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Biomedical subjects

H Durand

Publications and source records attributed to H Durand.

At least 19 recordsLinked to original sources
PubMed2006

Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus.

Lipoprotein associated phospholipase A2 (Lp-PLA2) modulates low-density lipoprotein (LDL) oxidation by hydrolysing oxidised phospholipids present on particle surfaces. We investigated whether Lp-PLA2 activity and PLA2G7 A379V genotype were related to mediators of atherosclerosis in a diabetic study. Plasma Lp-PLA2 activity (taken in men only) and A379V genotype were investigated with regards to metabolic syndrome (MS), UKPDS risk score, and oxidised LDL (oxLDL/LDL), in a cohort of Caucasian men and women (n=783, age 62.5+/-13.7 years). After adjustment for type of diabetes, CHD status, and statin use, those individuals with features defining the MS (WHO guidelines) had higher Lp-PLA2 activity (35.6+/-11.9 nmol/min/ml) compared to those without (33.0+/-10.8 nmol/min/ml) (p=0.02). Quartiles of UKPDS coronary heart disease (CHD) risk score were also positively associated with Lp-PLA2 activity (p=0.006, p=0.004 linear trend). Those men in the highest quartile of oxLDL/LDL level had the lowest Lp-PLA2 activity (31.3+/-10.5 nmol/min/ml) when compared to the middle two (32.3+/-9.8 and 35.9+/-10.9 nmol/min/ml, respectively) and lowest quartile (35.6 +/-12.5 nmol/min/ml; p=0.03, p=0.004 linear trend). There was no significant association between A379V genotype and Lp-PLA2 enzyme activity (p=0.34) or oxLDL/LDL (p=0.32). Lp-PLA2 activity is an independent predictor of CHD risk and MS in a sample of subjects with diabetes mellitus. The association of Lp-PLA2 activity with oxLDL/LDL suggests that Lp-PLA2 may be a modulating factor in the process of atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase.

The ubiquitin-proteasome pathway regulates gene expression through protein degradation. Here we show that the F-box protein betaTrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB bZIP family of transcription factors, and controls its stability. Association between the two proteins depends on ATF4 phosphorylation and on ATF4 serine residue 219 present in the context of DSGXXXS, which is similar but not identical to the motif found in other substrates of betaTrCP. ATF4 ubiquitination in HeLa cells is enhanced in the presence of betaTrCP. The F-box-deleted betaTrCP protein behaves as a negative transdominant mutant that inhibits ATF4 ubiquitination and degradation and, subsequently, enhances its activity in cyclic AMP-mediated transcription. ATF4 represents a novel substrate for the SCF(betaTrCP) complex, which is the first mammalian E3 ubiquitin ligase identified so far for the control of the degradation of a bZIP transcription factor.

Activating Transcription Factor 4↗
PubMed2001

[Churg-Strauss syndrome. Retrospective study of 20 cases].

Churg-Strauss syndrome (CSS) is a disorder characterised by hypereosinophilia and systemic vasculitis complicating a preexisting asthma. Twenty cases have been studied. Mean duration of asthma before CSS was 8 years, the peripheral-blood eosinophilia, always > 1,700/microL, went above 5,000/microL in 17 cases. The clinical manifestations were the following: 20 impairements of general state with fever, 13 peripheral neuropathies, 15 cutaneous injuries, 10 pericardial or myocardial attacks, 10 digestive impairements, 9 muscular and articular diseases, 7 renal diseases--all of them linked with the vasculitis--and 9 upper respiratory tract involvements. Pleuropulmonary or cardiac anomalies have been discovered at the chest X-ray in 14 cases. The diagnosis has been histologicaly confirmed in 15 cases. No clinical or biological or evolutive distinction was noticed between the 15 positive biopsy patients and the 5 negative ones. During 8.4 (+/- 7.9 years) the evolution was caracterised by relapses which have always been announced by increasing eosinophilia. Eighteen patients have been successfully treated with corticoids alone or associated with cyclophosphamid in 9. Survival at 5 years was 85%. Five deaths occured because of CSS (2 because of an unadapted treatment). We have to focus the need for an emergency treatment of CSS. The diagnosis can be done by clinical investigation only, before any anatomopathologic results.

Adolescent↗
PubMed2000

[Pneumopathies caused by inhalation of hydrocarbons: apropos of 3 cases].

We report three personal cases of hydrocarbide aspiration pneumonia. High-viscosity non-volatile hydrocarbides (paraffin oil, for instance) cause often pseudotumoral exogenous fat-aspiration lung disease. Low-viscosity volatile hydrocarbides (petroleum, gasoline, white spirit, for instance) cause acute pseudo-infectious lung disease with dyspnea and fever which usually resolves within a few weeks but which may also be life-threatening. Purely symptomatic treatment has greatly progressed with advances in intensive ventilatory assistance. Gastric emptying with emetic agents or lavage procedures is dangerous and must be avoided except for exceptional cases. When required, the airways must be protected with tracheal intubation. Volatile hydrocarbides should be stored in protected areas in containers with safety stoppers which children cannot open.

Adult↗
PubMed1999

Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP.

Activation of NF-kappaB transcription factors requires phosphorylation and ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36 phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36 phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32-Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome.

Cell Cycle Proteins↗
PubMed1999

The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.

Defects in beta-catenin regulation contribute to the neoplastic transformation of mammalian cells. Dysregulation of beta-catenin can result from missense mutations that affect critical sites of phosphorylation by glycogen synthase kinase 3beta (GSK3beta). Given that phosphorylation can regulate targeted degradation of beta-catenin by the proteasome, beta-catenin might interact with an E3 ubiquitin ligase complex containing an F-box protein, as is the case for certain cell cycle regulators. Accordingly, disruption of the Drosophila F-box protein Slimb upregulates the beta-catenin homolog Armadillo. We reasoned that the human homologs of Slimb - beta-TrCP and its isoform beta-TrCP2 (KIAA0696) - might interact with beta-catenin. We found that the binding of beta-TrCP to beta-catenin was direct and dependent upon the WD40 repeat sequences in beta-TrCP and on phosphorylation of the GSK3beta sites in beta-catenin. Endogenous beta-catenin and beta-TrCP could be coimmunoprecipitated from mammalian cells. Overexpression of wild-type beta-TrCP in mammalian cells promoted the downregulation of beta-catenin, whereas overexpression of a dominant-negative deletion mutant upregulated beta-catenin protein levels and activated signaling dependent on the transcription factor Tcf. In contrast, beta-TrCP2 did not associate with beta-catenin. We conclude that beta-TrCP is a component of an E3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin.

Animals↗
PubMed1998

Dictyostelium discoideum cells shed vesicles with associated DNA and vital stain Hoechst 33342.

Dictyostelium discoideum cells are highly resistant to xenobiotics. We previously observed that these primitive eukaryotic cells contain a 170-kDa P-glycoprotein, mediating multidrug resistance in mammalian cells, but nonfunctional in Dictyostelium cells. We show here that D. discoideum cells vitally stained with the DNA-specific dye, Hoechst 33342, release fluorescent material in their culture medium. Electron microscopy and lipid analysis demonstrate the vesicular nature of this material. Moreover, nucleic acids associate with these extracellular vesicles independently of Hoechst vital staining. The main vesicular DNA component exhibits a size > 21 kb. Shedding of microvesicles during cell growth is not concomitant with programmed cell death. We propose that these extracellular vesicles are involved in a new cellular resistance mechanism against xenobiotics. Furthermore, since the association of DNA with vesicles occurs in physiological growth conditions and independently of vital staining, the new shedding process might be involved in a more general intercellular mechanism.

Animals↗
PubMed1998

A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif.

HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate binding to Vpu, and an F box near the N terminus is involved in interaction with Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4 degradation. These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis.

Binding Sites↗
PubMed1997

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity. Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function. Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues. We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs. In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis. We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively. Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d. No toxic effect was seen in adenovirus-treated mice. Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content. Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice. These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis.

Acetyltransferases↗
PubMed1996

[Withdrawal syndrome in 2 drug addicts after intravenous injection of buprenorphine?].

Adequate dosage of sublingual buprenorphine is now recommended for substitution treatment of severe opioid dependance. We report two cases of acute discomfort, probably linked to withdrawal syndrome, after an IV injection of high doses of buprenorphine in opiate dependant patients. Data on the pharmacokinetics and neurobiochemical aspects of buprenorphine are compared with those of other opiates. A major issue of this work is a guideline for inducing substitution treatment with this "unique" partial agonist/antagonist of endorphinic receptors.

Acute Disease↗
PubMed1996

Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation.

The Vpu and CD4 cytoplasmic domains were found, by using a two-hybrid assay in yeast, to interact in the absence of their membrane anchor domains. Studies on several deletion and point mutants revealed that the overall structure of the Vpu cytoplasmic domain is required for this interaction. The Vpu amino acid residues involved in the interaction with CD4 were identified. Deletion of the C-terminal residues of Vpu, required for CD4 degradation, as well as the double mutation on the casein kinase II phosphorylation sites S52N-S56N, also involved in CD4 degradation, resulted in the loss of interaction with CD4 and in the inability to induce CD4 degradation. These results suggest that the ability of Vpu to mediate the degradation of CD4 is linked to its capacity to physically interact with CD4. However, additional mutagenesis on the S52 site revealed that the interaction between the cytoplasmic domains of Vpu and CD4 is not sufficient for in vitro Vpu-mediated CD4 degradation.

Amino Acid Sequence↗
PubMed1995

Quantitative analysis of transforming growth factor beta 1 messenger RNA in the liver of patients with chronic hepatitis C: absence of correlation between high levels and severity of disease.

Transforming growth factor beta 1 (TGF beta 1) is a cytokine involved in liver fibrogenesis. Previous semiquantitative studies of patients with chronic viral hepatitis showed that liver TGF beta 1 messenger RNA (mRNA) was increased, compared with normal controls and with patients with chronic hepatitis C virus (HCV) infection who responded favorably to interferon alfa (IFN alpha) treatment. To evaluate its potential prognostic significance, we measured liver TGF beta 1 mRNA, using a new competitive reverse gene amplification assay, in a total of 35 patients with chronic HCV. This technique was reproducible and sensitive; we could measure as few as 5,000 molecules of TGF beta 1 mRNA per microgram of total liver RNA. In patients with chronic HCV, the mean level of TGF beta 1 mRNA was 200-fold higher than in controls. However, no correlation could be found between TGF beta 1 mRNA and either the biological (serum amino-terminal peptide of type III procollagen) and histological (Knodell scores) indices of liver fibrosis or a favorable response to IFN alpha therapy. In 9 patients, second liver specimens were obtained after treatment; in most cases, TGF beta 1 mRNA levels and hepatic histological findings varied in parallel. These data are consistent with the hypothesis that TGF beta 1 plays a role in stimulating liver fibrogenesis during chronic HCV, despite the lack of prognostic value of TGF beta 1 mRNA levels measured before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗