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The National Institutes of Health announces three specific monoclonal antibodies that strongly inhibit and/or immunoblot the human cytochrome P450 2J2 (CYP2J2).

Cytochrome P450s catalyze the NADPH-dependent oxidation of arachidonic acid to various eicosanoids found in several species. The eicosanoids are biosynthesized in numerous tissues including pancreas, intestine, kidney, heart and lung where they are involved in many different biological activities.

This invention relates to the use of several peptides from the salivary glands of various sand fly species for the control of leishmania infection. Many of these peptides were shown to be effective in eliciting potent immune responses in animal models and are excellent candidates for the development of vaccines against the disease. A vaccine comprising one of the peptides was used to protect mice challenged with parasites and salivary gland homogenates.

Tumor Necrosis Factor alpha (TNF-alpha) is a multifunctional cytokine that mediates inflammation, immune regulation, and cellular proliferation. This cytokine is converted to its active form by TNF-alpha converting enzyme (TACE). Pathological increases in TNF-alpha activity have been associated with a wide variety of inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer. Inhibiting the conversion of TNF-alpha to its active form by inhibiting TACE represents a potential treatment for these diseases.

This mouse has been generated by targeted gene disruption. The mouse provides a model to investigate the function of the chemokine receptor CX3CR1, which is a proinflammatory receptor for the leukocyte chemoattractant CX3CL1 (aka fractalkine). As an example, the mouse is in use in the study of atherosclerosis. Further, the mouse may serve as a model study the role of the immune system during infection with pathogens as well as other immunologically mediated diseases and responses to tumors.

Bitter taste has evolved in mammals as a central warning signal against ingestion of poisonous or toxic compounds. However, many beneficial compounds are also bitter and taste masking of bitter tasting pharmaceutical compounds is a billion dollar industry. The diversity of compounds that elicit bitter-taste sensations is vast and more than two dozen members of the TAS2R bitter taste receptor gene family have been identified.

Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

The vanilloid receptor (VR) is a cation channel predominantly expressed on the peripheral processes and perikarya of nociceptive primary afferent neurons. Previous studies have shown that activation of the peripheral receptors by agonists such as capsaicin from hot peppers, or the much more potent resiniferatoxin, produces acute pain sensation which may be followed by desensitization. These inventors discovered that administration of VR agonists in the vicinity of neuronal cell bodies expressing the VR receptor can actually destroy those cells.

Expression of the HIV-1 Vif protein in the absence of other viral factors such a Tat and Rev is extremely inefficient due to the presence of inhibitory sequences on its mRNA. This invention uses codon optimization to remove such inhibitory sequences without altering the amino acid sequence of the protein. The modified vif gene in the resulting pcDNA -hVIF vector is expressed under the control of the CMV promoter. In this, the protein functions as wild type and is more amendable to high-level expression in mammalian cells.

The invention includes a mouse in which the IL-21 receptor gene is disrupted by homologous recombination, the disruption being sufficient to prevent expression of the IL-21 receptor and thus to inhibit the action of IL-21. The invention also includes a mouse in which both the IL-21 receptor gene and the IL-4 gene are simultaneously disrupted in fashions being sufficient to inhibit the action of IL-21 and the production of IL-4. In a homozygous state, these mutations produce a mouse that has diminished B cell function.

The invention relates to the discovery that humanized antibodies to the interleukin-2 receptor (IL-2R) such as (daclizumab) are effective in treating multiple sclerosis (MS). In particular, it has been discovered that patients who have failed to respond to therapy with interferon-beta show dramatic improvement when treated with daclizumab, with patients showing both a reduction in the total number of lesions and cessation of appearance of new lesions during the treatment period. Daclizumab is effective both in combination with interferon-beta and alone.