Abstract: Compositions and methods are provided for the treatment of demyelinating autoimmune disease. Therapeutic doses are administered of an ordered peptide comprising a repeated motif {SEQ ID NO: 1} [1E2Y3Y4K]n, where n is from 2 to 6. Some specific peptides of interest include those having the sequence {SEQ ID NO: 4} EYYKEYYKEYYK. The peptide may consist only of the ordered repeats, or may be extended at either termini by the addition of other amino acid residues. For therapy, the peptides may be administered topically or parenterally, e.g. by injection at a particular site, including subcutaneously, intraperitoneally, intravascularly, or the like or transdermally, as by electrotransport. In a preferred embodiment, subcutaneous injection is used to deliver the peptide. The subject methods are used for prophylactic or therapeutic purposes. The compositions of the invention may also contain other therapeutically active agents, e.g. immunosuppressants, &bgr;-interferon, steroids, etc.

Abstract: The present invention relates to the identification of a binding between NMDA receptor (NMDA-R) subunits and a protein tyrosine phosphatase (PTP), e.g., PTPL1. The present invention provides methods for screening a PTPL1 agonist or antagonist that modulates NMDA-R signaling. The present invention also provide methods and compositions for treatment of disorders mediated by abnormal NMDA-R signaling. The present invention further provides methods for isolating PTPL1 from a biological preparation.

Abstract: A range of aziridin-1-yl nitrobenzamides are provided for use as prodrugs in conjunction with nitroreductase (NR) enzymes. The amides may have 1 or 2-substituents which may be bulky and polar. For example, 5-(aziridin-1-yl)-N-[2-(4-morpholino)ethyl]-2,4-dinitrobenzamide of Formula (A) was found to be highly active against all NR+ cell lines tested.

Abstract: A compound of the formula wherein, independently at each occurrence, v, w, and x are selected from C, N, O, and S, with H substitution as needed to fulfill open valence sites; y and z are selected from N and C, with H substitution as needed to fulfill open valence sites, with the proviso that each of w, v, x, y and z is not simultaneously C; the ring formed from v, w, x, y and z may be saturated or unsaturated; and R1, R2, R3 and R4 are selected from hydrogen, alkyl, aryl, alkaryl, aralkyl, heteroalkyl, and heteroaryl; wherein any adjacent two of R1, R2, R3 and R4 may join together to form a 5, 6 or 7-membered carbocyclic or heterocyclic ring, with the proviso that each of R1, R2, R3 and R4 is not simultaneously hydrogen. Pharmaceutical compositions of said compounds, and methods of use in the treatment of biological conditions including cellular hyperproliferation, are disclosed.

Abstract: An expandable space frame is manufactured by linking a plurality of flexible joints through spacing arms to form a closed structure. The spacing arms are sterically offset, linking the bottom of one joint to the top of the next joint in an stepwise fashion. The offset allows the frame to be collapsed with minimal steric hindrance between the centered joints. This lack of steric hindrance permits a very high ratio of the expansion to compression diameters for the frame. The space frame forms the basis for different types of stents. A spiral frame, or a series of individual frames are linked to each other to form a luminal stent, or are linked to longitudinal struts to form the support structure for a stent. The stents formed from the expandable space frame can be designed to have a number of additional features as set forth herein.

Abstract: Nucleic acid compositions and polypeptides encoding a red-shifted form of firefly luciferase are provided. These red-shifted luciferases are characterized by spectrum of light emission having detectable emissions at 610 nm (luc610), preferably a primary peak at 610 nm. The nucleic acid compositions find use in various systems as a reporter gene, and are of particular interest for use as a reporter with in vivo systems, because of the efficient transfer of red light through tissues. The red-shifted luciferase may be combined in such assays with luciferases emitting at other spectra, in order to monitor multiple processes simultaneously.

Abstract: The invention provides adenoviral vectors (preferably replication competent) comprising both an E3 sequence and at least one adenoviral gene under transcriptional control of a target cell-specific transcriptional response element. These vectors display significantly improved cytotoxicity, which is especially useful in the cancer context, in which selective destruction of target cells is desirable. The invention further provides host cells comprising the vectors. The invention further provides methods of using the adenoviral vectors.

Abstract: Novispirin peptides are antimicrobial agents with potent activity against Gram-negative bacteria. The peptides are nonhemolytic, exhibit reduced in vitro cytotoxicity relative to other antimicrobial peptides, and were well-tolerated in vivo after intravenous injection. Novispirins also bind lipopolysaccharide (LPS), a property that may mitigate symptoms associated with Gram-negative bacterial infection. A pharmaceutical composition comprising novispirin as an active agent is administered to a patient suffering from or predisposed to a microbial infection, particularly Gram-negative bacterial infections.

Abstract: An automated particle sorter having a fluid flow path, which places single biological particles in an optical cuvette. An exciting light irradiation system having a light source emits a source of light through the cuvette. The light excites a fluorescent substance present on the particle, and the emitted light is detected by a light detection apparatus containing at least two detection elements for measuring the fluorescence emitted from the fluorescent substance. A light separation element separates the fluorescence from the exciting light. A data processor compares the signal received from the fluorescent light; and from the background autofluorescent signal, and according to pre-set parameters, controls the position of a collection conduit between two set points. The first being a collection set point for the collection of objects having a first phenotype and the second being a set point for the collection of objects having a second phenotype.

Abstract: The invention provides a means of closed exchange of implanted medical device components. An exchanger is brought into contact with the implanted medical device in situ. The component is withdrawn from the implanted device and brought into a closed chamber of the exchanger. Without breaking the contact between implanted device and exchanger, the replacement component is then moved from its position in the exchanger, and inserted into the correct position in the implanted device. The surfaces of the implanted device are not brought into contact with the outside environment, thereby minimizing the possibility of introducing contaminants into the body during the exchange process. The invention is particularly useful for devices that are difficult to position and re-position, thus making it advantageous to exchange only an expended component, rather than the entire device.

Abstract: A novel polymorphism in the human PC-1 gene is characterized, which is associated with an increased predisposition to developing insulin resistance. The polymorphism affects heterozygous and homozygous carriers of the allele. The subject nucleic acids and fragments thereof, encoded polypeptides, and antibodies specific for the polymorphic amino acid sequence are useful in determining a genetic predisposition to insulin resistance. The encoded protein is useful in drug screening for compositions that affect the activity of PC-1 and insulin receptor activity or expression.

Abstract: Mammalian progenitor or stem cells are expanded in vitro by increasing the levels of &bgr;-catenin in the cell. The expanded cells substantially maintain their original phenotype including the ability to give rise to multiple types of differentiated cells. The intracellular levels of &bgr;-catenin may be manipulated by providing exogenous &bgr;-catenin protein to the cell, or by introduction into the cell of a genetic construct encoding &bgr;-catenin. The &bgr;-catenin may be a wild-type or stabilized mutant form of the protein. Preferably the long term cell culture medium substantially lacks stromal cells and cytokines.

Abstract: A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor &agr;); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells.

Abstract: The present invention relates to the use of proteins which are differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as biomolecular targets for brain tumor treatment therapies. Specifically, the present invention relates to the use of immunotherapeutic and immunoimaging agents that specifically bind to human protein tyrosine phosphatase-zeta (PTP&zgr;) for the treatment and visualization of brain tumors in patients. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention.

Abstract: Neurological dysfunction is prevented or treated by the administration of ligands that activate the GPR30 receptor. Ligands include estrogens and structurally related molecules. Preferably the GPR30 ligand is an orally available drug that can cross into the brain from blood. Screening methods are provided for ligands that do not activate other estrogen receptors, and therefore do not have the classical estrogenic effects attributable to these receptors.

Abstract: Replication-competent adenovirus vectors specific for cells which allow a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise and adenoviral gene under control of a transcription regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells.

Abstract: Nucleic acid compositions encoding a pro-apoptotic protein, Bok (Bcl-2-related ovarian killer) are identified. Bok has conserved Bcl-2 homology domains 1, 2 and 3 and a C-terminal transmembrane region present in other Bcl-2 related proteins, but lacks the BH4 domain found only in anti-apoptotic Bcl-2 proteins. Over-expression of Bok induces apoptosis. Cell killing induced by Bok is suppressed by co-expression with selective anti-apoptotic Bcl-2 proteins. Bok is highly expressed in the ovary, testis and uterus, particularly in granulosa cells, the cell type that undergoes apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic protein with wide tissue distribution and hetero-dimerization properties facilitates elucidation of apoptosis mechanisms in reproductive and other tissues, and provides a means for manipulating apoptosis.

Abstract: Pharmaceutical compositions and compounds are provided. The compounds of the invention have anti-proliferative activity, and may promote apoptosis in cells lacking normal regulation of cell cycle and death. In one embodiment of the invention, formulations of the compounds in combination with a physiologically acceptable carrier are provided. The pharmaceutical formulations are useful in the treatment of hyperproliferative disorders, which disorders include tumor growth, lymphoproliferative diseases, angiogenesis. The compounds of the invention are substituted pyrazoles and pyrazolines.

Abstract: Replication-competent adenovirus vectors specific for target cells and methods of use of such viruses are provided. These adenoviruses comprise a first adenoviral gene under control of a cell specific heterologous (i.e., non-adenoviral) transcriptional regulatory element (TRE) and at least a second gene under control of a second heterologous TRE, where the heterologous TREs are different from each other in polynucleotide sequence but functional in the same cell. The adenoviral gene can be, for example, a gene required for adenoviral replication. The second gene can be, for example, a second adenoviral gene or a transgene, such as a gene which can contribute to cytotoxicity in the target cell. Adenoviral replication can be restricted to target cells in which the heterologous TREs are functional and thus, the adenovirus vectors can provide selective cytotoxicity to the target cells, particularly neoplastic cells.

Abstract: The immunogenicity of an antigen is enhanced by increasing the specific antigen presenting function of dendritic cells (DC) in a mammalian host. The host is treated with a DC mobilization agent to increase the number of circulating DC precursors. The host is then given a local, injection of antigen in combination with a DC activating agent. The activation step promotes recruitment and maturation of the DC, along with antigen-specific activation and migration from the tissues to lymphoid organs. These DC then effectively interact with, and present processed antigen to, T cells that are then able to respond to the antigen. In one aspect of the invention, the antigen is a tumor antigen, and is used to enhance the host immune response to tumor cells present in the body.