Biomedical subjects

A Michel

Publications and source records attributed to A Michel.

At least 109 records · Page 6Linked to original sources

PubMed1996

Different mechanisms involved in relaxation of guinea-pig trachea by endothelin-1 and -3.

The effects of endothelin-1 and endothelin-3 were investigated on carbachol-contracted guinea-pig isolated trachea. Endothelin-1 and endothelin-3 (0.1-100 nM) induced partial dose-dependent relaxation of the precontracted preparations. The endothelin-1-induced relaxation was markedly attenuated by haemoglobin (10 microM) and methylene blue (10 microM) and by epithelium removal. In contrast, endothelin-3-induced relaxation was not affected by haemoglobin, methylene blue or epithelium removal. The large conductance Ca(2+)-activated K(+)-channel blocker, charybdotoxin, antagonized the endothelin-1- and the endothelin-3-induced relaxation to the same extent. These results show that both endothelin-1 and endothelin-3 relaxant activities are modulated by charybdotoxin-sensitive K(+)-channels, while the nitric oxide pathway is only involved in endothelin-1 relaxant effects.

Animals↗

PubMed1996

Protein tyrosine kinases in activation signal of human basophils through the immunoglobulin E receptor type l.

Human basophils activated through high-affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) are involved in the late phase of the allergic reaction. To investigate the possible involvement of protein-tyrosine kinases in this activation we used human acute basophilic leukemia (ABL) cells in culture as well as a pure population of normal basophils in vitro-derived from human bone marrow precursor cells (HBMB). ABL cells were 50-80% basophils at various stages of maturation as assessed by staining, morphology, ultrastructure, and flow cytometry analysis, and only basophils in ABL cells expressed Fc epsilon RI. Aggregation of Fc epsilon RI by IgE and anti-IgE, IgE and antigen, or anti-Fc epsilon RI monoclonal antibodies on ABL cells or on HBMB, led to increased tyrosine phosphorylation of 120-, 100-, 80-, 72-, 50- to 65-, and 38-kDa substrates. Tyrosine phosphorylations in ABL cells were in basophils because 1) they were detected after a 5-s stimulation, 2) they were observed under conditions where mediator release is minimal, i.e., in the absence of extracellular calcium, 3) hapten addition during antigen stimulation resulted in almost total disappearance of tyrosine phosphorylations within 30 s. There was correlation between histamine release and tyrosine phosphorylation in anti-IgE dose-responses and in dose-responses of the tyrosine kinase inhibitor genistein. The tyrosine kinase p72syk was detected in the cells. Stimulation of ABL cells for 1 min resulted in extracellular calcium-independent tyrosine phosphorylation and activation of p72syk. Therefore, tyrosine kinases are involved in the early steps of human Fc epsilon RI signaling in basophils. Tyrosine kinases and their substrates could represent new potential therapeutic targets to prevent the development of the allergic reaction.

Aged↗

PubMed1996

Solution conformation by NMR and molecular modeling of three sulfide-free somatostatin octapeptide analogs compared to angiopeptin.

The conformation in dimethylsulfoxide of the somatostatin derivative angiopeptin and of three disulfide-free analogs was estimated by two-dimensional nuclear magnetic resonance spectroscopy at room temperature. The resulting 3D molecular graphics were compared and shown to reflect the observed differences in the inhibition of restenosis after rat aorta balloon injury by these octapeptide inhibitors. Angiopeptin and its active analog 2 displayed a relatively rigid conformation of the cyclic hexapeptide backbone due to the presence of two well-defined hydrogen bonds, further stabilized by a third hydrogen bond outside the ring. No such constraints were detected for the two biologically inactive analogs, which, compared to 2, had a two-atom longer or shorter hexapeptide ring. The well-defined structure of compound 2 may serve as an improved pharmacophore for this new class of drugs.

Amino Acid Sequence↗

PubMed1996

Smooth muscle relaxant activity of A1- and A2-selective adenosine receptor agonists in guinea pig trachea: involvement of potassium channels.

The relaxant activities of N6-cyclopentyladenosine (CPA), an A1-selective agonist, and of 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), a potent A2-receptor agonist, in the carbachol-contracted guinea pig isolated trachea have been evaluated. Both CPA and CPCA induced concentration-dependent relaxations of the guinea pig trachea, CPCA demonstrating a more potent but less efficient activity. 8-Cyclopentyl-1,3-dimethylxanthine (CPT) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (10 microM), both selective and potent A1-adenosine receptor antagonists, induced only a weak inhibition of CPA while 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM), a selective A2-adenosine receptor antagonist, failed to antagonize the relaxant activity of CPA. These results indicate that a major component of the tracheal relaxant activity of CPA occurred by a mechanism which is insensitive to the antagonist potency of A1- and A1-xanthine adenosine antagonists and therefore was not mediated by A1- or A1-adenosine receptors activation. The relaxant activity of CPCA was inhibited by DMPX, which supported the involvement of A2-adenosine receptors. Glibenclamide (10 microM), an inhibitor of KATP-channels, inhibited the relaxant activity of CPCA, whereas it was without effect on CPA. Iberiotoxin (180 nM), an inhibitor of the large-conductance CA2(+)-activated K+ channel, inhibited the relaxant action of CPA and CPCA. However, verapamil can offset the inhibition of CPA provided by iberiotoxin which suggests that such an antagonism does not represent an interaction between the toxin and CPA at the level of the large-conductance CA2(+)-activated K(+)-channel gating but rather functional antagonism attributable to the promotion of CA2+ influx by the toxin. In contrast, verapamil only partially reversed the inhibition of CPCA relaxant activity provided by iberiotoxin. Taken together, these results suggest that A2-adenosine receptor subtypes are coupled to KATP-channels and large-conductance CA2(+)-activated K(+)-channels in the guinea pig trachea whereas the unidentified adenosine receptor subtype, involved in CPA relaxant activity, is not.

Adenosine↗

PubMed1996

Effects of SCA40 on human bronchi and on guinea pig main bronchi in vitro. Comparison with cromakalim.

The aim of this study was to examine the activity of SCA40, a novel charybdotoxin-sensitive potassium channel opener, against a variety of spasmogens or against electrical field stimulation in guinea pig isolated main bronchi and in human isolated bronchi; the effects of SCA40 were compared with those of cromakalim. Like cromakalim, SCA40 reduced the contractility of guinea pig and human isolated bronchi precontracted with acetylcholine 10(-6) M or neurokinin A 10(-6) M, SCA40 being more efficient and more potent than cromakalim. Moreover, on guinea pig isolated main bronchi, SCA40 can exert a preventive effect on contractions induced by acetylcholine, neurokinin A or capsaicin, that is, it shifts to the right the concentration-effect curves of these substances, whereas cromakalim has no such effect. The effects of cromakalim were antagonized by glibenclamide 10(-5) M, whereas the effects of SCA40 were inhibited by tetraethylammonium (TEA 10(-2) M) and charybdotoxin (3 x 10(-8) M), but this inhibitory effect of TEA was reversed by nifedipine (10(-6) M). Electrical field stimulation of guinea pig isolated main bronchi induced two successive contractile responses. Both contractions were significantly reduced by SCA40 (10(-6) and 10(-5) M) and cromakalim (10(-5) M). Since cromakalim was unable to inhibit the effects of acetylcholine or neurokinin A, it might be suggested that for this latter compound the inhibition seems to take place prejunctionally and to affect the release of neuromediators produced by electrical field stimulation. In contrast, in the case of SCA40, a postjunctional effect seems to be likely, owing to its preventive effects, although a prejunctional effect cannot be excluded. Finally, on guinea pig isolated main bronchi, SCA40 (10(-8)-10(-6) M) did not potentiate the relaxant effect of isoprenaline or sodium nitroprusside, suggesting a lack of functional manifestation of inhibition of phosphodiesterase for these concentrations. In conclusion, these results demonstrate that SCA40 is a potent and efficient relaxant of guinea pig and human airway smooth muscle, and is able to inhibit, in the guinea pig isolated main bronchi, the contractions induced by electrical field stimulation. It has an effect on TEA-sensitive K+ channels, but this effect is probably not involved in its relaxant effect which does not also rest on an inhibitory effect of phosphodiesterase.

Acetylcholine↗

PubMed1996

Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim.

1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and PDE V (4.32 +/- 0.11; n = 4). 3. Human polymorphonuclear leukocytes (PMNs) stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP) produced a concentration-dependent superoxide anion generation and elastase release. SCA40 (1 nM-10 microM) produced a concentration-related inhibition of FMLP (30 nM approximately EC50)-induced superoxide production (-log IC50 = 5.48 +/- 0.10; n = 6) and elastase release (-log IC50 = 5.50 +/- 0.26; n = 6). Rolipram was an effective inhibitor of superoxide generation and elastase release (-log IC50 values approximately 8) while SKF94120 and levcromakalim were scarcely effective. 4. FMLP (30 nM) and thimerosal (20 microM) induced leukotriene B4 production and elevation of intracellular calcium concentration in human PMNs. The production of leukotriene B4 was inhibited by SCA40 in a concentration-related manner (-log IC50 = 5.94 +/- 0.22; n = 6) but SCA40 was less effective against the elevation of intracellular calcium. Rolipram was an effective inhibitor of leukotriene B4 synthesis (-log IC50 approximately 7) and intracellular calcium elevation (-log IC50 approximately 6) while SKF94120 and levcromakalim were scarcely effective. 5. It is concluded that SCA40 is an effective inhibitor of the inherent tone of human isolated bronchus. The bronchodilatation produced by SCA40 appears mainly related to PDE inhibition since the potency of SCA40 as a relaxant of human isolated bronchus was found to be close to its potency as inhibitor of PDE III activity isolated from human bronchus. In addition, SCA40 exhibited inhibitory effects on human PMN function stimulated by FMLP. These effects may be related to the ability of SCA40 to inhibit PDE IV from human PMNs while the contribution of PDE V inhibition is uncertain. We found no evidence of a role for levcromakalim-sensitive plasmalemmal K+-channels in human PMNs.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1996

Tuberculosis in buffaloes (Syncerus caffer) in the Kruger National Park: spread of the disease to other species.

Tuberculosis, caused by Mycobacterium bovis, was recently diagnosed in a cheetah (Acinonyx jubatus), two lions (Panthera leo) and a chacma baboon (Papio ursinus) from the Kruger National Park (KNP). It is assumed that they contracted the disease directly or indirectly from tuberculous buffaloes in the park. Tuberculous granulomatous lesions in the lungs were extensive and constituted the predominant changes in all three animal species. These pulmonary lesions included tuberculous bronchiolitis and cavitation which would facilitate dissemination of M. bovis into the environment. Spread of the disease to free-ranging species (in which it has not previously been reported) that may act as maintenance hosts of the infection, is a matter of serious concern.

Acinonyx↗

PubMed1996

Designing a low cost bedside workstation for intensive care units.

The paper describes the design and implementation of a software architecture for a low cost bedside workstation for intensive care units. The development is fully integrated into the information infrastructure of the existing hospital information system (HIS) at the University Hospital of Giessen. It provides cost efficient and reliable access for data entry and review from the HIS database from within patient rooms, even in very space limited environments. The architecture further supports automatical data input from medical devices. First results from three different intensive care units are reported.

Computer Systems↗

PubMed1996

[International trade in living penaeid shrimp between countries in the Pacific and the Atlantic areas and in Europe].

The tremendous development of penaeid shrimp culture across the world over the past twenty years has led to international trade in eggs, larvae and spawners of the best shrimp species for aquaculture. Trade has involved, in particular, the following species: -Penaeus japonicus from Japan to Europe, the Pacific Islands and South America -P. monodon from South-East Asia to almost all tropical countries -P. vannamei and P. stylirostris from countries along the Pacific coast of South and central America to the United States of America, the islands of the South Pacific, countries along the Atlantic coast of the Americas and certain countries in Africa. In the 1980s, research conducted by American and French teams enabled the breeding of stocks of spawners in captivity. This resulted in the establishment of lines of captive broodstock outside natural areas of distribution, and the development of new breeding farms in previously unproductive regions. Trade related to movements of these species is facilitated by the absence of legislation in most countries; even when such legislation does exist, it is not always applied. These practices have led to the rapid development of world shrimp production, but have also contributed to the dissemination of pathogens. In recent years, the occurrence of serious epizootics - occasioning heavy losses world-wide - has led to a more cautious approach involving trade of post-larvae obtained from captive broodstock in which thorough control measures have been implemented for known diseases. Trade in wild shrimp will probably be abandoned progressively, to avoid the risk of introducing new pathogens. The main challenges for research in the near future are the development of diagnostic tools, to enable continuous control of captive broodstock, and the selection of strains which are resistant to the principal pathogens affecting these species.

Animals↗

PubMed1995

A novel transcriptional activator originating from an upstream promoter in human growth hormone gene.

Transcription of the human growth hormone gene can start in vitro and in vivo 197 base pairs upstream from the cap site of growth hormone mRNA (Courtois, S. J., Lafontaine, D., and Rousseau, G. G. (1992) J. Biol. Chem. 267, 19736-19743). We have now characterized the mRNA that originates from this optional promoter and have found that it occurs in human hypophysis and placenta but not in 10 other tissues. This mRNA contains an open reading frame for a protein of 107 residues that shares sequence similarity with three domains of hepatic nuclear factor-1alpha. With antibodies directed against a peptide corresponding to the C terminus of this protein, immunoreactive material was detected in a subset of cells of the adenohypophysis. When fused to the DNA-binding domain of the yeast transcription factor GAL4, the protein stimulated transcription from a GAL4-sensitive reporter gene in transiently transfected pituitary and placental cells.

Amino Acid Sequence↗

PubMed1995

Synthesis and processing of bovine herpesvirus-1 glycoprotein H.

The translation product of the bovine herpesvirus-1 (BHV-1) gH gene was identified and characterized. Synthetic peptides were used to generate specific antisera and a glycoprotein of 108K was precipitated by one of the antisera. Cross-immunoprecipitations with monoclonal antibodies to BHV-1 glycoprotein gp108 and the anti-gH peptide antiserum demonstrated that gp108 is the translation product of the gH open reading frame. Glycoprotein gH synthesis and intracellular processing was analyzed in infected Madin-Darby bovine kidney cells using anti-gp 108 monoclonal antibodies. Glycoprotein gH is expressed as a beta-gamma protein and could be detected by radioimmunoprecipitation as early as 2 hr postinfection. Cotranslational N-glycosylation of gH is essential for the recognition by monoclonal antibodies, suggesting that N-linked glycans are involved in protein folding or that they are targets for most of monoclonal antibodies used in this study.

Amino Acid Sequence↗

PubMed1995

The N- and C-termini of the tricarboxylate carrier are exposed to the cytoplasmic side of the inner mitochondrial membrane.

Polyclonal antibodies were raised in rabbits against two synthetic peptides corresponding to the N- and C-terminal regions of the rat-liver mitochondrial tricarboxylate carrier. ELISA tests performed with intact and permeabilized rat-liver mitoplasts showed that both anti-N-terminal and anti-C-terminal antibodies bind only to the cytoplasmic surface of the inner membrane, indicating that both termini of the membrane-bound tricarboxylate carrier are exposed to the mitochondrial intermembrane space. Furthermore, tryptic digestion of intact mitoplasts markedly decreased the binding of anti-N-terminal and anti-C-terminal antibodies to the tricarboxylate carrier. These results are consistent with an arrangement of the tricarboxylate carrier monomer into an even number of transmembrane segments, with the N- and C-termini protruding toward the cytosol.

Amino Acid Sequence↗

PubMed1995

Sequence, characterization and localization of a cysteine proteinase cathepsin L in Schistosoma mansoni.

A cDNA encoding Schistosoma mansoni cathepsin L was isolated from a cDNA library and sequenced. Alignment of the proposed amino-acid sequence with known members of cathepsin L shows highest homologies with sequences from mouse and rat. An expression plasmid was constructed in Escherichia coli to produce recombinant schistosome cathepsin L with an extension of six histidines at its N terminus. Using antibodies raised against the purified fusion protein, two polypeptide bands with approx. molecular masses of 38 and 31 kDa were identified in a schistosome extract. By use of specific radioiodinated inhibitors, a radioactively labeled protein could be detected at 31 kDa, suggesting that this is the active mature enzyme. The larger protein of 38 kDa did not react with the inhibitor, indicating that it represents the inactive precursor molecule. Immunohistological experiments revealed that the proteinase is localized in structures associated with the reproductive system of females and with the subtegumental region of the gynecophoric canal of males. However, Northern blot hybridization demonstrates that more transcripts are present in female parasites than in males. Genomic Southern blotting suggests that schistosome cathepsin L is expressed from a single-copy gene.

Amino Acid Sequence↗

PubMed1995

A female-specific cDNA sequence of Schistosoma mansoni encoding a mucin-like protein that is expressed in the epithelial cells of the reproductive duct.

Seven cDNA clones of Schistosoma mansoni containing the C-terminal part of the deduced sequence of a mucin-like protein have been identified. The protein contains 28% threonines, 20% serines, and has a pI of 3.4. On Northern blots of RNA of adult worms, the cDNA clones detect 2 transcripts of 1.65 and 4.2 kb which are expressed only in female worms. The tissue of gene expression, as revealed by in situ hybridization, is the epithelium surrounding the female reproduction duct proximal to its entrance into the ootype. Accumulation of N-glycosylation sites suggests that the protein, like other mucins, might form a protective layer, coating the lining of the duct. Regarding its acidic pI, we hypothesize a role in preventing premature egg-shell formation. This is the first female-specifically transcribed sequence, hitherto known in S. mansoni that is not expressed in the vitellaria.

Amino Acid Sequence↗

PubMed1995

New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature.

A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities. To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31). Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia. This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym "cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and migraine" (CADASILM) is proposed to better describe this particular subvariety of CADASIL.

Adult↗

PubMed1995

[Kidney injuries due to skiing].

From 1974 to 1993, the authors admitted 212 patients with renal trauma to their department. A large proportion of these cases were due to skiing accidents. Based on a retrospective study of 78 patients admitted to the Grenoble urology department, the authors describe the features of this trauma. 91% of patients were males with a mean age of 27.5 years, with 9% of type III trauma. Treatment was surgical in 55% of cases. Total nephrectomy was performed in 21% of patients. Partial nephrectomy was performed in 25.5% of cases, with a morbidity of 45%, predominantly consisting of fistulas.

Adolescent↗

PubMed1995

Pseudoneoplastic xanthogranulomatous pyelonephritis. A typical clinical presentation but unusual diagnosis and treatment.

Xanthogranulomatous pyelonephritis is a rare disease that may mimic various renal lesions, especially renal tumors, in its focal form. We report a case of pseudoneoplastic xanthogranulomatous pyelonephritis in a young woman. This case is unusual, because it was diagnosed by a percutaneous renal puncture and furthermore total renal recovery was achieved by antibiotic treatment alone.

Adult↗

PubMed1995

Endothelin-1 and endothelin-3 relax isolated guinea pig trachea through different mechanisms.

The effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) were investigated on carbachol-contracted guinea-pig trachea. ET-1 and ET-3 induced a dose-dependent relaxation of the precontracted preparations. ET-1-induced relaxation was attenuated by hemoglobin and methylene blue. By contrast, ET-3-induced relaxation was not affected by hemoglobin or methylene blue. The large conductance Ca(2+)-activated K(+)-channel blocker charybdotoxin antagonized ET-1- and ET-3-induced relaxations. These results show that charybdotoxin-sensitive K+ channels are involved in both ET-1 and ET-3 relaxant activities, whereas the nitric oxide pathway is involved only in ET-1 relaxant effects.

Animals↗