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Biomedical subjects

M Rousseau

Publications and source records attributed to M Rousseau.

At least 37 records · Page 2Linked to original sources

Absence of mutations in superoxide dismutase and catalase genes in patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is an adult-onset, neurodegenerative disorder characterized by a selective loss of the dopaminergic cells of the substantia nigra and by progressive motor decline. Studies have shown aberrant oxidative stress metabolism within the substantia nigra and other dopaminergic regions of the brain in patients with PD. OBJECTIVE: To screen the genes of three free radical detoxifying enzymes--copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase--for mutations in patients with PD. PATIENTS AND METHODS: A total of 107 unrelated patients with PD from two PD populations (familial and sporadic) were screened for mutations in the genes of copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase by single-strand conformation analysis. The diagnosis of PD was based on the clinical observations of resting tremor, rigidity, and bradykinesia. RESULTS: No mutations were identified. However, we did identify an amino acid substitution (glycine to aspartic acid) in exon 9 of the catalase gene in one patient; decreased red blood cell catalase activity was observed in this patient. CONCLUSION: Parkinson's disease is not caused by mutations in the genes of these three detoxifying enzymes. The exon 9 variant in the catalase gene in the one family with PD is most likely a silent mutation and not the genetic cause of PD in this family.

Adult↗

Human hepatic macrovesicular steatosis: a noninvasive study of mitochondrial ketoisocaproic acid decarboxylation.

Differentiating between alcoholic and nonalcoholic hepatic steatosis is often a difficult clinical task. However, decreased fatty acid mitochondrial oxidation appears as the main factor for alcoholic steatosis, whereas nonalcoholic steatosis may be due to other causes. We studied mitochondrial function, based on a 13C-ketoisocaproic acid (13C-KIC) breath test, in nine alcoholic and 12 nonalcoholic steatosis patients and 10 healthy volunteers. Our results showed a 42% 13C-KIC decarboxylation decrease in alcoholic steatosis patients, but not in nonalcoholic steatosis patients. This noninvasive breath test appears helpful for the diagnostic work-up of hepatic steatosis.

Adult↗

Characterization of the non-functional Fas ligand of gld mice.

Mice homozygous for either the gld or lpr mutation develop autoimmune diseases and progressive lymphadenopathy. The lpr mutation is characterized by the absence of functional Fas, whereas gld mice exhibit an inactive FasL due to a point mutation proximal to the extracellular C-terminus. The structural repercussions of this amino acid substitution remain unknown. Here we report that FasL is expressed at similar levels on the surface of activated T lymphocytes from gld and wild-type mice. Using a polyclonal anti-FasL antibody, indistinguishable amounts of a 40 kDa protein are detected in both gld and wild-type splenocytes. The molecular model of FasL, based on the known structure of TNF-alpha, predicts that the Phe --> Leu gld mutation is located at the protomer interface which is close to the FasR interaction site. We conclude that the gld mutation allows normal FasL biosynthesis, surface expression and oligomerization, but induces structural alterations to the Fas binding region leading to the phenotypic changes observed.

Amino Acid Sequence↗

Impact of the development of a multidisciplinary adverse drug reaction committee.

A multidisciplinary Adverse Drug Reaction (ADR) committee consisting of pharmacists, nurses, and physician was formed. The committee developed an ADR Reporting Form and a 24-hour ADR Reporting Hotline to simplify ADR Reporting throughout the hospital. An ADR Newsletter and an extensive inservice education program was also implemented. Suspected ADRs are investigated by a pharmacist and presented to committee. A formal report is then forwarded to the Pharmacy and Therapeutics Committee, as well as the clinical departments within the hospital. The establishment of a formalized multidisciplinary ADR committee was successful in generating 2.1 ADR reports per 100 hospital admissions. These ADRs were reported from a variety of healthcare professionals.

Adverse Drug Reaction Reporting Systems↗

Mechanism of carbon tetrachloride autoprotection: an in vivo study based on 13C-aminopyrine and 13C-galactose breath tests.

This study was conducted to evaluate in vivo the hepatotoxic effects of CCl4 administration to rats using 13C breath tests: aminopyrine breath test (ABT) was used to monitor CCl4-induced cytochrome P450 inactivation, and galactose breath test (GBT) to quantitatively measure the CCl4-induced decrease of liver function. The ABT results showed profound aminopyrine demethylation inhibition lasting for three days and complete recovery at day 7, while GBT results were decreased only one day after CCl4. The protection induced by a first CCl4 dose against a second one paralleled cytochrome P450 inactivation: a second CCl4 dose given three days after the first one induced no GBT decrease and a mild increase of serum transaminase activities. On the other hand, the second dose administered 7 days after the first one produced a GBT decrease similar to the one observed after the first one. These results should be taken into consideration to determine the optimal CCl4 dosing schedule in the rat CCl4-induced cirrhosis model.

Alanine Transaminase↗

The neurofibromatosis type 2 gene is inactivated in schwannomas.

Schwannomas are tumors arising from schwann cells surrounding peripheral nerves. Although most schwannomas are sporadic, they are seen in approximately 90% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominantly inherited disease with an incidence of 1:40000 live births. The NF2 gene has recently been isolated on chromosome 22 and encodes a putative membrane organizing protein named schwannomin. It is believed to act as a tumor suppressor gene based on the high frequency of loss of heterozygosity (LOH) on this autosome in both sporadic and NF2 associated schwannomas and meningiomas and the identification of inactivating mutation in NF2 patients. In this study we examined 61 schwannomas including 48 sporadic schwannomas (46 of which are vestibular schwannomas) and 12 schwannomas obtained from NF2 patients, for mutations in 10 of the 16 coding exons of the NF2 gene. Twelve inactivating mutations were identified, 8 in sporadic tumours and 4 in tumors from people with NF2. These results support the hypothesis that loss of function of schwannomin is a frequent and fundamental event in the genesis of schwannomas.

Base Sequence↗

[13C-urea breath test for the diagnosis of Helicobacter pylori infection. Comparison with histology].

OBJECTIVE: This study was to evaluate the 13C-urea breath test for the diagnosis of Helicobacter pylori infection compared with pathological data of gastric antrum and fundus endoscopic biopsies. METHODS: In 95 patients, the results of the 13C-urea breath test were retrospectivally compared with histology (standard and Giemsa staining). RESULTS: Using a ROC curve, the best cut-off value for the 13C-urea breath test was determined at + 3 delta 0/00 of breath isotopic enrichment. Compared with histology, the diagnostic values of the 13C-urea breath test were: sensibility 90.3%, specificity 97%, positive predictive value 98.2%, negative predictive value 84%. The false negative results of the breath test (6 out of 95) were obtained in patients with few H. pylori present in antral biopsies, or in patients under omeprazole therapy. The urea breath test was well correlated with the inflammation of the gastric mucosa (P < 0.0001). The isotopic enrichment in breath was well correlated to the number of H. pylori estimated by histological analysis (P < 0.05). CONCLUSIONS: The 13C-urea breath test is a non invasive and non radioactive diagnostic tool for H. pylori infection. Its excellent positive predictive value and its good negative predictive value guarantee its usefulness in clinical practice, especially for the control of eradication after anti-H. pylori therapy.

Biopsy↗

Natural history and patterns of current practice in heart failure. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

A total of 6,273 consecutive relatively unselected patients with heart failure or left ventricular dysfunction, or both (mean age 62 +/- 12 years, mean ejection fraction 31 +/- 9%), were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry over a period of 14 months. All patients were followed up for vital status and hospital admissions at 1 year. Ischemic heart disease was the underlying cause of failure or dysfunction in approximately 70% of patients, whereas hypertensive heart disease was considered to be primarily involved in only 7%. There were striking differences in the etiology of heart failure among blacks and whites: 73% of whites had an ischemic etiology of failure versus only 36% of blacks; 32% of blacks had a hypertensive condition versus only 4% of whites. The total 1-year mortality rate was 18%; 19% of patients had hospital admissions for heart failure and 27% either died or had a hospital admission for congestive heart failure during the 1st year of follow-up. Factors related to 1-year mortality or hospital admission for congestive heart failure included age, ejection fraction, diabetes mellitus, atrial fibrillation and female gender. There was no difference in mortality associated with congestive heart failure among blacks and whites, but hospital admissions for heart failure were more frequent in blacks. Digitalis and diuretic agents were the drugs most often used in these patients, who were often taking many medications in relation to severity of congestive heart failure symptoms and ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗

Clinical characteristics of patients in studies of left ventricular dysfunction (SOLVD).

The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the effects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less than or equal to 0.35 and symptoms of congestive heart failure (CHF) were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treatment directed for LV dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p less than 0.001). In the prevention trial, infarction was recent (less than or equal to 6 months) in 27% patients and remote (greater than 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p less than 0.001) and non-Caucasians (20 vs 14%; p less than 0.001), as well as the coexisting risk factors of hypertension (42 vs 37%; p less than 0.001) and diabetes (26 vs 15%; p less than 0.001) than did prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery bypass surgery was performed less often in women and non-Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Localization of peptidases in lactococci.

The localization of two aminopeptidases, an X-prolyl-dipeptidyl aminopeptidase, an endopeptidase, and a tripeptidase in Lactococcus lactis was studied. Polyclonal antibodies raised against each purified peptidase are specific and do not cross-react with other peptidases. Experiments were performed by immunoblotting after cell fractionation and by electron microscopy of immunogold-labeled peptidases. All peptidases were found to be intracellular. However, immunogold studies showed a peripheral labeling of the X-prolyl-dipeptidyl aminopeptidase, the tripeptidase, and the endopeptidase. This peripheral location was further supported by the detection of these three enzymes in cell membrane fractions in which none of the two aminopeptidases was present.

Journal Article↗

Comparative Study of 35 Bacteriophages of Lactobacillus helveticus: Morphology and Host Range.

This survey included 23 phages isolated from cheese whey and 12 temperate phages induced with mitomycin from their lysogenic host strains. All of the phages had an isometric head and a tail with a contractile sheath. In addition, short-tailed (160-nm-long) and long-tailed (260-nm-long) phages were distinguished. Short-tailed phages were by far the most widespread in French cheese factories (32 of the 35 phages studied). The study of phage relationships enabled two large groups of strains to be distinguished: those not or slightly sensitive to phages and those very sensitive to phages. There was an obvious relationship in the first group between phage sensitivity (or resistance) and the geographic origin of the strains. The second group contained primarily strains from large international collections and those isolated from commercial starters. The relationships among short-tailed phages, either temperate or isolated as lytic, suggest that lysogenic strains could be the major source of phages in French cheese factories.

Journal Article↗

Ureaplasma in semen and IVF.

Ureaplasma urealyticum (U.U.) screening has been systematically performed in tests carried out before IVF cycles. In 42% of the cases (306 couples), at least one partner presented a monomicrobian U.U. infection. U.U. infection of at least one fraction of the split ejaculate was observed in 32% of the cases and found in similar proportions at the prostatic and seminal vesicle levels. The U.U.-infected group presented a similar number of cytological abnormalities to the noninfected samples. However, there was a significant reduction in the pregnancy rate after embryo transfer in the infected group whereas U.U. did not alter fertilization parameters, embryo retrieval or pregnancy rates per puncture. The preliminary results of a complementary prospective study (70 couples) point to the likely role of sexually transmitted Ureaplasma at the endometrial level.

Adult↗

The murG gene of Escherichia coli codes for the UDP-N-acetylglucosamine: N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis.

Physiological properties of the murG gene product of Escherichia coli were investigated. The inactivation of the murG gene rapidly inhibits peptidoglycan synthesis in exponentially growing cells. As a result, various alterations of cell shape are observed, and cell lysis finally occurs when the peptidoglycan content is 40% lower than that of normally growing cells. Analysis of the pools of peptidoglycan precursors reveals the concomitant accumulation of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) and, to a lesser extent, that of undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide (lipid intermediate I), indicating that inhibition of peptidoglycan synthesis occurs after formation of the cytoplasmic precursors. The relative depletion of the second lipid intermediate, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)GlcNAc, shows that inactivation of the murG gene product does not prevent the formation of lipid intermediate I but inhibits the next reaction in which GlcNAc is transferred to lipid intermediate I. In vitro assays for phospho-MurNAc-pentapeptide translocase and N-acetylglucosaminyl transferase activities finally confirm the identification of the murG gene product as the transferase that catalyzes the conversion of lipid intermediate I to lipid intermediate II in the peptidoglycan synthesis pathway. Plasmids allowing for a high overproduction of the transferase and the determination of its N-terminal amino acid sequence were constructed. In cell fractionation experiments, the transferase is essentially associated with membranes when it is recovered.

Amino Acid Sequence↗

[Seroepidemiologic data on anisakiasis. Prophylactic consequences for fish products].

The Western blotting method allowed us to confirm the diagnosis in 7 cases of acute anisakiasis, to assess it in 5 cases of chronic anisakiasis, and to follow up the evolution. These chronic frames according to the question of their long term evolution, and the part played by Anisakis simplex in fish nutritional allergy increase the negative score of that parasite. This situation should lead to discuss preventive rules.

Acute Disease↗

[Seroepidemiological data on anisakiasis: prophylactic consequences in fish products].

The Western blotting method allowed us to confirm the diagnosis in 7 cases of acute anisakiasis, to assess it in 5 cases of chronic anisakiasis, and to follow up the evolution. These chronic frames according to the question of their long term evolution, and the part played by Anisakis simplex in fish nutritional allergy increase the negative score of that parasite. This situation should leave to discuss preventive rules.

Acute Disease↗