Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections, and autoimmune or other diseases in which activated macrophages are involved, such as septic shock, heumatoid arthritis and multiple sclerosis.

Abstract: Methods are provided for measuring the accumulation of advanced glycosylation endproducts (AGEs), and for lowering the accumulation of advanced glycosylation endproducts, which are predicated on the discovery that such AGEs and their precedent glycotoxins are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs relative to non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke, and to the treatment of such individuals with agents capable of reacting with glycosylation products to either avert or diminish the accretion of AGEs in the body.

Abstract: There is disclosed an adjuvant composition for potentiating the immunogenicity of an antigen, comprising water or an aqueous solution and hemozoin or .beta.-hematin.

Abstract: There is disclosed a structural genus of compounds, defined according to coordinates in three-dimensional space, that binds amino moieties on neighboring lysine residues in a tyrosine residue 29 pocket of the matrix protein component of the HIV preintegration complex (PIC), thereby preventing the PIC from binding to karyopherin .alpha. and preventing nuclear importation and integration of the HIV viral genome into the host cell DNA, thereby preventing viral infection.

Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

Abstract: The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.

Abstract: There is disclosed compound according to the formula: ##STR1## wherein A, independently,=CH.sub.3 or CH.sub.2 CH.sub.3, P=1 or 2; and ##STR2## wherein X=NH.sub.2, CH.sub.3 or CH.sub.2 CH.sub.3 ; X'=CH.sub.3 or CH.sub.2 CH.sub.3 ; Y=NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 ; and Z=H, CH.sub.3 or CH.sub.2 CH.sub.3 ; or ##STR3## wherein Y' and Z', independently,=H, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 or N.sup.+ (CH.sub.3).sub.3 ; Q is N or CH; and salts thereof.

Abstract: The present invention relates to therapeutic modalities and pharmaceutical compositions for the treatment of HIV-infection using cyclophilin A and its corresponding human cellular binding partner or receptor as a target for intervention. The present invention relates to the use of exogenous or engrafted sources of cyclophilins, anti-cyclophilin antibodies, cyclophilin decoys, soluble forms of cyclophilin-binding partners and small molecules which are supplied extracellularly, and act presumably by interrupting the binding of cyclophilin A with its cellular binding partner(s) or receptor(s) as a treatment for HIV-infection. The present invention further relates to the use of forms of cyclosporin A that have been derivatized by bulky or charged substituents to inhibit cellular uptake and minimize their immunosuppressive activities, which presumably act to disrupt cyclophilin binding to its cellular receptor, likewise as a treatment for HIV-infection.

Abstract: The present invention relates to advanced glycosylation endproducts, and particularly to the use of novel cyclopentenone aminoreductones, 3-alkylamino-2 -hydroxy-4-hydroxymethyl-2-cyclopenten-1-ones. Such AGEs can be used in various diagnostic and therapeutic methods.

Abstract: The present invention relates to advaced glycosylation endproducts formed by the reaction of arginine-lysine or lysine-arginine dipeptides, optionally as part of a larger protein or amino-containing-biomolecule, with reducing sugars. These AGEs can be used in various diagnostic and therapeutic methods.

Abstract: There is disclosed a genus of compounds that have anti-HIV infection therapeutic activity and inhibit nuclear localization of the HIV preintegration complex.

Abstract: The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.

Abstract: The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays.

Abstract: The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as ME-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays.

Abstract: The present invention relates to compositions and methods for inhibiting the aging of amino-containing amino acid, peptides, proteins and biomolecules. Accordingly, a composition is disclosed which comprises an agent or compound capable of reacting with the glycosyl-amino moiety of the early glycosylation product (also known as the Amadori product or the Heyns product) formed by the reaction of glucose, or other reactive sugars, with an amino-containing peptide, protein or biomolecule, thus stabilizing this early glycosylation product, and preventing its further reaction to form open-chain, carbonyl-containing advanced glycosylation end products. Suitable agents may contain a reactive aldehyde group. A preferred agent is acetaldehyde. The method comprises contacting the target biomolecule with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: Soluble and membrane associated forms of Mac-2 (also termed Carbohydrate Binding Protein ?CBP!-35 and L-34) recognizes and binds to Advanced Glycosylation Endproducts (AGEs) with higher affinity than it binds carbohydrates, such as its "natural" ligand, galactose. The level of soluble Mac-2 in plasma or serum provides a prognostic indicator of the susceptibility of an individual to AGE complications. Thus, the present invention includes various therapeutic and diagnostic utilities predicated on the identification and activities of Mac-2 for binding AGEs. Pharmaceutical compositions of the invention comprise an effective amount of Mac-2 admixed with a pharmaceutically acceptable carrier. Diagnostic utilities include assays such as immunoassays for the presence and amount of Mac-2 in a biological sample, e.g., serum or plasma. Such assays can be performed with labeled receptors, antibodies, ligands and other binding partners of Mac-2.

Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

Abstract: This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

Abstract: The present invention encompasses the use of the compounds of formula as given below to detect certain specific protein structures which are present in nuclear localization sequences ##STR1## wherein A is, independently CH.sub.3 or CH.sub.2 CH.sub.3 and R is ##STR2## and salts thereof.

Abstract: The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.