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Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

A stable line of human T cells (ACH-2) was developed in which cells infected chronically with the AIDS virus (HIV) remained nonproductive prior to exposure to phorbol esters or human cytokines. This situation mimics the latent state of HIV and the development of AIDS in humans and indicates that the full-blown disease may be triggered by cellular-derived substances (e.g., cytokines). This is the first description of such a cell line.

The invention discloses a vaccine which comprises lipooligosaccharide (LOS) isolated from N. meningitidis and conjugated to a carrier protein. The invention also discloses a method of making the acellular vaccine. The method consists of two main steps. In the first step the lipooligosaccharide (LOS), chosen so it does not contain the lacto-N-neotetraose human antigen (LNnT), is detoxified by a novel procedure which uses hydrazine to remove the O-linked fatty acids. In the second step, the detoxified LOS (dLOS) is covalently conjugated to a carrier protein such as Tetanus Toxoid (TT).

Ulcerative colitis (UC) is a chronic inflammatory disease of the colorectum and affects approximately 400,000 people in the United States. The cause of UC is not known, although an abnormal immunological response to bacterial antigens in the gut microflora is thought to be involved. Present treatments for UC include anti-inflammatory therapy using aminosalicylates or corticosteroids, as well as immunomodulators and diet.

Exposed collagen in injured blood vessels provides a substrate for platelets to adhere and aggregate initiating the first step in thrombosis, the formation of blood clots inside a blood vessel. Despite the essential role of platelets in vascular injury, excessive platelet aggregation may also result in thrombotic diseases such as stroke and heart attack.

Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.

The present invention is directed to novel small molecule agonists of the mammalian relaxin family receptor 1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: 1) vasodilation due to up-regulation of the endothelin system; 2) extracellular matrix remodeling; 3) moderation of inflammation by reducing levels of inflammatory cytokines; and 4) angiogenesis. Small molecule agonists of RXFP1 may be useful in treating acute heart failure (AHF), scleroderma, fibrosis, other conditions associated with the biology of relaxin, and in improving reproductive health and wound healing.

Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes.

This technology describes recombinant viruses that have weakened ability to establish and/or maintain latency and their use as live vaccines. The viruses have one or more genetic mutations that allow for continued replication but that inhibit latency. The vaccine materials and methods for their construction are exemplified with the virus that causes chickenpox and whose latent infection results in shingles, a condition that affects up to an estimated 1 million people per year in the United States alone. Additionally, there are veterinary applications of this technology.

Progressive multifocal leukoencephalopathy (PML) is a rare, fatal demyelinating disease of the brain caused by the polyomavirus JC (JCV) under immunosuppressive conditions. It is pathologically characterized by progressive damage of white matter of the brain by destroying oligodendrocytes at multiple locations. Clinically, PML symptoms include weakness or paralysis, vision loss, impaired speech, and cognitive deterioration. The prognosis of PML is generally poor. No effective therapy for PML has been established.