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Biomedical subjects

A Michel

Publications and source records attributed to A Michel.

At least 127 records · Page 7Linked to original sources
PubMed1995

Moving a hospital information system towards a client server architecture.

This paper is intended to give you an overview about the migration process of the Hospital Information System (HIS) at the University Hospital of Giessen towards an open client server based architecture. It describes the software architecture of the existing mainframe applications and the network interfaces involved in opening the centralized software architecture to a wide variety of remote applications.

Computer Communication Networks↗
PubMed1995

Pharmacological activities of imidazo[1,2-alpha]pyrazine derivatives.

The smooth muscle relaxant activity and other pharmacological properties of imidazo[1,2-alpha]pyrazine derivatives were compared with those of theophylline. Imidazo[1,2-alpha]pyrazine derivatives exhibited a potent smooth muscle relaxant activity regardless of the agent which had elicited the contraction and thus showed a broad spectrum of non specific smooth muscle relaxant activity. In the isolated guinea-pig atria, imidazo[1,2-alpha]pyrazine derivatives exhibited potent inotropic and chronotropic activities. As opposed to theophylline, the imidazo[1,2-alpha]pyrazine derivatives tested were unable to antagonize the adenosine-induced inhibition of spontaneous contractile activity of rabbit ileum. Furthermore, as opposed to theophylline, these derivatives did not exhibit a marked diuretic activity. Thus it appears that they do not act as adenosine receptor antagonists. Imidazo[1,2-alpha]pyrazine derivatives inhibited the total cAMP-phosphodiesterase (cAMP-PDE) and the total cGMP-phosphodiesterase (cGMP-PDE) activities of bovine trachea but with relatively low potencies, sharing a discrepancy between their activity on isolated tissues and their ability to inhibit PDE. It is suggested that imidazo[1,2-alpha]pyrazine derivatives may selectively inhibit type III and/or type IV phosphodiesterase isoenzymes involved in the regulation of the mechanical activity of cardiac and smooth muscle tissues.

Adenosine↗
PubMed1995

[Obstructive sleep apnea syndrome and cardiovascular diseases].

Obstructive sleep apnoea syndrome is due to pharyngeal obstruction of inspiratory airflow with preservation of thoraco-abdominal respiratory movements. This disease has been described for about thirty years, but is now the subject of growing interest. According to the increasingly abundant literature on this subject, OSAS is associated with essentially cardiovascular morbidity and mortality (systemic hypertension, pulmonary hypertension, heart failure, coronary heart disease, arrhythmias, cerebral vascular accidents and sudden death). The pathophysiology of its underlying mechanisms and its complications is complex and multifactorial. The diagnosis of this syndrome should be suspected on clinical interview (snoring, excessive daytime drowsiness, and apnoea during sleep) and is confirmed by polysomnography. Nasal continuous positive pressure with elimination of aggravating factors is the reference treatment in 1994. The diagnosis and management of this syndrome requires a multidisciplinary approach with collaboration between general practitioners, neurologists, maxillofacial/ENT surgeons, cardiologists and respiratory physicians.

Cardiovascular Diseases↗
PubMed1994

Estimates of antagonist affinities at P2X purinoceptors in rat vas deferens.

In functional studies pyridoxalphosphate-6-azophenyl-2',5'-disulphonic acid (iso-PPADS), suramin, GR200282 (4,4'-[carbonyl-bis(imino-3- benzoylimino)]-bis[5-hydroxy-naphthalene-2,7-disulfonic acid] tetrapotassium salt), cibacron blue, trypan blue and congo red, each produced specific antagonism of the contractile responses of isolated rat vas deferens, induced by alpha,beta-methylene ATP (alpha,beta-meATP), with antagonist pKB estimates of 6.6 +/- 0.3, 5.5 +/- 0.2, 5.1 +/- 0.3, 5.8 +/- 0.2, 4.7 +/- 0.2 and 4.6 +/- 0.2, respectively. In radioligand binding studies, iso-PPADS, suramin, cibacron blue, GR200282, trypan blue and congo red competed for the high affinity [3H]alpha,beta-meATP binding sites in rat vas deferens membranes with pKi estimates of 5.6 +/- 0.04, 5.5 +/- 0.08, 5.6 +/- 0.15, 5.6 +/- 0.04, 4.3 +/- 0.06 and 4.9 +/- 0.10, respectively. Comparison of pKB and pKi estimates revealed a good agreement between the two approaches for estimating measures of affinity for the putative antagonists, except in the case of iso-PPADS. However, we found that two populations of [3H]alpha,beta-meATP binding sites can be identified by iso-PPADS, 26.4% of these having low affinity (pKi of 4.4 +/- 0.2), and 73.6% having high affinity (pKi of 6.5 +/- 0.02) for iso-PPADS. The pKi of 6.5 obtained at the high affinity sites identified by iso-PPADS was close to the equivalent pKB value of 6.6 from functional studies. These studies therefore show a good agreement between pKB and pKi estimates for several antagonists, and suggest that the high affinity binding sites labelled with [3H]alpha,beta-meATP in rat vas deferens represents binding to functional P2X purinoceptors.

Adenosine Triphosphate↗
PubMed1994

Maturation of acute T-lymphoblastic leukemia cells after CD2 ligation and subsequent treatment with interleukin-2.

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL-2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high-affinity IL-2R.

Antibodies, Monoclonal↗
PubMed1994

Solid-state stereochemistry of (-)-scopolamine hydrobromide sesquihydrate, a new polymorph of the anticholinergic drug.

The solid-state structure of (-)-scopolamine hydrobromide sesquihydrate was determined by single-crystal X-ray diffraction analysis at low temperature. (Nr,C alpha-S)-(-)-Scopolamine hydrobromide sesquihydrate gives crystals belonging to the tetragonal space group P4(3)2(1)2, and at 180 K: a = 11.870(4), c = 26.193(3) A, V = 3691(1) A3, Z = 8, R(F) = 0.062, and Rw(F) = 0.059. Thermogravimetric analysis afforded a total weight loss of approximately 6%, consistent with a loss of 1.5 molecules of water and in accord with the sesquihydrate stoichiometry found by single-crystal X-ray crystallography. The unit cell dimensions, molecular structure, basic packing arrangement [minus the full water molecule], and the crystal system are all the same as that of the P4(1)2(1)2 hemihydrate form [R(F) = 0.09] reported earlier by Pauling and Petcher. This suggests that the previously reported "hemihydrate" description of the structure should be reconsidered. In addition to partial dehydration of the sesquihydrate crystal, non-observance of the eight water molecules might have arisen from their relatively large thermal motions at ambient temperature coupled with a lack of sufficient data versus the number of variable parameters. The phenyl ring syn-to-oxirane arrangement in the sesquihydrate form is the same as that in the corresponding crystalline methyliodide quaternary ammonium salt and in (-)-(Ns,C alpha-S)-hyoscyamine [atropine] hydrobromide, but differs from the elongated anti-to-oxirane arrangement in anhydrous (Nr,C alpha-S)-(-)-scopolamine hydrobromide.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography, X-Ray↗
PubMed1994

Grafting of a hepatitis B S-preS(2) T-cell epitope on lysozyme enhances the immunogenicity of lysozyme in responder mice primed with the T-cell epitope.

Subunit immunogens composed of well-defined T- and B-cell epitopes might represent a valuable approach to design vaccines. The reduction of the size of the T-cell epitope is clearly in the line of this strategy. In this study we evaluated the capacity of a hepatitis B S-preS(2) surface antigen-derived T-cell epitope (i.e., S2b) to enhance the humoral immune response towards lysozyme when covalently linked to this antigen. We hereby anticipated that new problems, related to processing of a subunit immunogen, may emerge when grafting minimalized T-cell epitopes on protein antigens. Indeed, insertion of a T-cell epitope containing peptide (i.e., S2b) in a new protein context does not warrant a correct processing of the T-cell epitope. To avoid such potential processing problems an acid labile linker between T-cell and B-cell epitopes was devised in order to provide a processing-independent cleavage site. Using a T-cell hybridoma specific for the S2b T-cell epitope the S2bC-lysozyme conjugate was found to be presented by functional antigen-presenting cells. However, fixed APC did not present the conjugate in vitro indicating that processing is required for the release and presentation of S2b. The ability of the conjugate to generate an enhanced immune response was investigated in vivo. In S2b-primed mice the S2bC-lysozyme conjugate was found to elicit a faster and higher anti-lysozyme humoral response, as compared to uncoupled mixtures of lysozyme and S2b.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Specific ligation of the HIV-1 viral envelope protein gp120 on human CD34+ bone marrow-derived progenitors.

The precise mechanisms of hematologic abnormalities observed during HIV infection remain unknown. In vitro experiments performed by various authors concerning the HIV toxicity on bone marrow-derived precursors did not allow them to determine whether this toxicity could be mediated through direct or non-direct effects, since it is today unclear if gp120 possesses a direct hematotoxic effect on human bone marrow progenies. The aim of our study was to determine whether labelled gp120 could specifically bind to the membrane of purified human normal CD34+ cells and to investigate the in vitro effect of the gp120 on their growth. To answer these questions, human CD34+ cells were purified from normal bone marrow samples, then labelled with monoclonal antibodies directed either against CD4 antigen or CD34 antigen and/or with FITC labelled gp120 and analyzed by FACS. Our results demonstrate the presence of about 5% of CD4+CD34+ cells and of nearly 12% of CD34+gp120+ precursors. Together with our results concerning the in vitro inhibitory effect of gp120 on the growth of the same purified CD34+ precursors, our data demonstrated the direct hematotoxic activity of HIV-derived gp120 and the possible HIV infection of hematopoietic progenitors through the interaction of gp 120 with CD34+ cell surface.

Antibodies, Monoclonal↗
PubMed1994

[Influence of kidney procurement techniques on urologic and vascular complications of the transplantation].

Surgical complications of renal transplantation, rejection and infectious diseases are factors contributing to poor renal graft survival. Factors directly concerning the donor can be involved in graft failure: age, medical history, causes of donor brain death. Urologic or arterial anatomic variations are often the source of difficult surgical conditions during renal transplantation. Technical errors during graft procurement must be avoided such as excess of traction or coagulation. Failure in perfusion preservation. As few renal grafts are available, it is thus essential to obtain optimal conditions to avoid failure in cadaver donor graft linked to technical errors during organ procurement.

Adolescent↗
PubMed1993

Defective calcium response in B-chronic lymphocytic leukemia cells. Alteration of early protein tyrosine phosphorylation and of the mechanism responsible for cell calcium influx.

To study defective signal transduction via the Ag receptor of B-chronic lymphocytic leukemia cells (B-CLL), we examine in this report the Ca2+ response triggered by anti-mu antibody in 23 patients previously classified in three phenotypic groups. Altered Ca2+ changes are essentially found in CLL group II whose leukemic cells are characterized by a marked expression of the CD11b Ag. B-CLL cells from patients with a defective Ca2+ response present an altered pattern of protein tyrosine phosphorylation after anti-mu stimulation in comparison with normal human B cells and B-CLL cells from patients having a normal Ca2+ response. Most of the proteins usually tyrosine phosphorylated after the triggering of cell-surface IgM are concerned. This includes the gamma 1 isoform of phospholipase C, although the protein is normally present in B-CLL cells. These findings suggest that the interruption of the phosphoinositide pathway in B-CLL cells is very proximal, at the level in the signaling cascade between activated surface Ig receptors and protein tyrosine kinases. Simultaneously, we demonstrate that some low responding patients exhibit a decreased Ca2+ response to thapsigargin, an agent known to release intracellular Ca2+ without inositol 1,4,5-trisphosphate production. This suggests that an altered functioning of the mechanism leading to the cell Ca2+ influx in B cells can be also involved in the decreased Ca2+ response observed in B-CLL cells.

Animals↗
PubMed1993

Solution- and solid-state structures of N-desmethylnefopam hydrochloride, a metabolite of the analgesic drug.

The solid-state structure of (+/-)-N-desmethylnefopam hydrochloride (1), a metabolite of the analgesic drug, was determined by single-crystal X-ray diffraction analysis. Compound 1 gave crystalline prisms belonging to the orthorhombic Pcab space group, and at ambient temperature (293 K), a = 9.939(2), b = 14.479(1), c = 20.148(3) A, V = 2899.5(8) A3, Z = 8, R(F) = 0.045, and Rw(F) = 0.025. The benzoxazocine ring of crystalline 1 is twisted into the boat-flattened (chair) [BfC] conformation, the phenyl ring resides in a relatively sterically unhindered exo-type ring position, whereas the O atom and NCH2Ar occupy sterically hindered positions between "boat" and "chair" regions. Dissolution of BfC crystalline 1 in CD2Cl2 solvent affords a dynamic conformational equilibrium (involving the putative twist-chair-flattened (chair) conformer) as shown by line broadening and weighted time-averaged vicinal coupling constants [-OCH2CH2N- segment] in the 1H NMR spectrum. The solution-state weighted time-averaged 50(1) degrees O-CH2-CH2-N dihedral angle, calculated by the R-ratio method, shows that the BfC conformation is the major contributor to time-averaged structure.

Analgesics↗
PubMed1993

Evaluation of the relaxant effects of SCA40, a novel charybdotoxin-sensitive potassium channel opener, in guinea-pig isolated trachealis.

1. Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. 2. SCA40 (0.01-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with 20 mM KCl but failed to inhibit completely the spasmogenic effects of 80 mM KCl. 3. Quinine (30 microM) antagonized the relaxant activity of SCA40 in 20 mM KCl-contracted guinea-pig isolated trachea. The ATP-sensitive K(+)-channel blocker, glibenclamide (3 microM), did not antagonize the relaxant activity of SCA40 in either 20 mM KCl or 1 microM carbachol-contracted isolated trachea. 4. SCA40 (0.01-10 microM) and isoprenaline (0.1 nM-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with carbachol 1 microM. 5. The large-conductance Ca(2+)-activated K(+)-channel blocker, charybdotoxin (60-180 nM), non-competitively antagonized the relaxant activity of isoprenaline on 1 microM carbachol-contracted trachea. The inhibition was characterized by rightward shifts of the isoprenaline concentration-relaxation curves with depression of their maxima. 6. The relaxant activity of SCA40 in 1 microM carbachol-contracted trachea was antagonized by charybdotoxin (60-600 nM) in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. 7. It is concluded that SCA40 is a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vitro. The relaxant activity of SCA40 does not involve ATP-sensitive K+-channels but rather large-conductance Ca2'-activated K+-channels or other charybdotoxin sensitive K+-channels.

Animals↗
PubMed1993

Cardiovascular effects of SCA40, a novel potassium channel opener, in rats.

1. Experiments have been performed to investigate the cardiovascular actions in the rat of SCA40, a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vivo and in vitro. 2. SCA40 (0.01-30 microM) caused a complete and concentration-dependent relaxation of rat isolated thoracic aorta contracted with 20 mM KCl but failed to inhibit completely the spasmogenic effects of 80 mM KCl. 3. The ATP-sensitive K(+)-channel blocker, glibenclamide (3 microM), failed to antagonize the relaxant action of SCA40 on 20 mM KCl-contracted rat isolated thoracic aorta. 4. SCA40 (0.001-100 microM) had dual effects on rat isolated atria. At low concentrations, SCA40 produced a concentration-dependent decrease in the rate and force of contractions. At higher concentrations (greater than 1 microM) SCA40 induced concentration-dependent increases of atrial rate and force. 5. In vivo, in normotensive Wistar rats, SCA40 elicited a dose-dependent (1-100 micrograms kg-1) decrease in mean arterial pressure which was accompanied by a moderate dose-dependent increase in heart rate. SCA40 (100 micrograms kg-1) had a slightly greater hypotensive effect than cromakalim (100 micrograms kg-1) but the duration of the hypotension was longer with cromakalim than with SCA40. 6. The hypotensive effect of SCA40 was not reduced by propranolol, atropine, NG-nitro-L-arginine methyl ester (L-NAME) or glibenclamide. 7. It is concluded that the mechanism by with SCA40 relaxes vascular smooth muscle in vitro and in vivo involves activation of K(+)-channels distinct from glibenclamide-sensitive ATP-sensitive K(+)-channels.

Animals↗
PubMed1993

Interleukin 4 inhibits the proliferation and promotes the maturation of human leukemic early B cells.

The effects of interleukin 4 (IL-4) on human leukemic precursor B-cell lines were investigated. Recombinant IL-4 (rIL-4) was added to three acute lymphoblastic leukemia-derived pre B-cell lines: Reh, Km3 and Nalm-6. Our results show that rIL-4 significantly decreases continuous proliferation of Reh and Km3 cells while Nalm-6 cells have a limited response in this respect. This rIL-4 effect is dose-dependent and can be neutralized by anti-IL-4 monoclonal antibody (mAb). Furthermore, rIL-4 down-regulated IL-3-induced proliferation of Reh cells. Phenotypic analysis of rIL-4-treated cells points to significant induction of surface marker maturation of leukemic cells by this cytokine. Together, these in vitro data suggest that IL-4: 1) inhibits the proliferation and 2) promotes the differentiation of certain human leukemic B-cell precursors.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1993

[Effects of toxins, apamine, charybdotoxin and iberiotoxin on the relaxation of the smooth muscular fiber induced by imidazo(1,2-a)pyrazine derivative].

Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. We investigated the effect of different toxins, known to be K(+)-channel blockers on guinea-pig smooth muscle relaxant activity of SCA40. The small conductance Ca(2+)-activated K(+)-channel blocker apamin (100 nM) did not antagonize the relaxant activity of SCA40 in 1 microM carbachol-contracted isolated guinea pig trachea. The large conductance Ca(2+)-activated K(+)-channel blocker, iberiotoxin (30, 60 and 180 nM) antagonized the relaxant activity of SCA40 in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. The relaxant activity of SCA40 in 1 microM carbachol-contracted isolated trachea was antagonized by both charybdotoxin (60 nM) and iberiotoxin (60 nM), but the antagonism induced by iberiotoxin appears to be more potent than that induced by charybdotoxin. It is concluded that the potent relaxant activity of SCA40 on guinea-pig airway smooth muscle in vitro involves a charybdotoxin and iberiotoxin sensitive K(+)-channel.

Animals↗
PubMed1993

Basket cells or shadow cells of Gumprecht: a scanning electron microscope study, and the correlation between percentages of basket cells, and cells with altered chromatin structure (dense cells), in chronic lymphocytic leukemia.

For over 50 years the received wisdom has been that the shadow cells of Gumprecht otherwise known as basket cells (BC) are in artefact, produced during preparation of films when a drop of blood is spread on a slide. The assumption has been that they are therefore of no significance. They are commonly seen in blood films from patients with lymphoproliferative syndromes and particularly in chronic lymphocytic leukemia (CLL). In 96 patients with CLL a statistically significant correlation existed between the basket cells observed in films and the lymphocytes with dense chromatin (DC) determined by flow-cytometry. There was no statistically significant correlation between the number of BC and DC, and the anatomic-clinical stage of the disease.

Chromatin↗
PubMed1993

Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy.

In Brown-Norway rats HgCl2 induces an autoimmune disease due to a T-dependent B cell polyclonal activation. This disease is marked by the production of numerous antibodies including antiglomerular basement membrane (GBM) antibodies. Rats exhibit a biphasic glomerulopathy with heavy proteinuria. Initially anti-GBM antibodies are found linearly deposited; they precede the appearance of membranous glomerulopathy. Rats recover spontaneously even if HgCl2 injections are pursued, but mechanisms at play are unclear. We have assessed the effects of transplanting the spleen from a BN rat, either at the acme of the disease or at the time of convalescence, into naive BN rats, some of which were then injected with HgCl2. Transplantation of a spleen from HgCl2-injected rats at the acme of the disease dramatically protects BN rats from all the manifestations of the mercury disease. BN rats transplanted with a spleen from HgCl2-injected rats at the time of convalescence only exhibited a typical membranous glomerulopathy with heavy proteinuria but without circulating anti-GBM antibodies. Antilaminin antibodies were eluted from the glomeruli. This study shows that spleen cells from HgCl2-injected rats are able to confer tolerance to HgCl2-induced autoimmunity. It also shows that some B cell clones escape this tolerance. Finally, this study strongly suggests that membranous glomerulopathy, responsible for proteinuria in this model, is related to the presence of antilaminin antibodies.

Animals↗