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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 91 records · Page 5Linked to original sources
PubMed2001

Mammalian postmitotic nuclei reenter the cell cycle after serum stimulation in newt/mouse hybrid myotubes.

Cell cycle reentry and dedifferentiation of postmitotic cells are important aspects of the ability of an adult newt and other urodele amphibians to regenerate various tissues and appendages [1]. In contrast to their mammalian counterparts, newt A1 myotubes are able to reenter S phase after serum stimulation of a pathway leading to phosphorylation of the retinoblastoma protein, pRb [2]. The activity in serum is not due to mitogenic growth factors but is generated indirectly by the activation of thrombin and subsequent proteolysis [3]. In this paper we describe the formation of interspecies hybrid (heterokaryon) myotubes by the fusion of mouse C2C12 [4] and newt A1 [5, 6] myogenic cells. The C2C12 nuclei reenter the cell cycle upon serum stimulation of the hybrids, while C2C12 homokaryon myotubes remain arrested under these conditions. These findings indicate that the postmitotic arrest of the mouse nuclei is undermined by the pathway activated in the newt cytoplasm. The hybrid myotubes provide a new model for the manipulation of the postmitotic arrest in both mammalian and newt differentiated cells.

Animals↗
PubMed2001

Confirmation of the retinopetal/centrifugal nature of the tyrosine hydroxylase-immunoreactive fibers of the retina and optic nerve in the weaver mouse.

The number of tyrosine hydroxylase-immunoreactive fibers in the nerve fiber layer is increased in the retina of the weaver compared to control mice (Dev. Brain Res. 121 (2000) 113). To confirm the retinopetal/centrifugal nature of these fibers, a newly devised whole-mounted optic nerve technique allowed us to determine, during development, their first appearance within the optic nerve (post-natal day 12) compared to retina (post-natal day 13). One such fiber was also observed looping in the retina of a monkey fetus.

Animals↗
PubMed2001

A new DNA polymorphism in the 5' untranslated region of the human SREBP-1a is related to development of atherosclerosis in high cardiovascular risk population.

Sterol-regulatory element binding proteins (SREBPs) are ubiquitous transcription factors that regulate the genes encoding key proteins in the control of cholesterol homeostasis. We looked for mutations or polymorphisms within the sequences of the SREBP-1a gene critical for the synthesis and/or activity of the protein in 204 asymptomatic men. A single G deletion at base pair -36 of the translation initiation site (designated G-) was found using single-strand conformation polymorphism (SSCP), in addition to three rare variants. This new marker was then assessed for its influence on the lipid parameters of 812 men at high cardiovascular risk, and on the presence of echographic atherosclerotic plaque in their peripheral arteries. The allelic frequency of the -36delG polymorphism was 0.58. At least one plaque was found in the carotid in 24% of subjects, in the femoral arteries of 48%, and in the aorta of 25%. There were significant associations between the -36delG polymorphism and mean total cholesterol (p=0.02) and LDL-cholesterol (P=0.02). There was a graded relationship between the G- allele and the presence of carotid plaque (r=0.084, P=0.02). In addition, there was a statistically significant interaction between the -36delG genotype and the apoE phenotype for plasma LDL-cholesterol (P=0.04) and apoB (P=0.05), suggesting a gene-gene interaction. Stepwise multiple regression analysis for lipid traits, risk factors, and apoE phenotype showed an independent association between carotid plaque and the -36delG polymorphism (beta=0.311, P=0.03). Thus, we have identified a new polymorphism in the 5' untranslated region of the SREBP-1a gene, and demonstrated its association with an atherogenic lipid profile and echographic plaques.

5' Untranslated Regions↗
PubMed2001

[From gene to disease; tumor necrosis factor receptor and a syndrome of familial periodic fever].

Familial Hibernian fever (FHF) is a rare hereditary syndrome that causes periodic attacks of fever and inflammation. It is an autosomal dominantly inherited disorder. The gene involved in FHF encodes for a receptor for tumour necrosis factor (TNFR1). These mutations are thought to result in impaired shedding of the receptor from the cell membrane, leading to deficient curtailing of the inflammatory reaction. The acronym TRAPS (TNF-receptor associated periodic syndrome) has been proposed as a more accurate name.

Alleles↗
PubMed2001

Effect of hypertension on viscoelasticity of large arteries in humans.

Two traditional methodologic approaches, the analysis of the arterial pressure waveform in the time domain and the measurement of pulse wave velocity along the arterial tree, have been extensively used to determine the distensibility of large arteries in humans. They have shown that large artery walls are stiffened in the presence of hypertension. However, several methodologic limitations, especially the incapability of these methods to take into account the physiologic pressure-dependence of arterial distensibility, have led to the development of new approaches for characterizing more in depth the elastic and viscous properties of large arteries. The noninvasive recording of instantaneous pressure and diameter waveforms in superficial arteries (carotid or femoral) by means of tonometry and ultrasonography allows, via appropriate model of the arterial wall, determination of the pure elastic properties as well as the wall viscosity of the vessel. Using case (hypertensive)-control (normotensive) studies it has been found that elastic alteration (stiffening) was preferential in the femoral artery rather than in the carotid artery and that viscous alteration (increased wall viscosity) was relatively uniform in both arteries. This topographic dissociation between elastic and viscous responses of the arterial wall to hypertension suggests that the elastic alteration might be a local phenomena dependent on the singularities of the arterial system, whereas abnormal wall viscosity may reflect a more general influence of hypertension on large artery smooth muscle, the likely determinant factor of viscosity. Therefore, the elastic and viscous components of the arterial walls should be considered independently when assessing the development of hypertensive vascular change and its response to antihypertensive treatment.

Arteries↗
PubMed2001

Analysis of the relationship between triglyceridemia and HDL-phospholipid concentrations: consequences on the efflux capacity of serum in the Fu5AH system.

The high triglyceride/low HDL-cholesterol trait is a common finding in the general population. The aim of the present study was to analyze and interpret the relationships between triglycerides (TG), HDL-related parameters and serum cholesterol efflux potential in an asymptomatic population including both normo- and hyperlipidemic individuals. In a large sample (n = 1143) of this population, there was a negative correlation between TG and HDL-cholesterol (HDL-C) (r = -0.49, P<0.0001) whereas the negative correlation between TG and HDL-phospholipid (HDL-PL) (r = -0.29, P<0.0001) was weaker, leading to a strong positive correlation between TG and HDL-PL/C ratio (r = 0.58, P<0.0001). Thus, increased TG concentrations were associated with an enrichment of HDL with PL. Since we have demonstrated previously that HDL-PL is the major determinant for cholesterol efflux potential from Fu5AH rat hepatoma cells, we determined the effect of the variations in HDL lipid composition on the cholesterol efflux capacity in a subsample of 198 subjects. Compared with normolipidemic subjects (NLP) (TG< or = 1.7 mmol/l; LDL-C< or = 4.1 mmol/l, n=58), hypertriglyceridemic subjects (HTG) (TG>1.7 mmol/l, n=63) exhibited lower HDL-C levels (1.08+/-0.21 vs. 1.25+/-0.32, P=0.0003) whereas they showed similar HDL-PL concentrations (1.25+/-0.21 vs. 1.25+/-2.7) and, thus, higher HDL-PL/C ratio (1.17+/-0.15 vs. 1.02+/-0.14, P=0.0001). The relative efflux capacity of serum measured in the Fu5AH system (5% serum, 4 h incubation at 37 degrees C) was on average identical in the HTG and NLP groups. Thus, this study provides evidence that despite decreased HDL concentrations, as determined routinely by the HDL-C assay, some HTG subjects maintained serum cholesterol efflux capacity thanks to the enrichment of HDL with PL.

Adult↗
PubMed2001

Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima-media thickening in asymptomatic men at risk for cardiovascular disease.

Epidemiological data regarding the preventive role of vitamin E in the pathogenesis of atherosclerosis have yielded conflicting results, possibly because endpoints considered were clinical events but not detection of atherosclerosis per se. Otherwise, it has been suggested that the measure of the erythrocyte alpha-tocopherol level may be more suitable to assess the human tocopherol status than its plasma level. We investigated the association between early atherosclerosis in superficial arteries assessed noninvasively and the alpha-tocopherol status in 261 asymptomatic men at risk for cardiovascular disease. alpha-Tocopherol concentrations in plasma, HDL, and erythrocytes were determined using a reverse-phase HPLC method. Detection of carotid plaques and measure of carotid intima-media thickness (IMT) were performed using high-resolution B-mode ultrasonography. The main result of this study is the observation of a negative correlation (P<0.01) between carotid IMT and erythrocyte alpha-tocopherol concentration, independently of conventional cardiovascular risk factors, whereas no such association has been found with plasma (total or HDL) alpha-tocopherol concentrations. No association has been evidenced between alpha-tocopherol concentrations and carotid plaques. These results emphasize the primary protective role of vitamin E in the early phases of atherosclerosis and the significance of the erythrocyte alpha-tocopherol concentration as a marker of atherosclerosis.

Arteriosclerosis↗
PubMed2001

[Metopic craniosynostosis, probable effect of intrauterine exposure to maternal valproate treatment].

UNLABELLED: Metopic craniosynostosis may be an adverse effect of valproic acid exposed fetus. CASES: We report two infants with metopic craniosynostosis, born to mothers who were treated with valproic acid. In one case, a prenatal diagnosis was made. In the other case, only the male dizygotic twin was affected. CONCLUSION: Trigonocephaly may be a symptom of valproate embryofoetopathy detectable by antenatal ultrasound examination.

Abnormalities, Drug-Induced↗
PubMed2001

Neighbourhood renewal and health: evidence from a local case study.

This article presents findings from a before-and-after study of the effects of neighbourhood renewal on residents' health. Survey data were analysed using multivariate logistic regression. Before the renewal programme, damp and draughts had significant independent effects on respiratory health problems. Draughts and perceived community safety were associated with mental health problems. Children's mental health was associated with parental mental health. Following the renewal work, improvements occurred in both adults' and children's mental health, and smoking declined sharply. Respiratory health did not improve and there was no change in use of health services. Neighbourhood renewal in deprived areas can have an important role in improving community health.

Adolescent↗
PubMed2001

Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants.

In an effort to discover new antioxidant natural compounds, seven plants that grow in France (most of them in the Limousin countryside) were screened. Among these plants, was the extensively studied Vitis vinifera as reference. For each plant, sequential percolation was realized with five solvents of increasing polarities (hexane, chloroform, ethyl acetate, methanol, and water). Free radical scavenging activities were examined in different systems using electron spin resonance (ESR) spectroscopy. These assays were based on the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), the hydroxyl radicals generated by a Fenton reaction, and the superoxide radicals generated by the X/XO system. Antiproliferative behavior was studied on B16 melanoma cells. ESR results showed that three plants (Castanea sativa, Filipendula ulmaria, and Betula pendula) possessed, for the most polar fractions (presence of phenolic compounds), high antioxidant activities in comparison with the Vitis vinifera reference. Gentiana lutea was the only one that presented a hydroxyl scavenging activity for the ethyl acetate and chloroform fractions. The antiproliferative test results showed that the same three plants are the most effective, but for the apolar fractions (chloroform and hexane).

Antioxidants↗
PubMed2001

Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is an autosomal recessive inflammatory disorder characterised by recurrent episode of fever associated with lymphadenopathy, abdominal distress, joint involvement and skin lesions. We recently demonstrated that mutations in the mevalonate kinase gene (MVK) are associated with HIDS. Direct DNA sequencing was done to screen the entire coding region of MVK in 25 unrelated patients with HIDS. Mutations were detected in the coding region of the gene including 11 missense mutations, one deletion, the absence of expression of one allele, as well as three novel polymorphisms. Seven of these mutations are novel. The large majority of the patients were compound heterozygotes for two mutations. Of these, V377I (G-->A) is the most common mutation occurring in 20 unrelated patients and was found to be associated with I268T in six patients. Mutations were associated with a decrease of mevalonate kinase (MK) (ATP:mevalonate 5-phosphotransferase, EC 2.7.I.36) enzymatic activity but not as profound as in mevalonic aciduria, a syndrome also caused by a deficient activity of MK. In HIDS the mutations are located all along the protein which is different from mevalonic aciduria where MK mutations are mainly clustered to a same region of the protein. On the basis of this study, we propose that the diagnostic screen of MVK in HIDS should be first directed on V377I and I268T mutations. Three patients are also described to illustrate the genotypic and phenotypic overlap with mevalonic aciduria.

Adult↗
PubMed2001

Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases.

BACKGROUND: Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE. METHODS: In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case-control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non-invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study). RESULTS: The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study. CONCLUSIONS: These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.

Adolescent↗
PubMed2001

Marital status and cardiovascular risk in French and Swedish automotive industry workers--cross sectional results from the Renault-Volvo Coeur study.

OBJECTIVES: To compare the coronary risk profiles in a sample of the French and Swedish automotive industry employees who were married/cohabitant, divorced or single (never married). DESIGN: A cross-sectional study comparison from biological and questionnaire data between the French and Swedish samples. SETTING: Occupational health departments at Renault (employees from the north-west of France) and Volvo (employees from the south-west of Sweden). SUBJECTS: Two random samples of males aged between 45 and 50 years were examined in 1993, from Renault 1000, and from Volvo 1000. MAIN OUTCOME MEASURES: Biological data including cholesterol, blood pressure as well as the Framingham risk index. Self reported information regarding marital status, smoking, exercise, alcohol habits, and work stress assessed by the Karasek method, private social support indices, and type A behaviour according to the Bortner scale. RESULTS: More employees were married/cohabitant and fewer divorced or single at Renault. Apart from waist/hip ratio being marginally lower in Swedish single men, compared with married and divorced, no significant difference in biological cardiac risk factors (total cholesterol, blood pressure or Framingham risk index) was seen between the subgroups from any of the two countries. Compared with married/cohabitant men, it was shown that in men living alone smoking was more prevalent at Renault and Volvo. These men also showed less type A behaviour, a lower work control and a lower work support and fewer close friends. Alcohol consumption was reported in smaller amounts for Volvo employees living alone compared with married or divorced employees. Married/cohabitant and divorced staff showed similar values regarding all measured variables when compared within each country. CONCLUSIONS: Employees living alone in both France (Renault) and Sweden (Volvo) automotive companies seem to have increased nontraditional cardiac risk factors pertaining to life style and social network compared with married or divorced men. These results, in combination with the finding that more Volvo than Renault employees were living alone, suggest a higher risk for coronary heart disease amongst Volvo employees. This hypothesis will be evaluated in the 5 and 10 years follow up study.

Alcohol Drinking↗
PubMed2001

[Importance of prevention of infectious complications in pediatric hematologic-oncologic patients].

The control of severe infectious complications by preventive strategies, early diagnosis of infections and empiric broad-spectrum antibiotic therapy contributed to a marked improvement of survival in children with cancer over the last 20 years. This article overviews of the importance of prevention of infectious complications in immunocompromised pediatric patients with hematologic or oncologic diseases. The particular challenge of this age group with respect to the acquisition and the spread of pathogens, the spectrum of causative microorganisms and the principal issues of anti-infectious prophylaxis are considered.

Adult↗
PubMed2001

[Non-pharmacologic strategies to prevent and control infectious complications in pediatric hematology/oncology patients].

Preventive strategies besides the use of prophylactic antibiotic or antifungal regimens are fundamental ingredients of infection control in pediatric hematology-oncology patients. The clinical spectrum and the routes of transmission of infectious diseases in children have to be considered and preventive strategies should be adjusted to host dependent risk factors, in particular to the degree and duration of severe immunosuppression (i.e. neutropenia). This article overviews practical guidelines to prevent exposure and to reduce external sources of infection in immunocompromised children. Scientific evidence from controlled randomized studies is lacking or incomplete for many of these measures. A systematic and pragmatic approach to the critical control points of patient care in pediatric hematology/oncology is prudent to solve this problem in clinical practice. The corresponding recommendations are categorized in IV different levels of evidence.

Age Factors↗