Abstract: The present invention relates to molecules which function as selective modulators of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role, such as neurodegenerative diseases, rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney disease, cystic kidney disease, precystic kidney disease, microbial infections, including Chlamydia infections, E. coli infections, H. pylori infections and its secondary effects including gastric ulcers, Coxiella Brunetti (Q-fever) infections and Streptococcus pneumonia infections, fungal infections including Paracoccidiodes brasiliensis and Candida albicans and their secondary effects including lung edema.

Abstract: The present invention features novel withanolides, as well as analogs and salts thereof, for use in the treatment of proliferative disease, cardiovascular disease, neurodegenerative disease and inflammatory disease.

Abstract: A method of treating an inflammatory condition involving TNF-? in a mammal by administering to a patient a composition with an effective amount of an isolated alkaline protease in an amount effective to inactive TNF-?. The invention also involves compositions, including pharmaceutical compositions containing an isolated alkaline protease in an amount effective to inactive TNF-? especially those from Aspergillus oryzae and/or serve as a transepithial carrier.

Abstract: The present invention provides a crystallized NC1 domain hexamer of Type IV collagen, and methods for making the crystal, wherein the NC1 domain hexamer is crystallized such that the three dimensional structure of the crystallized NC1 domain hexamer can be determined to a resolution of at least 3 ? or better. The present invention also provides a method for designing compounds to inhibit angiogenesis, tumor growth, tumor metastasis, endothelial cell adhesion and/or proliferation, and/or basal lamina assembly, comprising analyzing the three dimensional structure of a crystallized Type IV collagen NC1 domain hexamer produced by the methods of the invention, and identifying and synthesizing compounds that target regions of the NC1 domain that have been identified by the analysis as being important for type IV collagen heterotrimer and hexamer assembly.

Abstract: A method for treating diabetic neuropathy is disclosed consisting of administering pyridoxamine or a salt thereof.

Abstract: The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions.

Abstract: The instant invention provides methods and kits for inhibiting angiogenesis, tumor growth and metastasis, and endothelial cell interactions with the extracellular matrix, involving contacting the tumor or animal tissue with at least one isolated type IV collagen NCl &agr; chain monomer. In a specific embodiment of the invention, the isolated domain of type IV collagen comprises the NCl (&agr;1), (&agr;2), (&agr;3), or (&agr;6) chain monomer, or protein constructs having substantially the same structure as the NCl (&agr;1), (&agr;2), (&agr;3), or (&agr;6) chain monomer.

Abstract: The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions.

Abstract: The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions. The instant invention also teaches methods to treat or prevent diabetes associated hyperlipidemia, cellular redox imbalances, hypercholesterolemia, hypertriglyceridemia, and atherosclerosis, comprising administering the compounds of the invention to a mammal in need thereof.

Abstract: The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions. The instant invention also teaches new methods to treat or prevent oxidative modification of proteins, including low density lipoproteins, to treat or prevent lipid peroxidation, and to treat or prevent atherosclerosis, comprising administering an amount effective of one of the compounds of the invention to treat or prevent the disorder.

Abstract: The instant invention provides compositions and methods for modeling post-Amadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions. The instant invention also teaches new methods to treat or prevent diabetic nephropathy, oxidative stress, and protein crosslinking, comprising administering an amount effective of one of the compounds of the invention to treat or prevent the disorder.

Abstract: The instant invention provides methods and kits for inhibiting angiogenesis, tumor growth and metastasis, and endothelial cell interactions with the extracellular matrix, involving contacting the tumor or animal tissue with at least one isolated type IV collagen NC1 &agr; chain monomer. In a specific embodiment of the invention, the isolated domain of type IV collagen comprises the NC1 (&agr;1), (&agr;2), (&agr;3), or (&agr;6) chain monomer, or protein constructs having substantially the same structure as the NC1 (&agr;1), (&agr;2), (&agr;3), or (&agr;6) chain monomer.

Abstract: The instant invention demonstrates that the 7S domain of type IV collagen disrupts cell aggregation and tissue development. Structural changes in mesoglea, inhibition of cell proliferation, and changes in cell differentiation patterns accompanies the blockage of cell aggregates which indicate that blockage may be due to alterations in mesoglea (extracellular matrix) structure with accompanying effects on cell behavior. Type IV collagen has a critical role in the initial formation of mesoglea and that perturbation of mesoglea formation affects cell division, cell differentiation, and morphogenesis.

Abstract: The F. necrophorum gene expressing leukotoxin was sequenced and cloned. The leukotoxin open reading frame (lktA) is part of a multi-gene operon containing 9,726 bp, and encoding a protein containing 3,241 amino acids with an overall molecular weight of 335,956 daltons. The protein encoded by the gene was truncated into five polypeptides having overlapping regions by truncating the full length gene into five different sections and amplifying, expressing, and recovering the protein encoded by each of these sections. Additionally, a region upstream of the gene was sequenced and the polypeptide encoded by that nucleotide sequence was purified and isolated. These polypeptides along with the full length protein are then tested to determine their immunogenicity and protective immunity in comparison to the efficacy of immunization conferred by inactivated native leukotoxin in F. necrophorum culture supernatant.

Abstract: The present invention provides novel compounds, pharmaceutical compositions, methods, and kits for inhibiting the conversion of Amadori compounds to post Amadori advanced glycation endproducts, and for treating and preventing chronic tissue damage and diabetic complication

Abstract: The present invention provides novel compounds, pharmaceutical compositions, methods, and kits for inhibiting the conversion of Amadori compounds to post Amadori advanced glycation endproducts, and for treating and preventing chronic tissue damage and diabetic complication.

Abstract: The present invention provides improved dialysis compositions and methods for dialysis comprising utilizing the disclosed AGE inhibitors, together with methods to reduce dialysis-related complications and disorders.

Abstract: The present invention provides improved dialysis compositions and methods for dialysis comprising utilizing the disclosed AGE inhibitors, together with methods to reduce dialysis-related complications and disorders.

Abstract: The present invention provides novel compounds, pharmaceutical compositions, methods, and kits for inhibiting the conversion of Amadori compounds to post Amadori advanced glycation endproducts, and for treating and preventing chronic tissue damage and diabetic complication

Abstract: The present invention provides methods to isolate and purify components required for bone-induction using extracts of Saos-2 cells or proteins released by Saos-2 cells into conditioned tissue culture medium. In addition, the present invention provides a method of augmenting bone growth locally comprising implanting the near osteoprogenitor cells the bone inducing agent isolated in the methods of the present invention, together with a mechanically suitable biodegradable carrier.