PubMed Health⌕ Search

Biomedical subjects

C Lavergne

Publications and source records attributed to C Lavergne.

8 recordsLinked to original sources
PubMed2000

[How to calculate the completeness of ascertainment of a morbidity register? Example of the Isere childhood handicap register in Grenoble, France].

BACKGROUND: It should no longer be necessary to demonstrate the importance of knowing the completeness of ascertainment for a morbidity register, particularly with respect to the interpretation of prevalence rates and their trends, but also when using register data for etiological studies. METHOD: The study covered 9 generations of children born between 1980 and 1988. All of these children lived in the Isère department in SouthEast France, and each of them had at least one major deficiency, according to the inclusion criteria laid down by the RHEOP ("Registre des Handicaps de l'Enfant et Observatoire Périnatal", in French, or Childhood Handicap Register and Perinatal Observatory). These children were recruited from four different data sources. The completeness of ascertainment of the register was estimated first by means of the capturerecapture method, based on two sources that were shown to be independent by the Wittes method. Following this, loglinear models were used. The advantage of this was the absence of restrictions involved in adhering to the necessary validity conditions before applying the capture-recapture method, and the possibility of introducing heterogeneity variables, such as the number of deficiencies per child, for example. RESULTS: The applied capturerecapture method, with two main sources that have been found to be independent, gives an overall completeness of ascertainment of 86% CI(95%)[8291], with a variation of between 76% CI(95%)[6787] and 97% CI(95%)[93100] when the number of deficiencies per child is taken into account. After application of the loglinear models, the results obtained are very close to those obtained with the capture-recapture method, both in the case of estimation of the overall completeness of ascertainment and in the case of the completeness of ascertainment that is estimated according to the number of deficiencies variable. The similarity of the results obtained by the two methods appears to support our empirical study, but is only possible because of the validity of certain conditions (the interactions of the order of three were not significant) which can only be verified using statistical tests in the linear log models. CONCLUSION: If the application conditions of the capture-recapture method are carefully adhered to, it becomes possible, without the help of software, to produce a correct estimate of the number of missing cases. Nevertheless, it would be unreasonable to continue using this method alone since log linear models have been found to be independent of these validity conditions.

Child↗
PubMed1996

Control of SHB gene expression by protein phosphorylation.

To increase our understanding of the role of the Src homology 2 (SH2) domain-containing protein Shb in the mitogenic signal transduction, Shb mRNA contents were determined in the fibroblast-like NIH3T3 cells and the insulin producing beta TC-1 cells under various conditions. In NIH3T3 cells, the serine/ threonine phosphatase inhibitor okadaic acid and the tyrosine kinase inhibitor genistein increased Shb mRNA contents, the protein kinase C activating phorbol ester 12-O-tetradecanoyl 13-acetate (TPA) decreased the Shb mRNA content, whereas the tyrosine kinase inhibitor tyrphostin 25 and the mitogen platelet-derived growth factor (PDGF-BB) had no effect. In beta TC-1 cells, okadaic acid and genistein increased the Shb mRNA content, whereas tyrphostin 25 and serum were without effect. Okadaic acid and genistein decreased the rates of beta TC-1 cell DNA synthesis. It is concluded that expression of the SHB gene is under a complex mode of regulation involving at least three different protein kinases. As a consequence of this, it is likely that SHB gene expression is significantly modulated by conditions of specific activation of certain pathways, whereas its expression appears little influenced by serum and a mitogen.

3T3 Cells↗
PubMed1995

Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins.

The molecular interactions of the Src homology 2 (SH2) domain and the N-terminal proline-rich sequence motifs (pro-1 to pro-5) of the SH2 protein Shb with other components were presently characterised. Using a degenerate phosphopeptide library the preferred binding site for the Shb SH2 domain was determined to pTyr-Thr/Val/Ile-X-Leu at positions +1 to +3 relative the phosphotyrosine residue. Experiments with competing peptides and platelet-derived growth factor (PDGF) beta-receptor mutants with Y to F substitutions in autophosphorylation sites revealed multiple binding sites for the Shb SH2 domain in the receptor. The Shb SH2 domain also binds to in vitro phosphorylated fibroblast growth factor receptor-1 (FGFR-1) mainly through position Y776. The receptor experiments suggest that other residues besides the +1 to +3 positions may also be of significance for Shb binding. The pro-4/pro-5 motif of Shb binds in vitro particularly well to the Src, p85 alpha PI3-kinase and Eps8 SH3 domains expressed as GST fusion proteins. However, the GST-SH3 domain fusion proteins tested bind in vitro to peptides corresponding to the pro-1 to pro-5 motifs of Shb with low affinity and selectivity, suggesting that sequences outside the core proline motif may also be important for Shb-SH3 domain interactions. In vivo association between Shb-SH3 domain proteins v-Src and Eps8 was detected by coimmunoprecipitation. PDGF treatment did not affect the association between Eps8 and Shb. The data suggest that Shb is an adaptor protein linking SH3 domain proteins to tyrosine kinases or other tyrosine phosphorylated proteins.

Amino Acid Sequence↗
PubMed1994

Shb is a ubiquitously expressed Src homology 2 protein.

To identify serum-inducible genes in the insulin-producing cell line beta TC-1, a library subtraction screening procedure was performed on serum-deprived (G0) and serum-restimulated (G1) insulin-producing beta TC-1 cells. A cDNA containing a motif with strong homology to Src homology 2 (SH2) domains was found using this procedure and called Shb. The Shb cDNA contains two methionine codons in its N-terminus and thus may code for two proteins of 67 and 56 kDa, each with one SH2 domain in its C-terminus. No other structural similarity to proteins with catalytic activity could be detected, suggesting that Shb is a so called adaptor. Shb contains the proline-rich sequence PPPGPGR between the two proposed initiator methionines which resembles a sequence for binding to Src homology 3 (SH3) domains. A second proline-rich sequence was detected after the second methionine codon. The Shb cDNA hybridized to a similar or identical mRNA of 3.1 kb expressed in mouse brain, liver, kidney, heart, NIH3T3 fibroblasts and beta TC-1 cells. Western blot analysis of the same tissues using an antiserum directed against a synthetic peptide corresponding to a part of the SH2 domain of Shb, revealed reactivity with two proteins of 56 and 67 kDa. In addition, a third reactive component of 40 kDa was detected in most tissues. Transfection and transient expression of the Shb cDNA in COS-1 cells yielded increased expression of the 67, 56 and 40 kDa proteins. Transfection and stable expression of the Shb cDNA in pig aortic endothelial cells showed increased expression primarily of the 67 kDa protein. A fusion protein consisting of the SH2 domain of Shb linked to glutathione S-transferase showed increased binding to glycoproteins of cells stimulated with platelet-derived growth factor (PDGF-BB). Furthermore, the autophosphorylated PDGF beta-receptor but not the autophosphorylated epidermal growth factor (EGF) receptor bound specifically to immobilized fusion protein. It is concluded that Shb is a novel SH2-containing protein with proline-rich domains and therefore probably involved in the signal-transduction of some ligand-activated tyrosine kinase receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Logistic regression model to estimate the risk of unbalanced offspring in reciprocal translocations.

The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis.

Adolescent↗
PubMed1992

Modulation of growth-related gene expression and growth inhibition by cyclic adenosine 3',5'-monophosphate-elevating agents in the insulin-producing cell line beta TC1.

We studied the involvement of the cAMP pathway in the regulation of beta TC1 cell growth with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the activator of adenylate cyclase forskolin. We examined the effect of the increase in cAMP content on the serum-induced resumption of the cell cycle of quiescent cells. IBMX and forskolin both inhibited the mitogenic effect of serum in a concentration-dependent manner. Intracellular cAMP levels were, respectively, enhanced 3.0- and 8.6-fold by IBMX (0.5 mM) and forskolin (20 microM) within 1 h. IBMX and forskolin were also inducers of insulin release, indicating that the growth-arrested beta TC1 cells have retained the essential characteristics of the normal differentiated beta-cells. The effects of IBMX and forskolin were correlated with a modulation of cell cycle-related gene expression. IBMX induced expression of the c-fos gene, which was further enhanced by the simultaneous addition of serum, whereas forskolin alone elicited maximal induction of this gene. Interestingly, c-jun expression was only enhanced with forskolin. We also studied the effects of IBMX and forskolin on the expression of the simian virus-40 T-antigen controlled by the rat insulin II promoter in beta TC1 cells. IBMX and forskolin inhibited the serum-induced accumulation of simian virus-40 T-antigen mRNA in quiescent as well as exponentially growing beta TC1 cells.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Cell cycle and gene expression in the insulin producing pancreatic cell line beta TC1.

The pancreatic cell line beta TC1, established from insulinomas of transgenic mice carrying a hybrid insulin-promoted large T antigen gene, has retained several characteristics of normal cells, including the insulin content and inducibility of insulin secreting by glucose. We show here that the growth of beta TC1 cells is arrested in low serum-concentration medium. Cells exposed for three days to 0.25% fetal calf serum ceased to incorporate [3H]thymidine but were still able to resume the cell division cycle upon addition of serum. In this cell line, we have determined by cytofluorometry the cell cycle kinetic parameters to be of 21 h, 10 h 30 min and 12 h for the G1, S and G2/M phases, respectively. Quiescent beta TC1 cells constitutively expressed the protooncogene c-jun that codes for the transcriptional factor AP1, as well as cdc2, another cell cycle-related gene. A large transient increase in the expression of the c-fos gene was obtained rapidly, 30 min after addition of serum and a similar increase in c-jun expression after one hour. Expression of the cdc2 gene was also enhanced to a lesser extent. The same effects were also observed in the presence of cycloheximide, thus proving that the expression of these three genes is directly stimulated by serum growth factors. Consequently, quiescent beta TC1 cells provide a good model for studying the short- and long-term effects of growth factors on Beta-cell proliferation.

Animals↗