Abstract: The present invention relates to novel immunogenic compositions (e.g., vaccines), the production of such immunogenic compositions and methods of using such compositions. More specifically, this invention provides unique immunogenic molecules comprising an HMGB1 polypeptide (e.g., an HMGB1 B-box polypeptide) and an antigen. Even more specifically, this invention provides novel fusion proteins comprising an isolated HMGB1 polypeptide and an antigen such that administration of these fusion proteins provides the two signals required for native T-cell activation.

Abstract: A method of treating a subject with a cytokine-mediated inflammatory disorder comprising administering to the subject an effective amount of a pharmaceutically acceptable cholinesterase inhibitor, provided that the inhibitor is not galantamine.

Abstract: A method of treating a patient suffering from pancreatitis comprising treating said patient with a therapeutically effective amount of a cholinergic agonist selective for an ?7 nicotinic receptor in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from a macrophage wherein said condition is acute pancreatitis. The compounds of the present invention include a quaternary analog of cocaine; (1-aza-bicyclo[2.2.2]oct-3-yl)-carbamic acid 1-(2-fluorophenyl)-ethyl ester; a compound of formula (I), a compound of formula (II), a compound of formula (III), a compound of formula (IV), and an oligonucleotide or mimetic capable of attenuating the symptoms of acute pancreatitis wherein the oligonucleotide or mimetic consists essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an ?7 cholinergic receptor. The variables of formulae (I), (II), (III) and (IV) are described herein.

Abstract: Methods and compositions are disclosed for the use of dextrothyroxine (D-T4) to treat sepsis, inflammation, and conditions and diseases in which it is desirable to inhibit macrophage migration inhibitory factor (MIF).

Abstract: The present invention provides a method for distinguishing benign human papilloma virus (HPV)-infected tissue from HPV-related lesions that have undergone malignant transformation. In one embodiment, the invention comprises a simple histochemical staining method and details a novel process for examining HPV-infected cells by determining susceptibility to enzymatic DNA digestion. Residual virion-associated DNA is seen only in benign HPV-infected lesions, while absence of residual DNA is seen with malignant transformation. In another embodiment, the invention comprises immunohistochemical assay methods for examining HPV-infected cells, utilizing antibodies to HPV L1 proteins. These methods can be used to predict biologic behavior of HPV-infected lesions. The invention can improve current cervical cancer screening programs, and improve clinical management of patients by defining malignant potential of HPV-infected tissue more accurately.

Abstract: The invention relates to methods and materials involved in diagnosing SLE. More particularly, the invention relates to methods and materials involved in diagnosing SLE, diagnosing severe SLE, and assessing a mammal's susceptibility to develop severe SLE. For example, the invention provides nucleic acid arrays that can be used to diagnose SLE in a mammal. Such arrays can allow clinicians to diagnose SLE based on a simultaneous determination of the expression levels of many genes that are differentially expressed in SLE patients as compared to healthy controls.

Abstract: Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

Abstract: The present disclosure provides biomarkers that are predictive a subject's responsiveness or non-responsiveness to an anti-TNF therapy. The biomarkers, compositions, and methods described herein are useful in selecting appropriate treatment modalities (e.g., an anti-TNF therapy or a non-anti-TNF therapy) for a subject suffering from a disease such as an immune disorder.

Abstract: The subject invention discloses a method for determining the prognosis and probable clinical course of a subject diagnosed with B-CLL. Specifically, the invention involves comparing CD38 expression in a biological sample from the subject containing B-CLL cells to a baseline level of CD38 expression, wherein an elevated level of CD38 expression in relation to the baseline level of CD38 expression may indicate poor prognosis or aggressive course of disease in the subject. Also disclosed is a method for determining whether the Ig V genes of the B-CLL cells of a B-CLL patient are mutated, comprising comparing CD38 expression in a biological sample from the subject containing B-CLL cells to a baseline level of CD38 expression, wherein a lower level of CD38 expression in relation to the baseline level indicates IG V gene mutation.

Abstract: Provided are methods of identifying a genetic profile influencing the relative probability of a subject manifesting a phenotype that is at least partially heritable. Also provided are methods of determining the relative likelihood that a subject will manifest a phenotype that is at least partially heritable. Additionally, methods of determining the relative risk of a human subject for manifesting schizophrenia are provided. Further provided are methods of screening a human embryo in vitro for the risk of becoming a human manifesting schizophrenia. Also, methods of identifying a single nucleotide polymorphism (SNP) variant affecting the risk of a human subject for manifesting schizophrenia are provided. Methods of screening for a compound that may affect schizophrenia are additionally provided.

Abstract: Methods and compositions are disclosed for protecting an organ or tissue from inflammation and organ injury following ischemia, reperfusion, and trauma through the administration of an HMGB1 protein within a time period sufficient to protect the organ or tissue from injury.

Abstract: Compounds of Formula (I), pharmaceutical compositions comprising compounds of Formulae (I a) or (VII) and a method of treating a subject with an inflammatory cytokine-mediated disorder comprising administering to the subject a compound of Formulae (I a) or (VII a). The variables of Formulae (I), (I a), (VII) and (VII a) are described herein.

Abstract: A method of treating a patient suffering from pancreatitis comprising treating said patient with a therapeutically effective amount of a cholinergic agonist selective for an ?7 nicotinic receptor in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from a macrophage wherein said condition is acute pancreatitis. The compounds of the present invention include a quaternary analog of cocaine; (1-aza-bicyclo[2.2.2]oct-3-yl)-carbamic acid 1-(2-fluorophenyl)-ethyl ester; a compound of formula (I), a compound of formula (II), a compound of formula (III), a compound of formula (IV), and an oligonucleotide or mimetic capable of attenuating the symptoms of acute pancreatitis wherein the oligonucleotide or mimetic consists essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an ?7 cholinergic receptor. The variables of formulae (I), (II), (III) and (IV) are described herein.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk of exhibiting sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

Abstract: The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.

Abstract: An antibody or an antigen binding fragment thereof which binds to mammalian ?7 subunit of a nicotinic acetylcholine receptor or its functional variant and which is an agonist of said receptor or variant. Pharmaceutical compositions comprising same. A method of treating a subject suffering from an inflammatory condition comprising administering to said subject an antibody or an antigen-binding fragment as described herein.

Abstract: A method of inhibiting the release of a proinflammatory cytokine in a cell is disclosed. The method comprises treating the cell with a cholinergic agonist. The method is useful in patients at risk for, or suffering from, a condition mediated by an inflammatory cytokine cascade, for example endotoxic shock. The cholinergic agonist treatment can be effected by stimulation of an efferent vagus nerve fiber, or the entire vagus nerve.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk of exhibiting sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: This document relates to methods and materials involved in diagnosing SLE. For example, this document relates to methods and materials involved in diagnosing SLE, diagnosing severe SLE, and assessing a mammal's susceptibility to develop severe SLE. For example, this document provides nucleic acid arrays that can be used to diagnose SLE in a mammal. Such arrays can allow clinicians to diagnose SLE based on a simultaneous determination of the expression levels of many genes that are differentially expressed in SLE patients as compared to healthy controls. In addition, methods and materials for assessing SLE activity, determining the likelihood of experiencing active SLE, and detecting SLE treatment effectiveness are provided herein.