Abstract: The present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

Abstract: Cell encapsulating devices capable of maintaining large numbers of viable cells are provided containing an inert, substantially cell-free core that displaces cells, a permeable membrane and a zone for maintaining cells. The permeable membrane surrounds the core such that the zone of cells is bounded by the core and the permeable membrane. A preferred device contains a polytetrafluoroethylene permeable membrane and a flexible polymer core having a plurality of ridges and valleys running lengthwise along the core. The cell zone may contain support means for cell attachment and the core may have an outer boundary containing a material that promotes cell adhesion. Preferably, the cell zone has a thickness such that at least about 10% of the cells, more preferably at least about 50% or 80%, in a cell layer located closest to the outer boundary of the core remain viable. The thickness is preferably less than 500 microns such as 25 to 250 microns or 50 to 100 microns.

Abstract: Novel cell lines useful for trans-complementing E1-deleted adenoviral vectors are described. The cell lines are capable of providing high yields of E1-deleted adenoviral vectors in the absence of replication-competent adenovirus over multiple passages.

Abstract: Purified compounds comprising truncated insulin-like growth factor binding protein (IGFBP) capable of binding to an antibody specific for the compound or to an insulin-like growth factor wherein the truncated IGFBP has a decreased affinity for insulin-like growth factors (IGFs) are described. Recombinant DNA molecules encoding the truncated IGFBPs are also described along with recombinant microorganisms and cell lines containing the DNA molecules and methods for producing the truncated IGFBPs using recombinant hosts containing the relevant DNA molecules. Methods for stimulating mitogenic activity and also for treating a bone disorder in mammals are also described.

Abstract: Novel cell lines useful for trans-complementing E1-deleted adenoviral vectors are described. The cell lines are capable of providing high yields of E1-deleted adenoviral vectors in the absence of replication-competent adenovirus over multiple passages.

Abstract: The present invention relates to the finding that cyclin D1 interacts in a ligand-independent fashion with coactivators of the SRC-1 family. The direct interaction of cyclin D1 enhances estrogen receptor (ER) mediated transcription and provides a novel target for the development of assays for substances which modulate the cell cycle. The invention provides assay methods for the prevention of growth of tumours, for assays for compounds useful in the prevention of tumours and compounds obtainable by such assays.

Abstract: The present invention relates to a protein containing an SRCR domain, a nucleic acid encoding such a protein and a method to produce same. The invention further relates to the use of the nucleic acid and the protein and antibodies directed against the protein.

Abstract: The present invention describes an efficient retroviral or viral based method that allows easy and quick identification of gene transfer in living, transduced mammalian cells. Retroviral and viral vector producer cells were generated containing a gene for an improved humanized red-shifted, Green Fluorescent Protein (hRGFP) which increases the resulting fluorescence yield after excitation. This humanized, red-shifted GFP (hRGFP) gene was cloned into several vectors and transfected into various packaging cell lines to produce vibrant green fluorescence after excitation with blue light at 450-490 nm. These vectors represent a substantial advance over currently available gene transfer marking systems or wild-type GFP marker systems none of which have been stably transfected into cells.

Abstract: The present invention relates to a novel potassium channel protein expressed exclusively in the brain, a DNA molecule having a sequence encoding this protein, a vector containing the DNA molecule, a host cell containing this vector, and a method for obtaining the potassium channel protein, wherein mRNA is extracted from human cells or tissue capable of producing the potassium channel protein of the present invention. Then, use is made of two primers between which the channel protein mRNA or a part of the mRNA region is located by using the thus extracted mRNA as a template. By carrying out a reverse transcriptase-polymerase chain reaction, the channel protein cDNA or a part thereof can be obtained. Thereafter, the channel protein can be produced by integrating the thus obtained novel potassium channel cDNA or a part of the same into an appropriate expression vector and then effecting its expression in a host cell.

Abstract: The present invention provides a human glutamate receptor and related DNA compounds useful not only in assays for potential pharmaceuticals but also in methods for molecular biology techniques.

Abstract: Methods and products for stimulating hematopoiesis, preventing low levels of hematopoietic cells and producing increased numbers of hematopoietic and mature blood cells are provided. The methods and products can be used both in vivo and in vitro. The methods involve administering an agent of Formula I: wherein m is an integer between 0 and 10, inclusive; A and A1 are L-amino acid residues such that the A in each repeating bracketed unit can be the same or a different amino acid residue; the C bonded to B is in the L-configuration; the bonds between A and N, A1 and C, and between A1 and N are peptide bonds; and each X1 and X2 is, independently, a hydroxyl group or a group capable of being hydrolyzed to a hydroxyl group in aqueous solution at physiological pH. A particularly preferred agent that is useful in practicing the invention is a ValBoroPro.

Abstract: The present invention provides a method of inhibiting angiogenesis within a tissue by providing exogenous SLED to cells associated with the tissue. The presence of exogenous SLED inhibits angiogenesis within the tissue, in part by interfering with the ability of vascular endothelia to expand within the tissue. The invention also provides a method for determining the severity of a tumor be assaying for the presence of SLED within the tumor. To facilitate the inventive methods, the present invention provides pharmaceutical compositions including sources of SLED.

Abstract: Compositions and methods are provided for endopeptidases and their production, and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides. These compositions and methods utilize recombinant PACE 4 and 4.1, mammalian endopeptidases that are specific for dibasic amino acid sites. Therapeutic compositions and methods employing PACE 4 or 4.1 or their inhibitors are also provided.

Abstract: Small specific binding molecules, such as single variable domain antibodies (Dabs) and Fv fragments, can be coupled to solid plastics surfaces or to tracers such as enzymes by means of linkers comprising polypeptides containing from 5 to 20 amino acids and which are hydrophobic and/or contain at least one lysine residue. The coupling can be achieved without significant loss of specific binding activity. The combined Dab/linker or Fv/linker can be prepared by expression in genetically-modified organisms.

Abstract: Attenuated recombinant viruses containing DNA coding for a cytokine and/or a tumor associated antigen, as well as methods and compositions employing the viruses, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least on of: human tumor necrosis factor; nuclear phosphoprotein p53, wildtype or mutant; human melanoma-associated antigen; IL-2; IFN&ggr;; IL-4; GNCSF; IL-12; B7; erb-B-2 and carcinoembryonic antigen. The recombinant viruses and gene products therefrom are useful for cancer therapy.

Abstract: The invention is related to antibodies which specifically react with connective tissue type-human mast cells, a production method of the antibodies, hybridomas which produce the antibodies, a production method of the hybridomas and antigen proteins recognized by the antibodies. After cord blood cells were cultured in the presence of SCF and IL-6, they were further cocultured with primary culture of human skin fibroblasts, and connective tissue type-human mast cells were thus obtained. A rat was immunized using the cells, hybridomas were prepared and selected by an ordinary method, and novel monoclonal antibodies were harvested from the culture supernatant of the selected hybridomas. The monoclonal antibodies specifically reacted with connective tissue type-human mast cells.

Abstract: MPROT12 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MPROT12 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: Methods for detection of the onset or presence of sporadic basal cell carcinoma in an animal by measuring for elevated levels of ectopic expression of Gli1 in the animal's epidermal tissue sample suspected of harboring sporadic basal cell carcinoma.

Abstract: The invention relates to monoclonal antibodies against leucocyte-specific G protein-coupled receptors (L-GCR). These antibodies are obtainable by the following steps: (a) introduction of an L-GCR-coding nucleic acid into cells and expression of L-GCR, (b) immunization of an animal with L-GCR-expressing cells of (a), and (c) fusion of spleen cells from the immunized animal of (b) with myeloma cells and production of monoclonal L-GCR antibody-producing hybridoma cells. Furthermore, the invention relates to processes for the production of such antibodies, their use and kits containing the same. In addition, the invention concerns a process for the production of monoclonal GCR antibodies.

Abstract: The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which has a biological activity of human &kgr;-casein, the system comprising a 5′-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5′-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence selected from the intron sequences presented in SEQ ID NO:30. The invention also relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide.

Abstract: A culturing system and method particularly useful for producing cellular products such as viral pathogens of cells. It includes a mass transfer culture segment, stacked filter plates to adjust the medium composition, and a product removal and concentration segment. The mass transfer culture segment utilizes changed directional flow of the medium to maximize cell growth and production of product. The stacked filter plates allow addition of sterile fresh medium and removal of growth inhibitory substances.

Abstract: The present invention relates to a method of serum-free production of recombinant proteins and adenoviral vectors; cell lines viable in a serum-free medium and method of obtaining same.

Abstract: Stably-transformed human cell lines containing a reporter gene operatively linked to an IL-4-responsive element are provided. In some embodiments a human Fc&egr;RII IL-4-responsive element is used. In other embodiments a human germline &egr; transcript promoter is used as the responsive element. Also provided are methods for using such transformed cell lines to screen for agonists and/or antagonists of human interleukin-4.

Abstract: An nNOS associated protein designated PIN-1 (Protein Inhibitor of nNOS) has been identified. It physically interacts with nNOS and inhibits its activity. Multiple lines of evidence indicate that PIN-1 is a regulator of nNOS: it is physiologically associated with nNOS, and it inhibits its catalytic activity. The extraordinary evolutionary conservation of PIN-1 and preliminary evidence that it interacts with multiple proteins, suggests that it may be a major biological regulatory protein influencing numerous physiological processes.