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The ubiquitous use of antibiotics has resulted in the selection of bacteria that are relatively resistant to these drugs. Furthermore, few drugs are effective against viral and fungal microorganisms. There is therefore a continuing need to identify novel agents that reduce or inhibit the growth of such microorganisms, or to identify ways of modifying existing agents in order to give them superior antimicrobial activities, or to identify agents that may recruit inflammatory cells.

Bacterial toxins such as cholera toxin and diphtheria toxin catalyze the ADP-ribosylation of important cellular target proteins in their human hosts, thereby, as in the case of cholera toxin, irreversibly activating adenylyl cyclase. In this reaction, the toxin transfers the ADP-ribose moiety of Nicotinamide Adenine Dinucleotide (NAD) to an acceptor amino acid in a protein or peptide. ADP-ribosylation leads to a peptide/protein with altered biochemical or pharmacological properties. Mammalians proteins catalyze reactions similar to the bacterial toxins.

Available for licensing and commercial development is a non-breathhold flow sensitive navigator technique for reducing respiratory motion artifacts in magnetic resonance (MR) images. The method, called Rapid Motion Perception (RaMP), tracks bulk translational motion of the heart in real-time. The position of the blood volume is a direct representation of the heart position. RaMP tracks fast-moving blood volume during systole as a marker for the heart position, while suppressing stationary or slow moving spins.

Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, stroke, and gangrene of the extremities. It is also the principal cause of death in the United States.

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.

The invention provides a deflectable tip guiding device, such as a catheter, that enables the operator to vary the radius of curvature of the tip of the catheter. This is a novel variation on the classic "fixed fulcrum" tip deflectors used in minimally invasive procedures in open surgical treatments. The described device permits a more comprehensive ability to navigate complex geometric pathways in patient's body and enables better access to target structures (e.g., to all endomyocardial walls from a transaortic approach).

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.

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.

Available for licensing are methods and devices for selectively delivering therapeutic substances to specific histological or microanatomical areas of organs (e.g., introduction of the therapeutic substance into a hollow organ space such as the hepatobiliary duct or the gallbladder lumen) at a controlled pressure, volume and/or rate which allows the substance to reach a predetermined cellular layer.

Available for licensing is a technique for improving magnetic resonance imaging (MRI) that employs steady state free precession (SSFP). One such technique, fast imaging with steady-state free precession (FISP), is a well established and is a fast MR imaging method commonly used to evaluate cardiovascular anatomy and function. FISP provides high signal to noise ratio (SNR) images with excellent contrast between blood and the myocardium. However, these images are often contaminated with high signal from fatty tissue resulting in image artifacts.