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: The present invention relates to compositions and methods for inhibiting the release and/or biological activity of migration inhibitory factor (MIF). In particular, the invention relates to the uses of such compositions and methods for the treatment of various conditions involving cytokine-mediated toxicity, which include, but are not limited to shock, inflammation, graft versus host disease, and/or autoimmune diseases.

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 a method for treating an individual having a disease caused by cytokine-mediated toxicity comprising administering to the individual an effective amount of (a) an antibody that binds to an MIF polypeptide, wherein the MIF polypeptide has a molecular weight of about 12.5 kDa in combination with (b) anti-TNF.alpha., anti-IL1, anti-IFN-.gamma., IL-1RA, a steroid, a glucocorticoid, or IL-10.

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: 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: There is disclosed a method for anti-viral therapy treatment with the Pertussis toxin beta subunit oligomer, wherein the oligomer is composed of from two to ten subunits of PTX selected from the group consisting of S2, S3, S4, S5, and combinations thereof.

Abstract: There is disclosed a method for helping to prevent miscarriages during pregnancy, comprising administering an effective amount of a fetuin polypeptide.

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 compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.

Abstract: The present invention is directed to methods for detecting the presence of advanced glycosylation endproducts using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to diagnostic methods for diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.

Abstract: The present invention relates generally to methods and compositions for treating amyloidogenic diseases such as Alzheimer's disease and the development of type II diabetes, in which deposition of amyloid in organs such as the brain and pancreas interfere with neurological function and insulin release, respectively. The methods and compositions are directed toward increasing the activity of scavenger cells within the body at recognizing and removing amyloid deposits from affected tissues and organs. Scavenger cells may be targeted to amyloid deposits by means of spontaneously-occurring chemical modifications called advanced glycosylation endproducts (AGEs). Compositions are described which increase scavenger cell activity towards AGE-modified amyloid.

Abstract: There are disclosed filters for tobacco combustion products that, when employed in conjunction with exposure to tobacco smoke, inhibit the accumulation of AGEs and AGE-like tobacco- and tobacco smoke-derived adducts in individuals exposed to tobacco smoke. There is further disclosed a use of ascorbic acid and derivatives thereof for the preparation of filters to inhibit the accumulation of advanced glycation endproducts (AGEs) and AGE-like tobacco- and tobacco smoke-derived adducts in individuals exposed to tobacco smoke.

Abstract: The present invention is directed to compositions and devices based upon the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions and devices having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.

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 present invention is directed to methods for partitioning advanced glycosylation endproducts out of a biological sample using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and particular fragments thereof, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to therapeutic methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain to remove AGEs from biological material. The invention further relates to compositions and devices for partitioning AGEs away from a sample.

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 is directed to methods for inhibiting the cross-linking of advanced glycosylation endproducts in a subject suspected of having elevated levels of AGEs by using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and particular fragments thereof, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to therapeutic methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain to remove AGEs from biological material. The invention further relates to compositions for inhibiting the cross-linking of AGEs in a subject in need of such therapy.

Abstract: Methods are disclosed for measuring the accumulation of advanced glycosylation endproducts (AGEs), which are predicated on the discovery that such AGEs 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 over non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke. Methods are also disclosed for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, as well as for the treatment of the ambient to lower AGE levels. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. All such methods and corresponding materials are contemplated and included.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.