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Biomedical subjects

L Chiche

Publications and source records attributed to L Chiche.

At least 91 records · Page 5Linked to original sources
PubMed1993

Xenotransplantation: baboons as potential liver donors? Scientific and ethical issues.

The dramatic development of liver transplantation compared to a relative shortage of donors has brought a renewed interest to xenotransplantation. Because of anatomical and immunological compatibilities, nonhuman primates are the most appropriate donors. The aim of this work was to analyze the different problems of a baboon-to-man liver xenotransplantation. Thirty baboons bred in a French Primatology Center were studied. The analysis of anatomical, microbiological, and immunological data showed that only 8 baboons out of 30 were suitable as donors for xenotransplantation. Considering these data and the ethical issues, the actual feasibility of xenotransplantation programs is discussed.

Animals↗
PubMed1992

Effect of extended cold ischaemia with UW solution on graft function after liver transplantation.

Studies in animals on the use of UW solution in liver transplantation have shown an inverse relation between cold ischaemia time (CIT) and graft function. There are few clinical data on this relation in human beings. We have investigated the effect of extended cold ischaemia in a prospective study. We assessed early graft function and subsequent outcome for 306 consecutive elective liver transplantations; for analyses, grafts were grouped according to CIT (< 12 h group A, > or = 12 h group B), since a preliminary study identified 12 h as a significant cut-off point. Initial graft function was better in group A than group B, as shown by maximum alanine aminotransferase activity (mean 623 [805] vs 946 [1148], p = 0.02), bile production on days 1-3 (p < 0.05), maximum serum bilirubin by day 10 (206 [166] vs 244 [163] mumol/l, p = 0.04), and frequencies of primary non-function (1 [0.4%] vs 4 [7%], p = 0.006) and hepatocyte necrosis on routine biopsy sample after reperfusion (18% vs 31%, p = 0.04). Long-term outcome was also better in group A than group B; graft and patient survival rates were higher and fewer retransplantations were needed. These findings suggest that cold ischaemia in UW solution for longer than 12 h is a risk factor for graft function and patient survival. We recommend that the limit of the safe CIT be reconsidered.

Adenosine↗
PubMed1992

Study of kidney and liver viability in the rat after exclusive aortic perfusion using intracellular ATP measurement.

To find whether the liver can be procured after exclusive aortic perfusion, three organ perfusion models were used in three groups of donor rats. Group 1 underwent liver wash-out via the portal vein; in group 2, the kidneys alone were perfused via the aorta; and group 3 underwent simultaneous aortic perfusion of liver and kidneys. All perfusion flow rates in the three groups were adjusted to physiological values. Harvested organs were transplanted and recipient animals were killed 4 h after transplantation to study liver and kidney viability by using intracellular ATP measurement. Liver ATP was lower (P < 0.005) in the portal perfusion group (group 1: 1.396 +/- 0.412) than in the aortic perfusion group (group 3: 2.181 +/- 0.061). Kidney ATP was comparable in groups 2 and 3:1.066 +/- 0.09 vs 1.059 +/- 0.273 (mumol/g) tissue). Liver cooling was quicker with portal perfusion than with the aortic flush (20 degrees C in 20 s vs 15 degrees C in 60 s). Aortic perfusion at a physiologic flow rate has no detrimental effect on renal viability studied by intracellular ATP measurement. We conclude that liver cooling via the aortic route only is a good alternative to portal perfusion and seems to give good preservation. Application of this observation to emergency procurement in humans is still the subject of controversy.

Adenosine Triphosphate↗
PubMed1992

[What role is left to surgery in portal hypertension?].

The place of surgery in the treatment of gastrointestinal haemorrhage in cirrhotic patients remains controversial. Emergency surgery may be considered when other haemostatic techniques fail. In this situation, the decision to operate must be taken rapidly, as the prognosis depends on the patient's preoperative status and the degree of hepatocellular failure (HCF). Elective surgery for portal hypertension completes with long-term sclerotherapy, and randomised prospective comparative studies have not been able to clearly distinguish between the two methods. The objective of the various operations proposed is to prevent recurrent haemorrhage without inducing any mortality or major morbidity (particularly encephalopathy). Partial, selective anastomoses and devascularisations appear to satisfy these objectives. The choice of technique depends on the portal flow rate, the type of varices, the degree of HCF and the surgeon's experience. Lastly, liver transplantation should be considered when portal surgery is decided in order to select a procedure which does not compromise the possibility of future transplantation and also as an alternative to portal surgery, particularly in young subjects with already severely impaired liver function.

Anastomosis, Surgical↗
PubMed1992

The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years.

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗
PubMed1991

Determination of the structure of [Nle7]-endothelin by 1H NMR.

[Nle7]-endothelin was synthesized and studied by 1H NMR and distance geometry calculations. The NMR study was performed first in DMSO-d6 and then in 50% acetonitrile/water since this peptide aggregates in pure water. In both cases, all spin systems were identified and assigned with the aid of two-dimensional spectroscopy (2D): COSY (for scalar couplings) and NOESY (for dipolar couplings). On the basis of the acetonitrile/water NMR parameters, and using the DISGEO program, a three-dimensional structure of [Nle7]-endothelin is proposed and discussed.

Acetonitriles↗
PubMed1990

Protein model structure evaluation using the solvation free energy of folding.

A systematic study of solvation free energy of folding for proteins with known crystallographic structures is presented. There is a linear relationship between the solvation free energy of folding and the protein size. This relationship, which can be rationalized by a simple model of chain folding, allows prediction of the solvation free energy of folding for proteins for which no high resolution structures are available. All misfolded structures analyzed show solvation free energies higher than predicted; however, some of the misfolded structures have values close enough to the predicted values so that one must be very careful when using such a criterion to check the correctness of a protein model.

Enzymes↗
PubMed1990

[Anatomical and microbiological study of the conditions for baboon-man liver xenograft].

This work assesses the anatomical and infectious problems of heteroplastic transplantation from a baboon to a man. The study was carried out with 30 baboons of the primatology laboratory of the CNRS. The aspects studied included the anatomic structure and the biology of the liver, the microbial and parasitic population, and the serological features. Out of these 30 animals, 8 were selected as potential donors.

Animals↗
PubMed1989

1H 2D NMR and distance geometry study of the folding of Ecballium elaterium trypsin inhibitor, a member of the squash inhibitors family.

The solution conformation of synthetic Ecballium elaterium trypsin inhibitor II, a 28-residue peptide with 3 disulfide bridges, has been studied by 1H 2D NMR measurements. Secondary structure elements were determined: a miniantiparallel beta-sheet Met 7-Cys 9 and Gly 25-Cys 27, a beta-hairpin 20-28 with beta-turn 22-25, and two tight turns Asp 12-Cys 15 and Leu 16-Cys 19. A set of interproton distance restraints deduced from two-dimensional nuclear Overhauser enhancement spectra and 13 phi backbone torsion angles restraints were used as the basis of three-dimensional structure computations including disulfide bridges arrangement by using distance geometry calculations. Computations for the 15 possible S-S linkage combinations lead to the proposal of the array 2-19, 9-21, 15-27 as the most probable structure for EETI II.

Amino Acid Sequence↗
PubMed1989

Use of restrained molecular dynamics in water to determine three-dimensional protein structure: prediction of the three-dimensional structure of Ecballium elaterium trypsin inhibitor II.

Refinement of distance geometry (DG) structures of EETI-II (Heitz et al.: Biochemistry 28:2392-2398, 1989), a member of the squash family trypsin inhibitor, have been carried out by restrained molecular dynamics (RMD) in water. The resulting models show better side chain apolar/polar surface ratio and estimated solvation free energy than structures refined "in vacuo." The consistent lower values of residual NMR constraint violations, apolar/polar surface ratio, and solvation free energy for one of these refined structures allowed prediction of the 3D folding and disulfide connectivity of EETI-II. Except for the few first residues for which no NMR constraints were available, this computer model fully agreed with X-ray structures of CMTI-I (Bode et al.: FEBS Lett. 242:285-292, 1989) and EETI-II complexed with trypsin that appeared after the RMD simulation was completed. Restrained molecular dynamics in water is thus proved to be highly valuable for refinement of DG structures. Also, the successful use of apolar/polar surface ratio and of solvation free energy reinforce the analysis of Novotny et al. (Proteins 4:19-30, 1988) and shows that these criteria are useful indicators of correct versus misfolded models.

Amino Acid Sequence↗