Abstract: Hypersecretion of mucus in the lungs is inhibited by the administration of an epidermal growth factor receptor (EGF-R) antagonist. The EGF-R antagonist may be in the form of a small organic molecule, an antibody, or portion of an antibody that binds to and blocks the EGF receptor. The EGF-R antagonist is preferably administered by injection in an amount sufficient to inhibit formation of goblet cells in pulmonary airways. The degranulation of goblet cells that results in airway mucus production is thereby inhibited. Assays for screening candidate agents that inhibit goblet cell proliferation are also provided.

Abstract: Secretory gland cells, particularly pancreatic and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Abstract: Hypersecretion of mucus in the lungs is inhibited by the administration of an epidermal growth factor receptor (EGF-R) antagonist. The EGF-R antagonist may be in the form of a small organic molecule, an antibody, or portion of an antibody that binds to and blocks the EGF receptor. The EGF-R antagonist is preferably administered by injection in an amount sufficient to inhibit formation of goblet cells in pulmonary airways. The degranulation of goblet cells that results in airway mucus production is thereby inhibited. Assays for screening candidate agents that inhibit goblet cell proliferation are also provided.

Abstract: The present invention features methods for treatment or prevention of infection by intracellular pathogens (e.g., Mycobacterium species) by administration of an immunomodulatory nucleic acid molecule. In one embodiment, immunomodulatory nucleic acid molecule are administered in combination with another anti-pathogenic agent to provide a synergistic anti-pathogenic effect.

Abstract: Peptidic compositions having FGF receptor affinity, as well as fusion proteins and oligomers of the same, are provided. The subject peptidic compounds are characterized by having little or no homology to naturally occurring bFGF. The subject fusion proteins include the peptidic composition linked to an oligomerization domain, either directly or through a linking group and optionally further include a heparin binding domain. The subject peptidic compositions, fusion proteins and oligomers thereof find use in a variety of applications, including both research and therapeutic applications, in which FGF receptor ligands are employed.

Abstract: Primordial germ cells are extracted from post blastocyst embryos of an ungulate such as extracting primordial germ cells from the gonadal ridges of 25-day porcine embryos or 34-40 day bovine embryos. The primordial germ cells are cultured in long term culture (over 30 days) resulting in cells which resemble embryonic stem cells in morphology and with respect to maintaining pluripotency. The cells obtained can be maintained for several months in culture and can be genetically manipulated using homologous recombination technology in order to insert desired genetic material into the genetic compliment of the cell at a desired location. The genetically manipulated cell can be inserted into a blastocyst obtained from the same species of animal as the cell was derived in order to produce a chimeric ungulate which ungulate may, via its genetic engineering, produce desired pharmaceutical products.

Abstract: The presence of clonal macrophages in pre-cancerous and cancerous tissue represents an early stage of the disease in which clonal expansion of macrophages occurs due to HIV integration or other genetic mutation. Clonally expanded macrophages induce proliferation of surrounding tissue leading to cancerous tumor growth. The invention provides methods and kits for diagnosis of HIV- and non-HIV-associated clonal expansion of macrophages in pre-cancerous and cancerous tissue. The invention also provides methods for the treatment of cancers induced by clonal macrophage expansion and proliferation of surrounding tissue.

Abstract: The invention provides methods for T helper-independent activation of an antigen-specific cytotoxic T lymphocyte response in an individual. The methods generally involve administering to an individual an immunostimulatory nucleic acid molecule in an amount effective to increase an antigen-specific CTL response in the individual. The invention further provides methods for increasing chemokine secretion, which can block HIV infection.

Abstract: The invention features methods for delivering a polypeptide to the bloodstream of a subject by introduction of a nucleic acid construct into secretory gland cells(e.g., cells of salivary gland, pancreas, or liver). In general, the method involves introduction of a nucleic acid construct into a secretory gland duct, which introduction results in expression of a gene product encoded by the introduced construct and delivery of the gene product into the bloodstream of the subject.

Abstract: The present invention provides isolated SRTA-70 proteins that mediate immunoglobulin class switch recombination in antibody-producing cells, and methods of procuding such proteins. The invention further provides isolated polynucleotides encoding SRTA-70 proteins, as well as vectors and host cells comprising the polynucleotides. The invention further provides methods of using SRTA-70 proteins to identify agents that modulate immunoglobulin class switch.

Abstract: The invention provides a method for selectively activating a target cell, where the target cell expresses a receptor activated superiorly by a synthetic ligand (RASSL) having decreased binding affinity for a selected natural ligand and normal or near normal binding affinity for a synthetic small molecule agonist. Thus, RASSL-mediated activation of target cells does not occur to a significant extent in the presence of natural G protein-coupled receptor ligand, but is significantly stimulated upon exposure to a synthetic small molecule. RASSL-expressing target cells are selectively activated by exposing of the cells to an appropriate synthetic small molecule, which in turn binds the RASSL, resulting in G protein activation and triggering of a specific cellular response associated with G protein activation (e.g., cellular proliferation or cellular secretion).

Abstract: Disclosed is a method for enhancing an immune response to a substance, such as an antigen or microbial pathogen. The immune response can be, for example, production of IgG2 antibodies. The method comprises administering an immunostimulatory nucleotide sequence (ISS) to a subject at least one hour prior to exposure to the substance by the subject. The subject may be exposed to the substance either naturally, as with an environmental pathogen, or by administration, as with a known antigen. The method can be used for protecting or immunizing a subject against an antigen or pathogen, providing more effective immunization than if the ISS were co-administered with the substance. The method can be used prophylactically or therapeutically. In preferred embodiments, the ISS comprises a CG, p(GC) or p(IC) DNA or RNA nucleotide sequence. Of these, a CG containing nucleotide sequence is preferred. The ISS can further comprise a pG nucleotide sequence.

Abstract: The invention relates to methods for preventing or reducing antigen-stimulated, granulocyte-mediated inflammation in tissue of an antigen-sensitized mammal host by delivering an immunostimulatory oligonucleotide to the host. In addition, methods for using the immunostimulatory oligonucleotides to boost a mammal host's immune responsiveness to a sensitizing antigen (without immunization of the host by the antigen) and shifting the host's immune responsiveness to a Th1 phenotype to achieve various therapeutic ends are provided. Kits for practicing the methods of the invention are also provided.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: The present invention features non-human transgenic animal models for Alzheimer's disease (AD) and CAA, wherein the transgenic animal is characterized by 1) expression of bioactive transforming growth factor-&bgr;1 (TGF-&bgr;1) or 2) both expression of bioactive TGF-&bgr;1 and expression of a human amyloid &bgr; precursor protein (APP) gene product. The transgenic animals may be either homozygous or heterozygous for these alterations. Bigenic animals are further characterized by development of AD-associated and/or CAA-associated pathology within about two to three months of age, and at about twelve months of age are characterized by a reduced number of neuritic plaques relative to singly transgenic animals. The invention also features methods of screening for biologically active agents that facilitate reduction of &bgr;-amyloid deposits in vivo and methods for facilitating reduction of formation of neuritic plaques in a subject susceptible to AD.

Abstract: Cell fusion assays for identifying antiviral compounds are provided. In the cell fusion assays of the subject invention, a first cell that stably expresses on its surface an envelope protein of an enveloped virion and a second cell that stably expresses a receptor for the envelope protein on its surface are employed. The first and second cells each contain one component of a two component Tat reporter system that produces a detectable product in the presence of cell fusion. In practicing the subject screening methods, the first and second cells are first contacted with each other under cell fusion conditions in the presence of a candidate inhibitory agent. Next, the presence or absence of the detectable product is detected. Finally, the inhibitory activity of the candidate agent is derived from the presence or absence of the detectable product. Also provided are high throughput embodiments of the subject methods.

Abstract: The present invention provides elements derived from a human RANTES promoter that induce expression of a heterologous coding sequence. The invention further provides expression vectors comprising the elements, and host cells comprising the expression vectors. The invention further provides methods of inducing the expression of a heterologous protein in a host.

Abstract: Cultured brain slices are treated with a free radical generator, in the presence of a lysosomal enzyme inhibitor (specifically an inhibitor of two cathepsins). The treated brain slices rapidly develop autofluorescent lipofuscin granules—a universal feature of brain aging. Other correlates of the aged brain are also induced by this treatment, thereby providing an in vitro model for (1) the study of brain aging; (2) assessment of anti-brain aging drugs; and (3) therapeutics directed at the clinical condition referred to as neuronal ceroidlipofuscinosis.

Abstract: The invention provides a triggering mechanism for actuating a trigger signal in response to a pre-determined rate of fluid flow through the mechanism. Triggering mechanism generally includes a sliding piston within an air channel, held in place by a resistance structure. Further provided are aerosol delivery devices having triggering mechanism.

Abstract: The present invention provides isolated an polynucleotide comprising a polymorphic nucleotide sequence from a diacylglycerol acyltransferase (DGAT) gene, wherein at least one a polymorphism is associated with a condition relating to DGAT activity. The invention further provides diagnostic assays for detecting the presence in a nucleic acid sample of a polymorphism in a DGAT gene that is associated with a condition relating to DGAT activity, and for detecting a propensity to develop a condition associated with DGAT activity. The invention further provides treatment methods.