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Biomedical subjects

M Rousseau

Publications and source records attributed to M Rousseau.

At least 19 recordsLinked 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

[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

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

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

Surgical angioplasty of the left main coronary artery.

The conventional surgical treatment of isolated critical stenosis of the left main coronary artery restores a less physiologic perfusion of the myocardium, leads to occlusion of the left coronary ostium, and consumes an appreciable length of bypass material. Starting in June 1985, 23 surgical angioplasties have been performed in 22 patients. The left main stem was approached posteriorly in the first 11 patients, and an anterior approach was preferred in the last 12 because of better exposure. The onlay patch consisted of saphenous vein in the first 14 patients; pericardium was preferred in the last nine. The five failures occurred early. Four of these occurred in patients older than 60 years in whom calcifications of the left main stem had been seen on the preoperative angiogram. Eighteen procedures (78.3%) succeeded, but one patient (5.5%) died later of a massive air embolism. The 17 survivors are free of symptoms (maximal stress test combined with thallium scintigraphy) after a mean follow-up of 24.3 months. Angiographic restudy at an average of 8 months was obtained in 14 patients (82.3%) and revealed an excellent result in 13. In five patients, a late angiographic restudy (22 to 37 months) still revealed perfect patency of the left main stem. Provided that well-defined contraindications (calcifications, involvement of the distal bifurcation, older age) are respected, surgical angioplasty deserves a place in the array of surgical strategies.

Adult

Localization by hand-held gamma probe of tumor labeled with antibody "cocktail".

Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.

Adenocarcinoma

An assessment of prolonged reactivity of seven monoclonal antibodies against CX-1 tumor xenografts using a hand-held gamma-detecting probe.

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.

Adenocarcinoma

Sequential mammary grafting. Clinical, functional, and angiographic assessment 6 months postoperatively in 231 consecutive patients.

Between September 1985 and November 1987, 246 sequential mammary grafts were performed in 231 consecutive patients. Seventy-eight percent had triple vessel disease, and 33% required an urgent procedure. The length of the internal mammary artery pedicle was the only limitation to its use. No account was taken of the free cut-end flow of the internal mammary artery. There were 14 bilateral sequential mammary grafts and 15 free sequential mammary grafts. Of the 531 sequential mammary anastomoses, 482 were built with the left internal mammary artery; 113 (21%) were diamond-shaped anastomoses. The right internal mammary artery was brought through the transverse sinus in 44 cases, 10 times for sequential grafting of circumflex branches. Taking into account the adjunctive venous anastomoses and the single internal mammary artery anastomoses, there were 4.5 distal anastomoses per patient, 2.8 being mammary anastomoses and 2.3 being sequential mammary anastomoses. The hospital mortality rate was 2.6%. The prevalence of perioperative myocardial infarction was 5.2%. Follow-up was complete and averaged 15.4 months. Six patients (2.7%) still had angina pectoris. One hundred fifty-seven (71%) patients were recatheterized 6 months after the operation, and 95% of the sequential mammary anastomoses were still patent. The patency rate of the diamond-shaped mammary anastomoses was 94.5% and that of the anastomoses corresponding to the right internal mammary arteries brought through the transverse sinus was 94.3%. The gratifying functional results (maximal stress test combined with exercise thallium scintigraphy) obtained at an average of 6 months postoperatively illustrated the surprising physiologic adaptability of the internal mammary artery. As the attrition rate of the mammary artery grafts beyond 6 months postoperatively is thought to be minimal, gratifying long-term results with widespread use of sequential mammary grafts can be anticipated.

Adult

Bacteriophages of lactobacilli.

Lactobacilli are members of the bacterial flora of lactic starter cultures used to generate lactic acid fermentation in a number of animal or plant products used as human or animals foods. They can be affected by phage outbreaks, which can result in faulty and depreciated products. Two groups of phages specific of Lactobacillus casei have been thoroughly studied. 1. The first group is represented by phage PL-1. This phage behaves as lytic in its usual host L. casei ATCC 27092, but can lysogenize another strain, L. casei ATCC 334. Bacterial receptors of this phage are located in a cell-wall polysaccharide and rhamnose is the main component of the receptors. Ca2+ and adenosine triphosphate (ATP) are indispensable to ensure the injection of the phage DNA into the bacterial cell. The phage DNA is double-stranded, mostly linear, but with cohesive ends which enables it to be circularized. The vegetative growth of PL-1 proceeds according to the classical mode. Cell lysis is produced by an N-acetyl-muramidase at the end of vegetative growth. 2. The second group is represented by the temperate phage phi FSW of L. casei ATCC27139. It has been shown how virulent phages originate from this temperate phage in Japanese dairy plants. The lysogenic state of phi FSW can be altered either by point mutations or by the insertion of a mobile genetic element called ISL 1, which comes from the bacterial chromosome. This is the first transposable element that has been described in lactobacilli. Lysogeny appears to be widespread among lactobacilli since one study showed that 27% of 148 strains studied, representing 15 species, produced phage particles after induction by mitomycin C. Similarly, 23 out of 30 strains of Lactobacillus salivarius are lysogenic and produce, after induction by mitomycin C, temperate phages, killer particles, or defective phages. Temperate phages have also been found in 10 out of 105 strains of Lactobacillus bulgaricus or Lactobacillus lactis after induction by mitomycin C. Phages so far studied of the latter 2 and closely related lactobacilli, either temperate or isolated as lytic, may be divided into 4 unrelated groups called a, b, c and d. Most of these phages are found in group a and an unquestionable relationship has already been shown between lytic phages and temperate phages that belong to this group. Lytic phage LL-H of L. lactis LL 23, isolated in Finland, is one of the most representative of those of group a and has been extensively studied on the molecular level.

Bacteriophages