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Biomedical subjects

M Renaud

Publications and source records attributed to M Renaud.

At least 19 recordsLinked to original sources

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

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

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

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

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

[A new approach for transfusion of neocytes: the Neocel system].

Young red cells (neocytes) were prepared in a double transfer pack having a long, narrow separation bag that allows for a density gradient column to be established during centrifugation. The lighter fraction of red cells (neocyte fraction) was then expressed into a second delivery bag. Phthalate ester density distribution curves showed that 87.1% of the neocyte units had greater than 85% enrichment, i.e. more than 85% of the cells had densities lower than the midpoint density of the original red cell unit, thalassemic patients receiving neocytes had an average decrease of 21.1% in red cells per kg/yr as compared to their frozen red cell requirement, and an average of 6.9% fewer transfusions.

Blood Transfusion

Proton and carbon-13 nuclear magnetic resonance spectroscopy of diastereoisomeric 3- and 17 beta-tetrahydropyranyl ether derivatives of estrone and estradiol.

Protection of 3- and 17 beta-hydroxyl groups of estrone and estradiol as tetrahydropyranyl ether derivatives led to mixtures of 2'(R)- and 2'(S)-diastereoisomers which were separated by crystallization (3-tetrahydropyranyl ethers), or by thin-layer chromatography (17-tetrahydropyranyl ethers), and characterized by 1H and 13C nuclear magnetic resonance (NMR). Assignments for NMR signals of estradiol 3,17 beta-ditetrahydropyranyl ether were facilitated by comparison with those of its 15 zeta, 16 zeta-dideuterio analog and by 2D 1H-13C heteroshift correlation experiments. Diastereoisomers of 3-tetrahydropyranyl ether derivatives could be identified through the 13C NMR doublet signals of the anomeric C-2' and the aromatic C-4 carbon atoms in CDCl3. Diastereoisomers of 17-tetrahydropyranyl ether derivatives were recognized from characteristic modifications of 1H NMR signals of H-2', H-6', H-1, H-17, and 18-CH3 protons as well as from the 13C NMR doublet signals corresponding to C-2', C-4', C-6', C-12, C-13, C-16, and C-17 carbon atoms. Low-temperature experiments showed a splitting of the C-2', C-6', and C-17 13C NMR signals of each of the two 17-tetrahydropyranyl ether isomers. The downfield signal (equatorial conformer) of the three resulting doublets was more intense for the 17-tetrahydropyranyl ether 2'(S)-isomer, whereas the upfield signal (axial conformer) was more intense for the 2'(R)-isomer.

Carbon Isotopes

Mitochondrial development during Drosophila oogenesis: distribution, density and in situ RNA hybridizations.

The changes in distribution and density of mitochondria and the level of mitochondrial RNA during Drosophila oogenesis were studied simultaneously in the 3 cell types ie follicle cells, nurse cells and oocyte, making up the egg chamber. Up to stage 6, mitochondrial density (mitochondrial and cellular areas ratio) was elevated and increased similarly in both follicle and nurse cells. Thereafter the mitochondrial density of follicle cells continued to increase and that of the nurse cells declined markedly while the nurse cell mitochondria assembled in dense groups and decreased in size. This can be related to a transfer of nurse cell cytoplasm, including mitochondria, to the oocyte. In the oocyte from stage 4 to stage 7 we observed a significant decrease of the mitochondrial density due to the absence of mitochondrial biogenesis. Then the cytoplasm transfer caused mitochondrial density to increase up to the level found in the nurse cells at the end of oogenesis. The mature oocyte contains enough mitochondria to supply 15,000 somatic cells. Our results strongly suggest that the variations in size, distribution and density of mitochondria relate to the particular energetic requirements of the different cell types during the first half of oogenesis. Later they relate to the developmental requirements of the nurse cells and the oocyte, in particular the storage of mitochondria in the oocyte. The level of mitochondrial RNA was studied through in situ hybridization. Throughout oogenesis the follicle and nurse cell RNA evolved similarly. Up to stage 9, there was no change in RNA densities in these cells, suggesting a correlation with the cell volume and/or the nuclear DNA content. Thereafter the cellular RNA concentration declined rapidly. In the oocyte the RNA concentration evolved differently especially from stage 10 to the end, the RNA density being stabilized. This can be related to the injection of nurse cell mitochondria, followed by their assignment to reserve status. Our results suggest that the mt RNA density is under extramitochondrial control mechanisms.

Animals

Expression of six mitochondrial genes during Drosophila oogenesis: analysis by in situ hybridization.

We have done a comparative analysis of RNA from six mitochondrial genes (rDNA, ND2, COI, COIII, ND4-ND5, Cyt b) during Drosophila oogenesis, using in situ hybridization. This study showed the same variation for each of these transcripts, which is similar to that obtained with the total mitochondrial RNA (Tourmente et al. (1990) Biol. Cell 60, 119-127). A constant RNA density until stage 9, followed by a rapid decline, was observed in follicle and nurse cells. These results confirm those previously obtained (Tourmente et al., (1990) Biol. Cell 60, 119-127), in favor of the existence of a correlation between the mtRNA level and the cell volume and/or the nuclear DNA content, and suggest a global extra-mitochondrial, transcriptional control mechanism. We also show that the relative proportions of the different RNA are similar, whatever the stage and cell type examined, even though the total mtRNA quantity is different. They are comparable to those previously obtained by Northern analysis of Drosophila embryos (Berthier et al. (1986) Nucleic Acids Res. 14, 1400-1412, suggesting a posttranscriptional control independent of the cell type. Surprisingly, we have detected an extra-mitochondrial hybridization for COIII, both in light and electron microscopy. Northern analysis of poly(A)+RNA from ovaries or cultured cells revealed an 1.7 kb extra-mitochondrial RNA, which is probably of nuclear origin.

Animals

Postcataract extraction ptosis: effect of the bridle suture.

Postcataract extraction ptosis is a common complication of cataract surgery. While many factors have been implicated in its etiology, trauma to the superior rectus/levator complex is considered the most important factor. We prospectively evaluated the effect of two superior rectus bridling techniques on the degree and severity of ptosis present three months after cataract surgery. All other potential variables were controlled for. Bridling the tendon of the superior rectus muscle using the direct, subconjunctival (open) approach results in significantly less severe ptosis than the standard technique of indirect transconjunctival (closed) bridling.

Adult

[Development of fetal semiology in North America].

A survey of the emergence of fetal semiology in the 17 editions of the Williams' Textbook of Obstetrics used by North-American medical students since 1900 was carried out. Three periods were identified: 1906-1950: the fetus, seen as a part of its mother, is ignored until birth and is of no interest to the obstetricians. From the fifties', the decrease in maternal mortality and progress in physiology and therapeutics permitted to study the fetus and a greater attention given to the care of the sick newborn. Since 1970, the availability of ultrasonography has contributed in making the fetus the second patient for obstetricians. It is now possible to study its growth, integrity, health, and well-being. Furthermore, the fetus is now accessible to establish a prenatal diagnosis.

Embryonic and Fetal Development

Characterization of rabbit lactate dehydrogenase-M and lactate dehydrogenase-H cDNAs. Control of lactate dehydrogenase expression in rabbit muscle.

Two cDNA clones were isolated, one corresponding to the mRNA coding for lactate dehydrogenase-M (LDH-M), the other to the mRNA coding for lactate dehydrogenase-H (LDH-H). The cDNA inserts consist of the entire open reading frame for LDH-M and a partial sequence, from amino acid 117 to 332, for LDH-H. Using these two clones as probes we demonstrate that: (a) the abundance of mRNA is muscle-type dependent; (b) the ratio M/H subunit for protein and mRNA is well related in the muscles studied; and (c) the M + H mRNA level is not relative to the total LDH activity.

Amino Acid Sequence

A new approach to neocyte transfusion: preliminary report.

A method has been developed using phthalate oils to quality control units of young red cells (neocytes). Neocytes prepared by the NEOCEL system have a mean young red cell enrichment of 90% with only 3.4% less than 80%. Neocytes prepared in a blood cell processor have an average enrichment of 81% with 27% less than 75%. Based on a 12 month period, the patients as a group have received an average of 14% fewer transfusions and an 18% decrease in red cells per kg/yr as compared to frozen red cells.

Blood Component Removal

The right to refuse in Québec: five-year evolution of a new mode of expressing risk.

In this article, the authors trace the outstanding stages in the institutionalization in Québec of the right to refuse, from its conception in 1978 to its application in more than 1200 cases (as of July 1985) since 1981. The major issue over the first five years of application has been the evolution of norms used as guidelines by inspectors in justifying or not justifying a refusal. The notions of danger and of normality of working conditions and personal conditions were widely debated and clarified. As a new mode of expressing risks for workers and a new mode of regulation for the state, the right to refuse has undergone a reduction in its scope through this process.

Accidents, Occupational

[From social epidemiology to the sociology of prevention: 15 years' research on the social etiology of disease].

Social epidemiology is this field of inquiry that regards the role of social and psychological factors in the aetiology of chronic diseases. In his examination of the evolution of the field, the author stresses the reconceptualization efforts that have been done in the 70's and that gave meaning to research on stress, traits or types of personalities and social support. In conclusion, this research tradition is viewed as perhaps overemphasizing the identification of risk factors while underemphasizing the explanation of the conditions under which good health is maintained.

Disease

RNA mapping on Drosophila mitochondrial DNA: precursors and template strands.

Drosophila melanogaster mitochondrial DNA (mtDNA) is closely related to the mammalian and amphibian mtDNA except for gene organization. In Drosophila, genes are distributed in clusters alternatively coded on each strand. Besides the eleven major foreseeable transcripts previously described (MERTEN and PARDUE, 1981, J. Mol. Biol., 153, 1-21), we have characterized two poly A+ transcripts, one major and one minor which could correspond respectively to the ND3 and ND6 reading frames, and 27 poly A+ minor transcripts (0.2 to greater than 3.2 kb) which are distributed along the mtDNA except in the rRNAs, ND 1 and A+ T rich regions. The mapping and length of 25 of these transcripts strongly suggest a precursor role. They would be processed at the level of tRNA or tRNA-like sequences. Most of them are transcribed from the template strand of each gene cluster and their distribution is in agreement with the hypothesis of several transcription origins and terminations located near the extremities of each gene cluster. Quantitatively our results show a large variation in each presumptive mature transcript compared to the other, even in a given gene cluster, suggesting a specific degradation of some of the mature transcripts.

Animals

Cross-blot and cross-dot system: a high-performance system for the detection of antigen-antibody complexes on nitrocellulose.

We present a reliable, simple, and quick system for screening antibody-antigen complexes on nitrocellulose. The apparatus necessary for this system is inexpensive and easy to use, and it can be adapted to blot or dot analysis without any modification. The number of antibody-antigen combinations that can be tested in one experiment ranges from 25 to 31 for blot analysis and from 345 to 600 for dot analysis. This system also offers numerous experimental advantages: it makes it possible to estimate with only one experiment the contribution of the different reaction stages to background noise and so allows unambiguous interpretation of the antibody-antigen reaction. Furthermore, this system can be used for any hybridization experiment on nitrocellulose.

Animals