Abstract: The present invention relates to diagnostic tests, methods and kits that are useful to assess a subject's risk of developing a pathologic condition related in part to the presence of HDL oxidation product.

Abstract: In one aspect, the present invention provides isolated oxidation resistant mutant apoA-I polypeptides comprising an amino acid sequence substantially homologous to SEQ ID NO:4, the mutant apoA-I polypeptide comprising a combination of: (1) a conservative amino acid substitution at residue Tyr192; and (2) at least one conservative amino acid substitution at residue Met86, Met112, or Met148, wherein the mutant apoA-I polypeptide is resistant to modification by an oxidizing agent. In another aspect, the invention provides a method of promoting cholesterol efflux activity in a mammalian subject in need thereof, the method comprising the step of administering an effective amount of an oxidation resistant apoA-I agonist to the subject to promote cholesterol efflux.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop or is suffering from, cardiovascular disease. In one embodiment, the method comprises detecting a measurable feature of at least two biomarkers in an HDL subfraction, or in a complex containing apoA-I or apoA-III isolated from a biological sample obtained from the subject, wherein the at least two biomarkers are selected from the group consisting of apoA-I, apoA-II, apoB-100, Lp(a), apoC-I, and apoC-III, combinations or portions and/or derivatives thereof, and comparing the measurable features of the at least two biomarkers from the biological sample to a reference standard, wherein a difference in the measurable features of the at least two biomarkers from the biological sample and the reference standard is indicative of the presence or risk of cardiovascular disease in the subject.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop, or is suffering from, cardiovascular disease. The methods comprise detecting an amount of at least one biomarker in a biological sample, or HDL subfraction thereof, from the subject, and comparing the detected amount of the biomarker to a predetermined value, where a difference between the detected amount and the predetermined value is indicative of the presence or risk of cardiovascular disease in the subject. In some embodiments, the biomarker comprises at least one of ApoC-IV, Paraoxonase 1, C3, C4, ApoA-IV, ApoE, ApoL1, C4B1, Histone H2A, ApoC-II, ApoM, Vitronectin, Haptoglobin-related protein, and Clusterin, or combinations thereof.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop or is suffering from, cardiovascular disease. In one embodiment, the method comprises detecting a measurable feature of at least two biomarkers in an EMT subfraction, or in a complex containing apoA-I or apoA-III isolated from a biological sample obtained from the subject, wherein the at least two biomarkers are selected from the group consisting of apoA-I, apoA-II, apoB-100, Lp(a), apoC-I, and apoC-III, combinations or portions and/or derivatives thereof, and comparing the measurable features of the at least two biomarkers from the biological sample to a reference standard, wherein a difference in the measurable features of the at least two biomarkers from the biological sample and the reference standard is indicative of the presence or risk of cardiovascular disease in the subject.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop or is suffering from, cardiovascular disease. In one embodiment, the method comprises detecting a measurable feature of at least two biomarkers in an HDL subfraction, or in a complex containing apoA-I or apoA-II isolated from a biological sample obtained from the subject, wherein the at least two biomarkers are selected from the group consisting of apoA-I, apoA-II, apoB-100, Lp(a), apoC-I, and apoC-III, combinations or portions and/or derivatives thereof, and comparing the measurable features of the at least two biomarkers from the biological sample to a reference standard, wherein a difference in the measurable features of the at least two biomarkers from the biological sample and the reference standard is indicative of the presence or risk of cardiovascular disease in the subject.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop, or is suffering from, cardiovascular disease. The methods comprise detecting an amount of at least one biomarker in a biological sample, or HDL subfraction thereof, from the subject, and comparing the detected amount of the biomarker to a predetermined value, where a difference between the detected amount and the predetermined value is indicative of the presence or risk of cardiovascular disease in the subject. In some embodiments, the biomarker comprises at least one of ApoC-IV, Paraoxonase 1, C3, C4, ApoA-IV, ApoE, ApoL1, C4B1, Histone H2A, ApoC-II, ApoM, Vitronectin, Haptoglobin-related protein, and Clusterin, or combinations thereof.

Abstract: The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop, or is suffering from, cardiovascular disease. The methods comprise detecting an amount of at least one biomarker in a biological sample, or HDL subfraction thereof, from the subject, and comparing the detected amount of the biomarker to a predetermined value, where a difference between the detected amount and the predetermined value is indicative of the presence or risk of cardiovascular disease in the subject. In some embodiments, the biomarker comprises at least one of ApoC-IV, Paraoxonase 1, C3, C4, ApoA-IV, ApoE, ApoL1, C4B1, Histone H2A, ApoC-II, ApoM, Vitronectin, Haptoglobin-related protein, and Clusterin, or combinations thereof.

Abstract: The present invention relates to diagnostic tests, methods and kits that are useful to assess a subject's risk of developing a pathologic condition related in part to the presence of HDL oxidation product. Measuring the quantity of one or more HDL oxidation products present in the blood is useful in evaluating risk for developing or evaluating the severity of a disease or evaluating response to treatment for such a disease as, for instance, cardiovascular disease.

Abstract: The present invention relates to diagnostic tests, methods and kits that are useful to assess a subject's risk of developing a pathologic condition related in part to the presence of HDL oxidation product. Measuring the quantity of one or more HDL oxidation products present in the blood is useful in evaluating risk for developing or evaluating the severity of a disease or evaluating response to treatment for such a disease as, for instance, cardiovascular disease.

Abstract: The present invention relates to diagnostic tests, methods and kits that are useful to assess a subject's risk of developing a pathologic condition related in part to the presence of HDL oxidation product. Measuring the quantity of one or more HDL oxidation products present in the blood is useful in evaluating risk for developing or evaluating the severity of a disease or evaluating response to treatment for such a disease as, for instance, cardiovascular disease.

Abstract: In one aspect, the present invention provides isolated oxidation resistant mutant apoA-I polypeptides comprising an amino acid sequence substantially homologous to SEQ ID NO:4, the mutant apoA-I polypeptide comprising a combination of: (1) a conservative amino acid substitution at residue Tyr192; and (2) at least one conservative amino acid substitution at residue Met86, Met112, or Met148, wherein the mutant apoA-I polypeptide is resistant to modification by an oxidizing agent. In another aspect, the invention provides a method of promoting cholesterol efflux activity in a mammalian subject in need thereof, the method comprising the step of administering an effective amount of an oxidation resistant apoA-I agonist to the subject to promote cholesterol efflux.

Abstract: The disclosure describes a method for detecting conditions indicative of sepsis. In one embodiment of the invention, an increase in the level of 3-chlorotyrosine or 3-bromotyrosine from the normal level in a sample of body fluid or tissue is indicative of early sepsis or infection. In another embodiment of the invention, the level of 3-chlorotyrosine or 3-bromotyrosine is measured or monitored to determine the response to therapeutic treatment of the infective condition in which a reduction in the level that existed prior to the treatment is an early sign or indication that the treatment is working in vivo. In a preferred embodiment, the method of the invention is illustrated in a clinically relevant mouse model of sepsis.

Abstract: The disclosure describes a method for detecting conditions indicative of sepsis. In one embodiment of the invention, an increase in the level of 3-chlorotyrosine or 3-bromotyrosine from the normal level in a sample of body fluid or tissue is indicative of early sepsis or infection. In another embodiment of the invention, the level of 3-chlorotyrosine or 3-bromotyrosine is measured or monitored to determine the response to therapeutic treatment of the infective condition in which a reduction in the level that existed prior to the treatment is an early sign or indication that the treatment is working in vivo. In a preferred embodiment, the method of the invention is illustrated in a clinically relevant mouse model of sepsis.

Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of 3-chlorotyrosine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.

Abstract: A non-invasive method for the determination of oxidative stress in a patient by urinalysis is disclosed. The method comprises quantifying the level of o,o'-dityrosine in a sample of the urine of said patient and comparing with the corresponding level of said compound in a normal or control sample, whereby a substantially elevated level of said o,o'-dityrosine is indicative of oxidative stress in said patient.

Abstract: A noninvasive method for the determination of oxidative stress in a patient is disclosed. The method comprises quantifying the levels or relative distribution of a pair of compounds, o,o'-dityrosine and o-tyrosine, in a sample of the patient's urine and comparing with the corresponding levels or relative distribution of the compounds in a normal or control sample.

Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of p-hydroxyphenylacetaldehyde-lysine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.