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Biomedical subjects

M Renaud

Publications and source records attributed to M Renaud.

At least 19 recordsLinked to original sources
PubMed2001

The 'biodrug' concept: an innovative approach to therapy.

Cell engineering technology using recombinant microorganisms has created new opportunities in the development of innovative drugs. This article presents the use of living genetically engineered microorganisms, such as bacteria or yeasts, as a new delivery vehicle to the gastrointestinal tract. This 'biodrug' concept was demonstrated using recombinant Saccharomyces cerevisiae expressing the plant cytochrome P450 73A1. This enzyme provides a relevant model for potential therapeutic applications, such as 'biodetoxication' in the digestive environment. An artificial gastrointestinal tract simulating human digestion was chosen as a powerful tool to validate the biodrug concept. This approach offers a novel strategy for drug discovery and testing.

Artificial Organs↗
PubMed2000

Dynamic in vivo (31)P nuclear magnetic resonance study of Saccharomyces cerevisiae in glucose-limited chemostat culture during the aerobic-anaerobic shift.

The purpose of this work was to analyse in vivo the influence of sudden oxygen depletion on Saccharomyces cerevisiae, grown in glucose-limited chemostat culture, using a recently developed cyclone reactor coupled with (31)P NMR spectroscopy. Before, during and after the transition, intracellular and extracellular phosphorylated metabolites as well as the pHs in the different cellular compartments were monitored with a time resolution of 2.5 min. The employed integrated NMR bioreactor system allowed the defined glucose-limited continuous cultivation of yeast at a density of 75 g DW/l and a p(O(2)) of 30% air saturation. A purely oxidative metabolism was maintained at all times. In vivo (31)P NMR spectra obtained were of excellent quality and even allowed the detection of phosphoenolpyruvate (PEP). During the switch from aerobic to anaerobic conditions, a rapid, significant decrease of intracellular ATP and PEP levels was observed and the cytoplasmic pH decreased from 7.5 to 6.8. This change, which was accompanied by a transient influx of extracellular inorganic phosphate (P(i)), appeared to correlate linearly with the decrease of the ATP concentration, suggesting that the cause of the partial collapse of the plasma membrane pH gradient was a reduced availability of ATP. The complete phosphorous balance established from our measurement data showed that polyphosphate was not the source of the increased intracellular P(i). The derived intracellular P(i), ATP and ADP concentration data confirmed that the glycolytic flux at the level of glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and enolase enzymes is mainly controlled by thermodynamic constraints.

Adenosine Diphosphate↗
PubMed1999

Determinants of paradoxical CD4 cell reconstitution after protease inhibitor-containing antiretroviral regimen.

OBJECTIVES: We evaluated the parameters influencing CD4 cell reconstitution after the introduction of highly active antiretroviral therapies in real life, as well as the frequency and the determinants of the discrepancies occurring between virus and CD4 cell count evolution. DESIGN AND METHODS: A total of 317 pre-treated patients starting a protease inhibitor (PI)-containing regimen were prospectively followed for 2 years on an intent-to-treat basis for CD4 cell counts and viral loads. RESULTS: The CD4 cell counts rapidly increased from baseline (50/mm3) by a median of 50/mm3 at month 2 (+0.72 CD4 cells/mm3/day) and up to 137/mm3 at the last follow-up (second slope: +0.16 CD4 cells/mm3/day). Two independent major factors among five parameters tested significantly affected the first phase, which was negatively correlated to the slope of CD4 cell decline before PI initiation, and was positively correlated to baseline CD4 cell counts (P = 0.0001); the second phase was mostly affected by the mean viral load reduction over time (P = 0.0001). Paradoxical CD4 cell reconstitution (15% of cases) was defined by a rapid or slow CD4 cell increase contrasting with a minor or strong viral reduction, respectively. The role of previous CD4 cell decline and the low effect of viral load reduction during the first 2 months explain the early paradoxical CD4 cell responses. The major influence of viral load reduction on the long-term reconstitution, however, reduces such paradoxical responses at 2 years. CONCLUSIONS: Early paradoxical CD4 cell reconstitution after the introduction of a PI are explained by the major influence of previous disease progression on the early CD4 cell increase, whereas the magnitude of viral load reduction over time reduces such paradoxical evolutions in the long term.

Adult↗
PubMed1999

[Immunologic reconstruction after antiretroviral treatment].

DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection.

Antiviral Agents↗
PubMed1999

Restoration of the immune system with anti-retroviral therapy.

Clinical benefits of highly active anti-retroviral treatments (HAART) are increasingly evidenced by resolving opportunistic infections and malignancies, as well as declining hospitalization and mortality rates [1]. This suggests that potent and sustained suppression of viral replication, at least to some extent, is associated with reconstitution of the immune system even in adult patients treated at advanced stages of the disease. Increased susceptibility to opportunistic infections and tumors mainly results from the loss of memory CD4+ T cell reactivity against recall antigens which is an early event in HIV disease progression. Primary responses of naive CD4+ T cells against new pathogens are suppressed even earlier in the course of HIV disease, and the progressive depletion in naive CD4+ T cells reflects profound alterations in T cell regeneration capacities. Previous studies revealed that monotherapy with ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+ T cell responses to recall Ags only when detectable prior to onset of therapy, suggesting that the loss of CD4+ T cell reactivity might be irreversible at advanced stages of the disease [2]. In contrast our group demonstrated more recently that restoration in CD4+ T cell reactivity to specific antigens was feasible when HAART was administered in progressors [3]. Here we address some of the questions raised by immune restoration with HAART when administered at advanced stages of the disease.

Adult↗
PubMed1999

[Antiretroviral therapy and immune reconstitution].

The course of the HIV infection has been dramatically modified since the introduction of highly active antiretroviral therapy (HAART) combining inhibitors of the HIV-1 reverse transcriptase and protease. Despite some controversies about the extent to which the immune system can normalize, it is generally admitted nowadays that a numerical and functional CD4 cell profile more akin to asymptomatic HIV-infected individuals can be restored in AIDS patients and can confer host protection against opportunistic events. The best hallmark of such immune restoration is the massive decline in the mortality and morbidity related to AIDS that have been registered in all industrialized countries. These changes involve a recirculation of mature peripheral T cells, a regeneration of naive T cells from thymic origin and a restoration of memory CD4 T cell réactivities. Although these recent advances warrant increased optimism, HAART by reducing the virus burden is unable to restore immunity against HIV itself, except when introduced at the very early stage after virus inoculation. The single condition required for immune reconstitution is an efficient and durable inhibition of virus replication. These positive effects can be obtained at late stages of the disease even when the patients have been heavily pre-treated. They also demonstrate that HIV does not definitively alter the lymphoid tissues nor the immune defenses, even aller years of infection and severe immune suppression, except for HIV-specific CD4 T helper cells.

CD4 Lymphocyte Count↗
PubMed1997

A rapid and reliable method for metabolite extraction in yeast using boiling buffered ethanol.

A simple and reliable method for the efficient inactivation of metabolism and for quantitative metabolite extraction from yeast cells is presented. It is based on the use of a boiling solution made of 75% ethanol (volume/final volume) buffered with 70 mM-Hepes (final concentration), pH 7.5, to guarantee the stability throughout the whole procedure of a large variety of metabolites, including all glycolytic intermediates, nucleotides, pyridine nucleotides and organic acids compounds. The extraction is fast, requiring only 3 min incubation of yeast cells in the ethanol-buffered mixture maintained at 80 degrees C. It can be carried out either directly by spraying the cells into the boiling mixture, or after quenching the whole culture in 60% methanol kept at -40 degrees C. Extracts are subsequently concentrated by evaporation under partial vacuum and the residue is resuspended in a small volume of water. This concentration step and the use of a highly sensitive analytical method allow us to quantify metabolites in less than 10 mg dry weight cells. This method, which can be applied to other fungi, could be very helpful for the determination of true metabolites in mutants generated through the EUROFAN programme and for metabolic flux analysis.

Buffers↗
PubMed1997

Female and male physicians' attitudes toward prenatal diagnosis: a Pan-Canadian survey.

Despite widespread use over the past 20 years, prenatal diagnosis (PND) remains a controversial technique because of the moral and organizational dilemmas that it raises in many countries. In order to assess attitudes to PND within the Canadian medical profession, a survey was carried out involving over 3000 physicians offering PND (general practitioners, obstetricians, pediatricians, and radiologists). Several scales were developed to measure (1) physicians' willingness to broaden access to PND, (2) acceptability of abortion when a fetal anomaly is diagnosed, and (3) physicians' directiveness in regard to abortion. This article discusses results concerning the attitudes and opinions of male and female physicians toward prenatal diagnosis, which differed on the three scales. Female physicians are more liberal than their male colleagues with regard to access to amniocentesis and selective abortion and have a less directive relationship with their patients. These tendencies are similar to those observed in prior studies. They are particularly marked for general practitioners and radiologists. Various explanatory hypotheses are examined.

Abortion, Eugenic↗
PubMed1996

[Androgens and feminine behavior].

Our actual knowledges of the relationships between androgens and various aspects of the female behaviour are coming from experimental studies performed in various animal species or from observations performed in the woman in situations such as puberty, menstrual cycle, menopause, congenital hyperplasia of the adrenal, polycystics ovaries clearly rising up testosterone levels. The role of androgens in the sexual differentiation, as well as in sexual, aggressive, artistic and cognitive behaviour is investigated in the present work. However, animal data must be modulated in view of specific psychosocial factors in the woman.

Androgens↗
PubMed1995

Androgens inhibit the proliferation of a variant of the human prostate cancer cell line LNCaP.

UNLABELLED: The paradoxical androgen response of R2, a subline of the human prostate cancer cell line LNCaP, is described here. Two androgens (DHT and R1881) decreased, in a dose-dependent manner, R2 cell proliferation and [3H]thymidine incorporation. These ligand and cell specific effects were accompanied by an increase in the metabolism of the vital dye MTT and in cell protein content. Both androgens increased the doubling time and the percentage of G0-G1 cells. No evidence of androgen-induced apoptosis was found. Cloning allowed the selection of two cell populations on the basis of the response to 10 nM of R1881. Long term culture of uncloned R2 cells with R1881 modified reversibly the pattern of androgen response. R2 was compared to the androgen-stimulated LNCaP-FGC subline to investigate the causes of their different androgen responsiveness. The androgen receptor (number, affinity for hormones and antihormones, sedimentation constant and molecular weight) and androgen receptor genes (exon size and exon 8 sequence) were found to be identical in the two sublines. EGF stimulated LNCaP-FGC but not R2. Both cells were slightly stimulated by basic FGF but were insensitive to IGF-I and TGF beta 1. IN CONCLUSION: (1) androgens inhibit the proliferation of R2 cells possibly by introducing a G0-G1 block; (2) this inhibition is incomplete because, at least in part, the R2 cell population is heterogeneous; (3) chronic androgen treatment induces reversible cell adaptation; and (4) there is no evidence that the loss of the classical stimulatory effect of androgen on cell proliferation and the gain of inhibitory effect are due to androgen receptor alteration or to a specific action of one of the four growth factors tested.

Amino Acid Sequence↗
PubMed1995

Selective abortion: a new moral order? Consensus and debate in the medical community.

The authors discuss the results of a survey of the attitudes of Canadian and French (Picardie, Nord-Pas de Calais) physicians toward selective abortion of fetal anomalies detected by ultrasound, amniocentesis, or chorionic villus sampling. The study documents the threshold of acceptability of abortion of fetuses with selected anomalies, as well as the physicians' own perceptions of their role in the decision to abort. While there was no consensus among all Canadian physicians regarding the acceptability of abortion, more than 55 percent from France and Quebec would accept selective abortion of a fetus affected with trisomy 21, Duchenne muscular dystrophy, cystic fibrosis, Huntington's chorea, or spina bifida. In the province of Quebec, Anglophone physicians showed a greater acceptance of abortion than did their French-speaking colleagues. In reference to the physician's role in the decision to abort, French physicians are more directive than North American physicians. Cultural predispositions may explain these differences in attitudes.

Abortion, Eugenic↗
PubMed1993

Is selective abortion for a genetic disease an issue for the medical profession? A comparative study of Quebec and France.

This article discusses the results of a study of the stand and attitudes of physicians from the Picardie, Nord-Pas-de-Calais region in France and the province of Quebec (Canada) regarding abortion following the diagnosis of a fetal anomaly by ultrasound, amniocentesis, or chorionic villus sampling. The study examined the degree of acceptability of abortion for several specific conditions as well as the physicians' perceptions of their role in the women's decision to abort. The study shows a consensus (over 75 per cent of the physicians surveyed) for aborting a fetus with trisomy 21. There is a similar consensus, except among Francophones in Quebec, for muscular dystrophy, cystic fibrosis, and Huntington disease. Conversely, there is no consensus (below 60 per cent) for several anomalies. In these cases, Quebec Anglophone physicians find abortion more acceptable than Quebec Francophone or French physicians. Concerning the role of the practitioners in the decision to abort, physicians in France tend to be much more directive than their overseas colleagues. Several hypotheses are suggested to explain the difference between the three groups surveyed.

Abortion, Therapeutic↗
PubMed1992

Synthesis and characterization by 1H and 13C nuclear magnetic resonance spectroscopy of 17 alpha-hexanoic derivatives of 5 alpha-dihydrotestosterone and testosterone.

The synthesis and characterization of 17 alpha-(6'-hexanoic acid) derivatives of 5 alpha-dihydrotestosterone and testosterone, useful as ligands for affinity chromatography purification or as precursors for affinity-labeling of androgen-binding proteins, is described. Alkynylation of 3-ethylenedioxy-, 3 beta-hydroxy-, and 3 beta,5-dihydroxy-5 alpha-androstan-17-one precursors with the potassium derivative of 5-hexyn-1-ol led to the corresponding 17 alpha-(6'-hydroxyhex-1'-ynyl) derivatives, which were hydrogenated over 10% Pt-C catalyst to give 17 alpha-(6'-hydroxyhexyl) derivatives. Chromic acid oxidation of the primary hydroxy group of the 3-ethylenedioxy-17-hexyl intermediate into carboxylic acid followed by acid cleavage of the 3-ketal group gave 17 alpha-(5'-carboxypentyl)-5 alpha-dihydrotestosterone, which was also obtained directly by chromic acid oxidation of the 3 beta-hydroxy intermediate. Chromic acid oxidation of the primary hydroxy group of the 3 beta,5 alpha-dihydroxy precursor resulted in a 5 alpha-hydroxy-3-oxo intermediate, which was dehydrated to give 17 alpha-(5'-carboxypentyl)testosterone. The 17 alpha configuration of these derivatives and of synthetic precursors was established by comparing their molecular rotations and their 1H and 13C nuclear magnetic resonance (NMR) spectra including solvent effects, with data reported for 17 alpha- or 17 beta-substituted steroid analogs as well as with 1H and 13C NMR reference data recorded in this work for 17 alpha-ethynyltestosterone, 17 alpha-ethynyl-19-nortestosterone, 17 alpha-ethyl-19-nortestosterone, 17 alpha-methyltestosterone, and 17 alpha-methyl-5 alpha-dihydrotestosterone.

Caproates↗
PubMed1992

Cloning and nucleotide sequence of the csp1 gene encoding PS1, one of the two major secreted proteins of Corynebacterium glutamicum: the deduced N-terminal region of PS1 is similar to the Mycobacterium antigen 85 complex.

Two proteins, PS1 and PS2, were detected in the culture medium of Corynebacterium glutamicum and are the major proteins secreted by this bacterium. No enzymatic activity was identified for either of the two proteins. Immunologically cross-reacting proteins were found in a variety of C. glutamicum strains but not in the coryneform Arthrobacter aureus. The gene encoding PS1, csp1, was cloned in lambda gt11 using polyclonal antibodies raised against PS1 to screen for producing clones. The csp1 gene was expressed in Escherichia coli, presumably from its own promoter, and directed the synthesis of two proteins recognized by anti-PS1 antibodies. The major protein band, of lower M(r), was detected in the periplasmic fraction. It had the same M(r) as the PS1 protein band detected in the supernatant of C. glutamicum cultures and presumably corresponds to the mature form of PS1. The minor protein band appears to be the precursor form of PS1. The nucleotide sequence of the csp1 gene was determined and contained an open reading frame encoding a polypeptide with a calculated molecular weight of 70,874, with a putative signal peptide with a molecular weight of 4411. This is consistent with the M(r) determined for PS1 from C. glutamicum culture supernatant and E. coli whole-cell extracts. The NH2-half of the deduced amino acid is similar (about 33% identical residues and 52% including similar residues) to the secreted antigen 85 protein complex of Mycobacterium. The csp1 gene in C. glutamicum was disrupted without any apparent effect on growth or viability.

Amino Acid Sequence↗
PubMed1992

Burden of care of families not living with young schizophrenic relatives.

A program that provides comprehensive support services to young schizophrenic adults and their families in Montreal was evaluated after one year to assess the needs of families, especially single-parent families, after the young adult patient left home. Results of the evaluation, which employed a case-control design, showed that compared with families receiving the usual services, families in the program reported feeling less burdened by the patients' personal problems. They also received more services and had more contact with professionals. Patients living away from home spent more than 18 hours a week in face-to-face contact with their families. Single parents of mentally ill young adults spent much less time with their offspring and expressed more need for services and a greater burden of care than married parents.

Activities of Daily Living↗