A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by Streptomyces sp. A92-3081 10. They were isolated and purified by extraction and several chromatographic, activity-guided steps.

Cynomolgus monkey is one of the macaque species currently used as an animal model for experimental surgery and medicine, in particular, to experiment new drugs or therapy protocols designed for the prevention of allograft rejection. In this field, it is of utmost importance to select histoincompatible recipient-donor pairs. One way to ensure incompatibility between donor and recipient is to check their major histocompatibility complex (MHC) genotypes at the loci playing a determinant role in histocompatibility. We report in this paper on the cynomolgus monkey DRB polymorphism evidenced by sequencing of amplified exon 2 separated either by denaturing gradient gel electrophoresis (DGGE), or by cloning. By the study of 253 unrelated animals from two populations (Mauritius and The Philippines), we characterized 50 exon 2 sequences among which 28 were identical to sequences already reported in Macaca fascicularis or other macaque species (Macaca mulatta, Macaca nemestrina). By cloning and sequencing DRB cDNA, we revealed two additional DRB alleles. Out of the 20 haplotypes that we defined here, only two were found in both populations. The functional impact of DR incompatibility was studied in vitro by mixed lymphocyte culture.

These data demonstrate that most TNF- and LT alpha-producing cells are bone marrow derived and radiosensitive, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow cell transplantation. The genotype of the donor bone marrow cells determines the functional and structural phenotype of the TNF-LT alpha-deficient adult murine host, with the exception of lymph node formation. These findings may have therapeutic implications for the restoration of genetically defined immunodeficiencies in humans.

This study was undertaken to determine the effects of L-carnitine addition to the diet during submaximal exercise in endurance-trained humans. Ten subjects (VO2max: 62 ml.kg-1.min-1) performed a control test (C) (45 min of cycling at 66% of VO2max) followed by 60 min of recovery in a sitting position. Each subject repeated this trial after 28 days of placebo (P) and L-carnitine (L-C) treatment (double-blinded cross-over design). The dose of each treatment was 2 g/day. There were no differences between the C and P tests. The respiratory quotient was lower (p less than 0.05) with treatment than with P or C during exercise. In addition, oxygen uptake, heart rate, blood glycerol, and resting plasma free fatty acid concentrations presented a nonsignificant trend toward higher values in L-C than in the C or P groups. These observations suggest an increased lipid utilization by muscle during exercise in the L-C-treated group. This effect has further possibilities for improving performance during submaximal exercise.

FTY720 is an effective immunosuppressant in prevention of acute kidney allograft rejection in cynomolgus monkeys and synergizes with cyclosporine and/or RAD in yielding rejection-free allograft survival.