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Biomedical subjects

A Michel

Publications and source records attributed to A Michel.

At least 163 records · Page 9Linked to original sources
PubMed1990

Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat.

The metabolism of atrial natriuretic peptide (ANP) and Cys-105-Phe-106-cleaved ANP (ANP) was studied during constant infusion of 125I-labelled peptides in rats. Analysis of circulating radioactivity indicated rapid clearance of ANP and ANP', with mean half-lives of 0.42 and 1.04 min respectively. H.p.l.c. fractionation of plasma taken during the infusion of labelled ANP revealed the presence of three radioactive fragments, the major one co-eluting with 125I-ANP'. These fragments correspond to cleavage products previously found to be generated in vitro by the action of endopeptidase 24.11 (E-24.11). On evaluating the effects of peptidase inhibitors, a significant increase in the half-life of ANP was observed with phosphoramidon (t1/2 7.8 min) and aprotinin (t1/2 5.4 min). A maximal inhibition of ANP degradation was obtained when both inhibitors were given simultaneously (t1/2 15 min). In blood samples taken during infusion of 125I-ANP and phosphoramidon, the intact peptide accounted for more than 90% of total circulating radioactivity, and no cleavage product was present in detectable amounts. Phosphoramidon had no effect on the metabolism of infused ANP'. In contrast, when 125I-ANP' was infused together with aprotinin, the rate of degradation of the infused peptide was reduced by more than 80%. It is proposed that two different peptidase activities, E-24.11 and a kallikrein-like proteinase, are responsible for the cleavage of ANP in the circulation. The Cys-Phe-cleaved ANP would in turn be degraded by kallikrein and not by E-24.11.

Amino Acid Sequence↗
PubMed1990

Feeding pattern of liver-transplanted rats.

It has been proposed that the liver is involved in the control of food intake (FI). Various studies utilizing hepatic vagotomy have cast doubt on the role of hepatic metabolic receptors. Feeding patterns of male adult Lewis rats were continuously recorded in one group of animals after orthotopic liver transplantation (T), without reestablishing arterial flow. Rats of a second group were dearterialized (D) and had their livers freed from the hepatic pedicle, while rats of a third group were laparotomized (L) and served as sham-operated controls. Meal pattern analyses and body weight (BW) changes were followed after surgery. When T rats began to recover BW, a fourth nonoperated control group (C) was added with BW paired to the T group. From days 15 to 25 the T rats gained significantly less BW than C rats and their 24-hour FI was reduced: daytime FI was augmented while nighttime FI was decreased. Meal number was unchanged. Daytime meal size was increased while nighttime meal size was diminished. Between days 50-60, the BW gain of the T group was nearly identical to that of D or L rats from days 15-25. Data from these two periods were compared. The 24-hour FI was identical, nighttime FI remained significantly lower in T rats. Because of variation in BW recovery of the T rats an additional comparison was made between the T rats after they recovered their BW following surgery, and the D and L rats (days 15-25). All feeding pattern parameters were identical in T, D and L rats. Liver transplantation was followed only by small long-lasting changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The use of Gd-DOTA in magnetic resonance imaging of experimentally induced mammary tumors.

Gd-DOTA contrast enhancement of MR images was evaluated on induced mammary tumors in female rats. A single intravenous injection of the carcinogenic N-nitrosourea ENU was administered to Wistar rats; this simple treatment led to a high percentage of mammary tumors without causing death. All the induced tumors were adenocarcinoma and their heterogeneousness depended on their size. The induced tumors did not have intra- or extravascular inflammatory spaces caused by heterotopic lesions, as is the case with implanted tumors. Before injection of Gd-DOTA, appearance of the patchy internal structure was clearly demonstrated on spin-echo images performed with long repetition times. Three doses of the paramagnetic contrast agent (0.1, 0.2, and 0.5 mmol/kg) were evaluated on two different T1-weighted MR sequences. Images were recorded before and repeatedly after intravenous injection of Gd-DOTA, and signal intensities and relaxation times were measured. On images acquired with the spin-echo 500/28 as well as the inversion-recovery 928/26/300 sequences, the results showed that 0.2 mmol/kg Gd-DOTA was the optimal dose for contrast enhancement and for clear visualization of the heterogeneousness of the mammary tumor.

Adenocarcinoma↗
PubMed1990

Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses.

Daily cyclosporine doses of 10 mg/kg body weight for 21 days in Wistar rats cause impairment in glucose homeostasis and changes in the amount of immunostainable hormones and in the ultrastructure of the cells of the pancreatic islets. CsA induces hyperglycemia and reduced glucose tolerance, and causes a decrease in immunoreactive insulin and an increase of somatostatin and pancreatic polypeptide (PP) immunoreactivities, leaving glucagon immunoreactivity unaffected. Ultrastructurally, different degrees of dilation of rough endoplasmic reticulum cisternae and enlargement of Golgi apparatus can be observed in B cells, together with a pronounced reduction in the number of secretory granules. Nevertheless, there were no apparent morphological changes of the other cytoplasmic organelles, suggesting that the drug, besides a depression of protein synthesis, as previously stated, also induces a substantial defect in granulogenesis, probably due to impairment in the intracellular transport of the hormone from the sites of synthesis to the secretory granules. The B cell alterations are not accompanied by any sign of B cell degeneration or death. Non-B cells did not show any of the ultrastructural changes found in B cells and were similar to those of the control rats. The above findings indicate that CsA at immunotherapeutic doses causes impairment in the secretory processes of B cells specifically. An hypothesis on the mode of action of CsA on B cells is drawn.

Animals↗
PubMed1990

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture.

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.

Adenosine↗
PubMed1990

[Immunosuppressive effect of cyclosporin A incapsulated into liposomes].

A preparation of cyclosporine A (CsA) in small liposomes (300 nm) was tested in a rat model of heterotopic cardiac allograft. At a daily dose of 1,5 mg/kg during 14 days, the graft survival rate was 30.4 +/- 2.8 days with a liposome-CsA solution versus 16 +/- 2.3 days with a Cremophore-CsA solution (p less than 0.01). Animals treated with the liposome-CsA preparation exhibited less weight loss than animals treated with cremophore-CsA solution (p less than 0.01). It is likely that the up-take of CsA by macrophages, when incapsulated into liposomes is dramatically enhanced; these cells have been pointed out at targets for IL2 inhibition by CsA.

Animals↗
PubMed1990

[Thrombolytic therapy in a case of prosthetic aortic valve thrombosis].

We present the case of a 40 year old woman, who had an aortic prosthetic valve, of the Björk Shiley type. Three months before admission she began with progressive dyspnea. She was admitted to the Cardiovascular Care Unit with a global cardiac failure. An aortic prosthetic valve thrombosis was diagnosed clinically (absence of the prosthetic click) and by radioscopy (a decrease in the movement of the valve disk, with an incomplete shunt). It was attributed to a secondary failure of the anticoagulant treatment. Despite the treatment she quickly developed a cardiogenic shock. A treatment with 750,000 UI of streptokinase in 30 min was started, followed by 100,000 UI during 12 hours, with total reversion of the hemodynamic features, as judged by clinical examination (recurrence of the prosthetic click), radioscopy (recurrence of the valve movement) and by Doppler echocardiography (reduction of the transvalvular gradient). No complications were observed, and in a follow up of 12 months she persisted asymptomatic. The prosthetic valve thrombosis is an infrequent and almost fatal complication. The classical therapy consists in surgery which is a procedure with a high mortality in patients with severe cardiac failure, and an emergency procedure, as it occurred in our patient. Despite the known success of the thrombolytic therapy in the prosthetic valve thrombosis of the right heart (tricuspid position) it was only in the last years that this treatment was reported in aortic or mitral position. Peripheric embolies were found in 13% of the cases, always with transitory symptoms. There are only 45 cases described in the world, and more experience is needed for definitive conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cloning and expression in Escherichia coli of a rat hepatoma cell cDNA coding for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

In liver, the 470-residue bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) catalyses the synthesis and degradation of fructose 2,6-bisphosphate, a potent stimulator of glycolysis. In rat hepatoma (HTC) cells, this enzyme has kinetic, antigenic, and regulatory properties, such as insensitivity to cyclic AMP-dependent protein kinase and lack of associated FBPase-2 activity, that differ from those in liver. To compare the sequence of the HTC enzyme with that of the liver enzyme, we have cloned the corresponding fully-coding cDNA from HTC cells. This cDNA predicts a protein of 448 residues in which the first 32 residues of liver PFK-2/FBPase-2 including the cyclic AMP target sequence have been replaced by a unique N-terminal decapeptide. The rest of the protein is identical with the liver enzyme. An N-terminally truncated recombinant peptide of 380 residues containing the PFK-2 and FBPase-2 domains was expressed in Escherichia coli as a beta-galactosidase fusion protein. It was recognized by anti-PFK-2 antibodies but its enzymic activities were barely detectable. In contrast, a cDNA fully-coding for the HTC enzyme could be expressed in E. coli as a beta-galactosidase-free peptide that exhibited both PFK-2 and FBPase-2 activities. This peptide had those PFK-2 kinetic properties of the HTC enzyme that differ from the liver enzyme. These data, together with immunoblot experiments, suggest that the lack of associated FBPase-2 activity in HTC cells results from a post-translational modification of the enzyme rather than from the difference in amino acid sequence. As well as this peculiar type of PFK-2/FBPase-2 mRNA, HTC cells also contained low concentrations of the liver-type mRNA. Unlike in liver, neither mRNA was induced by dexamethasone in these cells.

Amino Acid Sequence↗
PubMed1989

Emergency knee joint salvage utilizing a free musculofasciocutaneous flap based on the anterior tibial artery: case report.

A young adult male presented with a traumatic amputation at the upper third of his left leg and an extensive soft tissue loss around his left knee. A free musculofasciocutaneous flap was elevated on the anterolateral part of the amputated segment and transferred to the soft tissue defect around the proximal left tibia in order to avoid an above-knee amputation. The entire flap depends on the anterior tibial artery for its blood supply. The anatomy of the flap is outlined. The importance of the musculocutaneous blood supply as well as the presence of an extensive fascial component make the flap very reliable. An 18-month follow-up period showed a uniformly well-contoured soft tissue coverage and an optimal functional result.

Adult↗
PubMed1989

RFLP-discordance within the human phenylalanine hydroxylase locus.

A search for crossover events was performed in seven families with two phenylketonuria-affected children applying seven enzymes for the detection of eight restriction fragment length polymorphisms (RFLPs) by hybridisation with a human phenylalanine hydroxylase (PAH) cDNA probe. A discordance was detected within the PvuIIb-RFLP pattern of two affected sibs. This observation is most likely the result of a cross-over event in the PAH locus. Alternative explanations are discussed. Non-paternity could be excluded by DNA fingerprinting using the oligonucleotide probe (GTG)5.

Crossing Over, Genetic↗
PubMed1989

Effects of anxiolytic and anxiogenic drugs on exploratory activity in a simple model of anxiety in mice.

Chlordizaepoxide, pentylenetrazole, phenobarbital, N-methyl-beta-carboline-3-carboxamide (FG-7142), buspirone and the novel serotonin3 receptor (5-HT3) antagonist, 3-tropanyl-indole-3-carboxylate (ICS 205-930), were examined in the two-compartment exploratory model (Crawley and Goodwin, 1980). The results indicated that, utilizing the time mice spend in the dark side of the apparatus as an index of anxiety, increased the sensitivity of the model and enabled both anxiolytic and anxiogenic agents to be detected.

Animals↗
PubMed1989

CD1 expression on B-CLL lymphocytes.

In a previous report we showed that D47 CD1a monoclonal antibody positively labelled B-CLL cells of some patients. Six cases were selected to further characterize CD1 antigenic expression at the leukaemic cell surface using flow cytometry with a battery of six CD1a, two CD1b and two CD1c monoclonal antibodies. CLL cells were positively labelled with CD1a antibodies except OKT6 and NA1/34; in all cases they were CD1b negative and CD1c positive. These results suggested that CD1a, c epitopes can be detected on leukaemic B cells in addition to other T cell differentiation antigens. In view of recently published data demonstrating the presence of CD1c molecule in normal B cell subsets, our results further question the relationship of B-CLL with a restricted subpopulation of B cells.

Antibodies, Monoclonal↗
PubMed1989

Diagnostic and prognostic significance of myelomonocytic cell surface antigens in acute myeloid leukaemia.

Thirty-six cases of acute myeloid leukaemia (AML) were tested with a large battery of monoclonal antibodies (moAbs) detecting surface markers normally expressed by myelomonocytic, T and B lymphoid, megakaryocytic and erythroid lineages. Differences in antigenic expression were observed among the various FAB subgroups: HLA-class II molecules were found in almost all AML cases but not in the promyelocytic subgroup (M3); CD14 and CD36 antigens were detected in monocytic leukaemias (M4 and M5); the CD34 moAb (MY10) recognizing an epitope described on myeloid stem cells was positive in 88% of the M1 and 80% of the M3 cases. By a multivariate analysis, only the CD14b (MY4) discriminated significantly between M1-M2 and M4-M5 subgroups. Using Cox's model to assess the prognostic importance of variables including immunophenotyping on survival, we undertook a one by one analysis and found that the presence of CD17 antigen predicted for a shorter survival (P = 0.03). In addition this marker appeared more significant than other clinical and biological parameters.

Adolescent↗
PubMed1989

Pharmacokinetic study of tempo carboxylic acid, a nitroxyl MRI contrast media, in control and streptozocin diabetic rats.

The pharmacokinetics of tempo carboxylic acid (TCA), a nitroxyl contrast medium have been evaluated in control and streptozocin-diabetic rats. Previous magnetic resonance imaging (MRI) studies in diabetic rats showed prolongation of contrast visualization in the renal cavities after injection of TCA. Diabetes induced only slight alterations to the pharmacokinetic parameters. Rate constants and half lives were unchanged after four months of diabetes. A significant decrease of the apparent total body clearance and volume of distribution was observed while the area under the curve was increased. These alterations are not sufficient to explain MRI abnormalities which have to be elucidated.

Animals↗
PubMed1989

Beta-receptor properties in soleus muscles from spontaneously hypertensive rats.

We have compared the properties of beta-adrenergic receptors in slow-twitch, oxidative skeletal muscles (soleus) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at three different ages. The investigation was based on the hypothesis that the increase in Na+ content and decrease in fatigue resistance observed previously in the soleus of SHR might be the result of a down regulation of muscle beta-receptors. Activation of beta-adrenergic receptors in skeletal muscle stimulates sarcolemmal sodium-potassium adenosine triphosphatase, which produces an efflux of Na+ and an influx of K+. Receptor down-regulation would be expected to reduce hormonal stimulation of Na+ pump activity, particularly during exercise. The results of receptor binding studies, however, and an investigation of cyclic adenosine monophosphate (cAMP) production in response to applied epinephrine indicated that there were no significant differences in receptor properties in the soleus muscles of SHR and WKY rats. Receptor number and affinity were the same in the two strains, and the rate, magnitude, and duration of the increase in cAMP in response to 10(-6) M epinephrine were also similar. beta-Adrenergic receptor down-regulation does not appear to be a generalized phenomenon in tissues of SHR, despite the appearance of other physiological changes in the tissue.

Animals↗
PubMed1989

Prolongation of guinea pig-to-rat xenograft survival with BN 52063, a specific antagonist of platelet-activating factor.

Xenotransplantation between different species may possibly solve some of the difficulties associated with human donor organ availability. However, organ xenografts are very rapidly rejected, particularly in discordant donor-recipient combinations, due to the presence of natural cytotoxic antibodies in the recipient. The purpose of this study was to evaluate the efficacy of two potential inhibitors of a xenogeneic antigen-antibody reaction: Iloprost, an analogue of prostacyclin I2, and BN 52063, a PAF-antagonist. Heart (group A) or liver (group B) transplantations were performed in the guinea pig-to-Lewis rat donor-recipient combination. Fifteen minutes prior to revascularization of the graft an intravenous infusion was instituted using saline (0.01 ml/min) (groups A1 and B1), saline and dimethylsulfoxide (DMSO, 0.1 ml/min) (groups A2 and B2), Iloprost (2 ng/Kg/min) (groups A3 and B3) or BN 52063 (6 mg/Kg/min) (groups A4 and B4). Heart graft survival times (min) were 12.3 +/- 1.7 (A1), 13.4 +/- 2.2 (A2), 14.8 +/- 1.0 (A3), 18.3 +/- 1.4 (A4). Liver graft survival times (min) were 158.4 +/- 38.9 (B1), 129.6 +/- 14.4 (B2), 168.1 +/- 18.0 (B3) and 306.2 +/- 36.5 (B4). A significant prolongation (p less than 0.05) was observed in group A4 versus A1, A2, A3 and in group B4 versus B1, B2, B3. These results suggest that prevention of xenograft rejection using PAF-antagonist in association with other methods should be further investigated.

Animals↗