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Biomedical subjects

J M Launay

Publications and source records attributed to J M Launay.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Kinetics of sialylation of Neisseria gonorrhoeae by radiolabelled cytidine 5'monophospho-N-acetyl neuraminic acid].

Neisseria gonorrhoeae (Strain A) induces a sialyl-transferase when treated with a very low concentration of cytidine 5'monophospho-N-acetyl neuraminic acid, 2 x 10(-3) nmol.ml-1, a concentration which is insufficient to produce an adequate resistance to human serum complement. The sialyl-transferase activity was detected by measurement of fixed 14C radio-labeled sialyl groups. Without this stimulation, there was practically no transfer of sialyl groups. The gonococcal sialyl-transferase could be considered inducible.

Anti-Bacterial Agents↗
PubMed1996

[Demonstration of the immunoreactivity of polynuclear eosinophils for bombesin and substance P. A new concept of the neuro-immune axis].

Immunoreactivity for B and SP was detected by means of light and electron microscopy (by preembedding immunocytochemistry), in eosiniphilic polymorphonuclear leukocytes infiltrating the connective tissue of gastrointestinal and respiratory tract in mouse, rat and human ; and in human bronchoalveolar lavages in case of hypereosinophilia. This positive reaction depends on the use of an acetic-acid-containing-fixative (minimum 48 hours), and is located in the granules of eosinophils at their membrane level, and on eosinophil plasma membranes. Eosinophil peroxidases (catalases) should not affect the immunocytochemical reaction, since heating during a paraplast embedding and sodium-azide in electron microscopy procedure destroyed these enzymes. The membrane-bound immunoreaction for B and SP, with very close structural similarity, suggested cross-reactivity between the two neuropeptides, with recognition of one or several epitopes by the polyclonal antisera. One of these epitopes is probably associated with the C-terminal sequence of B (with tachykinin-like activity) and seems to be present in other neuropeptides such as SP ; another epitope would be the N-terminal sequence of SP (with bradykinin-like activity). Hence, eosinophils could be the source of tachykinin and bradykinin. Another hypothesis about the membrane immunolocalization (as yet unproved experimentally) would be a cross-reactivity due to recognition of electron-negative charges of membrane phospholipides. Lysophosphatidic acid could play a hormone-like activity and mimic B and SP activities, such as growth factors. Finally, anti-B and anti-SP antisera could contain anti-idiotype antibodies uncovering receptors. In conclusion : eosinophils might produce neuropeptides or neuropeptide-like substances, with, for instance, bronchoconstrictive activity by paracrine control and possible complementarity with nerve endings.

Animals↗
PubMed1995

Monoamine oxidase A and B activities in heavy smokers.

There is a strong association between depression and smoking. Because monoamine oxidase (MAO) inhibition leads to antidepressant effect and in vitro studies have shown that cigarette smoke inhibits MAO activity, it is conceivable that smoking may have an antidepressant effect, if smokers have reduced MAO activity. Therefore, we assessed platelet MAO-B activity and plasma concentration of catecholamine metabolites reflecting MAO-A activity in heavy dependent smokers and nonsmokers matched for sociodemographic characteristics. Platelet MAO-B activity, plasma 3,4-dihydroxyphenylglycol, plasma 3,4-dihydroxyphenylacetic acid, and plasma 3,4-dihydroxyphenylalanine concentrations were significantly lower in smokers than in nonsmokers, whereas plasma norepinephrine did not differ. Significantly more smokers reported previous history of depression, manic episode, panic attack, agoraphobia, and simple phobia. Smokers had higher scores (p < 0.001) on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scales. It is concluded that the activities of both forms of the MAO are reduced in heavy dependent smokers.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study.

The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5 mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint clinical and biochemical evaluations of therapeutic effects. Modest clinical benefits were achieved with both PLC and NTX, with marginally better overall results following NTX, and degree of improvement appeared to be related to plasma chemical profiles. Massively elevated levels of beta-endorphin were observed in all children with assays using C-terminal antibody but not with an N-terminal antibody assay. In addition, 70% of the children exhibited abnormally low levels of adrenocorticotropic hormone, and smaller subsets exhibited elevated norepinephrine (60%), arginine-vasopressin (50%), and serotonin (20%). The best clinical responders exhibited the clearest normalization of the elevated plasma chemistries, especially in C-terminal-beta-endorphin and serotonin. There was some evidence of therapeutic carry-over effects in both clinical and biochemical measures in those children who received NTX before PLC. The results suggest that NTX only benefits a subgroup of autistic children, who may be identified by the presence of certain plasma abnormalities. These results suggest a possible linkage between abnormal plasma chemistries, especially those related to the pro-opiomelanocortin system, and autistic symptoms.

Adolescent↗
PubMed1995

Drosophila 5-HT2 serotonin receptor: coexpression with fushi-tarazu during segmentation.

Serotonin, first described as a neurotransmitter in invertebrates, has been investigated mostly for its functions in the mature central nervous system of higher vertebrates. Serotonin receptor diversity has been described in the mammalian brain and in insects. We report the isolation of a cDNA coding for a Drosophila melanogaster serotonin receptor that displays a sequence, a gene organization, and pharmacological properties typical of the mammalian 5-HT2 serotonin receptor subtype. Its mRNA can be detected in the adult fly; moreover, a high level of expression occurs at 3 hr of Drosophila embryogenesis. This early embryonic expression is surprisingly organized in a seven-stripe pattern that appears at the cellular blastoderm stage. In addition, this pattern is in phase with that of the even-parasegment-expressed pair-rule gene fushi-tarazu and is similarly modified by mutations affecting segmentation genes. Simultaneously with this pair-rule expression, the complete machinery of serotonin synthesis is present and leads to a peak of ligand concomitant with a peak of 5-HT2-specific receptor sites in blastoderm embryos.

Amino Acid Sequence↗
PubMed1995

Identification of the cytoskeletal protein alpha-actinin as a platelet thrombospondin-binding protein.

Binding of the alpha-granular thrombospondin (TSP) to the plasma membrane of activated platelets has long been documented, yet the molecular mechanism involved in its secretion and surface expression have not been elucidated. Using a ligand blot binding assay where electrophoretically separated platelet proteins were incubated with purified 125I-labeled TSP, we observed a strong interaction of [125I]TSP with a 100 kDa single chain protein. On performing a platelet subfractionation, the 100 kDa protein was predominantly localized in the cytosol from which it was purified by preparative electrophoresis and was identified by amino acid sequencing to the cytoskeletal protein, alpha-actinin. We further demonstrated that [125I]TSP interacts with alpha-actinin in a specific manner and with a high affinity (Kd = 6.6 nM) in a solid-phase binding assay.

Actinin↗
PubMed1995

Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disorder characterized by increased serum immunoglobulin E levels. Bone fragility is part of this syndrome, which has recently been reported to be also associated with an imbalance in cytokine-secreting lymphocyte subpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investigated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible involvement of cytokines in causing the bone fragility associated with this disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal radius was two standard deviations below that of the aged-matched controls. Urinary pyridinoline excretion, a marker of bone resorption, was markedly increased in the two youngest patients. Adherent mononuclear cells derived from these patients were cultured in vitro and the bone resorbing activity (BRA) of the culture supernatant was measured by means of a fetal rat long bone assay. The BRA was up to 28% above the basal value. We compared the BRA and the cytokine production by the mononuclear cells of these patients to that of postmenopausal women. The BRA, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of interferon-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is similar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading to bone loss in HIES, which could be related to IgE-dependent mechanisms.

Adolescent↗
PubMed1995

A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers.

OBJECTIVE: To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers. METHODS: We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity. RESULTS: Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group. No difference occurred for withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3). CONCLUSION: In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.

Adult↗
PubMed1995

Helicobacter pylori infection: physiopathologic implication of N alpha-methyl histamine.

BACKGROUND/AIMS: In the gastric mucosa of Helicobacter pylori-infected subjects, we previously detected N alpha-methyl histamine (N alpha-MeHA), a minor catabolite of histamine and a potent agonist of histamine H3 receptors. The origin of N alpha-MeHA and its effects on gastric histamine and somatostatin in infected subjects were investigated. METHODS: Ten noninfected patients and 13 patients with intense colonization were compared. N alpha-MeHA content and its synthetic enzyme activity, N alpha-histamine methyltransferase, binding of [3H]N alpha-MeHA, histamine and somatostatin contents, and histidine decarboxylase activity were assayed in antral and fundic biopsy specimens and in cultured H. pylori strains. RESULTS: Gastric histamine and somatostatin contents as well as histidine decarboxylase activity were decreased in infected patients and were restored to normal after antimicrobial treatment. Both N alpha-MeHA and N alpha-histamine methyltransferase activity were present in the mucosa of infected patients and in cultured strains and were very low in noninfected patients or after eradication of H. pylori. [3H]N alpha-MeHA bound to gastric mucosa but not to cultured strains. The [3H]N alpha-MeHA specific binding sites were characterized as H3 receptors. The amount of bound [3H]N alpha-MeHA seemed correlated positively with somatostatin content and histidine decarboxylase activity and negatively with N alpha-MeHA content and N alpha-histamine methyltransferase activity. CONCLUSIONS: H. pylori is the main source of gastric N alpha-MeHA that may lower histidine decarboxylase activity and somatostatin content through H3 receptors.

Gastric Mucosa↗
PubMed1995

Serotonin, catecholamines, and spontaneous midgut carcinoid flush: plasma studies from flushing and nonflushing sites.

BACKGROUND/AIMS: Serotonin is the diagnostic hallmark of midgut carcinoids, but the pathophysiology of spontaneous flushing is unknown. The aim of this study was to assess to what extent serotonin and catecholamine blood levels are related in time with spontaneous midgut carcinoid flush. METHODS: Using specific radioenzymatic assays, we measured prospectively before, during, and after spontaneous flushing platelet-poor plasma and whole blood serotonin and plasma catecholamines and their metabolites in 10 patients with primary midgut carcinoids. Blood was drawn simultaneously from a forearm vein and an external jugular vein draining the flushing area. RESULTS: During flushing, plasma serotonin and norepinephrine levels increased (P < 0.001) over preflush levels at both sampling sites. Intraflush serotonin and norepinephrine were twice as high (P < 0.01) in external jugular (9.57 +/- 1.40 ng/mL and 857 +/- 33 pg/mL, respectively) than in antecubital plasma (4.59 +/- 0.73 ng/mL and 471 +/- 26 pg/mL). Preflush and postflush levels were similar at both venous sites. CONCLUSIONS: Vein plasma serotonin and norepinephrine levels do increase during midgut carcinoid flush, especially in the flushing area. This may reflect a local release secondary to flush but also suggests a role for these bioamines in the pathogenesis of flushing.

Adult↗
PubMed1995

Increased plasma serotonin in primary pulmonary hypertension.

PURPOSE: Pulmonary hypertension can occur in patients who have disorders associated with altered platelet serotonin storage, including collagen vascular disease and platelet storage pool disease. We tested the hypothesis that primary pulmonary hypertension (PPH) may be also associated with impaired handling of serotonin by platelets, resulting in increased plasma serotonin levels. PATIENTS AND METHODS: We used radioenzymatic assays to measure serotonin in platelets and plasma and serotonin released during in vitro platelet aggregation in 16 patients with PPH, and in 16 normal controls matched for age and sex. Six patients were restudied after heart-lung transplantation to determine whether serotonin abnormalities persisted after pulmonary arterial pressure returned to normal. RESULTS: Patients had decreased platelet serotonin concentration (1.8 +/- 0.6 x 10(-18) mol/platelet versus 3.2 +/- 0.2 x 10(-18) mol/platelet in controls; P < 0.01) and increased plasma serotonin concentration (30.1 +/- 9.2 x 10(-9) mol/L versus 0.6 +/- 0.1 x 10(-9) mol/L in controls; P < 0.001). Serotonin released during in vitro platelet aggregation was higher in patients than in controls. After heart-lung transplantation, platelet serotonin concentrations remained decreased and plasma levels remained increased. CONCLUSIONS: Abnormal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH. The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH.

Adult↗
PubMed1995

Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie.

Scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep. It belongs to the group of prion diseases also affecting man in which an abnormal isoform of the host-encoded prion protein (PrP) accumulating in the brain is responsible for neuronal death. Three main polymorphisms have been described in the sheep PrP gene, at positions 136, 154 and 171. A strong association between susceptibility/resistance to natural scrapie and a dimorphism at codon 136 of the ovine PrP gene has been reported in several breeds, including Romanov. This dimorphism, however, is not found in all scrapie-affected breeds. We have compared the PrP genotypes of Lacaune sheep obtained from enzootically affected flocks with those of apparently healthy sheep. A third variant at codon 171 was also evidenced. The results were compared with those obtained in a single experimental Romanov flock orally challenged with nematode parasites in which scrapie suddenly appeared and killed 80% of the sheep. We present evidence that, even in different epizootological circumstances, the major genetic factor controlling the susceptibility/resistance to natural scrapie in sheep, is represented by codon 171 genotype of the PrP gene. We also suggest that a modification of the allelic effects of codon 136 can occur in heavily infected animals.

Animals↗
PubMed1995

[Molecular genetics of familial and sporadic forms of human prion diseases].

Prion diseases, also known as transmissible subacute spongiform encephalopathies (TSSE), are rare neurodegenerative disorders of both humans and animals. Their biochemical hallmark is an accumulation in the brain of an abnormal form of the host-encoded prion protein (PrP). This pathological accumulation could result from a protein conformational change under the influence of unknown factors. The normal function of PrP is unknown. The abnormal form is thought to induce neurodegeneration when experimentally or accidentally introduced in recipient hosts. Such a possibility would explain the transmissible character of these diseases illustrated in humans by iatrogenic contamination. Considerable attention has been focused on the host PrP gene and its relation with the genetic susceptibility of humans and animals. Mutations in PRNP, the gene which encodes PrP in humans, are present in 17% of the patients and might be causative. In patients without any PRNP mutation, a coding polymorphism (129 Met/Val) defines a predisposing factor. Important progress in the molecular genetics of TSSE in both humans and animals have been performed for few years and point out that the development of different forms of these diseases, experimental, iatrogenic or spontaneous, are strongly dependent on the primary structure of the host PrP.

Animals↗
PubMed1995

Functional serotonin-2B receptors are expressed by a teratocarcinoma-derived cell line during serotoninergic differentiation.

Among immortalized teratocarcinoma-derived cells, the clone 1C11 is a committed precursor of the neuronal lineage. On day 2 of its serotoninergic differentiation, this clone expresses only one subtype of serotonin [5-hydroxytryptamine (5-HT)] receptor, which is functionally coupled to phosphatidylinositol hydrolysis. The identity of these receptors was established by comparing their properties with those of 5-HT2B receptors expressed by LMTK- fibroblasts stably transfected with the recently cloned murine cDNA NP75 (LM5 cells). In both cell types, the analysis of (+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)- 2-aminopropane HCl ([125I]DOI) binding revealed the presence of a single class of sites, the affinity of which was 1 order of magnitude lower than that reported for 5-HT2A receptors. In 1C11 cells differentiated for 2 days, as well as in LM5 cells, DOI binding was decreased by nonhydrolyzable analogs of GTP, indicating that the 5-HT2B receptor is functionally coupled to a G protein. The DOI-induced increase of phosphoinositide hydrolysis, which was correlated with both GTPase activity and binding data, is mediated by a Gq protein. This work demonstrates that the 5-HT2B receptor is functionally expressed before complete serotoninergic differentiation of 1C11 cells. The inducible 1C11 clone thus provides an in vitro model to investigate the possible role of the 5-HT2B receptor in the expression of the serotoninergic phenotype.

Animals↗
PubMed1995

[Prion protein: structure, functions and polymorphisms associated with human spongiform encephalopathies].

Transmissible subacute spongiform encephalopathies (TSSE), also known as prion diseases, are rare neurodegenerative disorders of both humans and animals. The biochemical hallmark of these diseases is an accumulation in the brain of an abnormal form of the host-encoded prion protein (PrP). This pathological accumulation could result from a protein conformational change under the influence of unknown factors. The normal function of PrP is unknown. The abnormal form is thought to induce neurodegeneration when experimentally or accidentally introduced in recipient hosts. Such a possibility would explain the transmissible character of these diseases illustrated in humans by iatrogenic contamination. Considerable attention has been focused on the host PrP gene and its relation with the genetic susceptibility of humans and animals. Mutations in PRNP, the gene which encodes PrP in humans, are present in 16% of the patients and might be causative. In patients without any PRNP mutation, a coding polymorphism (129 Met/Val) defines a predisposing factor. Since few years, important progress in the molecular genetics of TSSE in both humans and animals have been performed and point out that the development of different forms of these diseases, experimental, iatrogenic or spontaneous, are strongly dependent on the primary structure of the host PrP.

Genes, Viral↗
PubMed1994

The apolipoprotein E alleles as major susceptibility factors for Creutzfeldt-Jakob disease. The French Research Group on Epidemiology of Human Spongiform Encephalopathies.

Creutzfeldt-Jakob disease (CJD) is a rapid progressive mental and neurological disorder characterised by dementia and is both infectious and genetic. Pathogenic mutations and a predisposing polymorphism have been described in the prion protein gene and an abnormal prion product accumulates in the brain of affected patients. Apolipoprotein E (APOE), a protein of lipid metabolism, has been detected in some prion protein deposits. This ApoE exists as three common isoforms, coded by specific allele (epsilon 2, epsilon 3, epsilon 4). The presence of at least one epsilon 4 allele was described as a major risk factor for Alzheimer's disease, another neurodegenerative disorder. From a series of 61 patients with CJD we found that epsilon 4 allele of the APOE gene was a risk factor for the disease (p < 0.01). This association was observed in both definite and probable cases, and for patients with and without prion protein gene mutations. Moreover, in affected subjects, epsilon 2 allele of the APOE gene delayed occurrence of death (p < 0.01) independently of other known mutations influencing the phenotype of the disease. These effects on neurodegenerative disease associated with APOE alleles suggest a strong involvement of the APOE locus in brain metabolism.

Aged↗
PubMed1994

The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors.

The human serotonin 5-HT2B receptor, isolated from a human liver cDNA library, was transfected in COS-1 cells. Its pharmacological profile shows divergence with serotonin 5-HT2B receptors of other species. In particular, although strong correlation is observed between the human and the rat 5-HT2B receptor pharmacology, the correlation is almost as significant for the mouse 5-HT2B and the human 5-HT1D receptor agonists. The major sites of expression of its mRNA are in the human liver and kidney, with detectable expression in lung and heart. Therefore, this human 5-HT2B receptor could account for functions attributed to the peripheral 5-HT1D/5-HT2-like receptors, especially in the cardiovascular system. Thus, its detailed original pharmacology is of prime importance for therapeutic drug development.

Amino Acid Sequence↗