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Biomedical subjects

A Michel

Publications and source records attributed to A Michel.

At least 181 records · Page 10Linked to original sources
PubMed1989

[Development of an orthotopic hepatic transplantation technique in rats: what should the researcher's objectives be?].

The development of liver transplantation in man emphasises the need for more work in the field of experimental liver transplantation. For this purpose the model of orthotopic liver transplantation in the rat is very useful but difficult to establish as a safe and reproducible technique. The aim of this study concerning acquisition of the orthotopic liver transplantation model in the rat was to define precise objectives for future investigators. Two investigators without experience in microsurgery each performed 75 orthotopic liver transplantations, which were divided into five consecutive series. In each series survival times of the recipients after transplantation were analysed according to the mean duration of the operative procedure and the mean portal vein clamping time. For each investigator, mean duration of the operative procedure progressively decreased to reach a minimum at the 45th graft. From that time on, the portal vein clamping time became less than 17 minutes and a significant increase in the post operative survival time of the recipient was observed. However it was only from the sixtieth transplantation on, with stable portal vein clamping time but technical mistakes fewer that a high success rate was observed.

Anastomosis, Surgical↗
PubMed1989

[Neonatal ischemic necrosis of the arm in a premature infant].

A case of gangrene present at birth in the right upper limb of a twin premature infant is reported. As premature rupture of membranes was present, the role of ischemic compression is discussed. The etiology of ischemic lesions observed in the fetus and the newborn and their treatment is reviewed.

Arm↗
PubMed1988

Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site.

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.

Amino Acid Sequence↗
PubMed1988

Linkage disequilibrium between RFLP haplotype 2 and the affected PAH allele in PKU families from the Berlin area of the German Democratic Republic.

Probands from 26 PKU-affected families of the Berlin area were analyzed with respect to the allele frequency distribution of six RFLPs in linkage with the normal and the PKU alleles of the phenylalanine hydroxylase gene. These investigations confirm most of the RFLP haplotypes observed by Güttler and colleagues in the Danish population and describe two additional ones. They detect no significant differences in the single RFLP or RFLP haplotype distribution on the normal chromosomes in comparison with the Danish families and confirm a prevalent association of the RFLP haplotypes 1, 4, and 7 with the normal PAH allele. In contrast to the Danish investigations, in our study the PKU allele is found most frequently linked to haplotype 2, rather then to haplotype 3. In one of our patients we found a substitution of the normal 19-kb MspI fragment by a 13.5- and a 5.5-kb fragment, reported up to now only in one other German family.

Alleles↗
PubMed1988

Post-natal evolution of rat cardiac beta-adrenoceptors.

Cardiac beta-adrenoceptors (beta AR) were studied using membranes prepared at birth (day 0) and at days 7, 10, 15, 21, 30, 45 and 60. Saturation experiments using the antagonist ligand (125I)-iodocyanopindolol (ICYP) allowed the determination of beta AR number (Bmax) and ICYP dissociation constant (Kd), while (-)isoproterenol competition curves of ICYP binding, performed in the absence or presence of Gpp(NH)p (10(-4) M), were used to measure the relative proportions of high and low affinity states of the beta AR for the agonist and to assess the ability of beta AR to couple with the GTP-binding protein. Rat cardiac beta AR evolved at 3 distinct periods: during the first period (days 0-10), the receptor density and ICYP Kd were half that of adults, and beta AR were present only in an homogeneous high affinity state. The second period (days 15-21) was characterized by a progressive increase in beta AR number and ICYP Kd, while analysis of (-)isoproterenol competition curves indicated that beta AR were poorly coupled to the GTP-binding protein. In the third period (days 30-60), ICYP Bmax and Kd were respectively 53.9 +/- 1.2 fmoles/mg protein and 106.4 +/- 2.9 pM, while analysis of (-)isoproterenol competition curves showed the existence of high and low affinity binding states in equal proportions in the absence of Gpp(NH)p, and of one homologous low affinity state of the receptor in its presence. These data indicate that beta AR follow a postnatal evolution marked by an increase in beta AR density concomitant with a decrease in affinity toward the antagonist ligand ICYP, accompanied by the progressive appearance of a poorly-coupled beta AR. However, the number of efficiently coupled receptors was found to be similar in adult and newborn rats.

Animals↗
PubMed1988

Cholestatic effect of cyclosporine in the rat. An inhibition of bile acid secretion.

Cyclosporine administration in patients with organ transplants may cause cholestasis. In the rat, intraperitoneal administration of cyclosporine, 10 mg/kg, for three weeks did not cause liver function test abnormalities or hepatic histological lesions. However a significant reduction of bile flow and bile acid secretion rates was observed. The fact that reduction of bile flow was related to a decrease of the bile acid-independent flow suggests that cyclosporine-induced cholestasis results from an inhibition of bile acid secretion. Whether this inhibition is caused by the parental molecule or by cyclosporine metabolites needs to be clarified.

Animals↗
PubMed1988

Diabetes-induced rat tracheal segment supersensitivity to carbachol.

Contractile responses to carbachol of tracheal segments isolated (i) from rats made diabetic 4 months prior by a single intravenous injection (50 mg/kg) of streptozotocin (group B), and (ii) from diabetic rats that had been treated during the same period with a daily dose (2-4 U/animal) of long-acting insulin (group C) were compared with the contractile responses of trachea isolated from age-matched control animals (group A). Tracheal segments from group B were significantly more responsive to carbachol than those from group A or C at low, but not at high carbachol concentrations. Carbachol pD2 values were higher in group B (6.85 +/- 0.05) than in groups A (6.46 +/- 0.07) or C (6.37 +/- 0.06), but were not significantly different between groups A and C. These data indicate that diabetes induces a supersensitivity to carbachol in airway smooth muscles, possibly related to a diabetes-induced vagal autonomic neuropathy.

Animals↗
PubMed1988

Prevention of death following one-hour occlusion of the portal vein in the rat.

This study was conducted to evaluate various methods to reduce the mortality rate following acute portal vein occlusion in rat: systemic heparinization, intravenous saline infusion, enteral antibiotics and simultaneous clamping of the superior mesenteric artery were tested alone or in combination. Each of these treatments improved the survival rate after 45 or 60 min occlusion of the portal vein; combination of all treatments provided better results than each treatment alone. These results indicate that, following acute portal vein occlusion in the rat, several factors cooperate to cause death. The decrease in mean arterial blood pressure during occlusion of the portal vein was correlated with the mortality rate; this correlation was significant in the animals with 45 min occlusion of the portal vein. It appeared in this study that, when used in association, simple therapeutic methods are highly effective in improving the survival rate following acute portal vein occlusion in the rat.

Animals↗
PubMed1988

CD1 expression in B-CLL cells.

The peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or not clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs were chosen since they detected B or CD1-8 T cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B cell antigens recognized by BL14, Y2955 and anti-class II moAbs were constantly expressed in leukemic cells, while B-cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T cell markers including several epitopes of the CD1 group were also found to be present on the leukemic cell surface in several cases. To further extend these data, 6 cases were selected for labelling with a battery of 6 CD1a, 2 CD1b and 1 CD1c moAbs. These results suggested that CD1a,c epitopes can be detected on leukemic B cells in addition to other T cell differentiation antigens.

Antibodies, Monoclonal↗
PubMed1988

Discordant heart xenografts in the rat. Additional effect of plasma exchange and cyclosporine, cyclophosphamide, or splenectomy in delaying hyperacute rejection.

Natural antidonor antibodies are known to play a prominent role in hyperacute xenograft rejection. The aim of this work was to devise an experimental protocol to prolong the survival time of guinea pig heart xenografts transplanted into rats. A technique of continuous plasma exchange adapted to small animals was used to remove the natural cytotoxic antibodies from the recipient prior to the transplantation. In some experiments, cyclosporine (CsA), cyclophosphamide (CY), or splenectomy were associated with the plasma exchange. In this highly discordant xenogenic donor-recipient combination, the mean graft survival time in nontreated rats was 16 min. When an exchange of 1.5 plasma volume was performed 24 hr before the transplantation, no prolongation of the graft survival time was observed. When CsA, CY, or splenectomy were associated with the plasma exchange, the graft survival time was significantly increased by more than 2500% (up to 418 min with CsA). When used isolately, none of these 3 immunosuppressive methods was able to prolong the graft survival time. Natural cytotoxic antibodies were monitored by a complement-mediated cytotoxicity assay. After a plasma exchange, the titers decreased from 1:16-1:32 to 1:1-1:2. When no immunosuppressive method was associated with the plasma exchange, the antibodies returned to their initial level within the 24 hr that preceded the transplantation, and the graft was rejected as in nontreated animals. When an immunosuppressive method was associated with the plasma exchange, and particularly in the case of CsA, the titers remained low, and the hyperacute rejection was delayed. Therefore, it can be concluded that plasma exchanges, associated with CsA, are an efficient experimental protocol in the rat to increase the survival time of guinea pig heart xenografts. The effect of the treatment is correlated with the decrease in natural cytotoxic antidonor antibodies.

Animals↗
PubMed1987

Introduction of genomic diagnosis of classical phenylketonuria to the health care system of the German Democratic Republic.

The phenylketonuria (PKU) dispensary of the Children's Hospital of the Charité, Berlin, GDR, cares for about 140 affected families, representing about one-third of all PKU families in the GDR. Of these families, 15 expressed their desire for an additional child given the availability of a reasonably reliable prenatal diagnosis procedure. They were investigated by linked RFLP analysis applying a phenylalanine-hydroxylase-cDNA probe. Full genetic predictability for prospective fetuses could be obtained for all of them. In eight cases this was possible by the use of one restriction enzyme, and in the remaining seven by a combination of the information from two restriction-enzyme patterns. No recombination between linked RFLP and the PKU phenotype could be observed in 40 meioses from the investigation of eight families with two affected children each.

Delivery of Health Care↗
PubMed1987

Pharmacological activity and toxicity of apyramide: comparison with non-steroidal anti-inflammatory agents.

An experimental and comparative study was conducted on 1-(p-chlorobenzoyl)-2-methyl-5-methoxyindole-3-p-acetamidophenol acetate (Apyramide) and known anti-inflammatory agents. Apyramide was far less toxic than indomethacin in rats and mice by the oral or the i.p. route. It exhibited anti-inflammatory activity on carrageenin-induced paw oedema, cotton pellet granuloma and adjuvant arthritis, as well as analgesic and antipyretic activities. The acute ulcerogenic effect of Apyramide was lower than that of indomethacin.

Animals↗
PubMed1986

Hydrolysis of Pro-Ala dipeptides by lysosomal hydrolases. Models for the study of lysosomotropic amino acid prodrugs of penicillins.

Peptidic lysosomotropic prodrugs of antibiotics and antitumoral agents could be of advantage in chemotherapy, providing that free, active drug is released at, or close to, the desired site of action. Thus, aminoacyl derivatives of doxorubicin, e.g., where the drug is attached to the amino acid by a primary amino function, are sensitive to lysosomal hydrolases. We have examined whether a similar approach can be used for drugs carrying a carboxyl group such as beta-lactam antibiotics. Because the C adjacent to the carboxyl group in beta-lactams has the D configuration, we have examined and report here the synthesis and susceptibility of model peptides, namely Boc-D-Pro-L-Ala and Boc-L-Pro-L-Ala to lysosomal hydrolases. Hydrolysis of the D isomer proceeds considerably more slowly than that of the L isomer. Lysosomal carboxypeptidase(s) and/or amidases appear therefore to have a much narrower specificity than aminopeptidase(s), which will severely limit the applicability of the concept of peptidic lysosomotropic prodrugs.

Animals↗
PubMed1986

Topological similarities between a cyclic enkephalin analogue and a potent opiate alkaloid: a computer-modeling approach.

The cyclic enkephalin analogue H-Tyr-cyclo[-D-N delta-Orn-Gly-Phe-Leu-] (1-c) and the rigid narcotic alkaloid 7 alpha-[(1R)-1-hydroxy-1-methyl-3-phenylpropyl]-6,14- endo-ethenotetrahydrooripavine (PEO) were studied by using computer graphics methods to investigate potential geometrical congruencies of their respective pharmacophoric elements. Particular emphasis was placed on the relative spatial disposition of the tyramine moiety and the additional aromatic ring that occurs in both molecules. A three-dimensional vector map was generated defining the locus of the C21 aromatic ring for all those conformers of PEO having up to 10 kcal above the minimum energy conformer. A systematic conformational search on the cyclic peptide afforded four allowable sets of conformers whose side chain of the phenylalanine residue coincided with the vector map of PEO. Local energy minima for the peptide within the revised mutual vector space were found and subjected to bimolecular energy refinement with correspondingly local energy minima for the opiate alkaloid. Several low-energy conformers of the cyclic peptide were identified that permitted a good fit with the alkaloid provided that the tyramine moiety of the respective molecules does not coincide. In the designated conformations the basic nitrogen of the former occupies a distinct geometrical locus, and the side chain of the leucine residue has no structural correlate in the alkaloid.

Chemical Phenomena↗