Abstract: The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.

Abstract: Imaging techniques. The focus of an imaging device is varied while acquiring an image of an object. The resulting blurred image is deconvolved to generate, in one embodiment, a two-dimensional projection image of three dimensions of the object.

Abstract: The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.

Abstract: Compositions that bind viral proteins that are specifically expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, which are conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for removal of the infected cells. These antibodies are capable of distinguishing cells expressing EBV DNA from cells which are not expressing EBV DNA. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also disclosed.

Abstract: The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.

Abstract: Methods using magnetic resonance, such as nuclear magnetic resonance (NMR) spectroscopy or magnetic resonance imaging (MRI), are provided for detecting metabolites in a sample. The methods are useful for the diagnosis or prognosis of a disease such as cancer and can also be used to determine or monitor a treatment protocol. The methods are useful in characterizing speciation in biological samples where mixtures are often encountered and chemical shifts of the same structural group of similar molecules can produce complicated overlapping resonances.

Abstract: A method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells for bone marrow transplantation is disclosed. In this method, an effective amount of an ?1,3-fucosyltransferase, e.g., ?1,3-fucosyltransferase VI, is used in vitro to treat cord blood-derived hematopoietic stem cells to convert non-functional PSGL-1 or other ligands on the cell surface into functional forms that bind selectins, especially P-selectin or E-selectin. The treated cells have enhanced effectiveness in reconstituting bone marrow in patients in need of such therapy.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1).

Abstract: A method of inhibiting microvascular bleeding is provided. Antibody to protein C administered to a patient in a pharmaceutically acceptable carrier prevents anticoagulation by greater than 90% of activated protein C in human plasma.

Abstract: It has now been found that N-L-alpha-aspartyl-L-phenylalanine 1-methyl ester (APM) and/or one of its lower alkyl derivatives can be used to treat allergic contact dermatitis associated with irritating oils such as catechol-containing plant-derived antigens such as poison ivy, poison oak, poison sumac and Asian lacquer tree and oils containing capsaicin. Topical application of APM and/or derivative can reduce or alleviate the symptoms associated with irritation of the skin and/or mucous membranes caused by contact or inhalation of these oils or fumes from burning vegetation containing these oils.

Abstract: A number of octapeptides were generated from the sequences encoding the 60 kDa Ro/SSA peptide, the La/SSB autoantigen, the 70 kD nuclear ribonucleoprotein (nRNP), and the Sm B/B? polypeptide, which represent linear epitopes for autoantibodies present in the sera of SLE and SS patients. These peptides are useful in solid phase assays for patients characterized by the presence of these autoantibodies, and can be used to categorize patients as to the likelihood of developing certain conditions associated with SLE. The peptides are also potentially useful in treatment of these patients using immobilized peptide to remove autoantibody and to block binding of the autoantibodies with patient molecules reactive with the autoantibodies.

Abstract: It has now been found that the introduction of single stranded oligonucleotides of DNA or RNA, particularly RNA transcribed from portions of wild type prohibitin 3?UTR, into tumors leads to arrested cell proliferation. Significant reduction in the size of primary tumors has been observed following direct administration of prohibitin 3?UTR RNA. Induction of systemic immunity, as evidenced by the disappearance of metastases as well as the lack of tumor growth in rechallenged animals following prohibitin RNA therapy, has been observed. Thus, wild type RNAs transcribed from portions of a prohibitin 3?UTR, or single stranded DNAs comprised of portions of a prohibitin 3?UTR, or synthetically-made oligonucleotides of the same sequences, can be directly administered as therapeutic agents against tumors.

Abstract: Data consistent with autoimmune disease being caused by Epstein-Barr virus are shown. Based on this evidence, an effective vaccine would prevent the autoimmune disease in those vaccinated, modified or administered so that the vaccine is not itself capable of inducing autoimmune disease. In the case of anti-Sm, structures to be avoided in an Epstein-Barr virus-derived vaccine have been identified. Differences have been identified in the immune responses to Epstein-Barr infection between individuals who develop a specific autoimmune disease and those who do not. These differences are used to distinguish those who are at greater risk for developing specific autoimmune diseases from those who are a lesser risk. Assuming Epstein-Barr virus causes autoimmune disease and that Epstein-Barr virus remains latent in the patient for life, reactivation of the virus from the latent state is important in generating or maintaining the autoimmune response that culminates in autoimmune disease.

Abstract: The 3? untranslated region of the human prohibitin gene has been isolated for use in a cancer susceptibility screen and as a therapeutic agent for the treatment of cancer.

Abstract: A Ca2+ dependent recombinant antibody that specifically binds to a specific twelve peptide sequence (E D Q V D P R L I D G K) in the activation region of the Protein C has been constructed. The antibody does not bind to Activated Protein C and can be used to inhibit activation of Protein C by thrombin-thrombomodulin, in purification of Protein C, and in treatment of tumors.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined and were used to design substrate analogs of the natural -2 substrate that can inhibit the function of memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. The inhibition constant of OM99-2 is 1.6×10?9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, and the importance of the various residues in binding. This information is useful for designing new inhibitors to memapsin 2, for diagnosing and treating and/or preventing Alzheimer's disease.

Abstract: The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.

Abstract: The present invention provides novel methods of reducing memapsin 2 ?-secretase activity in a subject, decreasing levels of ?-amyloid peptide in the brain of a subject, treating Alzheimer's disease and/or reducing the size and/or number of ?-amyloid plaques in the brain of a subject. The methods may include the step of administering an effective amount of truncated memapsin 2 protein, anti-truncated memapsin 2 antibody, and/or nucleic acid encoding a truncated memapsin 2 protein or anti-truncated memapsin 2 antibody. The present invention also provides related pharmaceutical compositions and uses thereof.

Abstract: Data consistent with autoimmune disease being caused by Epstein-Barr virus are shown. Based on this evidence, an effective vaccine would prevent the autoimmune disease in those vaccinated, modified or administered so that the vaccine is not itself capable of inducing autoimmune disease. In the case of anti-Sm, structures to be avoided in an Epstein-Barr virus-derived vaccine have been identified. Differences have been identified in the immune responses to Epstein-Barr infection between individuals who develop a specific autoimmune disease and those who do not. These differences are used to distinguish those who are at greater risk for developing specific autoimmune diseases from those who are a lesser risk. Assuming Epstein-Barr virus causes autoimmune disease and that Epstein-Barr virus remains latent in the patient for life, reactivation of the virus from the latent state is important in generating or maintaining the autoimmune response that culminates in autoimmune disease.

Abstract: The assay of soluble endothelial protein C receptor (sEPCR) is useful to monitor effective thrombin levels and a hypercoagulable state. An assay for sEPCR is therefore useful to monitor ongoing effectiveness of anticoagulant therapy. A sEPCR ELISA assay is particularly useful for this purpose. A state of hypercoagulability in patients or normal individuals can also be identified by such an assay.