Abstract: Organic complexes of vanadium are provided, having the general structure VL3, where V is vanadium(III) and L is a monoprotic bidentate ligand that forms a five-membered, unsaturated vanadium containing ring, having vanadium coordinating oxygen or sulfur ring heteroatoms, and where the vanadium containing ring is fused to a six-membered heterocyclic ring. Preferably L is a hydroxypyrone or a hydroxypyridinone. The complexes have a number of uses, including the treatment of elevated blood glucose and related disorders, treatment of proliferative disorders, etc.

Abstract: A compound which is a 6-substituted seco indoline of the formula (I): wherein: X is halogen or OSO2R where R represents H or C1-5 alkyl optionally substituted with from 1 to 4 hydroxyl, acid (COOH) or amino groups which amino may be optionally substituted by one or two C1-5 alkyl groups; Y is N02, N3, NHOH, NHR, NRR, N═NR, N(O)RR, SR or SSR, where R is defined as above, but that in the case where Y is SSR or N═NR, then R can also be another moiety of formula (I); or Y is a group of formula:

Abstract: Methods are provided to specifically modulate the trafficking of systemic memory T cells, particularly CD4+ T cells, without affecting naive T cells or intestinal memory T cells. It is shown that systemic memory T cells, which are characterized as CD45Ra−, and integrin &agr;4&bgr;7−, express high levels of CCR4. Ligands of CCR4, such as TARC or MDC, act as an adhesion trigger, wherein upon CCR4 binding, these cells undergo integrin-dependent arrest to the appropriate vascular receptor(s). This arrest acts to localize the cells at the target site. The methods of the invention manipulate this triggering, and CCR4 mediated chemotaxis, to affect the localization of T cells in targeted tissues. In one embodiment of the invention, the active agent is a CCR4 agonist, that acts to enhance T cell localization. In an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity.

Abstract: Methods for isolating ZAP-3 genes are provided. Deletion of the ZAP-3 locus is associated with human tumors, particularly carcinomas. The ZAP-3 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like.

Abstract: Nucleic acid compositions encoding a pro-apoptotic protein, Bok (Bcl-2-related ovarian killer) are identified. Bok has conserved Bcl-2 homology domains 1, 2 and 3 and a C-terminal transmembrane region present in other Bcl-2 related proteins, but lacks the BH4 domain found only in anti-apoptotic Bcl-2 proteins. Over-expression of Bok induces apoptosis. Cell killing induced by Bok is suppressed by co-expression with selective anti-apoptotic Bcl-2 proteins. Bok is highly expressed in the ovary, testis and uterus, particularly in granulosa cells, the cell type that undergoes apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic protein with wide tissue distribution and hetero-dimerization properties facilitates elucidation of apoptosis mechanisms in reproductive and other tissues, and provides a means for manipulating apoptosis.

Abstract: Methods for isolating costal2 genes are provided. The costal2 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as identification of cell type based on expression, and the like.

Abstract: Pharmaceutical compositions and compounds are provided. The compounds of the invention have anti-proliferative activity, and may promote apoptosis in cells lacking normal regulation of cell cycle and death. In one embodiment of the invention, formulations of the compounds in combination with a physiologically acceptable carrier are provided. The pharmaceutical formulations are useful in the treatment of hyperproliferative disorders, which disorders include tumor growth, lymphoproliferative diseases, angiogenesis. The compounds of the invention are substituted pyrazoles and pyrazolines.

Abstract: Compositions and methods are provided for the enhanced in vitro synthesis of biological molecules where ATP is required for synthesis. Of particular interest is the synthesis of polymers, e.g. nucleic acids, polypeptides, and complex carbohydrates. A homeostatic system is used for production of ATP, where the required high energy phosphate bonds are generated in situ, e.g. through coupling with an oxidation reaction. The homeostatic energy source will typically lack high energy phosphate bonds itself, and will therefore utilize free phosphate in the reaction mix during generation of ATP. Since inorganic phosphate can be an inhibitory by-product of synthesis, the period of time when synthesis is maintained in vitro can be extended. The homeostatic energy source is provided in combination with an enzyme that catalyzes the creation of high energy phosphate bonds and with an enzyme that can use that high energy phosphate bond to regenerate ATP.

Abstract: Nucleic acid compositions are provided that encode a family of mammalian proteins expressed in the retina and brain. Members of the gene family are genetically linked to various neurosensory defects, including cochlear degeneration, peripheral retinal degeneration and cone-rod retinal dystrophy. The nucleic acid compositions find use in identifying DNA sequences encoding homologous or related proteins; for production of the encoded protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of neurosensory defects, identification of retinal cells based on expression, and the like. The DNA is further used as a diagnostic for genetic predisposition to the linked neurosensory defect.

Abstract: A genetic locus associated with asthma is identified. The genes within the locus, ASTH1I and ASTH1J, and the regulatory sequences of the locus are characterized. The genes are used to produce the encoded proteins; in screening for compositions that modulate the expression or function of ASTH1 proteins; and in studying associated physiological pathways. The DNA is further used as a diagnostic for genetic predisposition to asthma.

Abstract: The present invention provides a vector system that is useful for the generation of mutations in a recombination-based construction method. The invention further includes the incorporation of mutations generated by the method of the present invention into mouse embryonic stem cells and transgenic mice.

Abstract: The present invention features transgenic mice models for gene function, wherein the transgenic mice are characterized by having altered serotonin 5-HT6 receptor gene function. The transgenic mice may be either homozygous or heterozygous for a disruption in the endogenous 5-HT6 gene. Transgenic mice homozygous for a disruption in the endogenous 5-HT6 gene display a phenotype of increased anxiety behavior including diminished investigation of foreign objects and an elevation in stretched attend postures.

Abstract: Human hematopoietic stem cells are provided by separation of the stem cells from dedicated cells. The stem cells may than be maintained by regeneration in an appropriate growth medium. Means are provided for assaying for the stem cells as to their capability for producing members of each of the hematopoietic lineages. A method for treating a human by implanting a cellular composition comprising greater than 90% human hematopoietic stem cells is also disclosed.

Abstract: Disclosed are human pluripotent hematopoietic stem cell (PHSC) enriched compositions and methods for obtaining and using the compositions. A substantially homogeneous population of human hematopoietic cells characterized as CD34.sup.+, HLA-DR.sup.-, and c-kit receptor positive (KR.sup.+) and capable of in vitro self-renewal and differentiation to members of at least the erythroid, myeloid, and megakaryocytic lineages, is obtained by separating the population from a cellular mixture, for example by cytometric cell sorting techniques. Also disclosed is a method of obtaining persistent maintenance of grafted human hematopoietic cells in a mammal, which includes grafting a mammal in utero with a cellular composition enriched in human hematopoietic cells characterized as CD34.sup.+, HLA-DR.sup.- and capable of in vitro self-renewal and differentiation to members of the lymphoid, myeloid, erythroid and megakaryocytic lineages.

Abstract: Farnesyl derivatives, particularly farnesyl acetate, are used to reduce the level of protein farnesylation in a mammalian host. The activity of proteins which require farnesylation for function is thereby reduced. The compounds may be administered to patients to reduce the overall level of ras protein activity, either alone or in conjunction with other drugs which act as competitive inhibitors of farnesyl protein transferase.

Abstract: Methods and compositions are provided relating to novel IgE isoforms and their use in immune hypersensitivity diagnosis and treatment. The compositions include transcription and translation products of the immunoglobulin epsilon locus, specific probes for epsilon transcription products, and compounds which specifically bind epitopes of epsilon translation products. Novel products of the epsilon locus include the following transcription products and translation products thereof: CH4-M2", SEQ ID NO:02, residues 1-107 and, (SEQ. ID NO:06, CH4'-CH5-M1'-M2, (see SEQ ID NO:02, residues 1-72,SEQ ID NO:03 and SEQ ID NO:05) CH4'-CH5-M2'(SEQ ID NO:02, residues 1-72, SEQ ID NO:03 and SEQ ID NO:07 and CH4'-CH5-M2" (SEQ ID NO:02, residues 1-72, SEQ ID NO:03 and SEQ ID NO:06). Such epsilon products, specific probes and binding compounds find use in methods and kits for immune hypersensitivity diagnosis and treatment.

Abstract: Primordial tissue is introduced into immunodeficient hosts, where the primordial tissue develops and differentiates. The chimeric host allows for investigation of the processes and development of the xenogeneic tissue, testing for the effects of various agents on the growth and differentiation of the tissue, as well as identification of agents involved with the growth and differentiation.

Abstract: Methods and compositions are provided for the determination of cross-reactive alleles, where there is no antibody which will specifically distinguish between the two alleles. Particularly, the method employs an antibody which binds to the two alleles bound to a surface, an antibody specific for one of the alleles, a labeled conjugate which binds to a consensus sequence present in both alleles and positive and negative controls. By having an enhanced value where the interfering allele is present as compared to a value for the target allele, one can distinguish between the various alternatives involving the presence or absence of one or both alleles.

Abstract: A synthetic inhibitor of matrix metalloproteases, the tripeptide hydroxamate GM 6001, is administered to a patient suffering from an inflammatory disease of the central nervous system wherein the effect is mediated primarily through restoration of the blood-CNS barrier.

Abstract: Immunocompromised hosts comprising xenogeneic fetal lymph node tissue implanted in the ear pinna are provided. The chimeric hosts are prepared by inserting the xenogeneic lymph node tissue into the ear pinna and closing the incision. The tissue is found to be rapidly vascularized and can be productively infected with HIV.