Showing papers by "French Institute of Health and Medical Research published in 1985"
TL;DR: The results suggest that excitatory amino acids stimulate inositol phosphate formation directly, rather than indirectly by the evoked release and subsequent actions of adenosine4 or acetylcholine5.
Abstract: The major excitatory amino acids, glutamate (Glu) and aspartate (Asp), are thought to act at three receptor subtypes in the mammalian central nervous system (CNS). These are termed quisqualate (QA), N-methyl-D-aspartate (NMDA) and kainate (KA) receptors according to the specific agonist properties of these compounds revealed by electrophysiological studies. Although Glu has been shown to stimulate cyclic GMP formation in brain slices, direct regulation of second messenger systems (cyclic AMP, Ca2+ or inositol phosphates) subsequent to activation of excitatory amino-acid receptors, has not been extensively studied. Here we demonstrate that in striatal neurones, excitatory amino acids, but not inhibitory or non-neuroactive amino acids, induce a three- to fourfold increase in inositol mono-, di- and triphosphate (IP, IP, IP) formation with the relative potency QA greater than Glu greater than NMDA, KA. The Glu-evoked formation of inositol phosphates appears to result principally from actions at QA as well as NMDA receptors on striatal neurones. Our results suggest that excitatory amino acids stimulate inositol phosphate formation directly, rather than indirectly by the evoked release and subsequent actions of adenosine or acetylcholine.
782 citations
TL;DR: There is a close phylogenetic relationship between the conserved reverse transcriptase and endonuclease/integrase domains of the visna and AIDS viruses and the inclusion of the AIDS virus in the retroviral subfamily Lentivirinae is supported.
557 citations
TL;DR: Survival was higher for 2-day-old embryos than for 3- day-old babies, and for 2, 4, and 8-cell embryos more than for intermediate-cleavage-stage embryos, and the average viability of all 2-Day-old frozen-thawed embryos can be estimated at 19%.
426 citations
TL;DR: It is observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
Abstract: Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and a low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
409 citations
TL;DR: This paper tries to justify the choice of the average reference for multichannel evoked potential recording, and shows that the integral of the potential distribution over a sphere including current dipoles is null.
394 citations
TL;DR: Evidence is presented that these peptides have different modes of relaxing cerebral blood vessels in the cat, and the responses to SP and acetylcholine were absent in arteries where the endothelium had been removed, whereas the relaxations induced by CGRP and VIP persisted.
362 citations
TL;DR: It has been demonstrated that sera with anti‐microsomal autoantibodies from patients presenting Graves' or Hashimoto's thyroiditis diseases were able to bind to purified TPO and to inhibit in a dose‐dependent manner the mAb binding to purifiedTPO, suggesting that TPO is the thyroid antigen termed to date the microsomal antigen.
360 citations
TL;DR: The 21-base pair repeat elements of the SV40 promoter contain six tandem copies of the GGGCGG hexanucleotide (GC-box), each of which can bind, with varying affinity, to the cellular transcription factor, Sp1.
Abstract: The 21-base pair repeat elements of the SV40 promoter contain six tandem copies of the GGGCGG hexanucleotide (GC-box), each of which can bind, with varying affinity, to the cellular transcription factor, Sp1. In vitro SV40 early RNA synthesis is mediated by interaction of Sp1 with GC-boxes I, II, and III, whereas transcription in the late direction is mediated by binding to GC-boxes III, V, and VI.
344 citations
TL;DR: The results show that the capacity of this subpopulation of HT‐29 cells to grow and differentiate in the absence of sugar is a stable characteristic, and suggest that glucose metabolism interferes with the program of differentiation of HT-29 cells.
Abstract: In order to study the effect of glucose on the differentiation of cultured human colon cancer cells, a subpopulation of HT-29 cells was selected for its capacity to grow in the total absence of sugar. These cells (Glc-cells) exhibit, after confluency, an enterocytic differentiation, in contrast to cells grown with glucose (Glc+ cells), which always remain undifferentiated. The differentiation is characterized by a polarization of the cell layer with apical brush borders and tight junctions, and by the presence of sucrase-isomaltase. The differentiation of Glc- cells is reversible: the addition of glucose to postconfluent cultures of Glc- cells results in an inhibiting effect on the expression of sucrase-isomaltase; switching growing cultures of Glc- cells to the Glc+ medium for several passages results in a progressive reversion to the undifferentiated state, which is completed after seven passages. The dedifferentiation process is associated with a parallel, passage-related, increase in the rates of glucose consumption and lactic acid production, and decreases of intracellular glycogen content, which return to the values of the undifferentiated original Glc+ cells. The values of these metabolic parameters are correlated, at each passage, with the degree of dedifferentiation of the cells. When these dedifferentiated cells, after having been cultured in Glc+ medium for 20 passages, are switched back to the Glc- medium, they readily grow without mortality, and reexpress the same enterocytic differentiation as the parent Glc- cells. These results show that the capacity of this subpopulation to grow and differentiate in the absence of sugar is a stable characteristic. They further suggest that glucose metabolism interferes with the program of differentiation of HT-29 cells.
334 citations
TL;DR: The study by in vivo voltammetry of the variations in the striatal extracellular dopamine concentrations shows that the release of dopamine is under the influence of both the frequency of impulse flow and of dopaminergic striatal autoreceptors.
329 citations
TL;DR: A marked heterogeneity in immunostaining was observed among cells of the same type in several tissues, suggesting that there could be large differences in the hormonal sensitivity of individual cells.
Abstract: Five monoclonal antibodies were used for the immunocytochemical study of mammalian progesterone receptor (PR) Initial studies were aimed at defining the optimal experimental conditions for the detection of the receptor, with special emphasis on techniques likely to be used in clinical determinations and in immunoelectron microscopic localization Specific immunoperoxidase staining was observed either in fixed, frozen sections or in sections of paraffin-embedded tissue The latter method allowed a better preservation of cellular structures Among the eight fixatives tested, glutaraldehyde, picric-acid formaldehyde, and paraformaldehyde proved satisfactory Both indirect immunoperoxidase and the indirect antibody peroxidase-antiperoxidase methods could be used In immature rabbits or castrated guinea pigs primed by estrogen, ie in conditions where its ligand was absent (or present in very low concentration), the PR was confined to the nucleus of immunoreactive cells This was the case for all the cell ty
TL;DR: It is reported here that the genetic locus DOCRI-917 defined by the cloned DNA probe is located on chromosome 7, which is among the most common inherited diseases in Caucasian populations.
Abstract: Although cystic fibrosis (CF) is among the most common inherited diseases in Caucasian populations, the basic biochemical defect is not yet known. CF is inherited as an autosomal recessive trait apparently due to mutations in a single gene, whence the efforts made to identify the genetic locus responsible by linkage studies. Two markers have recently been identified that are genetically linked to CF: one is a genetic variation in serum level of activity of the enzyme paraoxonase, and the other is a restriction fragment length polymorphism (RFLP) identified with a randomly isolated DNA probe. We report here that the genetic locus DOCRI-917 defined by the cloned DNA probe is located on chromosome 7.
TL;DR: Striatum exerts a facilitatory influence on TSD cells by releasing these neurons from the tonic inhibitory nigral influence, discussed in the light of the current knowledge on the involvement of basal ganglia in eye/head orienting movements.
TL;DR: Recombinant plasmid clone B74 containing a human single-copy DNA segment of 6 kilobases (kb) was localized by in situ hybridization on band p113 of chromosome 18 to identify precisely a small supernumerary chromosome as an isochromosome i(18p).
Abstract: Recombinant plasmid clone B74 (also named D18S3) containing a human single-copy DNA segment of 6 kilobases (kb) was localized by in situ hybridization on band p113 of chromosome 18. This probe was then used in cytogenetic diagnosis to identify precisely a small supernumerary chromosome as an isochromosome i(18p).
TL;DR: The hippocampostriatal projections, that represent a link between the limbic and central motor mechanisms, could be under dopaminergic influence.
TL;DR: A rapid and efficient microscale method for in vitro site-directed mutagenesis by gene synthesis and its potential for the extensive mutational analysis of genes is described.
Abstract: We describe a rapid and efficient microscale method for in vitro site-directed mutagenesis by gene synthesis. Mutants are constructed by "shot-gun ligation" of overlapping synthetic oligonucleotides yielding double stranded synthetic DNA of more than 120 nucleotides in length. The terminal oligonucleotides of the DNA segment to be synthesized are designed to create sticky ends complementary to unique restriction sites of a polylinker present in an M13 vector. The oligonucleotides are hybridized and ligated to the M13 vector without any purification of the synthetic DNA segment. After cloning, about half of the progeny from such shot-gun ligations contained the predicted sequence demonstrating the efficacy of this method for gene synthesis and its potential for the extensive mutational analysis of genes.
TL;DR: The new benzamide derivative [125I]iodosulpride is a highly sensitive and selective ligand for D-2 dopamine receptors and displays a very low nonspecific binding to membrane or autoradiographic sections, suggesting larger physiological and pathophysiological roles for cerebral dopamine receptors than was previously thought.
Abstract: The new benzamide derivative [125I]iodosulpride is a highly sensitive and selective ligand for D-2 dopamine receptors and displays a very low nonspecific binding to membrane or autoradiographic sections. On autoradiographic images, D-2 receptors are present not only in well-established dopaminergic areas but also, in a discrete manner, in a number of catecholaminergic regions in which the dopaminergic innervation is still unknown, imprecise, or controversial, as in the sensorimotor cerebral cortex or cerebellum. This widespread distribution suggests larger physiological and pathophysiological roles for cerebral dopamine receptors than was previously thought.
TL;DR: In this article, the astroglial growth factor (AGF) was purified from bovine brain and two different methods were used, the second one including heparin-separharose affinity chromatography.
TL;DR: It is concluded that histamine modulates its own release from cerebral neurones by interacting with H3-presynaptic autoreceptors and via mechanisms similar to those previously evidenced on other aminergic systems.
TL;DR: Proteins of similar molecular mass appear to be involved in calcium fluxes: one is recognized by the ALB6 antibody while the other can be phosphorylated by the C‐subunit.
TL;DR: The data suggest that a sudden fall in erythrocyte sedimentation rate or in platelet and fibrinogen levels may mark the start of this complication and may be an indication for rapid steroid therapy.
TL;DR: The results indicate that N-nitroso compounds could easily be formed in vivo in the oral cavity during chewing or in the stomach after swallowing the quids, and the levels of N- Nitrosamines and alkaloids in betel quid extracts were determined before and after nitrosation at pH 7.1.
Abstract: In order to evaluate exposure of betel quid chewers to N-nitroso compounds, saliva and urine samples were collected from chewers of betel quid with or without tobacco, from tobacco chewers, from cigarette smokers and from people with no such habit, and were analysed for the presence of N-nitrosamines by gas chromatography coupled with Thermal Energy Analyzer and alkaloids derived from betel nut and tobacco by capillary gas chromatography fitted with nitrogen-phosphorous selective detector. The levels of the betel nut-specific nitrosamines, N-nitrosoguvacoline and N-nitrososoguvacine (the latter being detected for the first time in saliva), ranged from 0 to 7.1 and 0 to 30.4 ng/ml, respectively. High levels of tobacco-specific nitrosamines were detected in the saliva of chewers of betel quid with tobacco and in that of chewers of tobacco, ranging from 1.6 to 59.7 (N'-nitrosonornicotine), 1.0 to 51.7 (N'-nitrosoanatabine) and 0 to 2.3 [4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone] ng/ml. Urinary concentrations of certain N-nitrosamino acids, including N-nitrosoproline, were determined as a possible index of exposure to nitroso compounds and their precursors in the study groups: no clear difference was observed. The betel nut-specific alkaloid, arecoline, was present at high levels in the saliva of betel quid chewers with or without tobacco. Nicotine and cotinine were also detected in saliva and urine of chewers of tobacco and of betel quid with tobacco. In order to assess whether N-nitroso compounds are formed in vivo in the oral cavity during chewing or in the stomach after swallowing the quids, the levels of N-nitroso compounds in betel quid extracts were determined before and after nitrosation at pH 7.4 and 2.1. The results indicate that N-nitroso compounds could easily be formed in vivo. The possible role of N-nitroso compounds in the causation of cancer of the upper alimentary tract in betel quid chewers is discussed.
TL;DR: Human platelet glycoprotein Ib is a major integral membrane protein that has been identified as the platelet-binding site mediating the factor VIII/von Willebrand-factor-dependent adhesion of platelets to vascular subendothelium and both GP Ib and GP IX were found to occur in the same immunoprecipitin arc whether the platelets had been solubilized in the absence or presence of the calcium-dependent protease inhibitor, leupeptin.
Abstract: Human platelet glycoprotein Ib (GP Ib) is a major integral membrane protein that has been identified as the platelet-binding site mediating the factor VIII/von Willebrand-factor-dependent adhesion of platelets to vascular subendothelium. Recent evidence suggests that GP Ib is normally complexed with another platelet membrane protein, GP IX. In this study, human platelet plasma membranes were selectively solubilized with a buffer containing 0.1% (v/v) Triton X-100. The GP Ib complex (GP Ib plus GP IX) was purified to homogeneity in ∼ 30% yield by immunoaffinity chromatography of the membrane extract using the anti-(glycoprotein Ib complex) murine monoclonal antibody, WM 23, coupled to agarose. GP Ib and GP IX were subsequently isolated as purified components by immunoaffinity chromatography of the GP Ib complex using a second anti-(glycoprotein Ib complex) monoclonal antibody, FMC 25, coupled to agarose. As assessed by dodecyl sulphate/polyacrylamide gel electrophoresis, purified GP Ib was identical to the molecule on intact platelets and had an apparent relative molecular mass of 170000 under nonreducing conditions and 135000 (α subunit) and 25000 (β subunit) under reducing conditions. GP IX had an apparent Mr of 22000 under both nonreducing and reducing conditions. Purified Gb Ib complex and GP Ib inhibited the ristocetin-mediated, human factor VIII/von Willebrand-factor-dependent and bovine factor VIII/von Willebrand-factor-dependent agglutination of washed human platelets suggesting the proteins had been isolated in functionally active form. GP Ibα had a similar amino acid composition to that previously reported for its proteolytic degradation product, glycocalicin. The amino acid compositions of GP Ibβ and GP IX were similar but showed marked differences in the levels of glutamic acid, alanine, histidine and arginine. The N-termini of GP Ibα and GP IX were blocked; GP Ibβ had the N-terminal sequence, Ile-Pro-Ala-Pro-. On crossed immunoelectrophoresis, both GP Ib and GP IX were found to occur in the same immunoprecipitin arc(s) whether the platelets had been solubilized in the absence or presence of the calcium-dependent protease inhibitor, leupeptin. Binding studies in platelet-rich plasma indicated a similar number of binding sites (x± SD) for three anti-(glycoprotein Ib complex) monoclonal antibodies: AN 51, epitope on GP Ibα (22000 ± 2700, n= 3), WM 23, epitope on GP Ibα (21000 ± 3400, n= 3), FMC 25, epitope on GP IX (20100 ± 2700, n= 3), and FMC 25 (Fab′)2 (27100 ± 800, n= 2). The combined evidence suggests that GP Ib is normally bound to GP IX and that the stoichiometry of this complex is 1:1.
TL;DR: The results suggest that a fraction of bound heparin is internalized by the vascular endothelium, and was not available to degradation by purified microbial Heparinase.
TL;DR: During the last two decades, the important progress that has been made in the control of human reproduction, in medical care during pregnancy and the neonatal period, and more recently in in vitro fertilization has focused interest on the understanding of the causes of the high mortality rate.
Abstract: During the last two decades, the important progress that has been made in the control of human reproduction, in medical care during pregnancy and the neonatal period, and more recently in in vitro fertilization (Schlesselman, 1979; Biggers, 1981) has focused interest on the understanding of the causes of the high mortality rate among human conceptuses before, during, and shortly after birth. It has been recognized that chromosomal abnormalities are among the most important causes of this high mortality rate, and thus couples with a history of pregnancy wastage are now frequently referred to a geneticist for counseling.
TL;DR: The results obtained with cGK suggest a transitory intrinsic heterogeneity in the immature cerebellar cortex and a transient biochemical compartmentalization resulting from the differential expression of parts of the same genotype by clusters of PCs.
TL;DR: It is concluded that, contrary to previous results with experimental animals, the anti-P RU 486 has some progestomimetic activity in humans under specific conditions.
Abstract: The effects of the antiprogestin RU 486 on the human endometrium were investigated. Seventeen postmenopausal women were injected with estradiol benzoate (0.625 mg/d) for 15 days. Progesterone (25 mg/d) and/or RU 486 (100 or 200 mg/d) were given to groups of 2–3 women during the last six days of estradiol benzoate treatment. Serial blood samples were drawn for the measurement of plasma estradiol (E2), progesterone (P) and LH and FSH. An endometrial biopsy was performed on the last day of treatment and processed either for histology or for assays of DNA polymerase alpha (DNA pol), estradiol dehydrogenase (E2DH), and progesterone receptor (PR).
TL;DR: The findings suggest that hoarding activity is mediated by mesolimbic dopamine neurons, and it is hypothesized that this system is necessary for the facilitation of certain types of foraging responses under a high level of arousal.
Abstract: The consequences of 6-hydroxydopamine lesions of the mesolimbic dopamine system on hoarding behavior were investigated in the rat. Specific lesions of this system, at the level of either the ventral tegmental area or the nucleus accumbens, resulted in abolition or severe reduction of hoarding activity. Similar lesions of the forebrain noradrenaline neurons did not affect hoarding. In further experiments, amphetamine and apomorphine locomotor responses, spontaneous motor behavior, food intake and eating patterns, and the existence of any regulatory deficits were examined. A subtle disorganization of eating patterns was found in animals with mesolimbic-dopamine lesions. It was determined that the hoarding deficit could not be due to motor, ingestive, or regulatory impairments. In a final experiment, it was demonstrated that hoarding behavior can be restored to control levels in dopamine-lesion rats by prior treatment with the catecholamine presursor L-dopa. These findings suggest that hoarding activity is mediated by mesolimbic dopamine neurons, and it is hypothesized that this system is necessary for the facilitation of certain types of foraging responses under a high level of arousal.
TL;DR: It is suggested that red cell transfusion can be a long‐term efficient therapeutic measure to stop bleeding in uraemic haemodialysis patients.
Abstract: This study demonstrates that a low haematocrit is the main determining factor of the prolonged bleeding time often encountered in uraemic haemodialysed patients. Thirty-three patients submitted to regular haemodialysis and having a platelet count greater than 100 X 10(9)/l were investigated with the following tests: simplate bleeding time, blood cell count, platelet aggregation induced by ADP, collagen and sodium arachidonate, arachidonate induced MDA synthesis, tests for detection of an acquired storage pool disease, and factor VIII complex level. The results were compared to two other groups; one of uraemic patients not yet subjected to haemodialysis and another of healthy volunteers. The results were basically identical in the two groups of uraemic patients. The only consistent abnormality was a 30-35% reduction in the platelet MDA synthesis in comparison with control subjects. There was a negative correlation between the log bleeding time and the haematocrit (r = 0.78, P less than 0.01). Fourteen uraemic patients having a prolonged bleeding time were submitted to a red cell transfusion programme and were investigated a second time under identical conditions. There was no change in any of the platelet function tests or in the factor VIII complex level, but the bleeding time was normalized when the post-transfusion haematocrit was over 26% (nine patients). This study emphasizes the role of anaemia in the pathogenesis of the prolonged bleeding time in uraemia and suggests that red cell transfusion can be a long-term efficient therapeutic measure to stop bleeding in these patients.