Detection of Mutational Frequency in Human Bone Marrow

To date there have been no adequate methods to determine the frequency of mutations in humans. This invention discloses a method of measuring the mutational frequency of a mitochondrial DNA sequence by sequencing mitochondrial DNA from clonally expanded single cells such as CD34+ human stem cells. Sequencing for mitochondrial DNA polymorphisms and mutations may also be useful as a general method to detect minimal residual disease in leukemia. The mitochondrial genome is particularly susceptible to mutations and these may be used to measure genomic mutagenesis by virtue of comparison.

Diagnostics and Therapeutics for Hydrocephalus

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States. Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults. Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities. Improved diagnostics are needed for assessing the risks of developing this debilitating disease.

Oral Treatment of Hemophilia

This invention portrays a simple method for treatment of antigen-deficiency diseases by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. This method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Recombinant Plasmids for Soluble Immunoreceptors

Immunoreceptors initiate signals leading to the activation of immune system against invasion pathogens. A number of soluble receptors, representing the extracellular ligand binding domains of the immunoreceptors, have been expressed using a recombinant bacteria expression and reconstitution system. This set of 21 plasmids, which can be used as immunological research reagents or to develop diagnostic tools, comprise the following:

Peptides for Treatment of Tumor Necrosis Factor alpha Mediated Inflammatory Disease

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.

Mouse Lacking the Chemokine Receptor CX3CR1

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.

HIV-Dependent Expression Vector

This invention provides a DNA construct that can be useful for both diagnostics and AIDS therapeutics. The construct can be incorporated into a retrovirus or into a cell line. This construct mediates the expression of a selected gene in the presence of HIV replication, but is silent in the absence of HIV. The cell line with the incorporated construct can be used as an indicator line for the presence of replication-competent HIV. The virus containing the construct can be used to co-infect a population of HIV-infected cells.

A Tet-Regulated Mouse Model for Cataract

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.

Pain Control by the Selective Local Ablation of Nociceptive Neurons

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.

A Microfluidic Flow-Through Immunoassay for a Simultaneous Detection of Multiple Proteins in a Sub-Microliter Biological Sample

This invention presents a high throughput, multi-analyte microfluidic chip device. This device can be used for the detection and characterization of proteins, immuno-affinity assays as well as analyte detection in biological samples or other media. The sub-microliter volumes for use make this device applicable where biological samples are rare and difficult to obtain.

The device consists of a series of channels that are connected via communication ports for sample flow. The channels can be individually loaded with detection reagents via portals at their ends.

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