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Biomedical subjects

A Gérard

Publications and source records attributed to A Gérard.

At least 19 recordsLinked to original sources
PubMed2006

Genetic identification of the main opportunistic Mucorales by PCR-restriction fragment length polymorphism.

Mucormycosis is a rare and opportunistic infection caused by fungi belonging to the order Mucorales. Recent reports have demonstrated an increasing incidence of mucormycosis, which is frequently lethal, especially in patients suffering from severe underlying conditions such as immunodeficiency. In addition, even though conventional mycology and histopathology assays allow for the identification of Mucorales, they often fail in offering a species-specific diagnosis. Due to the lack of other laboratory tests, a precise identification of these molds is thus notoriously difficult. In this study we aimed to develop a molecular biology tool to identify the main Mucorales involved in human pathology. A PCR strategy selectively amplifies genomic DNA from molds belonging to the genera Absidia, Mucor, Rhizopus, and Rhizomucor, excluding human DNA and DNA from other filamentous fungi and yeasts. A subsequent digestion step identified the Mucorales at genus and species level. This technique was validated using both fungal cultures and retrospective analyses of clinical samples. By enabling a rapid and precise identification of Mucorales strains in infected patients, this PCR-restriction fragment length polymorphism-based method should help clinicians to decide on the appropriate treatment, consequently decreasing the mortality of mucormycosis.

Adult↗
PubMed2005

Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families.

Recent reports have demonstrated that mutations in the OPHN1 gene were responsible for a syndromic rather than non-specific mental retardation. Abnormalities of the posterior fossa with cerebellar hypoplasia have been demonstrated in all male patients reported to date. We report here a new family with X-linked mental retardation due to mutation in OPHN1 and present unpublished data about two families previously reported, concerning the facial and psychological phenotype of affected males and carrier females. Our study confirms that cerebellar hypoplasia is a hallmark of this syndrome. In addition, affected males display facial similarities that can help the diagnosis. Most carrier females have mild mental retardation and subtle facial changes.

Cytoskeletal Proteins↗
PubMed2005

Immunolocalization of sex hormone-binding globulin (SHBG) in human ovarian follicles and corpus luteum.

Sex hormone-binding globulin (SHBG), a hepatic carrier protein for sex steroids is expressed in different steroid-sensitive tissues, including Sertoli cells of the testis. It has been suggested that this protein may be one of the local regulators of spermatogenesis. The expression of SHBG in the ovary is currently unknown. We have previously demonstrated the synthesis of SHBG in granulosa-lutein cells from patients undergoing in vitro fertilization. In this study, the presence of SHBG in human ovarian follicles and corpora lutea is investigated, using immunohistochemistry on adult and fetal ovarian tissue sections. SHBG is localized in the whole granulosa layer at all stages of folliculogenesis, whereas, only isolated theca cells are immunostained. In primordial and primary follicles, the oocyte cytoplasm shows an intense immunostaining, which disappears after the secondary stage. In the microenvironment of the mature oocytes, SHBG is present in the surrounding cumulus cells, the perivitelline space, and nearby the oolemma. In the corpus luteum, SHBG is localized in large luteal cells, whereas, small luteal cells do not show any significant staining. By analogy with the testis, these results raise the question of an involvement of SHBG in the regulation of follicular maturation as well as in luteal function.

Adult↗
PubMed2005

Kainate/estrogen receptor involvement in rapid estradiol effects in vitro and intracellular signaling pathways.

Although the interactions between sex steroids and GnRH have been extensively studied, little is known about the mechanism of estradiol (E2) effects on GnRH secretion. In the present study, we used retrochiasmatic hypothalamic explants of 50-d-old male rats, and we observed that E2 significantly increased the glutamate-evoked GnRH secretion in vitro within 15 min in a dose-dependent manner. E2 also significantly increased the L-arginine-evoked GnRH secretion. E2 effects were time dependent because the initially ineffective 10(-9) M concentration became effective after 5 h of incubation. The E2 effects involved the estrogen receptor (ER) alpha because they were similarly obtained with the specific ER alpha agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole. The use of glutamate receptor agonists and antagonists indicated that E2 effects on GnRH secretion evoked by both glutamate and L-arginine involved the 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid/kainate receptors. Similar E2 effects on the kainate-evoked secretion were observed throughout development in both sexes. The observation of similar E2 effects using explants containing the median eminence alone indicated that the median eminence was a direct target for E2 rapid effects on the glutamate-evoked GnRH secretion. The signaling pathways involved in E2 effects included an increase in intracellular calcium and the activation of protein kinase A, protein kinase C, and MAPK. It is concluded that E2 can stimulate the glutamate- and nitric oxide-evoked GnRH secretion in vitro through a rapid pathway involving the ER and kainate receptor as well as through a slower mechanism responding to lower E2 concentrations.

Aging↗
PubMed2005

Influence of ploidy and metal-metal interactions on the accumulation of Ag, Cd, and Cu in oysters Crassostrea gigas thunberg.

The present study was designed to compare the response to contaminants in diploid with triploid specimens of the oyster Crassostrea gigas. The reproduction investment in bivalve molluscs has priority on somatic growth. Thus, genetic sterilization by triploidy induction enables the energy flux to be directed toward somatic growth and glucide storage. Bioaccumulation was examined for Ag (10 microg/L), Cd (10 microg/L), and Cu (30 microg/L) to determine if the response to metals follows similar patterns in diploid (2n) and triploid (3n) groups. The effect of ploidy was also evaluated as a function of dry weight of soft tissue and condition index. Moreover, the reciprocal influence of these metals on their incorporation was studied. The results showed that the major factor governing the degree of metal bioaccumulation by oysters is the nature of the metal introduced in the experimental medium. Thus, the uptake of Cd is proportionally more important than in the case of Ag and even more in Cu. For Cu-treated samples, the influence of ploidy on weight and metal body burden (and Cu concentration) was not significant, whereas for Ag and Cd, significant differences according to genetic type were evidenced by higher tissue weight and lower concentrations in triploid than diploid specimens. Metal-metal interactions study especially showed a reciprocal antagonism between Ag and Cu.

Animals↗
PubMed2005

[Neuroleptic drug utilization among schizophrenic outpatients].

BACKGROUND: Our objective was to describe and compare neuroleptic drug utilization patterns among French schizophrenic outpatients in public and private care settings. METHODS: A cross sectional survey was carried out by a random sample of 61 public and 112 private psychiatrists who registered for one month all schizophrenic adult outpatients treated with a neuroleptic drug. Among registered patients, each psychiatrist was to include a maximum of 18 patients (public setting) or 9 patients (private setting). Statistical analysis was weighted to take into account for psychiatrist activity level, assessed by patient registration. RESULTS: Psychiatrists included 934 patients in the public care setting and 927 patients in the private care setting. Patients were (mean+/-sd) 40.1+/-12.1 years old, 60.9% men. The patients' social and clinical characteristics were less favorable in the public setting than in the private setting: no professional activity (78.9% vs 65.1%), living in institution (7.2% vs 3.7%), under legal protection (35.1% vs 14.5%), drug abuse (9.6% vs 5.6%). An atypical neuroleptic was prescribed for 63.0% of patients and a classic neuroleptic for 49.7%, an association of neuroleptics for 22.0%. In both settings, the most prescribed neuroleptics were olanzapine (28.0%) and risperidone (18.6%) with a higher mean daily dosage in the public care setting. At least one neuroleptic treatment change (drug and/or dosage) occurred during the previous year for 44.9% and 39.2% patients, in public and private settings, respectively. In both settings, reasons for changes were mainly lack of efficacy (55.1%) and side effects (49.8%). CONCLUSION: Public and private care populations were different but not as much as expected. In both settings, atypical neuroleptics were the predominant drugs used in the treatment of schizophrenia outpatients. The high frequency of drug change for lack of efficacy or side effects demonstrates the difficulties with the use of the present neuroleptic armamentarium.

Adolescent↗
PubMed2004

Expression of sex hormone-binding globulin (SHBG) in human granulosa-lutein cells.

Sex hormone-binding globulin (SHBG) was classically thought to be a plasma steroid-carrying protein of hepatic origin, but recently, locally produced, membrane-bound SHBG has been shown to influence cell functions in several steroid-responsive tissues. In the ovary, SHBG is known to be present in the follicular fluid, but information about a possible intracellular presence of SHBG in this organ is still very scarce. In this study the presence of SHBG was assessed by immunohistochemistry in human granulosa-lutein cells (GLC) collected by follicle puncture for in vitro fertilization. SHBG was detected in the cytoplasm of GLC before and after in vitro culture for up to 96 h. The presence of full-length SHBG messenger RNA was demonstrated in GLC by reverse transcription-polymerase chain reaction (RT-PCR) in both cultured and uncultured cells. These results demonstrate a local synthesis of SHBG in GLC and raise the question of the physiological significance of these findings in follicular physiology.

Alternative Splicing↗
PubMed2004

Estradiol stimulation of pulsatile gonadotropin-releasing hormone secretion in vitro: correlation with perinatal exposure to sex steroids and induction of sexual precocity in vivo.

Our aim was to study the effect of estradiol (E2) on pulsatile GnRH secretion in vitro in relation to sex and development. When hypothalamic explants obtained from 5- and 15-d-old female rats were exposed to E2 (10(-7) m), a reduction of GnRH interpulse interval (IPI) occurred but not at 25 and 50 d of age. This effect was prevented by the estrogen receptor antagonist ICI 182.780 and the AMPA/kainate receptor antagonist DNQX but not by the AMPA and N-methyl-d-aspartate receptor antagonists SYM 2206 and MK-801. E2 did not affect GnRH IPI in hypothalamic explants obtained from male rats. Therefore, the possible relation between the female-specific effects of E2 in vitro and perinatal sexual differentiation was investigated. When using explants obtained from female rats masculinized through testosterone injection on postnatal d 1, E2 was no longer effective in vitro at 5 and 15 d. In addition, with explants obtained from male rats demasculinized through perinatal aromatase inhibitor treatment, E2 became capable of decreasing GnRH IPI in vitro at 15 d. To study the possible pathophysiological significance of early hypothalamic E2 effects, female rats received a single E2 injection on postnatal d 10. This resulted in reduced GnRH IPI in vitro on d 15 as well as advancement in age at vaginal opening and first estrus. In conclusion, E2 decreases the GnRH IPI in the immature female hypothalamus in vitro through a mechanism that depends on perinatal brain sexual differentiation and that could be involved in some forms of female precocious puberty.

Aging↗
PubMed2003

On the interaction between ultrasound waves and bubble clouds in mono- and dual-frequency sonoreactors.

Since the last decades, extensive work have been done on the numerical modeling of mono-frequency sonoreactors, we here consider the modeling of dual-frequency sonoreactors. We first present the basic features of the CAMUS code (CAvitating Medium under UltraSound), for mono-frequency excitation. Computation at low, medium and high frequency are presented. Extension of the numerical tool CAMUS is also presented: Caflisch equations are modified to take into account the dual-frequency excitation of the sound. We consider 28-56, 28-100 and 28-200 kHz sonoreactors. Fields of cavitation bubble emergence are quite different from the ones under mono-frequency. Study of spatio-temporal dynamics of cavitation bubbles in a 28-56 kHz sonoreactor is also considered. Taking into account the pressure field induced by the dual-frequency wave propagation, we compute the Bjerknes force applied on the cavitation bubble that is responsible for the bubble migration. A two phase flow approach allows to compute the bubble migration.

Journal Article↗
PubMed2003

DOK4 and DOK5: new Dok-related genes expressed in human T cells.

Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2002

[Neurological manifestations of Whipple disease].

Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least one and probably for two years. Third generation cephalosporins, rifampicin and chloramphenicol have been used successfully. PCR is recognized to be a useful tool for monitoring progress but it is sometimes difficult to reverse established neurological defects.

Disease Progression↗
PubMed2001

Spatio-temporal dynamics of cavitation bubble clouds in a low frequency reactor: comparison between theoretical and experimental results.

The propagation of ultrasound through a liquid induces the growth of inceptions and germs into bubbles. In a low frequency reactor, fragmentary transient bubbles emerge due to the acoustic driving. They violently collapse in one cycle and fragment into many smaller bubbles than in turn cavitate. This violent collapse is responsible for the mechanical effects of ultrasounds effects. The latter bubbles gather in a ball-shaped cloud and migrate to pressure antinodes. During their migration, their nonexplosive collapses mainly contribute to activate chemical reactions by producing OH. radicals. Mathematical modelling is performed as a new approach to predict the bubbles field. Through numerical simulation, we determinate emergence sites of mechanically active cavitation bubbles. Calculus are compared with aluminium foil degradation. The modelling of bubble migration allow us to have an insight on the privileged sites of the chemical reactions. Validation of the modelling is made through direct comparison with chemiluminescence photo. All experiments and computations are made in a 28.2 kHz sonoreactor.

Journal Article↗
PubMed2000

Concomitant herpes-like virus infections in hatchery-reared larvae and nursery-cultured spat Crassostrea gigas and Ostrea edulis.

Concomitant sporadic high mortalities were reported in France in May 1994 among batches of hatchery-reared larval Pacific oysters Crassostrea gigas and European flat oysters Ostrea edulis in 2 hatcheries, and in June and July 1994 among batches of cultured spat of both species in a shellfish nursery. Histological observation showed the presence of cellular abnormalities in moribund animals. Transmission electron microscopy revealed the presence of herpes-like virus particles in infected larvae and spat of both oyster species. This is the first description of a herpes-like virus infection in larval O. edulis. Viruses observed in diseased larvae and spat of both species are similar with respect to ultrastructure and morphogenesis. They were detected simultaneously in C. gigas and O. edulis larvae and spat, indicating possible interspecific transmission. Moreover, these viruses are associated with high mortality rates in both oyster species. An electron microscopic examination revealed hemocytes with condensed chromatin and extensive perinuclear fragmentation of chromatin. These data suggest that herpes-like viruses infecting oysters may induce apoptosis in oyster hemocytes.

Animals↗
PubMed2000

Haplosporidiosis in the Pacific oyster Crassostrea gigas from the French Atlantic coast.

Two cases of haplosporidian infection occurred during 1993 in Pacific oysters Crassostrea gigas from the French Atlantic coast. The localization and ultrastructure of the plasmodia are described. In situ hybridization of infected tissue sections was conducted with DNA probes for oyster-infecting haplosporidians. The Haplosporidium nelsoni-specific DNA probe MSX1347 hybridized with the C. gigas parasite, and the H. costale-specific probe SSO1318 did not hybridize. Total genomic DNA was extracted from the infected tissue sections for polymerase chain reaction (PCR) amplification of the haplosporidian. PCR amplifications with H. nelsoni-specific primers and with 'universal' actin primers did not yield the expected products of 573 and 700 bp, respectively. A series of primers was designed to amplify short regions of small subunit ribosomal DNA (SSU rDNA) from most haplosporidians. The primers encompass a highly variable region of the SSU rDNA and did not amplify oyster DNA. PCR amplification of the infected C. gigas genomic DNA with these primers yielded the expected-sized product from the primer pair targeting the shortest region (94 bp). This PCR product was sequenced and it was identical to the corresponding SSU rDNA region of H. nelsoni.

Animals↗
PubMed2000

Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y.

Leptin may act as a negative feedback signal to the hypothalamic control of appetite through suppression of neuropeptide Y (NPY) secretion and stimulation of cocaine and amphetamine regulated transcript (CART). We aimed at studying the effects of leptin, CART and NPY on the hypothalamic control of the pituitary-gonadal system. Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using retrochiasmatic hypothalamic explants from adult rats. In the female, GnRH pulse amplitude was significantly increased by leptin (10(-7) M) and CART (10(-6) M) irrespective of the estrus cycle phase while no such effects were seen in the male. The GnRH interpulse interval was not affected in both sexes. Passive immunoneutralization against CART caused a reduction in GnRH pulse amplitude in the female. A slight but significant increase in GnRH pulse amplitude was caused by NPY (10(-7) M) in the female. However, GnRH pulse amplitude was not affected by a Y5-receptor antagonist (10(-6) M) while the interpulse interval was significantly increased as shown previously in the male. The increase in GnRH pulse amplitude caused by leptin was totally prevented by coincubation with an anti-CART antiserum whereas it was not affected by coincubation with the NPY Y5-receptor antagonist (10(-7) M). In conclusion, leptin and NPY show separate permissive effects on GnRH secretion in the adult rat hypothalamus. In both sexes, NPY is prominently involved in the control of the frequency of pulsatile GnRH secretion through the Y5 receptor subtype. Leptin causes a female-specific facilitatory effect on GnRH pulse amplitude which is mediated by CART and which occurs irrespective of the estrus cycle phase.

Animals↗