Showing papers by "French Institute of Health and Medical Research published in 1979"
TL;DR: Sixty-eight convergent dorsal horn neurones have been recorded at the lumbar level in anaesthetized intact rats as discussed by the authors, and all cells received prominent Aα and C fibre afferents and correspondingly could be activated by high and low threshold stimuli applied to the peripheral excitatory receptive field.
Abstract: SUMMARYSixty-eight convergent dorsal horn neurones have been recorded at the lumbar level in anaesthetized intact rats. All cells received prominent Aα and C fibre afferents and correspondingly could be activated by high and low threshold stimuli applied to the peripheral excitatory receptive field.
1,217 citations
TL;DR: A heptacosapeptide with potent gastrin releasing activity has been isolated from porcine non-antral gastric and intestinal tissue and striking homology in the C-terminal region is seen with bombesin, accounting for the similar bioactivities of the two peptides.
853 citations
TL;DR: It is concluded that convergent neurones are specifically inhibited by DNIC, and the “contrast” between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells.
Abstract: (1) Diffuse noxious inhibitory controls (DNIC) were tested for their effect on noxious only, non-noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat. Unlike convergent neurones, as described in the previous paper, there was no effect of DNIC on these neurones. It is concluded that convergent neurones are specifically inhibited by DNIC. (2) The effect of DNIC could not be demonstrated for convergent neurones in the spinal animal. Thus the neuronal substrate for DNIC must involve supraspinal structures. (3) Because of the level of firing in convergent neurones induced by hair and touch receptors, presumably constantly and randomly activated in the freely moving animal, a noxious message arriving at higher centres may be partly masked by this background noise. On the basis of the known role of convergent neurones in nociception, we propose the following mechanism which may interpret this paradoxical convergence: two pools of convergent neurones are influenced by a painful peripheral stimulation, one segmental pool being activated whilst the remaining population of cells is inhibited; the "contrast" between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells. (4) These results and their theoretical implications are discussed with regard to the concept of the "analgesic system", certain clinical observations and the paradoxical pain relieving effects of counterirritation and some forms of acupuncture.
747 citations
TL;DR: The closed loop situation of hand pointing at a target has been experimentally divided into its static and dynamic components, and it is suggested that initial cues as regards hand and target position, improve the motor program by a better identification of initial and final states.
Abstract: In a task requiring an optimal hand pointing (with regards to both time and accuracy) at a peripheral target, there is first a saccade of the eye within 250 ms, followed 100 ms later by the hand movement. However the latency of the hand movement is poorly correlated with that of the eye movement. When the peripheral target is cut off at the onset of the saccade, there is no correlation between the error of the gaze position and the error of the hand pointing. This suggests an early parallel processing of the two motor outputs. The duration of hand movement does not change significantly when subjects either see or not see their hand (closed or open loop). In the open loop situation, the undershoot of the hand pointing increases with target eccentricity, whatever the subjects are allowed or not to do a saccade toward the target. It suggests that the encoding of eye position by itself is a poor index for an accurately guided movement of the hand.
579 citations
TL;DR: It is reported that an increase in cardiac work produced by mechanical overloading in rats induces the preferential synthesis of a cardiac myosin isoenzyme characterised by specific immunological and electrophoretic properties and exhibiting a lower ATPase activity.
Abstract: Since the first observation by Spann et al., it has become clear that in cardiac hypertrophy induced by a mechanical overloading, the velocity of shortening of the cardiac muscle (Vmax) is reduced (see ref. 2 for review). Most authors agree that this mechanical alteration is accompanied by a decrease in the Ca2+-dependent ATPase activity of myosin (see ref. 3 for review). The molecular basis of such changes was unknown because the structural modifications of the myosin molecule were ill-defined. Nevertheless, it has recently been shown that, like skeletal muscle myosin, cardiac myosin is composed of several polymorphic forms, comparable to isoenzymes. In the skeletal muscle, new functional requirements can induce changes in both contractile activity and type of myosin isoenzyme synthesised. We now report that an increase in cardiac work produced by mechanical overloading in rats induces the preferential synthesis of a cardiac myosin isoenzyme characterised by specific immunological and electrophoretic properties and exhibiting a lower ATPase activity. This adaptive change could account for the reduced shortening speed of this hypertrophied cardiac muscle.
510 citations
TL;DR: Serum samples and skin specimens from twenty patients with systemic lupus erythematosus were studied for antinuclear antibodies, C3 and C4 levels, circulating immune complexes, B and T lymphocytes and l upus hand test.
Abstract: Summary
Serum samples and skin specimens from twenty patients with systemic lupus erythematosus were studied for antinuclear antibodies, C3 and C4 levels, circulating immune complexes, B and T lymphocytes and lupus hand test. The patients were divided into three categories: Group I, six patients with inactive disease; Group II, eleven patients with mildly active disease without renal involvement; Group III, three patients with severely active disease and renal involvement. In Groups II and III, high levels of antinuclear antibodies, low C4 values, persistence of circulating immune complexes, reduction in T-lymphocyte number and positive lupus band test in uninvolved light exposed areas were usually associated with active lupus and tended to correlate with disease activity.
408 citations
TL;DR: This work reports that platelets can form and release PAF in experimental conditions in which the ADP and TXA2 pathways are fully blocked, and suggests PAF as a likely candidate for mediating the ‘third pathway’ of platelet aggregation.
Abstract: PLATELET aggregation is mediated by at least three distinct mechanisms1,2. The first involves the release of ADP and is inhibited by its conversion to ATP by the combination of creatine phosphate and creatine phosphokinase (CP/CPK). The second is mediated by metabolites of arachidonic acid, particularly thromboxane A2 (TXA2), and is blocked by aspirin or indomethacin, inhibitors of the arachidonate cyclo-oxygenase pathway3. It has been postulated that a third mechanism must exist, as neither CP/CPK nor aspirin, alone or combined, can inhibit aggregation induced by high concentrations of thrombin or the calcium ionophore A23187 (refs 1, 2, 4). Antigenic challenge of IgE-sensitised basophils releases a platelet-activating, factor (PAF), probably a 1-lysophosphatidylcholine5. PAF has a potent action on rabbit6,7 and human8,9 platelet aggregation and release which is independent of the cyclo-oxygenase arachidonate pathways6,10,11. We have also obtained PAF from A23187-stimulated rat peritoneal12 and alveolar (J.B., B. Arnoux and D. Duval, in preparation) macrophages. Moreover, thrombin and ionophore-induced platelet aggregation and the accompanying stimulation of phospholipase A2 (refs 13, 14) are inhibited by the phospholipase inhibitor bromophenacyl bromide (ref. 15 and B.B.V., F. Fouque and M.C., in preparation), suggesting that the third mechanism of platelet aggregation might involve a lipid mediator. These findings prompted us to investigate whether platelets can form and release PAF in experimental conditions in which the ADP and TXA2 pathways are fully blocked. We report here that this is indeed the case, and suggest PAF as a likely candidate for mediating the ‘third pathway’ of platelet aggregation.
389 citations
TL;DR: The results enable us to predict the primary sequence of two related polypeptides from region E1A of human subgroup C adenoviruses, and to study the structure of early ad2 mRNAs at the nucleotide level using molecular cloning procedures to amplify the appropriate mRNA sequences.
Abstract: The papova viruses and the human adenoviruses are widely used as a model system to study cell transformation in vitro. In subgroup C human adenoviruses, fragment HpaI-E, which comprises as little as 4.5% of the adenovirus type 5 (ad5) DNA, is sufficient for transformation of rat embryo cells1. Analysis of messenger RNAs (mRNAs) from the transforming region of adenoviruses type 2 (ad2) has identified several spliced mRN A species2–4. Promoter mapping studies indicate that the leftmost early region contains two separate transcription units, E1A and E1B (ref. 5) (Fig. 1a). Region E1A is approximately equivalent HpaI-E. The complete nucleotide sequence of the HpaI-E fragment of ad5 was recently reported6. However, the spliced nature of early adenovirus mRNAs prevents a prediction of the amino acid sequence of the corresponding polypeptides directly from the DNA sequence. To study the structure of early ad2 mRNAs at the nucleotide level, we have used molecular cloning procedures to amplify the appropriate mRNA sequences. In this report, clones corresponding to the 12S and 13S mRNA from region E1A (Fig. 1c) have been isolated and characterised by hybridisation and sequence analysis. Our results enable us to predict the primary sequence of two related polypeptides from region E1A of human subgroup C adenoviruses.
339 citations
TL;DR: Using the DOPAC/DA ratio as an index of the activity of the neurons, the mesocortical dopaminergic neurons were found to be selectively activated under stress since this ratio was increased in the frontal and cingular cortices but not in limbic structures such as the septum, the amygdala and the nucleus accumbens.
329 citations
TL;DR: It is concluded that a metabolic pathway possibly involving the Golgi apparatus, and contributing to the formation of the MDL is selectively affected in this mutant mouse Shiverer.
311 citations
TL;DR: It is concluded that HaI or HpaII sites can be divided in 3 classes according to their pattern of methylation in different tissues, and methylation at the sites located within and around the 3 genes which code for egg white proteins is in general lowest in oviduct of laying hen.
Abstract: The restriction enzymes HhaI and HpaII, whose activity is inhibited by cytosine methylation within their recognition sites, have been utilised as probes to study methylation in the vicinity of the ovalbumin gene in DNA from various chicken tissues. This was complemented by a preliminary study of methylation in the regions of chicken ovotransferrin (conalbumin), ovomucoid and beta-globin genes. From our data we conclude that HaI or HpaII sites can be divided in 3 classes according to their pattern of methylation in different tissues. In the first class of sites (mV class) the extent of methylation varies in different tissues. The patterns obtained show that methylation at the sites located within and around the 3 genes which code for egg white proteins is in general lowest in oviduct of laying hen, where these genes are expressed. However some sites are not methylated (m- class) and others are 95 to 100% resistant (m+ class) to digestion by HhaI or HpaII in the DNAs of all the tissues which were tested. Our study has also revealed a remarkable number of allelic variants for the presence of HhaI or HpaII sites in the region of the ovalbumin gene.
TL;DR: A clone which contains the complete chicken ovalbumin gene, including its leader coding sequences, has been isolated and it is concluded that the minimal size of the transcriptional unit for Ovalbumin is 7.7 kilobases.
Abstract: A clone which contains the complete chicken ovalbumin gene, including its leader coding sequences, has been isolated. From electron microscopic analysis of this DNA we conclude that the minimal size of the transcriptional unit for ovalbumin is 7.7 kilobases. The DNA sequence of the region surrounding the 5' end of the ovalbumin gene is presented. Comparison of this sequence with those of other eukaryotic genes reveals striking similarities, possibly related to a promoter region, approximately 30 base pairs upstream from the site coding for the 5' end of the mRNA.
TL;DR: The effects of thyrotropin-releasing hormone and 17 beta-estradiol on the electrical membrane properties of a prolactin-secretin pituitary cell line (GH3/B6) were studied with intracellular microelectrode recordings and reveal a rapid effect of both substances on the membrane.
Abstract: The effects of thyrotropin-releasing hormone and 17 beta-estradiol on the electrical membrane properties of a prolactin-secretin pituitary cell line (GH3/B6) were studied with intracellular microelectrode recordings. Of the cells tested, 50 percent were excitable and displayed calcium-dependent action potentials when depolarized. When injected directly on the membrane of an excitable cell, thyrotropin-releasing hormone and 17 beta-estradiol induced action potentials within 1 minute. The spiking activity was preceded by a progressive increase of the input resistance without any detectable change in the resting membrane polarization. The results reveal a rapid effect of both substances on the membrane of GH3/B6 cells. In the case of thyrotropin-releasing hormone, which has both a short-term effect on release of prolactin and a long-term effect on its synthesis, the induced electrical activity may be associated with the stimulation of prolactin production. The physiological implication of 17 beta-estradiol-induced, calcium-dependent spiking activity remains to be elucidated.
TL;DR: The analgesic effects of morphine microinjected into the nucleus raphé magnus (NRM) and the surrounding reticular formation of the rat were tested using vocalization after electric shock to the tail as the test for analgesia and results further substantiate the role of the NRM in analgesic mechanisms.
TL;DR: PAF was associated with large, acid phosphatase‐containing, adherent mononuclear cells and could not be held responsible for inactivation of PAF or inhibition of the PAF‐induced platelet aggregation.
Abstract: Platelet-activating factor (PAF) is a phospholipid mediator of anaphylaxis, released from basophils of several mammalian species, that aggregates platelets and releases their vasoactive amines. The ionophore A23 187 induced the release of PAF from rat and mouse peritoneal cells, a mixed cell population that was fractionated using 5–15 % Ficoll gradients and adherence to plastic petri dishes. PAF was associated with large, acid phosphatase-containing, adherent mononuclear cells. Mastocytes did not release PAF but released histamine by the action of ionophore or 48/80; they could not be held responsible for inactivation of PAF or inhibition of the PAF-induced platelet aggregation.
These data indicate that, besides blood basophils, peritoneal macrophages are a likely source for PAF, a result that adds a new important function to the macrophage: aggregation of platelets and liberation of their inflammatory and vasoactive substances.
TL;DR: The myelin-deficient mutant Shiverer (Shi/Shi) lacks basic protein (MBP) in the myelin of its central nervous system (CNS) as determined by radioimmunoassay.
TL;DR: The hypothesis of a local GABAergic network is supported by the failure to obtain important changes in GAD after lesions of NRD afferents and the presence in this nucleus of terminals, fibers and nerve cell bodies accumulating [3H]GABA.
TL;DR: The subthalamic nucleus appears to be a homogeneous closed nucleus whose Golgi type I neurons seem to belong to a single neuronal species that does not change from cat to man.
TL;DR: Analysis of the regional and subcellular distribution of vasoactive intestinal peptide in the brain of adult male rat, using a specific radioimmunoassay, suggests that hypothalamic nerve endings containing the peptide derive from neuronal cell bodies located both outside and within the MBH.
TL;DR: The conalbumin gene has been cloned and shown to consist of at least 17 exons approximately 60–200 base pairs long, with similarities with sequences present in homologous positions in other genes.
Abstract: The conalbumin gene has been cloned and shown to consist of at least 17 exons approximately 60–200 base pairs long. The DNA sequence upstream from the region coding f or the 5′ end of the mRNA shows similarities with sequences present in homologous positions in other genes. High and low frequency repetitive sequences are found both upstream from the conalbumin gene and within one intron.
TL;DR: This work shows that the GH3/B6 cells are highly responsive to VIP which stimulates in a concomitant manner both their PRL release and 3’,5’cyclic adenosine monophosphate (CAMP) production.
TL;DR: A moderately restricted protein diet securing only the minimal requirements had a beneficial effect on growth and survival of rats with reduced kidney mass, and avoiding any excess in proteins from the early stage of renal disease is suggested.
TL;DR: The natural history and clinico-pathological patterns of these diseases may, especially in the case of a chain disease, constitute a model providing unique opportunities for research into the pathogenesis of human lymphoid malignancies.
Abstract: Human heavy chain diseases are lymphoproliferative disorders characterized by the production of immunoglobulin molecules consisting of incomplete heavy chains devoid of light chains. Heavy chain diseases of the three main immunoglobulin classes have been described. Since the description ofthe first case by Franklin et al. (1964), close to 50 patients with gamma heavy chain disease have now been reported. The most frequent condition within the group of heavy chain diseases is a-chain disease (Seligmann et al. 1968) with more than 150 cases presently known to us. In contrast, /^-chain disease appears to be relatively rare since only 15 cases have been reported since its first description (Forte et al. 1970). Heayy chain diseases raise a number of interesting problems related to various fields such as the structure of the abnormal immunoglobulin, and the cellular genetic mechanisms responsible for the synthesis of a deleted heavy chain and, in most instances, the lack of production of light chains. In addition, the natural history and clinico-pathological patterns of these diseases may, especially in the case of a chain disease, constitute a model providing unique opportunities for research into the pathogenesis of human lymphoid malignancies.
TL;DR: The findings provide evidence that: (1) the hemodynamic mechanisms of systolic hypertension differ in younger and older patients, and (2) these hemodynamic differences should be taken into account when choosing drugs to decrease syStolic pressure.
Abstract: Arterial compliance and indexes of ventricular ejection were measured in 27 men with systolic hypertension. The patients were separated into two age groups, younger or older than age 35 years, and matched with normotensive control subjects. Arterial compliance was estimated from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple viscoelastic model. In the younger patients, arterial compliance and stroke volume were within normal ranges. Rapid ejection time was significantly reduced (P less than 0.001), indicating an increased venlocity in the first part of ventricular ejection. Systolic pressure decreased significantly after administration of propranolol, which also caused prolongation of rapid ejection time. In the older patients, indexes of ventricular ejection were within normal limits. arterial compliance was significantly reduced (P less than 0.01) and was negatively correlated with the level of systolic pressure (P less than 0.001). Systolic pressure decreased significantly after administration of sodium nitroprusside, which caused an increase in arterial compliance. These findings provide evidence that: (1) the hemodynamic mechanisms of systolic hypertension differ in younger and older patients, and (2) these hemodynamic differences should be taken into account when choosing drugs to decrease systolic pressure.
TL;DR: The cases of 2 patients who died from cirrhosis after receiving perhexiline maleate, a drug widely used in Europe for the treatment of angina pectoris, are reported, consistent with the view that prolonged administration of per hexilinemaleate may induce both histologic lesions resembling those of alcoholic liver disease and ultrastructural and histochemical lesions resemblingThose of phospholipidosis.
TL;DR: Human leukocyte interferon increased the expression of HLA‐A, B antigens and β2‐microglobulin on two lines of human lymphoblastoid cells and on peripheral blood lymphocytes.
Abstract: Human leukocyte interferon increased the expression of HLA-A, B antigens and beta 2-microglobulin on two lines of human lymphoblastoid cells and on peripheral blood lymphocytes. No effect was observed on the expression of HLA-DR antigens.
TL;DR: A major protein was extracted by 0.15 M sodium chloride from human pancreatic calculi and was found immunologically identical in ten different calculiand was present in different layers of the same stone.
TL;DR: The distribution of phospholipids and arachidonic acid between the two leaflets of the plasma membrane has been deduced by using values and those obtained from non-lytic treatment of intact platelets byospholipases.
TL;DR: Two large DNA fragments overlapping the chicken ovalbumin gene have been isolated by molecular cloning and analysis of these fragments provided a map of a 46,000-base pair region of the chicken genome, suggesting that duplications have occurred in the ovalbumIn gene region in the course of evolution.
Abstract: Two large DNA fragments overlapping the chicken ovalbumin gene have been isolated by molecular cloning. Analysis of these fragments provided a map of a 46,000-base pair region of the chicken genome. This region contains the complete ovalbumin gene (including its mRNA leader-coding sequence) and at least two other genes of unknown function. All three genes are orientated in the same direction and their expression in chicken oviduct is under hormonal control. The three genes share some sequence homologies, suggesting that duplications have occurred in the ovalbumin gene region in the course of evolution.
TL;DR: Observations of various LH- RH-reactive axonal tract endings exhibit that besides its major, direct, prehypophysotrophic action through the hypophyseoportal system, LH-RH may also be distributed by the blood of the vascular organ of the lamina terminalis, as neuroendocrine integrator neurons.
Abstract: Publisher Summary The hypothalamic topography of the luteinizing hormone-releasing hormone (LH-RH) reaction gives rise to the hypothalamoinfundibular tract and to the preopticoterminal LH-RH tract, fits closely with the hypothalamic LH-RH topography determined by biological or biochemical assays, by radioimmunoassays, or after hypothalamic disconnection. The modifications of immunoreactivity of the hypothalamoinfundibular and the preopticoterminal LH-RH tracts, as well as of the extrahypophyseal LH-RH pathway describe that the reactive material shown is in fact LH-RH, which is, at least in part, synthesized in the reaction, possibly in the form of a high-molecular-weight precursor. Observations of various LH-RH-reactive axonal tract endings exhibit that besides its major, direct, prehypophysotrophic action through the hypophyseoportal system, LH-RH may also be distributed by the blood of the vascular organ of the lamina terminalis. LH-RH neurons are thus seen not only as classical neurosecretory cells with solely pericapillary axon endings but also as neurons with multiple, portal, and extrahypophyseal efferents, as neuroendocrine integrator neurons.