Methods for Diagnosis of Atherosclerosis

The identification of more sensitive and specific markers of atherosclerosis that are non-invasive and cost-effective may have profound impacts on public health. One such strategy involves the detection of marker genes or their products in blood or serum. Such markers may help identify high-risk patients with subclinical atherosclerosis who may benefit from intensive primary prevention or they may help determine the activity of established disease for monitoring response to treatment, resulting in more targeted secondary prevention.

Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular Aging and Atherosclerosis

Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group.

Tristetraprolin (TTP) Knockout Mice

National Institutes of Health researchers have developed knockout mice that do not express Tristetraprolin (TTP). TTP is an AU-rich element (ARE) binding protein and the prototype of a family of CCCH zinc finger proteins. AREs were identified as conserved sequences found in the 3’ untranslated region (3’ UTR) of a variety of transiently expressed genes including early response genes, proto-oncogenes, and other growth regulatory genes. AREs function as instability sequences that target ARE-containing transcripts for rapid mRNA decay.

Monoclonal Antibody to the Protein NCOA6 (also called ASC-2, AIB-3)

The invention relates to monoclonal antibodies that bind to the transcription factor NCOA6 (ASC-2, AIB-3, TRB, TRAP250, NRC). The antibodies have proven successful reagents for Western blotting and for purifying complexes containing NCOA6. The Western blot experiments revealed that NCOA6 is over-expressed in several breast cancer cell lines, and the purification experiments identified a protein complex containing NCOA6 (the ASCOM complex). The monoclonal antibodies may be useful reagents for studying the role of NCOA6 in transcription and for studying the ASCOM complex.

TTP as a Regulator of GM-CSF mRNA Deadenylation and Stability

The disclosed invention provides materials and methods to treat granulocytopenia (low white cell count in the blood) which is characterized by a reduced number of granulocytes (relative) or an absence of granulocytes (absolute). This condition is commonly associated with cancer chemotherapy, but is seen less frequently in a number of conditions including the use of propylthiouracil, radiotherapy for marrow ablation for bone marrow transplantation, aplastic anemia, systemic lupus erythematosus, AIDS and a variety of other situations.

AAV5 Vector for Transducing Brain Cells and Lung Cells

The invention described and claimed in this patent application is related to the delivery of heterologous nucleic acids or genes to particular target cells. In particular, the application relates to methods of delivering a heterologous nucleic acid or gene of interest to particular target cells using an Adeno-Associated Virus of serotype 5 (AAV5). The particular target cells identified include the alveolar cells of the lung and cerebellar and ependymal cells of the brain.

Amelioration of Inflammatory Arthritis Targeting the Pre-ligand Assembly Domain (PLAD) of Tumor Necrosis Factor Receptors

The invention relates to compositions of matter and methods for treating arthritis by modulating Tumor Necrosis Factor Alpha (TNF-alpha) signaling. TNF-alpha plays a key role in the pathogenesis of numerous diseases including rheumatoid and septic arthritis, and other autoimmune and inflammatory diseases. TNF-alpha mediates its effects through receptors that contain a Pre-ligand Assembly Domain (PLAD). The inventors have discovered compounds that interfere with PLAD can block the effects of TNF-alpha in vitro.

Methods and Materials for Identifying Polymorphic Variants, Diagnosing Susceptibilities, and Treating Disease

This invention relates to materials and methods associated with polymorphic variants in two enzymes involved in folate-dependent and one-carbon metabolic pathways important in pregnancy-related complications and neural tube birth defects: MTHFD1 (5,10-methylenetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthase) and methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L). These enzymes are extremely important in the promotion of DNA synthesis, a process that is critical for normal placental and fetal development.

Versatile Reagent For Detecting Murine Leukemia Viruses

Monoclonal antibodies directed at the proteins of murine leukemia viruses (MuLVs) have some value as immunological reagents, but differ greatly in their applicability. The kit described in this invention uses a monoclonal antibody designated 83A25, which identifies almost all ecotropic, xenotropic, polytropic, and amphotropic MuLVs. It can be used in a wide variety of procedures, including focal immunofluorescence assays on live or fixed monolayers, immunoblotting, immunoprecipitation, immunohistochemical, and flow cytometric procedures.

Treatment for Ichthyosiform Skin Diseases

A synthetic composition that contains the transglutaminase 1 (TGase I) enzyme and a lipid vesicle, which can be used to provide ameliorative therapy for inherited autosomal recessive ichthyoses (ARI). Icthyoses are rare inherited skin disorders that result in extensive scaling of the skin. Because this abnormality can affect heat and fluid transfer through the skin, individuals with this disease may have an increased risk for dehydration and skin infections. Each year, more than 16,000 babies are born with some form of ichthyosis. Ichthyosis affects people of all ages, races and gender.