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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.

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.

Currently, adeno-associated virus (AAV) represents the gene therapy vehicle of choice because it has many advantages over current strategies for therapeutic gene insertion. AAV is less pathogenic than other virus types; stably integrates into dividing and non-dividing cells; integrates at a consistent site in the host genome; and shows good specificity towards various cell types for targeted gene delivery.

This invention relates to diphtheria toxin fusion proteins comprising a diphtheria toxin (DT) cell-killing component and a cell-binding component such as granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), or epidermal growth factor (EGF). Receptors for the latter three materials are present on many types of cancer cells; therefore, these fusion proteins bind preferentially to these cancer cells. A key feature is that these toxins are altered so as to require activation by a cell-surface protease that is overexpressed on many types of cancers.

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.

It is estimated that over 40 percent of the adult population in the United States has periodontal disease in one form or another. Periodontal Disease is a chronic infection of the periodontal ligament (PDL) and the adjacent bone and cementum. The effects of Periodontal Disease range from simple gum inflammation to, in extreme cases, tooth loss.

The noroviruses (known as "Norwalk-like viruses") are associated with an estimated 23,000,000 cases of acute gastroenteritis in the United States each year. Norovirus illness often occurs in outbreaks, affecting large numbers of individuals, illustrated recently by well-publicized reports of gastroenteritis outbreaks on several recreational cruise ships and in settings such as hospitals and schools. Norovirus disease is clearly important in terms of medical costs and missed workdays, and accumulating data support its emerging recognition as important agents of diarrhea-related morbidity.