Search PubMed⌕ Search

Biomedical subjects

M Bouvier

Publications and source records attributed to M Bouvier.

At least 91 records · Page 5Linked to original sources

Agonist-induced desensitization of dopamine D1 receptor-stimulated adenylyl cyclase activity is temporally and biochemically separated from D1 receptor internalization.

The regulation of the dopamine D1 receptor was investigated by using c-myc epitope-tagged D1 receptors expressed in Sf9 (fall armyworm ovary) cells. Treatment of D1 receptors with 10 microM dopamine for 15 min led to a loss of the dopamine-detected high-affinity state of the receptor accompanying a 40% reduction in the ability of the receptor to mediate maximal dopamine stimulation of adenylyl cyclase activity. After 60 min of agonist exposure, 45 min after the occurrence of desensitization, 28% of the cell surface receptors were internalized into an intracellular light vesicular membrane fraction as determined by radioligand binding and supported by photoaffinity labeling, immunocytochemical staining, and immunoblot analysis. Pretreatment of cells with concanavalin A or sucrose completely blocked agonist-induced D1 receptor internalization without preventing agonist-induced desensitization, indicating a biochemical separation of these processes. Collectively, these findings indicate that the desensitization of D1 receptor-coupled adenylyl cyclase activity and D1 receptor internalization are temporarily and biochemically distinct mechanisms regulating D1 receptor function following agonist activation.

Adenylyl Cyclases↗

High prevalence of hepatitis B, C, and E markers in young sexually active adults from the Central African Republic.

The Central African Republic is located in tropical Africa, where both the human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are highly endemic. The exact prevalence of hepatitis C virus (HCV) and hepatitis E virus (HEV) markers in this country is unknown. The aim of the study was to determine, according to HIV and HBV serostatus, the prevalence of these markers in young sexually active adults in the Central African Republic. One hundred and fifty-seven consecutive patients attending the National Centre for Sexually Transmitted Diseases in Bangui were included. The following serological markers were examined: (i) anti-HIV1 and anti-HIV2 antibodies; (ii) markers of HBV infection; (iii) anti-HCV antibodies; (iv) anti-HEV antibodies. Anti-HIV1 antibodies were found in 31 of the 157 patients (20%). The prevalence of anti-HBc antibodies, reflecting exposure to HBV, was 140/157 (89%) and 45 had detectable anti-HBs antibodies. Twenty-two patients (14%) were chronic carriers of hepatitis B surface antigen (HBsAg), but only one was HBe antigen-positive. Anti-HCV antibodies were found in 8 persons (5%) and anti-HEV antibodies in 38 (24%). No difference was found in the prevalence of these markers according to the presence or absence of anti-HIV antibodies. This study confirms the high rate of HIV infection, HBV exposure and chronic carriage of HBsAg in sexually active young adults in the Central African Republic. A high prevalence of HCV markers was found in this population, similar to that reported in neighbouring countries, together with a high rate of HEV markers, suggesting that HEV is endemic in this region.

Adolescent↗

Pitfall of stiff shoulder: inveterated posterior dislocation.

The authors relate the observation of an inveterated bilateral posterior dislocation, occurring during a generalized epileptic attack and mimicking a painful stiff shoulder. The clinical signs (i.e. aetiologic circumstances causing a forced internal rotation, limitation or absence of external rotation) and radiological data, especially the necessity of a profile X-ray, which lead to the diagnostic are reiterated. The interest of computerized tomography in the pre-operative assessment is underscored.

Epilepsy, Tonic-Clonic↗

CT and MRI evaluation of tenosynovitis of the rheumatoid hindfoot.

Thirty-nine patients with rheumatoid arthritis who had presented with tarsitis before, were investigated at the level of the rearfoot. The first 17 patients had CT with previous tenography when it was possible; the following 22 patients had MRI with gadolinium injection. Tendon involvement appeared in 52.9% of the cases on CT, and in 90% of the feet on MRI; therefore, in case of clinical or radiological signs of tarsitis, it appears that tendon involvement must be suspected. With the two procedures the tibialis posterior tendon lesions were very predominant. In the majority of the patients (31/39), there was associated involvement of two or more tendons. If there is a ruptured tendon, the authors think that one must be cautious with surgical tendinous transfer; indeed, the long-term results of this surgical procedure present a strong probability of being compromised in rheumatoid arthritis which is a progressive disease.

Adult↗

Hepatitis C virus infection and autoimmune thrombocytopenic purpura.

BACKGROUND/AIMS: Chronic hepatitis C virus infections are often associated with extra-hepatic immunological manifestations, including various autoimmune disorders. The aims of this study were: (i) to determine the prevalence of hepatitis C virus markers in patients with autoimmune thrombocytopenic purpura, and (ii) to determine whether a relationship could exist between autoimmune thrombocytopenic purpura and hepatitis C virus infections. METHODS: One hundred and thirty-nine patients with autoimmune thrombocytopenic purpura (45 men, 94 women, mean age 42 years, range 16-90) were studied. RESULTS: Anti-HCV antibodies were sought in their first and last available cryopreserved sera. In case of seropositivity, all their available cryopreserved sera were tested for anti-HCV antibodies and for HCV-RNA. Anti-HCV antibodies were detected in 14 of the 139 patients (10%). Four patients had transient anti-HCV seropositivity due to passive transfer of anti-HCV antibodies secondary to the infusion of intravenous immunoglobulin concentrates. Three patients seroconverted during follow up, due to intravenous drug use in one case, transfusion of non-HCV-screened blood units in one case, and infusion of intravenous immunoglobulins in one case. Seven patients had chronic hepatitis C discovered at the same time as autoimmune thrombocytopenic purpura. In two of them, hepatitis C virus transmission was the consequence of autoimmune thrombocytopenic purpura treatment but, in five cases, hepatitis C virus infection predated autoimmune thrombocytopenic purpura, so that the role of hepatitis C virus in autoimmune thrombocytopenic purpura could be suggested. CONCLUSIONS: Whereas hepatitis C virus does not appear to be the main etiological agent of autoimmune thrombocytopenic purpura can be envisaged. On the other hand, treatment of autoimmune thrombocytopenic purpura or autoimmune thrombocytopenic purpura-related symptoms by blood product infusion can be complicated by hepatitis C virus transmission.

Adolescent↗

Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients with chronic hepatitis C.

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible, at least in part, for the antiviral state established in cells in response to viral infections. The purpose of this work was to study the relationship between hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis C. Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigated, as well as PBMC of 10 control subjects. Then, the patients were treated with 3 mu interferon-alpha 2a three times per week. At month 3 of therapy, PBMC were sampled. Of the total PBMC samples obtained, half were used for determination of in vivo 2-5OAS activity. The remaining cells were cultured for 24 h in either the absence or presence of 500 U/ml of interferon-alpha 2a for the determination of in vitro 2-5OAS activity. The mean basal in vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in controls (p < 0.01). Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a "branched DNA"-based assay. Before treatment, interferon-alpha was detected in the serum of 2 patients in 27. After a 24 h culture of PBMC in the presence of interferon, in vitro 2-5OAS activity was significantly induced in the PBMC of both the patients and the controls. However, in vitro induction of 2-5OAS activity was significantly lower in the PBMC of the patients than in the PBMC of the controls (p < 0.01). At month 3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p < 0.0001). In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at month 3 of therapy were not significantly different. In conclusion, in vivo 2-5OAS activity is significantly induced in patients with chronic hepatitis C, but endogenously produced interferon-alpha does not seem to be involved. Chronic induction of 2-5OAS activity results in a decreased sensitivity of PBMC to exogenous interferon induction. Whether this phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.

2',5'-Oligoadenylate Synthetase↗

sIL-2R levels in rheumatoid arthritis: poor correlation with clinical activity is due in part to disease duration.

The serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in an attempt to determine whether they correlated with 'disease activity' in 59 patients suffering from rheumatoid arthritis. Our results indicate that serum levels of sIL-2R do not permit patients to be classified as having active or inactive disease according to standard clinical indices. A correlation between sIL-2R and disease duration could offer one explanation for the current discrepancies found in the literature.

Aged↗

Functional effects of long-term activation on human beta 2- and beta 3-adrenoceptor signalling.

The functional effects of long-term activation of beta-adrenoceptors were investigated by measuring adenylyl cyclase activity, cyclic AMP accumulation and cyclic AMP-dependent protein kinase activity in CHW and L cells expressing either human beta 2- or beta 3-adrenoceptors. Pre-incubation of CHW and L cells expressing beta 2-adrenoceptors with 10 microM isoprenaline for 24 h produced a marked reduction in the total receptor number and dramatically reduced the capacity of the receptor to stimulate adenylyl cyclase maximally. In contrast, the ability of beta 3-adrenoceptors number was observed in L but not in CHW cells. Maximal levels of intracellular cyclic AMP concentrations were reached during the first hour of receptor activation with isoprenaline in all four cell lines. In the absence of phosphodiesterase inhibitors, cyclic AMP decreased to basal levels within 24 h of continuous stimulation. This phenomenon occurred more rapidly in cells expressing the beta 2- than the beta 3-adrenoceptors. These results confirm that, at the level of adenylyl cyclase stimulation and cyclic AMP accumulation, the beta 3-adrenoceptor is more resistant than the beta 2-adrenoceptor to long-term desensitization. However, when cyclic AMP-dependent protein kinase activity was considered, a 24 h stimulation of beta 2- and when cyclic AMP-dependent protein kinase activity was considered, a 24 h stimulation of beta 2- and beta 3-adrenoceptor expressing cells led to the desensitization of the kinase in L but not in CHW cells. In conclusion, long-term desensitization may have distinct functional effects on cell signalling depending on the receptor subtype and the cell type considered. These findings might have practical implications for future strategies involving long-term therapies with receptor agonists.

Adenylyl Cyclases↗

Characterization of the vasorelaxant activity of tyramine and other phenylethylamines in rat aorta.

We recently reported that tyramine caused concentration-dependent relaxation of rat aorta, which was endothelium independent and was not exerted via alpha 1-adrenoceptors (AR), alpha 2AR, beta 1AR, beta 2AR, or receptors for 5-hydroxytryptamine, histamine, and adenosine. The present studies were done on endothelium-denuded strips to determine structure-vasorelaxant activity after blockade of beta AR by propranolol plus irreversible blockade of alpha 1AR with benextramine. Vasorelaxation under these conditions was limited to noncatecholamines, and their vasorelaxant potencies were methoxyphenamine > tyramine > p-hydroxyephedrine > L-amphetamine > L-ephedrine > phenylethylamine > synephrine > methoxamine > octopamine. beta 3AR agonists (BRL 37344 and CGP 12177A) did not produce vasorelaxation, although tyramine could compete for cyanopindolol binding to murine L cells expressing human beta 2AR or beta 3AR. There was no significant specific binding of [3H]tyramine to aortic membrane preparations after the inhibition of monamine oxidase. Yohimbine, which has a high affinity for Drosophila tyramine receptors, also caused dose-dependent vasorelaxation like tyramine. It is concluded that tyramine and several other phenylethylamines produce relaxation of rat aorta, which does not involve any of the known adrenoceptors but may be exerted via novel tyramine receptors.

Animals↗

Serotonergic antagonists differentially inhibit spontaneous activity and decrease ligand binding capacity of the rat 5-hydroxytryptamine type 2C receptor in Sf9 cells.

The activities of serotonergic antagonists as inverse agonists at the rat 5-hydroxytryptamine (5-HT)2C serotonin receptor were compared with their potencies in promoting receptor "down-regulation," after expression of the recombinant receptor in the baculovirus/Sf9 insect cell system. Baculovirus expression yielded high levels of 5-HT2C receptors (up to 10(6) receptors/cell), which were functionally coupled to polyphosphoinositide turnover in Sf9 cells through a pertussis toxin-insensitive pathway. The expressed receptor exhibited spontaneous activation of inositol phosphate production, which was inhibited in a dose-dependent manner by serotonergic antagonists, consistent with inverse agonist activity. The potencies of antagonists as inverse agonists correlated with their respective binding affinities determined in competition binding studies with membrane preparations. The maximal inhibition of spontaneous activity ranged from 32% inhibition for mianserin to no effect for spiroxatrine, indicating that antagonists differ in their intrinsic inverse efficacies. Antagonist treatment of intact Sf9 cells or membranes containing the 5-HT2C receptor, followed by washout of residual drug, resulted in a decrease (up to 90%) in the number of binding sites for [3H]mesulergine and [3H]5-HT, with no change in the affinity for [3H]mesulergine. The decrease in binding was irreversible, was not due to the presence of residual antagonist, and was not observed after treatment with agonists. This effect of antagonists in membranes was dose dependent, but the rank order of potency was clearly different from that for inverse agonist activity, indicating that the two effects reflect distinct actions of antagonists at the 5-HT2C receptor. The relative abilities of antagonists to produce loss of binding showed a good correlation with their reported abilities to down-regulate 5-HT2 receptors in vivo after chronic treatment, suggesting that these actions reflect the same underlying process.

Animals↗

Vertebral osteomyelitis due to Capnocytophaga.

The first case of vertebral Capnocytophaga infection in an immunocompetent subject is reported. The patient was a 75-year-old woman with low back pain and a decline in general health. Plain roentgenograms disclosed erosions in the upper endplate of L4 and the lower endplate of L3 with no lesions of the intervening disk. Magnetic resonance imaging confirmed that the disk was normal. The organism was identified only by a repeat vertebral biopsy with bacteriologic cultures in a CO2-enriched atmosphere. The patient achieved a full recovery. Patients with suspected bone infections should be evaluated for portals of entry (Capnocytophaga is a normal inhabitant of the oral cavity) and should undergo multiple microbiological studies aimed at detecting a broad range of organisms.

Aged↗

Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules.

An influenza virus matrix peptide in which either the charged amino or carboxyl terminus was substituted by methyl groups promoted folding of the class I human histocompatibility antigen (HLA-A2). A peptide modified at both termini did not promote stable folding. The thermal stability of HLA-A2 complexed with peptides that did not have either terminus was approximately 22 degrees C lower than that of the control peptide, whereas matrix peptide in which both anchor positions were substituted by alanines had its stability decreased by only 5.5 degrees C. Thus, the conserved major histocompatibility complex class I residues at both ends of the peptide binding site form energetically important sites for binding the termini of short peptides.

Amino Acid Sequence↗

Cell-specific down-regulation of the beta 3-adrenergic receptor.

Previous studies have shown that beta 3-adrenergic receptors, in contrast to the beta 1 and beta 2 subtypes, do not undergo desensitization following short term activation (minutes) with agonists. Longer activation (hours) has been shown to induce desensitization of the beta 3-adrenergic receptor in some, but not all, cases, suggesting that cell- or species-specific mechanisms may be involved. We investigated the contribution of the cell type to the pattern of beta 3-adrenergic receptor long term desensitization by studying, in parallel, two cell lines (Chinese hamster fibroblasts and murine Ltk- cells) expressing the human beta 3-adrenergic receptor. Sustained agonist-promoted down-regulation of the beta 3-adrenergic receptor could be induced in Ltk- cells, whereas only a transient and weak reduction of receptor number was observed in Chinese hamster fibroblasts. The half-life of the beta 3-adrenergic receptor was not affected by the agonist activation in either cell line, indicating that in contrast to the beta 2-adrenergic receptor, degradation of preexisting receptor protein does not contribute to down-regulation. Sustained reduction of receptor RNA levels, monitored by reverse transcriptase polymerase chain reaction, was exclusively shown in Ltk- cells and probably accounted for most of the observed down-regulation. Differences in the ability of the receptor to stimulate adenylyl cyclase activity in the two cell lines may be responsible for the distinct patterns of beta 3-adrenergic receptor down-regulation.

Adenylyl Cyclases↗

Effects of trandolapril on the sympathetic tone and reactivity in systemic hypertension.

Hemodynamic and autonomic evaluations were carried out after 2-3 weeks of treatment with placebo and at the end of 4 weeks of treatment with an angiotensin converting enzyme (ACE) inhibitor, trandolapril, 2 mg/day in 18 hypertensive patients (average age, 48 +/- 2 years) of either sex. This treatment lowered the mean arterial pressure in the whole group from 112 to 105 mm Hg (p < 0.05) without significant changes in basal heart rate or norepinephrine (NE) and epinephrine plasma levels. Based on daytime ambulatory blood pressure monitoring, the patients were separated into 2 equal groups of 9 patients: the better responders (R), with an average decrease in mean arterial pressure of 12 mm Hg, and the lesser responders (NR), with an average fall of mean arterial pressure of 2 mm Hg. Before treatment, the R group had a higher resting heart rate, a lower cardiac output (-16%), and a higher peripheral resistance (+22%) than the NR group (difference not significant). Moreover, the R group was also observed to have a 33% higher plasma NE level (p < 0.05) in the supine position, associated with a 52% higher NE response to standing (p < 0.05), and a 40% lower number of beta-adrenergic receptors on lymphocytes, suggesting a higher sympathetic tone and reactivity in that group. Following treatment with the ACE inhibitor, heart rate and plasma NE levels were not altered significantly in either group, suggesting a blunting of the baroreflex response concomitant with the lowered blood pressure, especially in the R group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗