Abstract: The present invention makes available a rapid, reproducible, robust assay system for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular protein, e.g., a receptor or ion channel. The subject assay enables rapid screening of large numbers of compounds to identify those which act as an agonist or antagonist to the bioactivity of the cellular protein. In particular, the assay of the invention makes use of a cell that harbors a protein that is responsive to a cellular signal transduction pathway. The protein is operatively linked to a polypeptide which causes a detectable signal to be generated upon stimulation of the pathway, e.g., when a compound interacts with and modulates the activity of a cellular receptor or ion channel of the cell.

Abstract: Porcine cardiomyocytes and methods for using the cardiomyocytes to treat disorders characterized by insufficient cardiac function are described. The porcine cardiomyocytes are preferably embryonic porcine cardiomyocytes. The porcine cardiomyocytes can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine cardiomyocytes can be modified such that an antigen (e.g., an MHC class I antigen) on the cardiomyocyte surface which is capable of stimulating an immune response against the cardiomyocytes in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cardiomyocyte when introduced into the subject. In one embodiment, the porcine cardiomyocytes are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject.

Abstract: Hybrid compounds comprising a first domain and a second domain are provided. The first domain and the second domain are preferably covalently linked, and the first domain comprises a domain which is capable of specific binding to Gb3; and the second domain comprising a moiety selected from the group consisting of drug moiety, a nucleic acid, a probe, a polypeptide, and a hook, with the proviso that the second domain is not a verotoxin or a fragment thereof. Mehtods of preapring and using the hybrid compounds are also provided.

Abstract: Methods for producing perfluorocarbon monomethanols or dimethanols are disclosed. The methods of the invention can provide branched perfluorocarbon monomethanols or dimethanols with good purity and yields.

Abstract: A new method, solid phase precipitation and extraction (SPPE), is disclosed and is particularly advantageous for purifying mixtures of synthetic peptides directly from a cleavage/deprotection mixture.

Abstract: An anchor library is described. A collection of recombinant vectors having a nucleic acid encoding a displayed peptide sequence is provided. The displayed peptide sequence of each of the vectors comprises X1(Y1)c1X2(Y2)c2X3(Y3)c3X4, wherein each X1, X2, X3 and X4 is an amino acid residue and any of X1, X2, X3 and X4 can be the same or different from any one other, wherein each Y1, Y2 and Y3 is alanine or glycine or a combination of alanine and glycine that is respectively c1, c2 and c3 amino acid residues long and any of Y1, Y2 and Y3 if present can be the same or different from any one other, wherein each of c1, c2 and c3 is 0 to about 20, wherein X1 and X4 are each attached to an amino acid residue that flanks the displayed peptide sequence. Preferably, at least about 105 to about 108 permutations of all possible permutations of the displayed peptide sequence are present in the anchor library.

Abstract: Novel &agr;-pyrones are described. The &agr;-pyrones are useful in a method for controlling &agr;-pyrone responsive states in a mammal. The method includes administering to a mammal a therapeutically effective amount of an &agr;-pyrone such that control of &agr;-pyrone responsive states in a mammal occurs. &agr;-Pyrone responsive states can be associated with undesirable cell proliferation such as bacteria or cancer. Packaged pharmaceuticals and pharmaceutical compositions including the novel &agr;-pyrones are also described.

Abstract: There is disclosed a liquid pharmaceutical composition comprising a therapeutic agent which comprises: one or more thyroid hormone or hormones; from about 40% to about 96% ethanol by volume; a pH adjusting agent so that the measured pH of the composition is from about 9 to about 12; and from about 4% to about 50% water by volume; which has utility in the treatment of disorders associated with an impairment of the thyroid hormone function in animals including human beings. The liquid composition may be delivered by a metered dosage delivery system such as an aerosol or pump-action spray.

Abstract: Compounds of the present invention include cell growth inhibitors which are peptides of Formula I, A-B-D-E-F-(G)r-(K)s-L  (I), and acid salts thereof, wherein A, B, D, E, F, G and K are &agr;-amino acid residues, and s and r are each, independently, 0 or 1. L is a monovalent radical, such as, for example, an amino group, an N-substituted amino group, a &bgr;-hydroxylamino group, a hydrazido group, an alkoxy group, a thioalkoxy group, an aminoxy group, or an oximato group. The present invention also includes a method for treating cancer in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound of Formula I in a pharmaceutically acceptable composition.

Abstract: Methods for using neural cells to treat chronic pain and/or spasticity are described. The neural cells can be derived from any mammal, and are preferably human or porcine in origin. The neural cells preferably are serotonergic cells or are gamma-aminobutryic acid (GABA)—producing cells. Neural cells can be obtained from adult, juvenile, embryonic or fetal donors. Neural cells can be modified to be suitable for transplantation into a subject. For example, the neural cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject or can be genetically modified to produce a factor.

Abstract: The invention provides a method of generating a set of polypeptide antigens derived from a protein (or portion thereof) which is expressed with some degree of sequence heterogeneity among naturally or artificially induced variants of the protein. The purpose is to provide a mix of antigens which can be used to immunize against the variants and, preferably, possible unknown or new variants that may arise.

Abstract: Methods of treating a subject having a disorder associated with LHRH activity are disclosed.

Abstract: The invention provides methods for the identification of members of a malignant lymphocyte clone by analysis of clonotypic DNA rearrangements of T cell or B cell receptor genes. The DNA or RNA from isolated single tumor cells is amplified by PCR using consensus primers to the VDJ region of the receptor genes, and the sequence of the VDJ region is obtained from each. The clonotypic sequence of the malignant clone is identified as the most frequent VDJ sequence amplified. Individual-specific PCR primers for the VDJ region are then designed based upon the clonotypic sequence. These specific PCR primers are used to detect and quantitate clonotypic cells in subsequent patient samples using in situ PCR or in situ RT-PCR. Fractionated or unfractionated samples of blood or bone marrow, as well as tissue sections can be analyzed.

Abstract: Isolated nucleic acid molecules encoding a novel protein, CIP104, that interacts with CIITA, an MHC class II transcriptional activator, are disclosed. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a CIP104 transgene. The invention further provides isolated CIP104 proteins and peptides, CIP104 fusion proteins and anti-CIP104 antibodies. Methods of using the CIP104 compositions of the invention are also disclosed, including methods for detecting CIP104 activity (e.g., CIP104 protein or mRNA) in a biological sample, methods of modulating CIP104 activity in a cell, and methods for identifying agents that modulate an interaction between CIP104 and CIITA.

Abstract: Methods for modulating production of a T helper type 2 (Th2)-associated cytokine, in particular interleukin-4, by modulating the activity of a transcription factor, in particular the proto-oncoprotein c-Maf, that regulates expression of the Th2-associated cytokine gene are disclosed. Methods for modulating development of T helper type 1 (Th1) or T helper type 2 (Th2) subsets in a subject using agents that modulate transcription factor activity are also disclosed. The methods of the invention can further involve use of agents that modulate the activity of additional transcription factors that contribute to the regulation of Th1- or Th2-associated cytokines, such as a Nuclear Factor of Activated T cells (NF-AT) protein and/or an AP-1 family protein. Compositions for modulating Th2-associated cytokine production, recombinant expression vectors and host cells, as well as screening assays to identify agents that modulate c-Maf activity, are also disclosed.

Abstract: Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.

Abstract: Benzimidazole derivatives of Formula I or a pharmaceutically acceptable salt thereof are MCP-1 antagonists and are thus useful in the treatment of inflammation, atherosclerosis, restenosis, and immune disorders wherein A is N or CH; where W, X, Y, and Z can be independently C—R2, C—R3, C—R4, C—R5, or N; no more than two of W, X, Y, and Z can be N in any one structure, R2, R3, R4, and R5 are as define in the specification.

Abstract: A Plasmodium falciparum gene encoding immunogenic SERA protein has been isolated by a) systematically screening a lambda gt11 recombinant DNA expression library with a murine monoclonal antibody directed against protein antigens of this pathogen, and b) systematically screening a lambda gt11 genomic cDNA and oligonucleotide probes directed against this pathogen. A 111 kDa protein has been shown to have immunogenic activity against parasite inhibitory antibodies. The gene encoding this protein, including the signal sequence and regulatory sequence in the adjacent 5′ flanking sequence has been isolated and sequenced. Isolation and characterization of genes encoding major protein antigens of P. falciparum make it possible to develop reagents useful in the diagnosis, prevention and treatment of malaria. In addition, the signal sequences or regulatory sequences of this gene can be used to stimulate the production of other useful genetic products.

Abstract: Therapeutic compounds and methods for modulating amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is modulated by the administration to a subject of an effective amount of a therapeutic compound comprising a phosphonate group and a carboxylate group, a congener thereof, or a pharmaceutically acceptable salt or ester thereof. In preferred embodiments, an interaction between an amyloidogenic protein and a basement membrane constituent is modulated.