Abstract: The present invention provides nucleotide sequences encoding human LTC4 synthase or variants thereof, which nucleotide sequences include a human LTC4 synthase genomic clone, and unique fragments thereof. The present invention also provides recombinant plasmids, and cells transformed therewith, including the LTC4 synthase gene sequences. The present invention further provides the chromosomal localization of the human LTC4 synthase gene, and also provides methods for identifying LTC4 synthase gene mutations that correlate with susceptibility to bronchial asthma. Diagnostic methods are also provided, as are methods for identifying LTC4 synthase modulators (i.e., compounds that alter the expression and/or activity of LTC4 synthase). The presents invention also provides functional equivalents of the LTC4 synthases, protein, and also methods of identifying LTC4 synthase inhibitors.

Abstract: Isolated nucleic acid molecules encoding a novel phospholipase A2, GXII PLA2, that is preferentially expressed in Th2 cells, are disclosed. The invention further provides recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, antisense nucleic acid molecules, non-human transgenic animals carrying a GXII PLA2 transgene and non-human transgenic animals deficient in GXII PLA2. The invention further provides isolated GXII PLA2 proteins and peptides, GXII PLA2 fusion proteins and anti-GXII PLA2 antibodies. Methods of using the GXII PLA2 compositions of the invention are also disclosed, including methods for detecting GXII PLA2 protein or mRNA in a biological sample, methods of modulating GXII PLA2 activity in a cell, and methods for identifying agents that modulate GXII PLA2 activity.

Abstract: An isolated nucleotide sequence encoding human leukotriene C4 synthase or variants of human leukotriene C4 synthase polypeptide, is provided. One embodiment is an isolated DNA sequence (SEQ ID NO.:1) encoding a human leukotriene C4 synthase polypeptide, that has three hydrophobic transmembrane domains. Also described are recombinant cells and plasmids containing the foregoing isolated DNA, preferably linked to a promoter. Isolated leukotriene C4 synthase is provided, having at least three hydrophobic transmembrane domains (SEQ ID NO.:2). Portions of the foregoing isolated human leukotriene C4 synthase polypeptide are also described. Antibodies with selective binding specificity for the polypeptides of the invention also are provided as well as a sensitive method for assay of human leukotriene C4. Methods for producing leukotriene C4 synthase as well as methods for testing for modulators of leukotriene C4 synthase activity are also described.

Abstract: A method for evaluating cyclosporine-related nephrotoxicity in a patient receiving cyclosporine therapy is disclosed. The method comprises measuring urine kallikrein content utilizing radioimmunoassay specific for human urine kallikrein. The value obtained is compared then to a pre-treatment value of urine kallikrein levels.Also disclosed is a means for predicting susceptibility to cyclosporine-related nephrotoxicity. Potential cyclosporine therapy patients are evaluated according to their baseline (pre-treatment) urinary kallikrein levels. Low initial levels of urine kallikrein are predictive of susceptibility to cyclosporine-related nephrotoxicity.Also disclosed is a method for monitoring cyclosporine-related nephrotoxicity during the course of cyclosporine treatment. Decreased urinary kallikrein indicates that cyclosporine administration should be decreased or terminated. Increased urinary kallikrein indicates that cyclosporine administration may be increased or maintained.

Abstract: Two eosinophilotactic tetrapeptides of amino acid sequence Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu have been isolated from extracts of human lung fragments. These tetrapeptides have been synthesized by solid phase peptide synthesis procedures and the synthetic and natural materials behaved similarly in analytical assays and bioassays. Novel N-terminal analogs have been prepared and have shown eosinophilotactic activity. Thus, the tetrapeptides disclosed herein have utility as therapeutic agents in the prophylaxis and/or treatment of parasitic diseases, anaphylaxis and bronchial asthma.