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Biomedical subjects

M Picard

Publications and source records attributed to M Picard.

At least 73 records · Page 4Linked to original sources
PubMed1997

Mating types and sexual development in filamentous ascomycetes.

The progress made in the molecular characterization of the mating types in several filamentous ascomycetes has allowed us to better understand their role in sexual development and has brought to light interesting biological problems. The mating types of Neurospora crassa, Podospora anserina, and Cochliobolus heterostrophus consist of unrelated and unique sequences containing one or several genes with multiple functions, related to sexuality or not, such as vegetative incompatibility in N. crassa. The presence of putative DNA binding domains in the proteins encoded by the mating-type (mat) genes suggests that they may be transcriptional factors. The mat genes play a role in cell-cell recognition at fertilization, probably by activating the genes responsible for the hormonal signal whose occurrence was previously demonstrated by physiological experiments. They also control recognition between nuclei at a later stage, when reproductive nuclei of each mating type which have divided in the common cytoplasm pair within the ascogenous hyphae. How self is distinguished from nonself at the nuclear level is not known. The finding that homothallic species, able to mate in the absence of a partner, contain both mating types in the same haploid genome has raised more issues than it has resolved. The instability of the mating type, in particular in Sclerotinia trifolorium and Botrytinia fuckeliana, is also unexplained. This diversity of mating systems, still more apparent if the yeasts and the basidiomycetes are taken into account, clearly shows that no single species can serve as a universal mating-type model.

Amino Acid Sequence↗
PubMed1997

Pharmacokinetics and metabolism of the novel anticonvulsant agent N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) in rats and humans.

N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) belongs to a new series of experimental anticonvulsants related to lidocaine. This study was undertaken to understand the pharmacokinetics and metabolism of D2624 in rats and humans, with emphasis on the possible formation of 2,6-dimethylaniline (2,6-DMA). After oral administration of stable isotope-labeled parent drug to rats and GC/MS analysis of plasma samples, two metabolites were identified: D3017, which is the primary alcohol, and 2,6-DMA, formed by amide bond hydrolysis of either D2624 or D3017. In urine, three metabolites of D2624 were identified: namely D3017,2,6-DMA, and D3270 (which is the carboxylic acid derivative of D3017). Based on plasma AUC analysis, D3017 and 2,6-DMA accounted for > 90% of the dose of D2624. After oral administration, D2624 was found to be well absorbed (93%), but underwent extensive first-pass metabolism in the rat, thus resulting in 5.3% bioavailability. Rat and human liver microsomal preparations were capable of metabolizing D2624 to D3017 and 2,6-DMA. The formation of D3017 was NADPH-dependent, whereas 2,6-DMA formation was NADPH-independent and probably was catalyzed by amidase(s) enzymes. In a single-dose (25-225 mg) human volunteer study, the parent drug (D2624) was not detected in plasma at any dose, whereas 2,6-DMA was detected only at the two highest doses (150 and 225 mg). D3017 was detected after all doses of parent drug, with approximate dose proportionality in AUC and a half-life of 1.3-2.2 hr. The metabolic behavior observed in humans suggests there is a marked species difference in the oxidative and hydrolytic pathways of D2624.

Aniline Compounds↗
PubMed1997

Methodological validation and clinical usefulness of carbon-14-urea breath test for documentation of presence and eradication of Helicobacter pylori infection.

UNLABELLED: A simple [14C]urea breath test (C-14-UBT) was validated with aims of determining accuracy in documenting both the presence and proof of eradication of Helicobacter pylori infection. METHODS: Fifty-six dyspeptic patients had endoscopy with biopsies and C-14-UBT. Eleven biopsy-proven H. pylori-negative patients allowed C-14-UBT normal value determination. Forty-three patients with recurrent peptic ulcer disease and biopsy-proven H. pylori infection were included in an antimicrobial eradication protocol. Endoscopy with biopsies and C-14-UBT were done again 8 wk after initiation of treatment in 35 patients. For C-14-UBT, 185 kBq (5 microCi) of [14C]urea was swallowed. Breath samples obtained up to 20 min were counted to calculate AS20, [(% 14CO2 dose excreted/mmol of CO2) x kg] at 20 min. Combined histologic and microbiologic analyses of antral biopsies were used as a gold standard. RESULTS: The positivity value was set as AS20 > 0.33% (mean + 3 s.d. of AS20 in H. pylori-negative patients). Diagnosis of H. pylori infection was correct with C-14-UBT in 55/56 patients (44 true-positive, 11 true-negative and 1 false-negative; sensitivity = 98%; specificity = 100%). As a proof of eradication, C-14-UBT correctly classified 33/35 patients (5 true-positive, 28 true-negative and 2 false-positive; sensitivity = 100%; specificity = 93%). The C-14-UBT global performance yielded sensitivity, specificity and accuracy of 98%, 95% and 97%, respectively. A significant correlation (r = 0.84) was found between AS20 and the number of H. pylori colonies on culture. CONCLUSION: This C-14-UBT is highly accurate both for diagnosis and proof of eradication of H. pylori infection and reflects the antral bacterial load. It is simple, fast and inexpensive, and it is therefore suitable for clinical practice.

Breath Tests↗
PubMed1996

Cholecystokinin A receptor antagonist inhibits feed memory in Japanese quail.

Cholecystokinin (CCK) modulates learning and memory processes in mammals. The main objective of this work was to study the effect of two cholecystokinin receptor antagonists (CCKA antagonist devazepide and CCKB antagonist PD135158) on feed memory processes in Japanese quail. Memorization of colored food was measured by comparing the feeding behavior of 6- to 8-day-old quails during two successive sessions of 10 min after a 30-min fast in the test box, intersession interval: 24 h. The CCKA antagonist devazepide (0.1 mg/kg, b.wt) injected after the first session appears to disrupt feed memory formation. The CCKB antagonist PD135158 at the same dose induced a similar trend, but no significant effect on feed memorization could be measured. It is suggested that CCKA antagonist inhibits feed memory processes.

Animals↗
PubMed1996

Premature death in Podospora anserina: sporadic accumulation of the deleted mitochondrial genome, translational parameters and innocuity of the mating types.

The Podospora anserina premature death syndrome was described as early growth arrest caused by a site-specific deletion of the mitochondrial genome (mtDNA) and occurring in strains displaying the genotype AS1-4 mat-. The AS1-4 mutation lies in a gene encoding a cytosolic ribosomal protein, while mat- is one of the two forms (mat- and mat+) of the mating-type locus. Here we show that, depending on culture conditions, death due to the accumulation of the deleted mtDNA molecule can occur in the AS1-4 mat+ context and can be delayed in the AS1-4 mat- background. Furthermore, we show that premature death and the classical senescence process are mutually exclusive. Several approaches permit the identification of the mat-linked gene involved in the appearance of premature death. This gene, rmp, exhibits two natural alleles, rmp- linked to mat- and rmp+ linked to mat+. The first is probably functional while the second probably carries a nonsense mutation and is sporadically expressed through natural suppression. A model is proposed that emphasizes the roles played by the AS1-4 mutation, the rmp gene, and environmental conditions in the accumulation of the deleted mitochondrial genome characteristic of this syndrome.

Alleles↗
PubMed1996

Safety and efficacy of total parenteral nutrition delivered via a peripherally inserted central venous catheter.

Central venous catheters for total parenteral nutrition (TPN) have traditionally been inserted via direct cannulation of the subclavian vein, but this technique requires physician participation and is associated with well-described complications. We report the single largest institutional experience with peripherally inserted central venous catheters (PICC lines) used exclusively for TPN in non-intensive care unit patients. From July 1991 to March 1994, 135 PICC lines were placed in 126 patients via the antecubital vein, advanced into the central venous system, and used only for TPN. Complication rates were determined and compared with those for TPN administered through a subclavian vein-inserted central catheter. Patient demographics were similar in each group with respect to age, type of disease process, acuity of illness, and indications for nutrition support. A cumulative number of 1381 TPN days (mean = 11 days per patient) comprised the PICC line experience. Comparison was made with 135 successive standard (subclavian) central lines inserted in 105 patients for TPN administration (1056 TPN days, mean = 10 days per patient). There was no difference in the overall rate of complications between the two groups. There were no major complications that prolonged hospitalization (eg, catheter-related sepsis or pneumothorax) in the PICC group compared with three such complications in the standard group. PICC lines can be used safely and effectively for TPN and are associated with an acceptable rate of complications.

Adult↗
PubMed1995

A nonmammalian homolog of the PAF1 gene (Zellweger syndrome) discovered as a gene involved in caryogamy in the fungus Podospora anserina.

The car1 gene of the filamentous fungus Podospora anserina was cloned by complementation of a mutant defective for caryogamy (nuclear fusion), a process required for sexual sporulation. This gene encodes a protein that shows similarity to the mammalian PAF1 protein (Zellweger syndrome). Besides sequence similarity, the two proteins share a transmembrane domain and the same type of zinc finger motif. A combination of molecular, physiological, genetical, and ultrastructural approaches gave evidence that the P. anserina car1 protein is actually a peroxisomal protein. This study shows that peroxisomes are required at a specific stage of sexual development, at least in P. anserina, and that a functional homolog of the PAF1 gene is present in a lower eucaryote.

Amino Acid Sequence↗
PubMed1995

Long-term risk stratification with dipyridamole imaging.

This study was undertaken to assess the reliability of clinical parameters and dipyridamole-thallium 201 images for predicting the occurrence of future cardiac events (nonfatal myocardial infarction or cardiac death). Dipyridamole myocardial perfusion imaging is routinely performed in patients who have possible or known coronary disease and a low exercise tolerance. A total of 753 patients underwent clinical assessment and semiquantitative dipyridamole-201TI imaging and were followed up as outpatients. Patients who underwent coronary revascularization during the follow-up period were excluded from the study because the decision to intervene would have been based at least in part on the test itself. There were 82 cardiac events and 54 noncardiac deaths, and 11 patients were lost to follow-up after a mean follow-up of 15 months. With use of a quantitative index reflecting the amount of jeopardized myocardium, patients could be stratified by dipyridamole imaging into subsets with coronary morbidity and mortality rates ranging from 1% to 89%, (p = 0.0001). When clinical and scintigraphic variables were subjected to backward stepwise logistic regression analysis, the significant predictors of cardiac events were the jeopardized myocardium index by scintigraphy (p < 0.0001), left ventricular hypertrophy on the electrocardiogram (p = 0.0009), and transient dipyridamole-induced left ventricular cavitary dilatation (p = 0.0073). Quantitative dipyridamole-201TI imaging appears to be a powerful predictor of future cardiac events in patients with coronary disease and a low exercise tolerance and is a potentially useful contributor to risk-profile assessment and to the treatment of these patients.

Aged↗
PubMed1995

Altered mating-type identity in the fungus Podospora anserina leads to selfish nuclei, uniparental progeny, and haploid meiosis.

In wild-type crosses of the filamentous ascomycete Podospora anserina, after fertilization, only nuclei of opposite mating type can form dikaryons that undergo karyogamy and meiosis, producing biparental progeny. To determine the role played by the mating type in these steps, the four mat genes were mutagenized in vitro and introduced into a strain deleted for its mat locus. Genetic and cytological analyses of these mutant strain, crossed to each other and to wild type, showed that mating-type information is required for recognition of nuclear identity during the early steps of sexual reproduction. In crosses with strain carrying a mating-type mutation, two unusual developmental patterns were observed: monokaryotic cells, resulting in haploid meiosis, and uniparental dikaryotic cells providing, after karyogamy and meiosis, a uniparental progeny. Altered mating-type identity leads to selfish behavior of the mutant nucleus: it migrates alone or paired, ignoring its wild-type partner in all mutant x wild-type crosses. This behavior is nucleus-autonomous because, in the same cytoplasm, the wild-type nuclei form only biparental dikaryons. In P. anserina, mat genes are thus required to ensure a biparental dikaryotic state but appear dispensable for later stages, such as meiosis and sporulation.

Alleles↗
PubMed1995

Interactions between human bronchoalveolar macrophages and Blastomyces dermatitidis conidia: demonstration of fungicidal and fungistatic effects.

The effects of human bronchoalveolar macrophages (BAMs) on Blastomyces dermatitidis conidia were investigated. Macrophage monolayers were incubated for 5 days with or without interferon (IFN)-gamma or macrophage colony-stimulating factor (M-CSF) before challenge with conidia for 48 h at 37 degrees C. Hyphal growth (germination) was inhibited 12% by resident BAMs (P < .05). In contrast, resident BAMs blocked conidial phase transition by 88% (P < .05). Intermediate forms, aggregates of large cells in clums (not conidia or yeasts by morphologic criteria), appeared after incubation with BAMs and grew into typical yeasts once removed from the BAMs. IFN-gamma and M-CSF inhibited the ability of BAMs to block phase transition but not germination. Human BAMs demonstrated fungicidal and fungistatic activity against B. dermatitidis conidia independent of reactive oxygen intermediates and had greater effects on phase transition than on germination. The phase transition-associated fungicidal and fungistatic activities of BAMs were inhibited by IFN-gamma and M-CSF.

Blastomyces↗
PubMed1995

Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine.

BACKGROUND: Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. MATERIALS: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. RESULTS: The Pentasa tablet appeared completely dissolved in the stomach by 117 +/- 18 min. Samarium oxide was first detected in the small intestine 60 +/- 5 min after its ingestion; it reached the colon after 280 +/- 13 min and it was completely absent from the small intestine at 360 +/- 26 min. Plasma concentrations of 5-ASA started to rise after 67 +/- 7 min and were maximal at 222 +/- 25 min. CONCLUSION: In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect.

Adult↗
PubMed1995

Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B.

A study was performed to assess the in vivo relevance of the in vitro antagonism between fluconazole and amphotericin B against Candida albicans. Combinations of fluconazole and amphotericin B were explored for their efficacies against acute (100% mortality in 2 to 5 days) or less acute (100% mortality in 30 days) invasive candidiasis infections in mice with healthy immune systems and immunocompromised mice. Treatment efficacy was assessed by protection from mortality and/or a reduction in the fungal burden in tissue. In models of acute infection in mice with healthy immune systems or less acute infection in immunocompromised mice, combinations of fluconazole and amphotericin B were superior to fluconazole alone, and the effects were at least additive. Combination therapy was at least as efficacious as amphotericin B alone. In a different model of less acute infection in mice with healthy immune systems, combinations of fluconazole and amphotericin B showed no interactions and were no better than either drug alone. We conclude that combination therapy with fluconazole and amphotericin B is not antagonistic in vivo, in contrast to published in vitro studies, and, consequently, suggest that combination therapy should be considered in the management of clinical candidiasis.

Amphotericin B↗
PubMed1995

Treatment of murine pulmonary blastomycosis with SCH 51048, a broad-spectrum triazole antifungal agent.

The in vitro and in vivo activities of a new broad-spectrum triazole derivative, SCH 51048, against Blastomyces dermatitidis were evaluated. As determined by using the new National Committee for Clinical Laboratory Standards proposed standard for susceptibility testing of yeasts, SCH 51048 was the most active of the four agents tested in vitro against 13 strains of B. dermatitidis. In a well-described murine model of acute pulmonary blastomycosis, SCH 51048 was comparable to amphotericin B and at least 30 times more active than itraconazole. On the basis of these experiments, clinical evaluation of SCH 51048 for the use in treatment of human blastomycosis should proceed.

Animals↗
PubMed1995

Gastric emptying of solid food in edentulous patients.

Whether mastication of food by teeth is a physiological contributor in the process of nutrient digestion remains a debatable issue. In this study we sought to determine whether mastication could influence the gastric emptying of solid food. In 8 edentulous patients, we measured the gastric emptying of a test meal ingested with or without their dental prostheses. Clinical dental evaluation and Helkimo chewing test were first performed to verify that the mastication deficiency was adequately corrected by the dental prostheses. A mixed meal containing ten cubes (1.5 cm) of beef liver labeled with 99mTc and mixed in a chicken stew was ingested by the subjects and followed by gamma camera external scintigraphy. The gastric emptying rate of the 99mTc-labeled liver was similar whether the meal was ingested with the denture properly inserted, allowing normal mastication of the liver cubes, or whether the food was swallowed unmasticated in the absence of functional prostheses (Tlag = 60 +/- 5 vs. 58 +/- 11 min, p = NS; T1/2 = 73 +/- 21 vs. 55 +/- 10 min, p = NS; Tlag+T1/2 = 133 +/- 19 vs. 114 +/- 17 min, p = NS). These results show that gastric trituration and emptying of solid food was not facilitated by prior mastication.

Dentures↗
PubMed1994

Increased longevity of EF-1 alpha high-fidelity mutants in Podospora anserina.

Various translation initiation and elongation factors seem to participate in the control of the cellular proliferation and the ageing process in higher eukaryotes. Studies indicate that EF-1 alpha, one of the translation elongation factors, may be one of the major components involved. We here present the cloning of the filamentous fungus P. anserina EF-1 alpha encoding gene and show that strains bearing high fidelity mutations in the EF-1 alpha gene have a drastically increased longevity as well as an impairment in sporulation. This suggests that EF-1 alpha involved in the sexual and senescence processes in lower eukaryotes, through the control of translational errors.

Amino Acid Sequence↗
PubMed1994

Climatic adaptation of laying hens.

Three hundred Warren Isabrown female day old chicks were raised for 18 weeks in 3 distinct artificial climates described as temperate (20 degrees C, 60% RH), hot dry (32 degrees C, 40% RH) and hot humid (32 degrees C, 90% RH). At 18 weeks each group was divided into 3 and re-allocated to 3 similar air-conditioned laying rooms as during the growing period. Different diets were fed to the 3 groups up to 18 weeks. The energy needed in order to produce the same average live body weight at 18 weeks was similar in all the 3 climatic chambers. The effect of treatments in the growing period was not significantly different (P > 0.05) for most of the parameters subsequently measured during the laying period. The exception was the body weight gain between 18 and 38 weeks and the food and energy intakes. However, apart from the sexual maturity, all these parameters were negatively influenced (P < 0.05) by the effect of hot climates during the laying period irrespective of method of rearing. The results of this study seem to indicate that ambient temperature experienced during the first 18 weeks after hatching has little effect on subsequent productivity and that rearing birds at high ambient temperature does not acclimatise them to these conditions better than rearing them under temperate conditions.

Adaptation, Physiological↗