Abstract: Isolated porcine hepatocytes, isolated populations of such hepatocytes and methods for using the hepatocytes to treat subjects with disorders characterized by insufficient liver function are described. The porcine hepatocytes can be either hepatocytes isolated from adult, immature, or embryonic swine. The porcine hepatocytes can be modified to be suitable for transplantation into a xenogeneic subject, for example, by altering 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 the subject (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof). The isolated porcine hepatocytes of the invention can be used to treat disorders characterized by insufficient liver function by administering the hepatocytes to a subject having such a disorder.

Abstract: This invention relates to methods for assaying the presence and/or risk of endometrial cancer by measurement of levels of matrix metalloproteinase-2 and/or matrix metalloproteinase-9 in uterine washings. The method may be qualitative or quantitative, and is adaptable to large-scale screening and to clinical trials.

Abstract: When stimulated through the T cell receptor(TCR)/CD3 complex without requisite costimulation through the CD28/B7 interaction, T cells enter a state of antigen specific unresponsiveness or anergy. This invention is based, at least in part, on the discovery that signaling though a common cytokine receptor &ggr; chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK kinase having a molecular weight of about 116 kD (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) and signaling through the &ggr; chain induces phosphorylation of the JAK kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.

Abstract: The present invention features methods and compositions for transdermal administration. In one embodiment, the invention features methods and compositions for transdermal administration of an amine containing compound having biphasic solubility and/or an agent which enhances the activity of the amine containing compound having biphasic solubility, e.g., a muscle relaxant, to relieve pain.

Abstract: The present disclosure identifies substances having the property of binding to cyclin dependent kinase (cdk) comprising: (i) a peptide including amino acid residue 84 to 103 of full length p16 protein, or an active portion or derivative thereof; or (ii) a functional mimetic of the fragment, active portion or derivative; the substance excludes full length p16, p15, p18 and p19 proteins. These substances are useful in tumor suppression by inhibiting the phosphorylation of Rb protein. Also described herein is the resolution of the amino acid motifs responsible for binding cdks, an FLD motif, corresponding to amino acid residues 90 to 92 of full length p16 protein, and an LVVL motif, corresponding to amino acid residues 94 to 97 of full length p16 protein. The substances disclosed herein can be used in the treatment of hyperproliferative disorders and to screen and design molecules having the similar properties.

Abstract: A broad class of pharmaceutical agents which react directly with electron carriers or with reactive species produced by electron transport to release a pharmacologically active molecule to effect a therapeutic functional change in the organism by a receptor or nonrecepter mediated action.

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 this system, the first cell is treated with a compound, and functional interaction of this compound with a cellular receptor yields a secreted signal. A second cell, bearing a receptor for this secreted signal, makes use of an indicator gene in a signaling pathway coupled to this second receptor. The subject assays include methods of identifying compounds which specifically modulate, for example, heterologous receptors coupled to the pheromone response pathway in yeast.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: The invention demonstrates that NFATp represses cartilage cell division and represses the chondrogenic program in cells and displays the properties of a tumor suppressor gene. In addition, the invention demonstrates that inhibition of NFATp activity promotes cartilage cell proliferation and differentiation. Methods for identifying modulators of cartilage growth and/or differentiation, using either NFATp-deficient cells or NFATp-containing indicator compositions, are provided. Methods of modulating cartilage cell growth and/or differentiation using agents that modulate the activity of NFATp are also provided. Methods for diagnosing disorders associated with aberrant cartilage cell growth and/or differentiation, by assessing a change in NFATp expression, are also provided.

Abstract: Compositions comprising cyaniding reagents for binding to Fc&ggr;RI receptors, and methods and kits for use therefor are provided.

Abstract: The invention deals with the derivatives of benzilidine having basic formula as follows (I): wherein X can be cyclohexanone, cyclopentanone, or acetone, while Y and Z can be either electron withdrawing, electron donating or steric group. Y may or may not be the same with Z. Methyl, ethyl, methoxy group or halogen were prefered in the experiment. The benzilidine cyclohexanone, benzilidine cyclopentanone, and benzilidine acetone derivates were found to be novel compounds showing anti-bacterial, antioxidant, and anti-inflammatory activities that enable them to be used for drug.

Abstract: Methods for modulating immune responses are provided. The methods involve contacting an immune cell with an agent that modulates interaction of a compound comprising a Lewis antigen with the immune cell such that production by the immune cell of at least one cytokine that regulates development of a T helper type 1 or T helper type 2 response is modulated. Stimulatory forms of the agent can comprise multivalent conjugates containing a Lewis antigen, such as a Lewisy, Lewisx or Lewisa-containing oligosaccharide, or a derivative thereof. Inhibitory forms of the agent can comprise non-crosslinked forms of a Lewis antigen, such as a Lewisy, Lewisx or Lewisa-containing oligosaccharide, or a derivative thereof. Stimulatory forms of the agent can be used in methods for stimulating a specific immune response to an antigen in vivo. Inhibitory forms of the agent can be used in methods for inhibiting allergic responses in vivo.

Abstract: Improved methods for detecting lesions in dense breast tissue are disclosed. The methods of the invention generally feature administration to a subject of an LHRH antagonist in an amount and for a period of time sufficient to reduce the density of breast tissue prior to generating an image of the breast tissue, for example by mammography, to detect a lesion in the breast tissue. Packaged formulations for reducing breast density in a subject prior to generating an image of the subject's breast tissue, comprising an LHRH antagonist packaged with instructions for using the LHRH antagonist to reduce breast density in a subject prior to imaging the breast tissue, are also disclosed.

Abstract: Methods for modulating production of a T helper type 2 (Th2)-associated cytokine, in particular interleukin-4, by modulating the activity of one or more transcription factors that cooperate with NF-AT family proteins to regulate expression of a Th2-associated cytokine gene are disclosed. In one embodiment, the activity of a maf family protein (e.g., c-Maf or a small maf protein, such as p18) is modulated. In another embodiment, the activity of a protein that interacts with an NF-AT family protein (e.g., NIP45) is modulated. Combination methods, for example wherein the activities of a maf family protein and an NF-AT protein are modulated or the activities of a maf protein and and NF-AT-interacting protein are modulated, are also encompassed by the invention. 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.

Abstract: The present invention relates to novel compounds and medical methods of treatment of inflammation, atherosclerosis, restenosis, and immune disorders especially those associated with lymphocyte or monocyte accumulation such as arthritis and transplant rejection. More particularly, the present invention concerns the use of 2-phenyl benzimidazole derivatives.

Abstract: The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

Abstract: Modified forms of human interleukin-1&bgr; converting enzyme (ICE) that display proteolytic activity and, furthermore, have increased stability compared to unmodified human ICE are disclosed. Nucleic acid molecules encoding a modified p10 subunit of ICE, and recombinant vectors and host cells incorporating such nucleic acid molecules, are also disclosed. A modified ICE protein of the invention can be used to cleave proteolytically ICE substrates and to identify modulators of ICE activity in screening assays. Moreover, due to its enhanced stability, the modified ICE of the invention is particularly suitable for use in the preparation of ICE crystals for X-ray crystallography.

Abstract: A method for the preparation of a ketone from a narcotic alkaloid having an allyl alcohol moiety is disclosed. The method includes mixing the narcotic alkaloid with an acid in the presence of a catalyst wherein the method is carried out in the substantial absence of hydrogen gas. The method is useful for preparing hydromorphone and hydrocodone compositions having novel impurity profiles. Compositions comprising hydromorphone and hydrocodone are also disclosed.

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr; (hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., Kd=10−8 M or less), a slow off rate for hTNF&agr; dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: Disclosed are compounds of the Formula I wherein: Z is C or nothing, provided that when Z is nothing, R3 and R4 are nothing; A is S, S═O or O═S═O; R1 and R2 are independently hydrogen, lower alkyl, halogen, hydroxy or lower alkoxy, (un)substituted aryl, (un)substituted arylalkyl, (un)substituted heteroaryl or(un)substituted heteroarylakyl; R3 and R4 independently represent hydrogen, lower alkyl, cycloalkyl, aminoalkyl, mono- or dialkylaminoalkyl, (un)substituted aryl or (un)substituted heteroaryl; R5 represents a (un)substituted carbocyclic group containing from 3-7 members, up to two of which members are optionally hetero atoms; or R5 is (CR6R7)—(CH2)n—XR8R9; X is S or N; R6, R7, R8, R9, and n are as defined in the specification. The compounds are useful in the treatment and prevention of the AIDS virus. Intermediates useful in the preparation of the final products, pharmaceutical compositions containing the final products are also taught.