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Biomedical subjects

B Duclos

Publications and source records attributed to B Duclos.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nitric oxide end products in patients hospitalized for diarrhoea.

OBJECTIVE: Increased nitric oxide (NO) has been demonstrated in inflammatory bowel diseases (IBD). Plasma and urinary nitrite and nitrate are usually considered to reflect global NO generation. Recently it has been suggested that plasma nitrate may be a discriminant indicator between infectious enterocolitis (IC) and IBD. To investigate this hypothesis we compared plasma and 24 h urinary nitrite and nitrate in 13 healthy controls, 44 patients with IBD [Crohn's disease (CD) n = 30; ulcerative colitis (UC) n = 14], 16 patients presenting with IC and seven chronic radiation enterocolitis (RE) patients. RESULTS: Despite a trend towards higher plasma nitrate in IC (54.6+/-11.4 micromol/l) than in the other groups (CD: 38.4+/-4.8, UC: 34.8+/-8.4, RE: 34.7+/-7.5, controls: 31.1+/-5.2), this difference was not statistically significant. Urinary nitrate was higher in IBD, IC and RE than in controls, with no difference between these groups. Nitrite concentrations were not different. Nitrate levels were positively correlated with blood and 24 h urinary neopterin (e.g. plasma nitrate and blood neopterin: r = 0.54, P<0.0001), and in some cases, to C-reactive protein. CONCLUSIONS: High nitrate (in our case only urinary nitrate) appears to be secondary to the magnitude of the inflammation rather than the aetiology of the diarrhoea. It should therefore more likely be considered as a marker of the severity of the inflammatory response rather than used as a discriminant indicator between IC and IBD patients.

Case-Control Studies↗
PubMed1999

A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: The aim of this randomized controlled study was to investigate the efficacy of ciprofloxacin compared with mesalazine in treating active Crohn's disease. METHODS: Patients with a mild to moderate flare-up of Crohn's disease (mean Crohn's Disease Activity Index [CDAI]; 217; range, 160-305) were randomized to receive ciprofloxacin 1 g/day or Pentasa 4 g/day for 6 wk. Complete remission was defined at wk 6 as a CDAI < or = 150 associated with a decrease (delta) in CDAI > 75. Partial remission was defined as a CDAI < or = 150 with 50 < delta CDAI < 75 or a CDAI > 150 with delta CDAI > 50 at wk 6. Group sequential procedure with triangular continuation regions was used to monitor the trial through the difference in complete remission rates, every 20 patients included. RESULTS: Inclusion of patients was stopped at the second step, i.e., after 40 inclusions, with the conclusion of no difference in complete remission rates between ciprofloxacin- and Pentasa-treated groups. Among the 18 patients taking ciprofloxacin, two decided to stop treatment during the trial and three were considered as treatment failures because of deterioration at wk 3. Among the 22 patients taking mesalazine, one patient was lost to follow-up and eight patients were considered as treatment failures. Complete remission was observed in 10 patients (56%) treated with ciprofloxacin and 12 patients (55%) treated with mesalazine and partial remission was observed in three and one patient, respectively. CONCLUSIONS: This study suggests that ciprofloxacin 1 g/day is as effective as mesalazine 4 g/day in treating mild to moderate flare-up of Crohn's disease.

Adult↗
PubMed1999

Cells of Escherichia coli contain a protein-tyrosine kinase, Wzc, and a phosphotyrosine-protein phosphatase, Wzb.

Two proteins of Escherichia coli, termed Wzc and Wzb, were analyzed for their capacity to participate in the reversible phosphorylation of proteins on tyrosine. First, Wzc was overproduced from its specific gene and purified to homogeneity by affinity chromatography. Upon incubation in the presence of radioactive ATP, it was found to effectively autophosphorylate. Two-dimensional analysis of its phosphoamino acid content revealed that it was modified exclusively at tyrosine. Second, Wzb was also overproduced from the corresponding gene and purified to homogeneity by affinity chromatography. It was shown to contain a phosphatase activity capable of cleaving the synthetic substrate p-nitrophenyl phosphate into p-nitrophenol and free phosphate. In addition, it was assayed on individual phosphorylated amino acids and appeared to dephosphorylate specifically phosphotyrosine, with no effect on phosphoserine or phosphothreonine. Such specificity for phosphotyrosine was confirmed by the observation that Wzb was able to dephosphorylate previously autophosphorylated Wzc. Together, these data demonstrate, for the first time, that E. coli cells contain both a protein-tyrosine kinase and a phosphotyrosine-protein phosphatase. They also provide evidence that this phosphatase can utilize the kinase as an endogenous substrate, which suggests the occurrence of a regulatory mechanism connected with reversible protein phosphorylation on tyrosine. From comparative analysis of amino acid sequences, Wzc was found to be similar to a number of proteins present in other bacterial species which are all involved in the synthesis or export of exopolysaccharides. Since these polymers are considered important virulence factors, we suggest that reversible protein phosphorylation on tyrosine may be part of the cascade of reactions that determine the pathogenicity of bacteria.

Adenosine Triphosphate↗
PubMed1999

Home parenteral nutrition: clinical and laboratory analysis of initial experience (1994-1997). Implications for patient management.

UNLABELLED: BACKGROUND/AIM AND METHOD: Severe malabsorption often necessitates prolonged parenteral nutrition. Home parenteral nutrition (HPN) offers the opportunity for treatment at home. We report clinical and laboratory data of initial 27 HPN patients of one center since its opening in 1994. RESULTS: Clinical and biological markers of nutritional status were normalized and well maintained in most patients. Except for vitamin E and selenium (lower in HPN patients), the other vitamin and micronutrient levels were normal. There was no obvious essential fatty acid deficiency. Cholestasis was usual, but only 1 patient had a severe hepatic disease. Catheter infection occurred 18 times in 13 patients, but the frequency decreased with time (from 4.2 to 1.7 infections/1,000 days on HPN). No patient died from HPN complications. Social rehabilitation and, in some patients, full professional rehabilitation were constant. CONCLUSIONS: These data confirm that HPN performed in centers with expertise allowed patients to overcome gut failure and to recover subnormal or normal nutritional status. Satisfactory social rehabilitation was obtained in all patients. HPN complications were rarely life-threatening, and their frequency decreased with experience.

Aged↗
PubMed1999

Management of common bile duct stones by laparoscopic cholecystectomy and endoscopic sphincterotomy: pre-, per- or postoperative sphincterotomy?

BACKGROUND/AIMS: The aim of this study was to evaluate the treatment of common bile duct stones (CBDS) by endoscopic sphincterotomy (ES) and laparoscopic cholecystectomy (LC), ES being performed either pre-, per- or postoperatively. METHODS: Between January 1990 and June 1997, 386 patients with a median age of 60 (range 18-92) years were treated for suspected or confirmed CBDS. The CBDS were uncomplicated in 264 cases (70%) but associated with a complication in 122 cases (30%), namely, cholangitis (69 cases) or acute pancreatitis (53 cases). ES combined with LC was carried out in 233 cases (60%): ES was preoperative (sequential treatment in two stages) in 197 cases (51%); peroperative in 30 cases (7%), or postoperative in 6 cases (2%). Laparoscopic extraction was performed in 58 cases (15%) and conventional surgery in 82 cases (21%). RESULTS: With respect to sequential treatment, endoscopic retrograde cholangiography showed the presence of CBDS in 117 cases (60%) and preoperative ES allowed the release of the CBDS in 82% of these cases. The complication rate of sequential treatment was 8% (15 cases) after ES and 7% (13 cases) after LC, with 1 death (0.5%). A peroperative ES performed after LC enabled evacuation of the CBDS in 28 cases (93%) without any complications or mortality. Postoperative ES was successful in 100% of cases with residual lithiasis in 16% (1 case) and a complication rate of 16% (1 case). CONCLUSION: Along with conventional surgery and laparoscopic extraction, ES combined with LC represents an effective alternative in the management of CBDS. Since it can be performed peroperatively, it allows a one-stage, minimally invasive treatment of most uncomplicated CBDS.

Adult↗
PubMed1999

p53-independent regulation of cyclin B1 in normal human fibroblasts during UV-induced G2-arrest.

Recently we demonstrated, using normal human fibroblasts (NHFs), that UVc radiation induces a G2/M arrest which was even more pronounced when p53 expression was inhibited. So, the aim of this study was to evaluate in NHFs the relationship between UV-induced G2/M arrest and cyclin B1 regulation and to investigate if p53 could contribute to the cyclin B1 regulation in these conditions. Following exposure of asynchronous NHFs to UV light, we showed that the induced G2/M arrest was accompanied by a dose-dependent down-regulation of cyclin B1 mRNA as evaluated by RT-PCR. Concomitantly, using flow cytometric analysis, we observed a strong accumulation of cyclin B1 protein which was correlated to the apparition of the G2/M arrest. In order to study the contribution of p53 to the cyclin B1 accumulation in response to UV exposure, we inhibited p53 induction using p53 antisense oligonucleotides. We found that the inhibition of p53 protein induction after UV exposure had no effect on the level of cyclin B1 mRNA. Moreover, although inhibition of p53 protein induction increased the number of the cells in the G2-M phase, the mean content of cyclin B1 protein was not augmented in these cells. These results indicate clearly that the induction of p53 protein following UV exposure does not regulate the level of cyclin B1 mRNA or protein in normal cells.

Cell Culture Techniques↗
PubMed1998

Functional characterization of the low-molecular-mass phosphotyrosine-protein phosphatase of Acinetobacter johnsonii.

The ptp gene of Acinetobacter johnsonii was previously reported to encode a low-molecular-mass protein, Ptp, whose amino acid sequence, predicted from the theoretical analysis of the nucleotide sequence of the gene, exhibits a high degree of similarity with those of different eukaryotic and prokaryotic phosphotyrosine-protein phophatases. We have now overexpressed the ptp gene in Escherichia coli cells, purified the Ptp protein to homogeneity by a single-step chromatographic procedure, and analysed its functional properties. We have shown that Ptp can catalyse the dephosphorylation of p-nitrophenyl phosphate and phosphotyrosine, but has no effect on phosphoserine or phosphothreonine. Its activity is blocked by ammonium molybdate and sodium orthovanadate, which are strong inhibitors of phosphotyrosine-protein phosphatases, as well as by N-ethylmaleimide and iodoacetic acid. Such specificity of Ptp for phosphotyrosine has been confirmed by the observation that it can dephosphorylate endogenous proteins phosphorylated on tyrosine, but not proteins modified on either serine or threonine. In addition, Ptp has been shown to quantitatively dephosphorylate two exogenous peptides, derived respectively from leech hirudin and human gastrin, previously phosphorylated on tyrosine. Moreover, site-directed mutagenesis experiments performed on Cys11 and Arg16, which are both present in the sequence motif (H/V)C(X5)R(S/T) typical of eukaryotic phosphotyrosine-protein phosphatases, have demonstrated that each amino acid residue is essential for the catalytic activity of Ptp. Taken together, these data provide evidence that Ptp is a member of the phosphotyrosine-protein phosphatase family. Furthermore, in search for the biological function of Ptp, we have found that it can specifically dephosphorylate an endogenous protein kinase, termed Ptk, which is known to autophosphorylate at multiple tyrosine residues in the inner membrane of Acinetobacter johnsonii cells. This represents the first identification of a protein substrate for a bacterial phosphotyrosine-protein phosphatase, and therefore constitutes a possible model for analysing the role of reversible phosphorylation on tyrosine in the regulation of microbial physiology.

Acinetobacter↗
PubMed1998

Inactivation of p53 in normal human cells increases G2/M arrest and sensitivity to DNA-damaging agents.

p53 mutations are found in about 70% of human cancers. In order to evaluate the role of these mutations in response to chemotherapeutic agents, it is important to distinguish between p53 response to DNA-damaging agents in normal and in tumour cells. Here, using normal human fibroblasts (NHFs), we show that cisplatin and UV radiation induce G2/M arrest which is temporally linked to p53-protein induction. To study the contribution of p53 to this G2/M arrest, we inhibited p53 induction in NHFs using p53 anti-sense oligonucleotides. Following exposure of NHFs to UV radiation, the inhibition of p53-protein induction leads to a greater accumulation of cells in the G2/M phase, but also to a decreased fraction of cells in the G1 phase. We propose that p53 does not induce G2/M arrest directly, and that the extent of this arrest may depend on the fraction of cells that do not stop at the G1 phase following exposure to DNA-damaging agents. Furthermore, inhibition of p53-protein induction leads to increased sensitivity of NHFs to UV radiation. These results suggest that inhibition of p53 protein enhances sensitivity to DNA-damaging agents in normal human cells.

Antineoplastic Agents↗
PubMed1998

Paclitaxel-anthracycline combination chemotherapy in relapsing advanced ovarian cancer after platinum-based chemotherapy: a pilot study.

Despite high response rates with platinum-based front-line chemotherapy, the prognosis for advanced ovarian carcinoma (AOC) is poor. Salvage chemotherapy for recurrent AOC was of little benefit before paclitaxel as single-agent therapy showed appreciable efficacy. Anthracyclines are effective, but are not often part of first-line therapy. In this pilot study, we investigated the feasibility of an anthracycline plus paclitaxel combination therapy for recurrent AOC. Twenty-four patients received 150 mg/m2 paclitaxel on day 1, with either 50 mg/m2 doxorubicin on day 1 or 75 mg/m2 epirubicin on day 1 every 3 weeks. A 27% overall response rate was obtained. Myelosuppression was the major toxicity, but was manageable. No myocardiac toxicity was observed. We conclude that paclitaxel-anthracyclines is a promising salvage combination therapy in AOC that should be investigated further.

Adolescent↗
PubMed1998

Crohn's disease stable remission after human immunodeficiency virus infection.

We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.

Adolescent↗
PubMed1998

Antioxidants inhibit the in vitro production of inflammatory cytokines in Crohn's disease and ulcerative colitis.

BACKGROUND: Modulation of cytokine secretion may be of interest in the treatment of Crohn's disease or ulcerative colitis. METHODS: The effect of three antioxidants - butylated hydroxyanisol, tetrahydropapaveroline and nordihydroguaiaretic acid - on the production of tumour necrosis factor (TNF), interleukin (IL) 1, IL-6 and IL-8 (measured by enzyme-linked immunosorbent assay) by peripheral mononuclear cells and biopsies of inflamed colonic mucosa from inflammatory bowel disease patients were studied. RESULTS: We observed a decrease in IL-1 and IL-6 production by peripheral mononuclear cells from inflammatory bowel disease patients (approximately 50% of control). The three drugs did not decrease IL-6 and IL-8 secretion by colonic biopsies, whereas they did inhibit IL-1 and, to some degree, TNF production. The cytokine-inhibitory effect of antioxidants seems to be more pronounced in ulcerative colitis than in Crohn's disease. CONCLUSION: Our results suggest that the studied antioxidants, or related compounds, may be of interest in inflammatory bowel disease treatment.

Adult↗
PubMed1998

[Spontaneous hyperintensity of the anterior pituitary gland in MRI T1-weighted images related to manganese deposits in a patient undergoing prolonged parenteral nutrition].

The signal abnormalities found on MRI in the basal ganglia in patients with an increased plasmatic level of manganese are well known. We report a case with a hyperintense signal in a patient with a high plasmatic level of manganese due to long term parenteral nutrition. The normal signal intensity of T2-weighted imaging in the anterior pituitary gland helps to differentiate the increased signal intensity of T1 weighted imaging due to deposition of manganese from hemorrhagic or fatty lesions.

Adult↗
PubMed1998

[A 1993-1995 epidemiological survey of home parenteral nutrition in approved centers for adults in France].

OBJECTIVES: A 1993-1995 three year epidemiological survey of home parenteral nutrition was performed through in France in approved centers for adults. METHODS: Data were retrospectively collected each year on a standardized questionnaire focussing on indications and short term outcome. RESULTS: All centers (n = 14) participated in the study and 524 new adult patients were recruited. The overall incidence was unchanged at 3.75 patients/10(6) adults. Indications for AIDS rose (8 to 18%) whereas other indications were stable. Prevalence increased by 19%: 4.40 adults/10(6) patients at 01.01.1996. At six months, the probability to stay on treatment was 19.5% for AIDS and cancer indications but 52% for others, whereas death rates were 59% and 9% respectively. CONCLUSIONS: For both cancer and AIDS indications, short-term treatment was due to a poor prognosis. For other diagnosis, complicated with a short bowel in 51% of cases, prognosis was excellent but associated with treatment dependency. The latter point focuses on the need for additional treatments in irreversible intestinal failure.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Characterization of a bacterial gene encoding an autophosphorylating protein tyrosine kinase.

Acinetobacter johnsonii harbors a protein tyrosine kinase activity that is able to catalyze autophosphorylation, like a number of eukaryotic tyrosine kinases. A biochemical and genetic analysis of this enzyme was performed. Maximum phosphorylation in vitro was obtained by incubating the kinase for 2 min at pH 7.0 in the presence of 5 mM magnesium chloride. In contrast to eukaryotic enzymes, no inhibitory effect of genistein and no phosphorylation of synthetic substrates such as poly (Glu80 Tyr20) or angiotensin II were observed. The analysis of the bacterial kinase by two-dimensional gel electrophoresis revealed the presence of at least five isoforms, all phosphorylated exclusively at tyrosine, which supports the concept that autophosphorylation occurs at multiple sites within the protein. The cloning and nucleotide sequencing of the gene encoding this kinase were achieved, which represents the first molecular characterization of a gene of this type in bacteria. An open reading frame of 2199 nucleotides encoding a protein of 82,373 Da was detected. The analysis of the deduced amino acid sequence suggested a possible involvement of the enzyme in cell recognition and bacterial pathogenicity. In addition, the cloning and sequencing of the region immediately upstream of the gene encoding the kinase revealed a novel open reading frame of 426 nucleotides encoding a phosphotyrosine protein phosphatase of 16,217 Da, which indicates that autophosphorylation on tyrosine is a physiologically reversible reaction.

Acinetobacter↗
PubMed1997

Hyperphosphorylation of beta-catenin on serine-threonine residues and loss of cell-cell contacts induced by calyculin A and okadaic acid in human epidermal cells.

Phosphorylation and dephosphorylation events may critically control junction assembly and stability, as well as regulate the formation of the cadherin-cytoskeleton complex, thus influencing the adhesive function of cells. In the present study, we have used specific activators and inhibitors of protein kinases and phosphatases to analyze the role of protein phosphorylation in the maintenance of epithelial architecture. Okadaic acid and calyculin A cell treatments induced two major effects: a dramatic alteration of the keratin network of epidermal cells and a complete disruption of cell-cell contacts. This loss in cell-cell contacts was not tissue and species restricted and the interactions of keratinocytes with the matrix were not involved. The observed changes were highly specific for these drugs and were obtained in the range of concentrations corresponding to the inhibition of protein phosphatase 1 (PP1). They were time- and dose-dependent, and reversible, excluding a cytotoxic effect of the drugs. A decrease in electrophoretic mobility of beta-catenin, a major protein involved in the regulation of intercellular adherens junctions, was observed in keratinocytes and fibroblasts treated with okadaic acid and calyculin A, suggesting a change in the protein phosphorylation level and/or protein conformation. Data from beta-catenin immunocomplex autoradiography performed after 32P in vivo incorporation in untreated and okadaic acid or calyculin A-treated HaCaT cells, demonstrated a higher level of phosphorylation of beta-catenin in treated cells compared to untreated ones. Analysis of 32P-labeled phosphoaminoacids demonstrated that beta-catenin was exclusively phosphorylated on serine-threonine residues but not on tyrosine residues. Immunoprecipitations and Western blotting using anti-phosphoserine and anti-phosphotyrosine antibodies confirmed these data. The change in beta-catenin phosphorylation on serine-threonine residues may play a role in the control of the cohesion between epithelial cells and may be involved in the regulation of the transduction signal.

Apoptosis↗