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Biomedical subjects

M Melchior

Publications and source records attributed to M Melchior.

17 recordsLinked to original sources
PubMed2006

Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study).

OBJECTIVE: To investigate the reasons for the excess risk of upper limb musculoskeletal disorders among manual workers compared with other workers in a random sample of 2656 French men and women (20-59 years old) participating in a study on the prevalence of work related upper limb disorders conducted by France's National Institute of Health Surveillance. METHODS: Prevalence ratios (PR) of physician-diagnosed musculoskeletal disorders of the shoulder, elbow, wrist, and hand (any of six leading disorders, rotator cuff syndrome, carpal tunnel syndrome) in manual versus non-manual workers were calculated using Cox regression models with a constant time of follow up and robust variance. RESULTS: 11.3% of men and 15.1% of women were diagnosed with an upper limb disorder. The risk was especially high in manual workers (PRs: 1.40 to 2.10). Physical work factors accounted for over 50% of occupational disparities overall, 62% (men) to 67% (women) for rotator cuff syndrome, and 96% (women) for carpal tunnel syndrome. The authors calculated that under lower levels of physical work exposures, up to 31% of cases among manual workers could have been prevented. CONCLUSIONS: In working men and women, upper limb musculoskeletal disorders are frequent. Physical work exposures, such as repetitive and forceful movements, are an important source of risk and in particular account for a large proportion of excess morbidity among manual workers.

Adult↗
PubMed2006

Lifelong socioeconomic trajectory and premature mortality (35-65 years) in France: findings from the GAZEL Cohort Study.

BACKGROUND: Studies conducted in the UK and Scandinavia show an inverse association between lifetime socioeconomic position and adult mortality. However, there are virtually no data from other countries and few investigations have examined non-cardiovascular mortality in men and women. METHODS: Lifelong socioeconomic trajectories (father's occupation, own occupation in young adulthood and in mid-life) and premature (< or = 65 years) mortality (all-cause, smoking-related cancer, diseases of the circulatory system and external causes) in the French GAZEL Cohort Study (14,972 men and 5,598 women, followed up between 1990 and 2004) were studied. Hazard ratios (HRs) were estimated using Cox's regression models adjusted for age, marital status, tobacco smoking, alcohol consumption, body mass index, and fruit and vegetable consumption. RESULTS: Men and women who experienced lifelong disadvantage or downward intergenerational mobility were at high risk of dying prematurely compared with those with a favourable trajectory (age-adjusted HRs for all-cause mortality: cumulative disadvantage: HR 1.61, 95% confidence interval (CI) 1.26 to 2.06 in men and HR 1.95, 95% CI 1.10 to 3.47 in women; downward mobility: HR 1.87, 95% CI 1.35 to 2.58 in men and HR 2.05, 95% CI 1.12 to 3.75 in women). Associations were strongest for mortality due to chronic diseases (smoking-related cancers and diseases of the circulatory system). These associations were partly explained by marital status, body mass index, alcohol consumption, cigarette smoking, and fruit and vegetable consumption. CONCLUSIONS: In France, where the leading cause of premature death is cancer, lifelong socioeconomic position is associated with the risk of dying before the age of 65 years. Adult factors seem more relevant than childhood socioeconomic circumstances.

Adult↗
PubMed2003

Do psychosocial work factors and social relations exert independent effects on sickness absence? A six year prospective study of the GAZEL cohort.

STUDY OBJECTIVES: The objective of this prospective cohort study was to determine whether psychosocial work characteristics and social relations exert independent effects on the incidence of sickness absence in a population of middle aged French employees over six years of follow up. DESIGN: This study included 9631 men and 3595 women participating in the French GAZEL cohort. Social relations (social networks, personal social support, and social relations satisfaction) were measured in 1994 by self report. Psychosocial work characteristics (decision latitude, psychological demands, and social support at work) were ascertained in 1995. Sickness absence data were collected independently. The authors studied the incidence of short (>7 days), intermediate (7-21 days), and long (>21 days) spells of absence from 1995 to 31 December 2001. Rate ratios associated with psychosocial exposures, adjusted on sociodemographic characteristics, and health behaviours, were calculated by means of log-linear Poisson regression. SETTING: A cohort of 20000 employees of France's national gas and electricity company (the GAZEL study). MAIN RESULTS: Among men and women, levels of decision latitude and personal social support below the median predicted 17% to 24% increases in absence rates. Low satisfaction with social relations and low social support at work lead to a 10% to 26% excess in sick leaves among men. No interactive effects were found between the variables under study. CONCLUSIONS: The quality of the work environment and of social relations affect sickness absence over an extended period of follow up. This study supports the hypothesis of independent, not interactive effects.

Adult↗
PubMed2003

[Epidemiology and social determinants of health inequalities].

BACKGROUND: The general approach of social epidemiology is based on the observation of a strong social stratification of health outcomes within populations: a similar stratification of factors associated with health must therefore also exist according to social status. To explain social differences in health, the natural approach for epidemiologists is to consider an imbalanced distribution of established risk factors according to the social position of individuals. As this approach has largely failed, two main other research areas were recently explored: (i) identification of "new" social risk factors; (ii) research of possible mechanisms of social differences in health. METHODS AND RESULTS: Identification of social risk factors: early events and life course, occupational factors, social relationships (social networks and support, discrimination, neighborhood characteristics), health care. Research of possible mechanisms of social differences in health in the context of specific theoretical frameworks: the materialist model, the psychosocial model and the eco-social model integrating the interaction between individuals'characteristics and their environment. COMPLEX METHODOLOGICAL PROBLEMS: definition and measurement of variables characterizing the social situation of individuals; quantification of social inequalities at population level. Observational methods must often rely on very long-lasting cohorts, and imply statistical methods that account for longitudinal data or are able to manage simultaneously individual and contextual data.

Cohort Studies↗
PubMed2001

Insulin-enhancing vanadium(III) complexes.

Simple, high-yield, large-scale syntheses of the V(III) complexes tris(maltolato)vanadium(III), V(ma)3, tris(ethylmaltolato)vanadium(III), V(ema)3, tris(kojato)vanadium(III) monohydrate, V(koj)3-H2O, and tris(1,2-dimethyl-3-hydroxy-4-pyridinonato)vanadium(III) dodecahydrate, V(dpp)3-12H2O, are described; the characterization of these complexes by various methods and, in the case of V(dpp)3-12H2O, by an X-ray crystal structure determination, is reported. The ability of these complexes to normalize glucose levels in the STZ-diabetic rat model has been examined and compared with that of the benchmark compound BMOV (bis(maltolato)oxovanadium(IV)), an established insulin-enhancing agent.

Animals↗
PubMed1999

Role of the tyrosine kinase pyk2 in the integrin-dependent activation of human neutrophils by TNF.

Secretion of inflammatory products from neutrophils can be induced by a combination of signals from ligated integrins and receptors for soluble, physiological agonists such as TNF. Here we identify pyk2 in primary human neutrophils; localize it to focal adhesions and podosomes; and demonstrate its tyrosine phosphorylation, activation, and association with paxillin during stimulation of adherent cells by TNF. Tyrphostin A9 emerged as the most potent and selective of 51 tyrosine kinase inhibitors tested against the TNF-induced respiratory burst. Tyrphostin A9 inhibited TNF-induced tyrosine phosphorylation of pyk2 without blocking the cells' bactericidal activity. Wortmannin, an inhibitor of phosphatidylinositol-3-kinase, potently blocked the TNF-induced respiratory burst and selectively inhibited tyrosine phosphorylation of pyk2. Thus, pyk2 appears to play an essential role in the ability of neutrophils to integrate signals from beta(2) integrins and TNF receptors.

Androstadienes↗
PubMed1999

Peptidomimetic fluoromethylketone rescues mice from lethal endotoxic shock.

BACKGROUND: Septic shock is a leading cause of mortality in intensive care units. No new interventions in the last 20 years have made a substantial impact on the outcome of patients with septic shock. Identification of inhibitable pathways that mediate death in shock is an important goal. MATERIALS AND METHODS: Two novel caspase inhibitors, (2-indolyl)-carbonyl-Ala-Asp-fluoromethylketone (IDN 1529) and (1-methyl-3-methyl-2-indolyl)-carbonyl-Val-Asp-fluoromethylketone (IDN 1965), were studied in a murine model of endotoxic shock. RESULTS: IDN 1529 prolonged survival when given before or up to 3 hr after high-dose LPS (p < 0.01) and increased by 2.2-fold the number of animals surviving longterm after a lower dose of LPS (p < 0.01). Despite its similar chemical structure, IDN 1965 lacked these protective effects. Both compounds inhibited caspases 1, 2, 3, 6, 8, and 9, and both afforded comparable reduction in Fas- and LPS-induced caspase 3-like activity and apoptosis. Paradoxically, administration of IDN 1529 but not IDN 1965 led to an increase in the LPS-induced elevation of serum cytokines related directly (IL-1beta, IL-18) or indirectly (IL-1alpha, IL-1Ra) to the action of caspase 1. CONCLUSIONS: A process that appears to be distinct from both apoptosis and the release of inflammatory cytokines is a late-acting requirement for lethality in endotoxic shock. Inhibition of this process can rescue mice even when therapy is initiated after LPS has made the mice severely ill.

Animals↗
PubMed1998

Acute parvovirus B19 infection associated with fulminant hepatitis of favourable prognosis in young children.

BACKGROUND: The cause of fulminant hepatitis (FH) in children is unexplained in up to 50% of cases. We report parvovirus B19 as an agent associated with FH in children and compare clinical characteristics of these patients with those of age-matched patients with FH of other origin. METHODS: 45 patients presented with FH. No cause was apparent in 21 patients. Parvovirus B19 genome was retrospectively sought by PCR in serum collected at admission in 41 patients. FINDINGS: Parvovirus B19 genome was detected in serum from four of 21 patients with unexplained FH (four of 11 younger than 5 years). No B19 DNA was detected in serum from patients with other types of FH or from 82 patients with biliary atresia. Parvovirus B19 IgM was detected in one of the four patients. Patients with parvovirus B19 infection had significantly lower bilirubin concentrations than age-matched patients with FH due to hepatitis A (nine) or other causes (nine) (poisoning with amanita excluded). All patients with parvovirus B19 survived without orthotopic liver transplantation, with restoration of normal liver function within 17 days. INTERPRETATION: In patients younger than 5 years with FH of unexplained origin, evidence of acute parvovirus B19 was associated with a distinct clinical pattern. In particular, low bilirubin concentrations and rapid recovery of liver function without transplantation were distinctive features.

Child, Preschool↗
PubMed1996

Characterization of a recombinant proteinase 3, the autoantigen in Wegener's granulomatosis and its reactivity with anti-neutrophil cytoplasmic autoantibodies.

Using the baculovirus/insect cells system, we have expressed a recombinant proteinase 3 (PR3) -- the neutrophil-derived serine protease autoantigen in Wegener's granulomatosis -- as a glycosylated intracellular and membrane-associated protein. Oligosaccharides accounted for the difference in molecular weights between recombinant (34 kDa) and neutrophil-PR3 (29 kDa). Whereas rabbit-anti-PR3 IgG recognized both recombinant and neutrophil-derived PR3, autoantibodies from Wegener patient sera recognized only neutrophil-derived PR3. Although oligosaccharides were not involved in PR3 epitope recognition, autoantibodies did not recognize the amino acid primary structure of recombinant PR3. Improper disulfide bond formation and/or lack of post-translational events in insect cells, may affect the conformation and/or lack of post-translational events in insect cells, may affect the conformation of PR3, precluding its reactivity with sera from WG patients.

Amidohydrolases↗
PubMed1996

Azurocidin, a natural antibiotic from human neutrophils: expression, antimicrobial activity, and secretion.

The azurophil granules of human PMN contain four antibiotic proteins, the serprocidins, which have extensive homology to one another and to serine proteases. Azurocidin, a member of this family, is a 29-kDa glycoprotein with broad spectrum antimicrobial activity and chemotactic activity toward monocytes. Insect cells transfected with a baculovirus vector carrying azurocidin cDNA produced a recombinant azurocidin protein. We purified the recombinant azurocidin protein from the culture medium of the infected cells and showed that it retained the antimicrobial activity of the native neutrophil-derived molecule. In addition, we present evidence that a 49-amino-acid region of the recombinant azurocidin protein is required for its secretion from insect cells.

Amino Acid Sequence↗
PubMed1995

The tasks of psychiatric nurses in long-term residential settings in The Netherlands.

The tasks of the psychiatric nurse, working in long-term psychiatric settings, are described and analysed in this study. A questionnaire was completed by 361 nurses in five different psychiatric hospitals in the Netherlands. Nurses appear to concentrate upon personal care tasks in and around their ward. This does not fit adequately the changes in psychiatric practice. By means of an externally oriented hospital policy, cooperation with other care agencies and a realization of a more patient-orientated and rehabilitation model of care, the nurse is better prepared for helping patients make their move to the community.

Adult↗
PubMed1992

Antineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis recognize conformational epitope(s) on proteinase 3.

Although proteinase 3 (PR3) has been identified as a major autoantigen in Wegener's granulomatosis, the precise antibody specificity(ies) and requirements for epitope recognition have not been characterized. We analyzed 11 sera containing antineutrophil cytoplasmic antibodies (cANCA) for binding to azurophilic granule proteins extracted from neutrophils under various conditions and for binding to native or rPR3. Ten of 11 (91%) of the cANCA sera bound to PR3 extracted by nonionic detergents when tested by immunoprecipitation or by IEF followed by capillary immunoblotting. Antibody binding to PR3 was retained when IEF was performed under dissociating conditions (8 M urea) indicating that PR3 is the major autoantigen in azurophilic granules and that association with other proteins is not required for antigenicity. In contrast, antigenicity was totally destroyed by exposure of PR3 to reducing agents or to low pH (less than 3.0) and was either lost or considerably diminished after boiling in SDS. cANCA sera also showed little or no binding to rPR3 expressed as a fusion protein in Escherichia coli or synthesized by wheat germ ribosomes in vitro. Inasmuch as PR3 enzymatic activity was partially retained after acid extraction, these findings indicate that cANCA bind to a limited number of conformational epitopes on PR3. In addition, IEF followed by capillary immunoblotting appears to be a sensitive and specific method to detect anti-PR3 antibodies in Wegener's granulomatosis.

Antibody Specificity↗
PubMed1991

Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases.

Human neutrophils contain in their azurophil granules four antibiotic proteins with extensive homology to serine proteases, collectively termed serprocidins. Azurocidin is the only member of the group that lacks proteolytic activity. Using a monospecific antibody, we isolated from human bone marrow a cDNA encoding the complete azurocidin protein in its mature form, along with an N-terminal 24 residue hydrophobic peptide. The N-terminal third of the mature protein sequence contains a cluster of positively charged amino acid residues, many of which are predicted to be surface exposed. The primary sequence is highly homologous to elastase, proteinase 3, cathepsin G, T-cell granzymes and other serine proteases. However, azurocidin has Gly for Ser and Ser for His substitutions in the catalytic triad. Southern blot analysis of human genomic DNA suggests the existence of a single azurocidin coding sequence.

Amino Acid Sequence↗
PubMed1990

Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils.

Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin. We previously purified one such entity, termed p29b. Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences. The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments. The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase. Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment. This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3. Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity. Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent.

Amino Acid Sequence↗
PubMed1985

Handicap research in Denmark.

In connection with recent social developments in Denmark increasing interest has been shown in research in the area of handicaps. Three Danish Research Councils (for Medicine, the Humanities and the Social Sciences) appointed a Committee to investigate this area of research. A survey conducted in the relevant fields gave evidence of much activity in this area. Very few research projects, however, integrated educational, psychological, medical, technical and social aspects. The need for more cooperation, information and training was therefore stressed as a prerequisite for better interdisciplinary handicap research in Denmark. Research seminars and workshops held in 1982-83 supported the results of the survey, especially as regards the need for training in the methods of interdisciplinary research and understanding among professionals (nurses, teachers, social workers, therapists, etc.). A formal coordination agency is recommended in order to establish the necessary cooperation among researchers, planners and users in Danish handicap research.

Denmark↗