to exons 5, 6, and 7, and 3' to exons 5 and 7 did not reveal any additional change. Therefore, the data strongly suggest that the observed GT-to-GC transition at the splice donor site of intron 6 generates an abnormally spliced mRNA in which the sequence of exon 5 is joined to the sequence of exon 7. Since skipping of exon 6 does not interfere with the coding frame of the mRNA, the resulting shortened polypeptide, albeit utilized in the assembly of a procollagen trimer, ultimately causes the Ehlers-Danlos Syndrome Type VII phenotype.

Alleles↗

Mapping of a human fibrillar collagen gene, pro alpha 1 (XI) (COL11A1), to the p21 region of chromosome 1.

Type XI collagen is a minor and poorly characterized structural component of cartilage. Recently, cDNA and genomic clones coding for the pro alpha 1 chain of human Type XI collagen, formerly 1 alpha collagen, have been isolated and fully characterized. Here we have used one such probe to establish the chromosomal localization of the pro alpha 1 (XI) collagen gene (COL11A1) by hybridization to filter-bound DNA isolated from flow-sorted chromosomes and by in situ hybridization on metaphase chromosomes. This combination of approaches has enabled us to locate COL1A11 in the p21 region of chromosome 1. This represents the first mapping of a Type XI collagen gene and the first assignment of a collagen locus to chromosome 1. These studies also provide additional evidence for the nearly uniform dispersion of the human fibrillar collagen genes in the human genome.

Chromosome Banding↗

Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells.

Constitutive expression of major histocompatibility complex class II genes is acquired very early in B-cell ontogeny and is maintained up to the B-cell blast stage. Terminal differentiation in plasma cells is, however, accompanied by a loss of class II gene expression. In B cells this gene system is under the control of several loci encoding transacting factors with activator function, one of which, the aIr-1 gene product, operates across species barriers. In this report human class II gene expression is shown to be extinguished in somatic cell hybrids between the human class II-positive B-cell line Raji and the mouse class II-negative plasmacytoma cell line P3-U1. Since all murine chromosomes are retained in these hybrids and no preferential segregation of a specific human chromosome is observed, the results are compatible with the presence of suppressor factors of mouse origin, operating across species barriers and inhibiting class II gene expression. Suppression seems to act at the level of transcription or accumulation of class II-specific mRNA, since no human, and very few murine, class II transcripts are detectable in the hybrids.

Animals↗

Larva migrans of the oral mucosa.

A case of buccal larva migrans is presented. This rare peculiar localization is discussed. The different treatments are mentioned with special regard to the topical and systemic use of the thiabendazole.

Administration, Oral↗

Taking charge--strategies for self-empowered health behavior among older people.

RECENT campaigns aimed at increasing awareness of health issues amongst older people have contributed much to the debates about health education and health promotion. Unfortunately though, publicity campaigns fail to address the very practical aspects of how we might help older people develop self-empowered health behaviour. This article considers firstly what it means to be poor and powerless and describes seven key factors which facilitate self-empowered health behaviour. These are then related to an innovative health project being developed with older people in Stoke-on-Trent, funded jointly by the Beth Johnson Foundation and the EEC under its Second Poverty Programme.

Aged↗

Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study.

Superimposition of cardioplegic arrest on acute low-cardiac-output states, as may occur after failure of percutaneous transluminal coronary angioplasty requiring emergency surgery, is associated with an increased operative risk. This increased risk is possibly attributable to reperfusion, which, after sequential episodes of myocardial ischemia, exacerbates tissue injury mediated by oxygen free radicals. One of the most cytotoxic of these active oxygen species is the hydroxyl radical, which is formed from superoxide anion and hydrogen peroxide through an iron-catalyzed reaction. This study assesses the effects of peroxidase, a hydrogen-peroxide scavenger, and of deferoxamine, an iron chelator, in isolated working rat hearts subjected to 30 minutes of low-flow ischemia (75% reduction in coronary flow) followed by 2 hours of cardioplegic arrest at 15 degrees C and by 30 minutes of normothermic reperfusion. Three groups of hearts (n = 7) were studied. Two groups were pretreated with either peroxidase (10,000 units/l) or deferoxamine (0.03 mM) during the last 15 minutes of the low-flow ischemic period. The third group received no prearrest intervention and served as a control group. In addition to hemodynamic determination, high-energy phosphate content [adenosine 5'-triphosphate (ATP)] and intracellular pH were monitored serially by 31P nuclear magnetic resonance spectroscopy. The two pretreated groups had better recovery of ATP levels and aortic flow values than did the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Contribution of nuclear magnetic resonance spectroscopy of phosphorus-31 and carbon-13 in the study of myocardial metabolism].

The use of NMR spectroscopy in the non-invasive assessment of myocardial metabolism has greatly increased over the last decade. The initial experiments were performed on isolated perfused heart preparations, but these have since been extended to whole animal and clinical studies. The use of the phosphorus-31 nucleus allows assessment of energetic metabolism and intramyocardial pH. Carbon-13 spectroscopy based on the use of substrates selectively enriched with the C-13 isotope enables the study of a specific chosen metabolic pathway and provides qualitative and quantitative information about the metabolic changes. Research is now preceding in two directions: firstly, the study of fundamental problems such as the mechanisms of ischaemia, the consequences of intracellular acidosis and the precise role of ATP and phosphocreatine: secondly, very active clinical and pharmacological research in using NMR in animal models of cardiac pathology. Finally, recent technological progress suggests that NMR spectroscopy will soon be used for direct studies of the human heart.

Carbon Radioisotopes↗

[Cardiac arrhythmia observed in 400 workers without obvious heart disease by Holter monitoring].

To obtain information on the cardiac rhythm characteristics of subjects without heart disease during their daily work, we examined the continuous 24-hour electrocardiographic recordings of 400 workers from 4 factories in Eastern France presenting with criteria of cardiac normality. Sex, age and socio-professional category were taken into account. Supraventricular extrasystoles were extremely common, being observed in 52 p. 100 of men and 39 p. 100 of women. In men, the frequency of these extrasystoles increased with age (p less than 0.001), and their number was less than 20 per 24 hours in 90 p. 100 of the cases. Ventricular extrasystoles were detected in 40 p. 100 of men and 32 p. 100 of women. They too were age-related, though not significantly. Their number was less than 10 per 24 hours in 68 p. 100 of the cases and 10 to 50 per 24 hours in 28 p. 100. These ventricular extrasystoles usually were monomorphous, regularly coupled (92 p. 100) and isolated. However, 2 attacks of tachycardia were discovered. Episodes of bradyarrhythmia (RR superior or equal to 1500 ms) were present in 25 p. 100 of men and 19 p. 100 of women. They occurred more frequently before the age of 35 than later (p less than 0.001) and the recordings confirmed that they were predominantly nocturnal. Recordings without "disorders of rhythm" were relatively rare (20 p. 100 of men, 28.5 p. 100 of women). Finally, there was no clear-cut correlation between the prevalence or characteristics of these various "rhythmic abnormalities" and the type of professional activity.

Adult↗

Organization of the human pro-alpha 2(I) collagen gene.

Sixty kilobases of cloned DNA containing the entire human pro-alpha 2(I) collagen gene and 22 kilobases of flanking sequences have been isolated. Like the homologous avian gene, the 1366 amino acid residues of the human pre-pro-alpha 2(I) chain are encoded by 52 exons, whose relative locations and sizes have been determined. Analysis of the 5'- and 3'-untranslated regions have confirmed their exact lengths, as well as conclusively established the nature of five polymorphic mRNA transcripts.

Amino Acid Sequence↗

Distinct mechanisms regulate MHC class II gene expression in B cells and macrophages.

In a previous series of studies, we had shown that the constitutive Ia expression in an immunoselected Ia-human B cell variant, RJ 2.2.5, could be restored by somatic cell hybridization with mouse B cells. These experiments allowed us to show the existence of a transacting activator factor(s) operating across species barriers and encoded by the aIr-1 locus located on mouse chromosome 16. The aim of the present study was to investigate whether the B cell constitutive Ia expression and the inducible Ia expression, as seen in macrophages treated with IFN-gamma, are controlled by similar intracellular factors. To this purpose, we constructed an interspecies somatic cell hybrid between the human Ia-RJ 2.2.5 B cells and the mouse Ia-P388 D1 macrophage cells. These murine cells transiently express Ia antigens when incubated with IFN-gamma. Our results show that RJ 2.2.5 X P388 D1 cell hybrids do not express either human or mouse class II gene products. Treatment with human recombinant IFN-gamma did not modify the MHC phenotype of either the hybrid cells or the human parental cells. On the other hand, treatment of the hybrid cells with murine recombinant IFN-gamma resulted in de novo expression of mouse Ia mRNA and corresponding cell surface antigens without, however, reinduction of the human class II-positive phenotype. Furthermore, treatment with the mouse lymphokine significantly increased the levels of human HLA class I mRNA and corresponding cell surface antigens in the hybrid cells, further reinforcing the notion of the existence of non-species-specific secondary mediators generated after receptor-ligand interaction in the IFN-gamma system. Together, these results indicate that in macrophages, the intracellular events taking place after binding of IFN-gamma with its own receptor and leading to the expression of a class II-positive phenotype do not operate via an activation of the aIr-1 locus and/or its products. Thus, at least in our experimental system, we can firmly establish a first, relevant distinction between constitutive and inducible class II gene expression. This difference, dictated by the specific differentiation program of each cell type, may be relevant for the understanding of the function of class II gene products.

Animals↗

The pro alpha 2(V) collagen gene is evolutionarily related to the major fibrillar-forming collagens.

A number of overlapping cDNA clones, covering 5.2 kb of sequences which code for the human pro alpha 2(V) collagen chain, have been isolated. Analysis of the structural data have indicated a close evolutionary kinship between the pro alpha 2(V) chain and the major fibrillar collagen types. Isolation and analysis of an 8 kb genomic fragment has further supported this notion by revealing a homologous arrangement of nine triple-helical domain exons. These studies have therefore provided conclusive evidence which categorizes the Type V collagen as a member of the Group 1 molecules, or fibrillar-forming collagens.

Amino Acid Sequence↗

beta-D-mannosidase in human polymorphonuclear leukocytes and lymphocytes: a comparative study.

All lymphocytes and polymorphonuclear leukocytes (PMNL) beta-D-mannosidase activities are adsorbed on DEAE-Trisacryl column at pH 7.0. Only one form is eluted with a 0.15 M linear gradient. The two enzymes isolated from either type of cells exhibit similar properties. The chromatographic profiles of beta-D-mannosidase from leukemic lymphocytes (chronic lymphoïd leukemia and hairy cells leukemia) differ from the normal ones by the presence of a more acidic minor form.

Humans↗