Biomedical subjects

A Munier

Publications and source records attributed to A Munier.

At least 19 recordsLinked to original sources

PubMed2005

[Extrapyramidal adverse effects of veralipride (Agreal), a drug used to treat hot flushes: a propos of 17 cases].

PURPOSE: Extrapyramidal disorders associated with veralipride therapy are rarely reported and often due to a drug misuse. METHODS: We evaluated cases of extrapyramidal disorders associated with veralipride. Cases were extracted from the regional pharmacovigilance centre of Amiens database. From January 1, 1995 to September 30, 2004, cases were selected on the basis of the occurrence of extrapyramidal disorders under veralipride therapy. RESULTS: Seventeen cases of veralipride-induced extrapyramidal disorders were found. They consist of 16 menopausal women and one old man with LH-RH antagonist-induced hot flushes. Mean age was 61 years (48-73). Adverse effects were acute dyskinesia (n=2) or parkinsonian syndrome, which occurred after several months or years of treatment (n=15). Parkinsonism was associated with other extrapyramidal symptoms in 8 cases: tardive dyskinesia (n=6), postural tremor (n=3), myoclonia (n=1), and trunk dystonia (n=1). In all cases, outcome was favorable after drug discontinuation. In most cases the tablet-free interval was not respected: this may lead to prolonged striatal D2 receptors blockade. It must be added that the diagnosis was often delayed and patients were considered as suffering from idiopathic Parkinson's disease. CONCLUSIONS: Prescribers should be aware that veralipride is a neuroleptic and could induce potentially severe extrapyramidal disorders. Increase veralipride prescription is expected due to the recent restriction of hormonal replacement therapy for menopause. The physicians should also use veralipride according to the Summary of the Product Characteristics.

Aged↗

PubMed2004

The Resource Mothers Study of Maternal Phenylketonuria: preliminary findings.

Women with phenylketonuria (PKU) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine. The Resource Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy. Resource Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy. Eight metabolic clinics in the United States participated in the study. Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aimed at controlling blood phenylalanine to 120-360 micromol/L. They were randomly assigned to receive the services of a Resource Mother (RM group) or to a control group. Fifty women were enrolled, and accounted for 44 pregnancies which resulted in 28 live births, and 6 spontaneous abortions. Ten women are currently pregnant and another 6 have not become pregnant. Fifty-six percent of enrolled women began the diet prior to becoming pregnant. Fifty-three percent of women in the Resource Mother group were in metabolic control by 10 weeks gestation as compared to 39% in the control group. In addition, women who began diet after pregnancy and had a Resource Mother attained metabolic control earlier (mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group). There was no difference in birth measurement z -scores of offspring born to women in the RM group compared to controls. All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning, and few women in either group remained on diet after delivery.

Female↗

PubMed2000

The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase.

We demonstrate here the catalytic activity and subcellular localization of the Nm23-H4 protein, product of nm23-H4, a new member of the human nm23/nucleoside diphosphate (NDP) kinase gene family (Milon, L., Rousseau-Merck, M., Munier, A., Erent, M., Lascu, I., Capeau, J., and Lacombe, M. L. (1997) Hum. Genet. 99, 550-557). Nm3-H4 was synthesized in escherichia coli as the full-length protein and as a truncated form missing the N-terminal extension characteristic of mitochondrial targeting. The truncated form possesses NDP kinase activity, whereas the full-length protein is inactive, suggesting that the extension prevents enzyme folding and/or activity. X-ray crystallographic analysis was performed on active truncated Nm23-H4. Like other eukaryotic NDP kinases, it is a hexamer. Nm23-H4 naturally possesses a serine residue at position 129, equivalent to the K-pn mutation of the Drosophila NDP kinase. The x-ray structure shows that the presence of Ser(129) has local structural effects that weaken subunit interactions. Site-directed mutagenesis shows that the serine is responsible for the lability of Nm23-H4 to heat and urea treatment, because the S129P mutant is greatly stabilized. Examination of human embryonic kidney 293 cells transfected with green fluorescent protein fusions by confocal microscopy shows a specific mitochondrial localization of Nm23-H4 that was also demonstrated by Western blot analysis of subcellular fractions of these cells. Import into mitochondria is accompanied by cleavage of the N-terminal extension that results in NDP kinase activity. Submitochondrial fractionation indicates that Nm23-H4 is associated with mitochondrial membranes, possibly to the contact sites between the outer and inner membranes.

Base Sequence↗

PubMed2000

The human Nm23/nucleoside diphosphate kinases.

Biochemical experiments over the past 40 years have shown that nucleoside diphosphate (NDP) kinase activity, which catalyzes phosphoryl transfer from a nucleoside triphosphate to a nucleoside diphosphate, is ubiquitously found in organisms from bacteria to human. Over the past 10 years, eight human genes of the nm23/NDP kinase family have been discovered that can be separated into two groups based on analysis of their sequences. In addition to catalysis, which may not be exhibited by all isoforms, evidence for regulatory roles has come recently from the discovery of the genes nm23 and awd, which encode NDP kinases and are involved in tumor metastasis and Drosophila development, respectively. Current work shows that the human NDP kinase genes are differentially expressed in tissues and that their products are targeted to different subcellular locations. This suggests that Nm23/NDP kinases possess different, but specific, functions within the cell, depending on their localization. The roles of NDP kinases in metabolic pathways and nucleic acid synthesis are discussed.

Amino Acid Sequence↗

PubMed1999

Cytoskeletal association of the A and B nucleoside diphosphate kinases of interphasic but not mitotic human carcinoma cell lines: specific nuclear localization of the B subunit.

The human A and B subunits of nucleoside diphosphate kinase (NDP kinase), encoded by the nm23-H1 and nm23-H2 genes, respectively, associate as homo- or heterohexamers to be catalytically active for the synthesis of nucleoside triphosphates. Despite 88% identity, they appear to possess specific functions. The nm23-H1 gene is implicated in tumor progression and metastasis, and the nm23-H2 gene product is a transcription factor for c-myc. To determine if these distinct functions reflect different subcellular localizations, the distribution of the A and B NDP kinases was analyzed by immunocytofluorescence microscopy in human breast cancer cell lines (MCF-7 and MDA-MB-231) using highly specific polyclonal and monoclonal antibodies. Interphasic cells exhibited a granular and filamentous cytoplasmic staining, particularly intense around nuclei, with both anti-NDP kinase A and B antibodies. The filamentous component observed with either anti-A or anti-B antibodies was altered in parallel to tubulin labeling with compounds interacting with microtubules, such as taxol and colchicine. Confirming published biochemical data, a partial colocalization with the vimentin network was observed in the MDA-231 cell line. A nuclear and nucleolar localization of NDP kinase B was shown by confocal microscopy which was not observed with the A enzyme. In dividing cells, NDP kinase labeling was punctiform and was not colocalized with the mitotic spindle. In conclusion, the A and B NDP kinases are similarly distributed in cytosol, associated partly to microtubules supporting a role in nucleotide channeling. Only the B enzyme is present in nuclei in accord with its role as a DNA binding protein. Their altered localization in dividing cells suggests colocalization with yet unidentified structures which are not intermediate filament aggregates.

Animals↗

PubMed1998

A new human nm23 homologue (nm23-H5) specifically expressed in testis germinal cells.

We have identified a cDNA encoding a 212 amino acid protein (Nm23-H5) with 27-31% identity to the human members of the nm23/nucleoside diphosphate (NDP) kinase gene family. The nm23-H5 gene is located on chromosome 5q23-31 and is transcribed as one main transcript of 1.1 kb which is highly and specifically expressed in testis, in the spermatogonia and early spermatocytes. Nm23-H5 possesses most of the residues conserved among NDP kinases plus an additional COOH-terminus end of 55 amino acids unique to this protein. However, under usual assay conditions, Nm23-H5 expressed in Escherichia coli did not exhibit NDP kinase activity. These results suggest that Nm23-H5 is specifically involved in early stages of spermatogenesis.

Amino Acid Sequence↗

PubMed1998

Role for PKC alpha and PKC epsilon in down-regulation of CFTR mRNA in a human epithelial liver cell line.

BACKGROUND/AIMS: In the liver, intrahepatic biliary cells are the sole site of expression of the cystic fibrosis transmembrane conductance regulator, the product of the cystic fibrosis gene. We examined the regulation of cystic fibrosis transmembrane conductance regulator gene expression by protein kinase C in the recently characterized human liver epithelial BC1 cell line which expresses, at early confluence, both biliary (cystic fibrosis transmembrane conductance regulator, cytokeratin 19) and hepatocytic (albumin) specific markers. METHODS: Expression of the cystic fibrosis transmembrane conductance regulator was examined at the mRNA level by Northern blot, reverse transcription-polymerase chain reaction and nuclear run-on assays and at the protein level by Western blotting. The functionality of this protein was tested by measurement of chloride efflux. Protein kinase C isotype expression and cytosol-to-membrane translocation were analysed by Western blotting. RESULTS: 1) Phorbol ester down-regulated cystic fibrosis transmembrane conductance regulator mRNA expression in a time- and dose-dependent manner through a post-transcriptional mechanism with concomitant inhibition of stimulated chloride efflux. 2) Phorbol ester also activated protein kinase C as indicated by the cytosol-to-membrane translocation of both protein kinase C alpha and epsilon the two major protein kinase C isotypes expressed by BC1 cells. 3) Further, maximal down-regulation of the cystic fibrosis transmembrane conductance regulator mRNA by the phorbol ester was inhibited by H7 and by GF 109203X, two known protein kinase C inhibitors. CONCLUSIONS: These findings provide the first evidence for phorbol ester-induced down-regulation of cystic fibrosis transmembrane conductance regulator mRNA expression in a human liver epithelial cell line and point to a role for the classical protein kinase C alpha and the novel protein kinase C epsilon in this process.

Cell Line↗

PubMed1998

Causes of blindness in the adult population of the Republic of Ireland.

BACKGROUND/AIM: Blindness in the developed countries affects 3.5 million people. This study was conducted on the causes of blindness in the Republic of Ireland based on the register of the National Council for the Blind of Ireland. The aim was to determine the prevalence of potentially avoidable blindness and to identify its causes. METHOD: Criteria for registration as blind are in Ireland: best corrected visual acuity of 6/60 (0.1) or less in the better eye or a visual field restricted to 20 degrees or less. Data on 5002 adults 16 years an older registered as blind were analysed. The causes of blindness are classified in 17 diagnostic categories. RESULTS: The leading causes of blindness are macular degeneration and glaucoma, each accounting for 16% (812 and 795). Cataract accounted for 11% (561), a third of these had an associated cause of blindness and one tenth had a cognitive deficit. Diabetic retinopathy ranked as the 11th cause of blindness and accounted for 3% (147). More than half of the patients were 65 years and older. CONCLUSION: 25% of blindness was potentially avoidable. The treatable causes were glaucoma and diabetic retinopathy in the working population and glaucoma and cataract over 65 years of age. Glaucoma is the most important, which raises the question of a screening programme. The prevalence of blindness of 3% due to diabetic retinopathy is lower than in most other series.

Adolescent↗

PubMed1997

nm23-H4, a new member of the family of human nm23/nucleoside diphosphate kinase genes localised on chromosome 16p13.

A novel human nm23/nucleoside diphosphate (NDP) kinase gene, called nm23-H4, was identified by screening a human stomach cDNA library with a probe generated by amplification by reverse transcription-polymerase chain reaction. The primers were designed from publicly available database cDNA sequences selected according to their homology to the human nn23-H1 putative metastasis suppressor gene. The full-length cDNA sequence predicts a 187 amino acid protein possessing the region homologous to NDP kinases with all residues crucial for nucleotide binding and catalysis, strongly suggesting that Nm23-H4 possesses NDP kinase activity. It shares 56, 55 and 60% identity with Nm23-H1, Nm23-H2 and DR-Nm23, respectively, the other human Nm23 proteins isolated so far. Compared with these proteins, Nm23-H4 contains an additional NH2-terminal region that is rich in positively charged residues and could indicate routing to mitochondria. The nm23-H4 gene has been localised to human chromosomal band 16p13.3. The corresponding 1.2 kb mRNA is widely distributed and expressed in a tissue-dependent manner, being found at very high levels in prostate, heart, liver, small intestine and skeletal muscle tissues and in low amounts in the brain and in blood leucocytes. Nm23-H4 naturally possesses the Pro-Ser substitution equivalent to the K-pn mutation (P97S) of Drosophila.

Amino Acid Sequence↗

PubMed1997

[Oncogenic activation of p21ras or pp60c-src in human colonic Caco-2 cells induces post-translation alterations of syndecan-1].

The protein encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study, we investigated the effect of oncogenic p21ras and Py-MT/pp60c-src on the synthesis of syndecan-1, a membrane anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells transfected with an activated (Val-12) human Ha-ras gene or the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. As compared to control vector-transfected Caco-2 cells, both oncogene-transfected cells exhibited: (1) a decrease in syndecan-1 specific activity; (2) a decrease in size and sulfation of syndecan-1 ectodomain glycosaminoglycan side chains; and (3) an active heparanase specifically degrading the heparan sulfate chains. In conclusion, the tumorigenic progression induced by oncogenic p21ras or Py-MT/pp60c-src is associated with marked alterations of syndecan-1 at the post-translational level.

Antigens, Polyomavirus Transforming↗

PubMed1996

Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes.

The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras and pp60c-src in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membrane-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated (Val 12) human Ha-ras gene or with the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines (1) contained smaller amounts of membrane-anchored PGs; (2) exhibited decreased syndecan-1 expression at the protein but not the mRNA level; (3) synthesized 35S-labelled syndecan-1 with decreased specific activity; (4) produced a syndecan-1 ectodomain with a lower molecular mass and reduced GAG chain size and sulphation; and (5) expressed heparanase degradative activity. These results show that the dramatic activation of the tumorigenic potential induced by oncogenic p21ras or Py-MT/pp60c-src in Caco-2 cells is associated with marked alterations of syndecan-1 expression at the translational and post-translational levels.

Antigens, Polyomavirus Transforming↗

PubMed1995

Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.

Although a reduced expression of nm23 has been shown to correlate with a high metastatic potential in some human cancers, in colorectal cancers, conflicting data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2, which encode the A and B subunits of nucleoside diphosphate kinase, efficient and simplified techniques were designed to selectively study nm23-H1 and -H2 expression in 35 colorectal cancers at both the protein and mRNA levels by immunoblotting, immunohistochemistry, and reverse transcription polymerase chain reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2 proteins were overexpressed in tumours compared with adjacent mucosa. This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of tumoral cells was seen by immunohistological staining. This suggests a dichotomy: an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23-H1 determination should be evaluated as a prognostic factor in human colorectal carcinoma.

Adenocarcinoma↗

PubMed1994

Enterocytic differentiation of the human Caco-2 cell line is correlated with down-regulation of fibronectin and laminin.

Human intestinal Caco-2 cells were used to examine the expression of fibronectin (FN) and laminin (LN) during enterocytic differentiation. Combination of immunoprecipitation, Western and Northern blotting revealed that Caco-2 cells expressed a classical FN and a variant form of LN: besides B1 and B2 chains, LN contained a 350-kDa heavy chain instead of the 400-kDa A chain. Throughout Caco-2 cell differentiation, FN and LN synthesis decreased at both mRNA and protein levels. These data indicate that enterocytic differentiation involves both transcriptional and/or post-transcriptional down-regulation of FN and LN gene expression.

Cell Differentiation↗

PubMed1994

Differences in both glycosylation and binding properties between rat and mouse liver prolactin receptors.

To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.

Animals↗

PubMed1991

Women's health education in rural Bangladesh.

Each year in Bangladesh scores of women and children suffer and die from diseases that are largely preventable or curable. In an effort to address this problem, CARE-Bangladesh established its Women's Health Education (WHE) program. The WHE program, which targets poor women in rural areas, was designed to teach women how to prevent and treat health problems which routinely afflict them and their families. The health education sessions emphasize preventative measures and cover topics concerning health and hygiene of women and children. Surveys are conducted immediately following course completion and again six months later to assess the short and long-term impact of the program. Surveys conducted at the end of the 12 week course period indicate that, on average, participants retain 97% of the material covered. Measurement of knowledge retention 6 months after course completion revealed only a 5% decline from the post-course survey results. These findings illustrate the program's success in increasing knowledge and awareness of health interventions. Since imparting knowledge is a first step toward changing behavior, WHE's success in this regard suggests a significant role for health education in preventing and treating common health hazards, and thus in improving the health status of women and children in developing countries.

Bangladesh↗

PubMed1989

Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens.

We have investigated the effect of TNF, a cytokine produced during most immunologic and inflammatory reactions, on HIV genome expression in human T lymphocytes. A CD4+ human T cell line (J.Jhan) was transfected with vectors permitting the expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the long terminal repeat (LTR) of HIV-1. rTNF was found to induce HIV LTR transactivation as intensely as PHA or phorbol esters. PHA enhanced TNF receptor expression in J.Jhan cells and acted synergistically with TNF on HIV LTR induction. TNF was also shown to induce well expression of a whole HIV provirus genome transfected into J.Jhan cells. The use of various CAT constructs carrying fragments of the HIV LTR, combined with bandshift assays, showed that TNF stimulates HIV transcription by acting on the kB-like enhancer element of the LTR through induction and/or activation of an NF-kB-like protein factor. Such findings are compatible with the hypothesis that TNF production participates in the pathogenesis of AIDS by enhancing HIV replication in T lymphocytes.

Animals↗

PubMed1989

Cytomegalovirus infection and trans-activation of HIV-1 and HIV-2 LTRs in human astrocytoma cells.

Susceptibility of a human astrocytoma cell line to human cytomegalovirus (HCMV) infection was investigated. Infection of U-373MG astrocytoma cells with two strains of HCMV resulted in both production of extracellular, infectious virus and expression of immediate early and early antigens within 18 hours and late antigens after 72 hours of infection. The kinetics of infection in U-373MG cells were the same as in human diploid fibroblasts (MRC-5). Since HCMV and human immunodeficiency virus (HIV) have reportedly been found in astrocytic cells in vivo, we studied the possible interaction between HCMV and HIV long terminal repeat (LTR) elements in this cellular environment. HCMV infection transactivated the LTR of HIV-1 and HIV-2 to similar levels. Interestingly, transfection of these cells with infectious HIV-1 provirus did not result in expression of gag, env, or F proteins detectable by immunofluorescence. However, provirus gene expression was not completely silent, since it transactivated HIV-1 LTR. The level of this transactivation was similar to that seen following cotransfection with a tat expression vector. These results suggest that opportunistic infection with HCMV may reactivate latent HIV genomes in glial cells.

Animals↗

PubMed1989

Prospective evaluation of weight gain in both nonorganic and organic failure-to-thrive children: an outpatient trial of a multidisciplinary team intervention strategy.

Failure-to-thrive (FTT) is categorized as organic (OFTT) or nonorganic (NFTT). Traditionally, it has been taught that children with OFTT are unable to grow well in spite of adequate care (calories, nurturance, medical supervision), whereas NFTT children will grow well when given adequate care. We undertook this study to determine whether NFTT and OFTT children could grow at similar rates when treated by a specialized multidisciplinary team that provided concrete, individualized therapies including psychosocial support, medical care, and hypercaloric diets. Eighty-six children were enrolled on referral to our outpatient FTT consultative clinic; 64 had NFTT and 22 had OFTT. Growth quotient analysis was used to determine growth outcomes over a 6-month follow-up period. Growth at a rate paralleling the growth curve produces a GQ equal to 1. Growth 2 times as rapid as expected gives a GQ = 2. Children in both groups grew extremely well. For NFTT, GQ = 1.67 +/- 0.56 (SD); for OFTT, GQ = 1.81 +/- 0.37 (SD), p = NS. OFTT children grew just as well as NFTT children when given adequate calories for catch-up growth. Our data indicate that weight gain alone cannot reliably differentiate OFTT from NFTT, as has been traditionally taught. They suggest that we make every attempt to maximize caloric intake in FTT children. They also suggest that a multidisciplinary team consisting of a pediatrician, child psychiatrist, nutritionist, nurse clinician, and social worker may be successful in managing FTT children.

Behavior Therapy↗