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Biomedical subjects

E Fournier

Publications and source records attributed to E Fournier.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Receptors for factors of the VEGF (Vascular Endothelial Growth Family)].

Growth factors of the VEGF (vascular endothelial growth factor) family comprises 4 well characterized members that play a crucial role in the biology of blood vessels. They interact with 3 high affinity tyrosine kinase receptors (FLT1/VEGFR1, FLK1/KDR/VEGFR2, FLT4/VEGFR3). VEGF/VEGFR interactions have essential functions in blood vessel formation during development, specific phases of adult life, and in some pathological processes with neo-vascularization such as tumor growth.

Adult↗
PubMed1996

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Bipolar Disorder↗
PubMed1996

Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population.

Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis.

Adult↗
PubMed1996

Interaction with the phosphotyrosine binding domain/phosphotyrosine interacting domain of SHC is required for the transforming activity of the FLT4/VEGFR3 receptor tyrosine kinase.

The FLT4 gene encodes two isoforms of a tyrosine kinase receptor, which belongs to the family of receptors for vascular endothelial growth factor. As the result of an alternative processing of primary mRNA transcripts, the long isoform differs from the short isoform by an additional stretch of 65 amino acid residues located at the C terminus and containing three tyrosine residues, Tyr1333, Tyr1337, and Tyr1363. Only the long isoform is endowed with a transforming capacity in fibroblasts. We show that this activity is related to the capacity of the tyrosine 1337-containing sequence to interact with the phosphotyrosine binding domain of the SHC protein. This demonstrates that a functional property of this newly described domain includes relay of mitogenic signals. In addition, it shows that the same receptor can mediate different functions through the optional binding of the phosphotyrosine binding domain and that the alternative use of this domain is sufficient to direct the signal toward different pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.

Manic depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome ot two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fulfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak lod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.

Alleles↗
PubMed1996

A clinical and neurophysiological study of a patient with an extensive transection of the spinal cord sparing only a part of one anterolateral quadrant.

In 1976, Noordenbos and Wall studied sensory functions in a woman with a surgically verified T3 spinal cord transection which spared only a part of the left anterolateral quadrant, We re-investigated this unique case 18 years after the lesion and included a comparable sensory examination, MRI of the spinal cord, somatosensory evoked potentials, PET-activation study during hand and foot vibration and analysis of flexion reflex modulation during the Jendrassik manoeuvre. Our results show that the residual anterolateral quadrant contains ascending pathways carrying a wide range of sensory information as well as descending pathways modulating flexion reflex activity at the spinal level. Moreover, the changes in sensory functions and the unique pattern of cortical activation suggest a functional reorganization of the connectivity between the periphery and the cerebral cortex. Changes of facilitation and/or of inhibition at different levels of the somatosensory system may account for these longterm plastic changes.

Evoked Potentials, Somatosensory↗
PubMed1995

Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor.

In humans, the FLT4 gene encodes two isoforms of a tyrosine kinase receptor, which differ in their carboxy terminal regions. As compared to the short form, the long form has an additional stretch of 65 amino acids containing three tyrosine residues (Y1333, Y1337 and Y1363). Once expressed in fibroblast cells, only the long form is able to elicit both anchorage-independent growth in a soft agar assay and tumors in nude mice, and thus appears endowed with a potential ligand-dependent transforming capacity. Replacement of tyrosine 1337 by phenylalanine abrogates the transforming capacity of the long form. This residue was identified as a potential autophosphorylation site, and a docking site for a substrate important in the signal transduction specific of the long FLT4 isoform. We demonstrate that the GRB2 and SHC cytoplasmic substrates are involved in FLT4 signal transduction. SHC interaction could be crucial to FLT4-mediated transforming activity associated with the long isoform. Finally, trancripts for the two forms are detected in tissues positive for FLT4 gene expression.

3T3 Cells↗
PubMed1995

[Incidents and side effects of metallic orthopedic and odontologic prostheses].

Sensitization and immune disorders from metallic prostheses are very unusual although most of them were metal-metal structures (nickel, cobalt or chromium alloys) during decades. Recent technical modifications; the use of new metal (titan-vanadium), of aluminum or ceramic prostheses eliminate these side effects; The clinical diseases may be regional (eczema, dermatitis, vascularitis) or general (diffuse dermatitis, itching). Some very rare systemic diseases have been described but their relation with the prosthesis is often uncertain. The positive patch tests are good indicators of the sensitization but their high prevalence of metal sensitization in the normal population excludes a safe diagnosis. The best demonstration remains the complete recovery of the disease after removal of the prosthesis.

Biocompatible Materials↗
PubMed1994

Effects of occupational lead exposure on motor and somatosensory evoked potentials.

In order to objectivate the effects of inorganic lead compounds on the nervous system, 17 men occupationally exposed have been recorded for Motor Electric Potentials (MEPs) of the abductor policis brevis muscles with transcranial, cervical root and peripheral electrical stimulations, for Somatosensory Evoked Potentials (SEPs) of median and tibial posterior nerves, and for Electromyography (EMG). Considering each subject, 16 out of the 17 lead exposed ones exhibited electrophysiological abnormalities, occurring at both peripheral and central levels for the somatosensory as well as for the motor systems. As compared to a normal control group, the lead exposed one showed decreased sensory and motor peripheral conduction velocities, increased motor central conduction time, and delayed cortical P22 SEPs component that could be interpreted as a sensory-motor cortical dysfunction. The respective contributions of MEPs and SEPs are compared to clinical, biological and EMG examinations in the evaluation of the neurotoxic effects of inorganic lead compounds.

Adult↗
PubMed1993

[A fatal case of viper bite in an adult in France].

Vipera bites in France are supposed to be benign. We report here, the case of a snake bite with fatal outcome due to hypoxemia and shock, occurring in a young woman without previous disease. This case could lead to reevaluate the indication of antivenomous serotherapy in the severe envenomations. However the tolerance of the new serums has to the confirmed.

Adult↗
PubMed1992

[Lymphocyte phenylvaleric acid hydroxylase activity (L-PVH), a new marker of peripheral neurotoxicity].

A reduction in the level of a new enzymatic assay--a phenyl valerate hydrolase (PVH)--has been found during the clinical evolution of toxic neuropathies (as almitrine-bismetilate ones) as well as alcoholic or diabetic neuropathies. The substrate and the enzymatic function are different from those used by M.K. Johnson for NTE. The method follows procedures comparable to NTE (differential determination after inhibition by paraoxon and by paraoxon plus mipafox or DFP). It may be useful to test possible neurotoxicity of drugs and chemicals.

Adult↗
PubMed1992

[Non-auditory responses to noise. Objective estimation. Experimental and individual analyses].

The physiological reactions to a strong noise are immediate and transitory: start, arousal reactions, postural oculo-cephalo-motor response, cardiovascular reactions with tachycardia and peripheral vasoconstriction, mydriasis. The chronic reactions to an occupational permanent noise are mostly a state of fatigue, lowering of the psychotechnic ability, aggressivity, transitory tachycardia and elevation of blood pressure, mainly diastolic. The best argument in favour of a correlation between these reactions and the noise is their reversibility with the cessation of the nuisance. The non-auditive responses to noise--including blood pressure variation--described for stimuli of moderate intensity considered as environmental nuisances are less evident. Among inhabitants of a town the neurophysiological examination of the modifications due to different demonstrate the evident perturbation of the sleep organisation: difficulties to fall asleep, need of a complementary rest. The epidemiological inquiries in noisy zones indicate however that, within a common population, 10% of the subjects feel very uncomfortable, but that 30% of them declare to be normal. The revendications and the trials against the factors of noise let us recommend to associate the efforts of physicians and of physiologists to those of acousticians experts. The different sonometric assays, the methods used in order to decide if a noise is a nuisance are described and should be widely used to demarcate very quiet territories (climatic areas) and sectors to be improved.

Hearing Loss, Noise-Induced↗
PubMed1992

[Vasospastic angina with angiographically normal coronary vessels of iatrogenic origin. Apropos of 2 cases].

Two cases of angina pectoris, induced by methylergometrine (Methergin) and by an association of ergotamine tartrate (Gynergene) and methysergide (Desernil) respectively, are reported. In both patients, angiography revealed spontaneous spasm in a coronary system free from any significant atheromatous stenosis. In the second case, a test administration of i.v. Methergin, administered during calcium-channel antagonist treatment a few days after the "guilty" drugs had been stopped was found to be negative. The outcome was favorable in both cases: the angina disappeared and the base-line and exercise ECG returned to normal. The hypothesis of coronary spasm induced by the treatment was adopted in both cases. In this context, the major iatrogenic etiologies of vasospastic angina are recalled, together with the prophylactic and therapeutic measures they call for.

Adult↗
PubMed1990

Superoxide anion generation by alveolar inflammatory cells in simple pneumoconiosis and in progressive massive fibrosis of nonsmoking coal workers.

We have examined superoxide anion (O2-) release by alveolar inflammatory cells recovered by bronchoalveolar lavage from the lower respiratory tract of 10 healthy nonsmokers and 25 nonsmoking pneumoconiotic patients, 11 with radiographic changes of simple pneumoconiosis (SP) and 14 with changes of progressive massive fibrosis (PMF). Significant increased number of cells was recovered from the lower respiratory tract from both patients with SP or with PMF. Alveolitis was made up predominantly of alveolar macrophages (AM) and an increased percentage of neutrophils in patients with PMF (3.3 +/- 0.7%). O2- release was evaluated using a superoxide dismutase (SOD)-inhibitable lucigenin-dependent chemiluminescence method. Spontaneous O2- generation by alveolar inflammatory cells from pneumoconiotic patients with SP was three to four times greater than that from 10 age-matched, healthy control subjects. O2- release by alveolar inflammatory cells from patients with PMF was dramatically increased when compared with that in patients with SP and with that in control subjects and was observed before and after stimulation by phorbol myristate acetate (PMA) (p less than 0.001). The increased O2- release was not due to a lack of enzyme antioxidant system within AM since intracellular superoxide dismutase was not lower in AM from patients than in AM from control subjects (p less than 0.05). Alteration of DLCO correlated with PMA-induced superoxide release by alveolar inflammatory cells in patients with PMF (p less than 0.05). Our data demonstrate that alveolar inflammatory cells from pneumoconiotic patients with PMF are in the activated state and release more oxygen-reactive species that do those from patients with SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Abnormal secretion of interleukin-1 and tumor necrosis factor alpha by alveolar macrophages in coal worker's pneumoconiosis: comparison between simple pneumoconiosis and progressive massive fibrosis.

The aim of this study was to compare the secretion of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by alveolar macrophages (AMs) harvested from patients with coal worker's pneumoconiosis (CWP) and control subjects. We observed higher levels of spontaneous TNF alpha and IL-1 secretion by AMs from patients with CWP than in those from healthy controls. We did not find any significant difference between the two groups in the incidence of simple pneumoconiosis and progressive massive fibrosis. In the group of coal miners without radiologic signs of pneumoconiosis, we found high levels of both cytokines in a subgroup of subjects still exposed to the mineral dust but not in the subgroup of subjects removed from exposure. These results indicate that AMs are involved in chronic lung inflammatory reactions to mineral dusts, partly by way of cytokine secretion. Moreover, cytokine secretion by AMs appears to be an early event that is detectable at the moment of mineral dust exposure. The results open new perspectives in the study of the mechanisms leading to CWP.

Bronchoalveolar Lavage Fluid↗
PubMed1990

[Coronary insufficiency caused by atherosclerosis. Current pathogenic concepts, clinical, angio-anatomic correlations and therapeutic deductions].

The multiplicity of clinical expressions of coronary artery failure results from the interaction between three processes which varies from one patient to another and from one time to another in a given patient. The three processes involved are: atheromatous coronary stenosis, arterial spasm and the development of a fibrino-thrombocytic thrombus. In stable angina pectoris, atheromatous narrowing, with smooth, regular outlines, no endothelial injury and little likelihood of complication by thrombosis predominates. In contrast, labile angina and myocardial infarction give rise to the same lesions: usually irregular stenoses, with a narrow neck and irregular outline. They correspond histologically to the rupture of an atheroma plaque, frequently complicated by the appearance in situ of a clot. In the authors' experience, complete arterial occlusion ensues in three out of four cases. The rate at which aggravation progresses and the variable degree of collateral circulation explains why a whole range of intermediate clinical expressions are possible, ranging from labile angina to sudden death of ischemic origin, and including various forms of infarction (both with and without the Q wave). Healing of these lesions may also be observed, usually resulting in progression of the coronary stenosis and sometimes of modification of left ventricular function of variable duration (myocardial stunning or hibernation). The importance of thrombotic phenomena in triggering the most serious forms of coronary artery failure (labile angina and myocardial infarction) provides a more precise identification of the place of thrombolytic treatment. In addition, it appears that there is no point in emergency revascularization of the ischemic myocardium. However, despite recent clinical progress, coronary artery disease remains a worrying illness which calls for primary prevention measures. Such measures must be undertaken as soon as possible if they are to be effective.

Angina Pectoris↗