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Biomedical subjects

P Bouchard

Publications and source records attributed to P Bouchard.

At least 19 recordsLinked to original sources
PubMed2003

[Pilot study and preliminary validation of the French version of a quality-of-life questionnaire specific for subjects with growth hormone deficiency].

This study forms part of a research project seeking to develop a standardized questionnaire by which clinicians can assess the impact of growth hormone (GH) deficiency and its treatment on the "perceived health" or health-related quality of life of adults. The specific aim of this study was to translate and adapt for French patients the AGHDA (Adult Growth Hormone Deficiency Assessment) a standardized health-related quality of life measure for use with GH-deficient adults, initially developed in the United Kingdom, and to collect data which could be used to assess the main psychometric characteristics of its French version the ISPA-HC (Indicateur de Santé Perceptuelle Adulte-Hormone de Croissance). The main properties analyzed are: 1/ The scale's acceptability, as determined by means of face-to-face interviews with a small number of subjects, then by an ad hoc questionnaire administered during a test-retest study; 2/ The scale's reliability, as determined by a test-retest study (with a 15-days interval between tests); 3/ The scale's concurrent validity, as expressed by comparison with scores obtained by means of a generic quality of life scale, the ISPN (the French version of the Nottingham Health Profile). The results of this first trial with the ISPA-HC are conforming to what one can expect from a good instrument. The ISPA-HC has been shown to have very good levels of reliability and internal consistency. Its scores show a close correlation with those of the ISPN (the French version of the Nottingham Health Profile). This instrument can be used to measure variations in the perceived health of subjects with growth hormone deficiency. Its responsiveness to change is to be examined in subsequent studies.

Adult↗
PubMed2002

Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats.

AIMS/HYPOTHESIS: We undertook the characterization of the capillary bed of the rat frontal cortex and their permeability properties in short-term and long-term diabetic rats. METHODS: Diabetes was induced by strepozotocin injection. Rats were maintained hyperglycaemic without insulin treatment during 4 to 5 months (short-term) and 8 to 13 months (long-term). Rats from an additional short-term hyperglycaemic group received an injection of exogenous dinitrophenylated albumin 15 min before being killed. Tissues were processed for electron microscopy and quantitative immunocytochemistry. Endogenous and dinitrophenylated exogenous albumin were revealed with high resolution over the capillary wall using specific antibodies and the protein A-gold complex. Morphometrical analyses were carried out. RESULTS: Albumin is transported across endothelial cells by plasmalemmal vesicles or caveolae and larger vacuolar structures. This transport increased in diabetic rats by an increment in the number of vesicles. Albumin distribution across the capillary basement membrane showed that the restrictive properties of the basement membrane present in normoglycaemic rats are altered in the diabetic condition, as was its thickness. Similar alterations of the basement membrane structure and function were encountered in old normoglycaemic rats but to a lesser extent. CONCLUSION/INTERPRETATION: The results indicate that diabetes seems to accelerate the ageing process of the vascular wall and that the central nervous system capillary bed is also a target for diabetic microangiopathy.

Animals↗
PubMed2002

Pharmacogenomic analysis of rhIL-11 treatment in the HLA-B27 rat model of inflammatory bowel disease.

Recombinant human interleukin-11 (rhIL-11) reduces the clinical signs and histological lesions of inflammatory bowel disease (IBD) in transgenic rats expressing the human major histocompatability complex (MHC) class I allele, HLA-B27. To elucidate the pharmacogenomic effects of rhIL-11 in this model, we examined the global gene expression pattern in inflamed colonic tissue before and following rhIL-11 treatment using oligonucleotide microarrays. In total, 175 disease-related genes were identified. Increased expression of genes involved in antigen presentation, cell death and inflammation, and decreased expression of metabolic genes was associated with disease. A total of 27 disease-related genes returned to normal expression levels following rhIL-11 treatment including the MHC class II gene RT1-DMbeta. rhIL-11 induced the expression of four intestinal epithelial growth factors. These gene expression patterns indicate that treatment of inflammatory bowel disease with rhIL-11 affects class II antigen processing and colonic epithelial cell proliferation and metabolism.

Animals↗
PubMed2002

Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen.

BACKGROUND: The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study. METHODS: A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles. RESULTS: The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed. CONCLUSION: The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel.

Adolescent↗
PubMed2001

Estrogen-induced vasoprotection is independent of inducible nitric oxide synthase expression: evidence from the mouse carotid artery ligation model.

BACKGROUND: Estrogen is vasoprotective in animal models of vascular injury, yet the mechanisms involved are incompletely understood. The role of inducible nitric oxide synthase (iNOS) in vascular repair is controversial, but many lines of evidence indicate that it plays a role in neointima formation after arterial injury and that 17beta-estradiol (E(2)) modulates iNOS expression. This study tested the hypothesis that E(2) reduces neointima formation after vascular injury via a mechanism that is dependent on modulation of iNOS expression. METHODS AND RESULTS: Male and female wild-type (iNOS(+/+)) mice and mice with homozygous deletion of the iNOS gene (iNOS(-/-)) were studied intact (INT) or after ovariectomy (OVX) and implantation of E(2) or vehicle (V) pellets. Mice were randomized to 8 groups based on sex, iNOS status, OVX, and treatment with E(2) or V. Twenty-eight days after carotid artery ligation, mice were euthanized, and occluded vessels were evaluated for neointima formation by morphometric analysis. There was a marked sexual dimorphism in neointima formation in both the iNOS(+/+) mice and the iNOS(-/-) mice. iNOS(+/+) INT females had a >90% reduction in neointima formation compared with iNOS(+/+) males, and iNOS(-/-) INT females had a 65% reduction in neointima formation compared with iNOS(-/-) males. The sexually dimorphic response was attenuated by OVX and restored by E(2) replacement in both iNOS(+/+) and iNOS(-/-) mice. CONCLUSIONS: These results demonstrate that the vasoprotective effects of E(2) after ligation vascular injury are, at least in part, independent of iNOS expression.

Animals↗
PubMed2001

PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.

Alterations of the gene encoding the pituitary transcription factor PROP1 were associated with congenital forms of multiple pituitary hormone deficiencies in several families. Among 23 patients with multiple pituitary hormone deficiencies screened for a PROP1 gene abnormality, nine belonging to eight unrelated families had homozygous PROP1 gene defects. All mutations were located in exon 2 and affected only two different sites: a homozygous AG deletion at codons 99/100/101 (n = 5); homozygous point mutations affecting codon 73: R73C (n = 2) or R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n = 1). R73H and R99X were never described. All patients were born to unaffected parents, and consanguinity was documented in two patients. They had complete GH, LH-FSH, and TSH deficiencies and normal basal levels of PRL. Delayed ACTH deficiency was diagnosed in four of nine patients. At magnetic resonance imaging the anterior pituitary was hypoplastic in seven patients and hyperplastic in two. This study found two novel mutations (R73H and R99X) and underlines the high incidence of PROP1 gene alterations in patients with multiple pituitary hormone deficiencies. A corticotroph deficiency was frequently observed in association with GH, TSH, and gonadotropin deficiencies and should be carefully sought during follow-up.

Adolescent↗
PubMed2001

Molecular characterization of the major membrane skeletal protein in the ciliate Tetrahymena pyriformis suggests n-plication of an early evolutionary intermediate filament protein subdomain.

Epiplasmin C is the major protein component of the membrane skeleton in the ciliate Tetrahymena pyriformis. Cloning and analysis of the gene encoding epiplasmin C showed this protein to be a previously unrecognized protein. In particular, epiplasmin C was shown to lack the canonical features of already known epiplasmic proteins in ciliates and flagellates. By means of hydrophobic cluster analysis (HCA), it has been shown that epiplasmin C is constituted of a repeat of 25 domains of 40 residues each. These domains are related and can be grouped in two families called types I and types II. Connections between types I and types II present rules that can be evidenced in the sequence itself, thus enforcing the validity of the splitting of the domains. Using these repeated domains as queries, significant structural similarities were demonstrated with an extra six heptads shared by nuclear lamins and invertebrate cytoplasmic intermediate filament proteins and deleted in the cytoplasmic intermediate filament protein lineage at the protostome-deuterostome branching in the eukaryotic phylogenetic tree.

Amino Acid Sequence↗
PubMed2001

The neuroendocrine regulation of the human ovarian cycle.

The menstrual cycle is now thought to be mainly determined by the ovary itself, which sends various signals to the pituitary and the hypothalamus. The hypothalamus is an autonomous pacemaker, with a pulse frequency that is modulated by ovarian signals; in turn, it is indispensable to ovarian function. In women, the ovarian cycle produces a single mature oocyte each month from puberty to menopause. This follicle is rescued from atresia, the genetically controlled ovarian apoptosis (or "programmed cell death"), involving 99.9% of the follicles. Follicular growth and maturation are mostly independent of gonadotropins from the stage of primordial to antral follicles. A complete intraovarian paracrine system is implied in this gonadotropin-independent follicular growth and in the modulation of the action of gonadotropins in the ovary. Follicle-stimulating hormone (FSH) allows the rescue of a minority of follicles from atresia and is indispensable only for the final maturation of the preovulatory follicle during the follicular phase of the cycle. Luteinizing hormone (LH) is responsible for the final growth of the dominant follicle in the late follicular phase. the induction of ovulation during the LH peak, and the survival of the corpus luteum during the luteal phase. The cyclical variations of gonadotropins are under the control of ovarian steroids (estradiol and progesterone) and peptides (inhibins). The cycle length is determined by the duration of terminal follicular growth and by the fixed life span of the corpus luteum. The ovarian cycle can be monitored as well at the level of target tissues of steroids, such as the endometrium. In fact, the endometrial maturation is synchronized to follicular development, and this synchronization is indispensable for successful implantation of the embryo. The improving knowledge of follicular and endometrial physiology will allow the development of new treatments of infertility, the design of new contraceptive techniques, and a better tolerance of treatments using sex steroids.

Biological Clocks↗
PubMed2001

[GnRH antagonists in IVF].

New GnRH antagonists are available in clinical practice. The different studies have confirmed the efficacy of these antagonists in preventing the LH surge. Two protocols have been described: in the multiple dose regimens, small doses of antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG. In the single dose protocol, one injection of a larger dose (3 mg) is proposed in the late follicular phase. Local and general tolerance of the two compounds is very good. The results obtained with both regimens as compared with GnRH agonists in long protocols are showing a reduction in the stimulation length, in the consumption of gonadotrophins and in the incidence of the OHSS. The pregnancy rates are comparable in the good prognosis patients selected in the published studies. When the final tuning of these new protocols will be done, the advantages of GnRH antagonists in reducing the complications and side effects of ovarian stimulation will give to GnRH antagonists an important place in IVF.

Chorionic Gonadotropin↗
PubMed2000

Coadministration of interleukin-18 and interleukin-12 induces a fatal inflammatory response in mice: critical role of natural killer cell interferon-gamma production and STAT-mediated signal transduction.

The administration of therapeutic doses of recombinant cytokines to patients with malignant disease can be complicated by systemic toxicities, which in their most severe form may present as a systemic inflammatory response. The combination of interleukin (IL)-18 and IL-12 has synergistic antitumor activity in vivo yet has been associated with significant toxicity. The effects of IL-18 plus IL-12 were examined in a murine model, and it was found that the daily, simultaneous administration of IL-18 and IL-12 resulted in systemic inflammation and 100% mortality within 4 to 8 days depending on the strain employed. Mice treated with IL-18 plus IL-12 exhibited unique pathologic findings as well as elevated serum levels of proinflammatory cytokines and acute-phase reactants. The actions of tumor necrosis factor-alpha did not contribute to the observed toxicity, nor did T or B cells. However, toxicity and death from treatment with IL-18 plus IL-12 could be completely abrogated by elimination of natural killer (NK) cells or macrophages. Subsequent studies in genetically altered mice revealed that NK-cell interferon-gamma mediated the fatal toxicity via the signal transducer and activator of transcription pathway of signal transduction. These data may provide insights into methods of ameliorating cytokine-induced shock in humans. (Blood. 2000;96:1465-1473)

Animals↗
PubMed2000

PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta.

SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways, the specificity of which is dictated by the intrinsic affinity of SH2 domains for the flanking sequences of phosphotyrosine residues. By using a modified yeast two-hybrid system and SHP-1 as bait, we have cloned a human cDNA, PILRalpha, encoding a 303-amino acid immunoglobulin-like transmembrane receptor bearing two cytoplasmic tyrosines positioned within an immunoreceptor tyrosine-based inhibitory motif. Substrate trapping in combination with pervanadate treatment of 293T cells confirms that PILRalpha associates with SHP-1 in vivo upon tyrosine phosphorylation. Mutation of the tyrosine residues in PILRalpha indicates the pivotal role of the Tyr-269 residue in recruiting SHP-1. Surface plasmon resonance analysis further suggests that the association between PILRalpha-Tyr-269 and SHP-1 is mediated primarily via the amino-terminal SH2 domain of the latter. Polymerase chain reaction amplification of cDNA in combination with genomic sequence analysis revealed a second gene, PILRbeta, coding for a putative activating receptor as suggested by a truncated cytoplasmic tail and a charged lysine residue in its transmembrane region. The PILRalpha and PILRbeta genes are localized to chromosome 7 which is in contrast with the mapping of known members of the inhibitory receptor superfamily.

Amino Acid Sequence↗
PubMed2000

Bioassays of gonadotropins.

Bioassays constitute a unique approach to determine the functional aspects of gonadotropins. Indeed, these highly complex glycoprotein hormones, including pituitary lutropin (LH) and follitropin (FSH), are heterogeneous in terms of both peptidic and carbohydrate moieties, and, as a consequence, the bioactivity of the different molecular forms often does not match their immunoreactivity. In this article, we review the different types of LH and FSH bioassays. Conventional methods for measuring FSH bioactivity are first described and include the in vivo Steelman and Pohley bioassay, the radioligand receptor assays (RRAs), the in vitro Sertoli cell bioassay, the in vitro granulosa cell bioassay, and the inhibin immunoassay. Recent methods based on cell lines transfected with cloned receptors, particularly the human FSH receptor, are then described. Methods for developing these assays are presented, and the advantages and disadvantages of the different bioassays are discussed.

Animals↗