Abstract: The present invention relates to the isolation of a cDNA clone encoding the calcium sensor in human placenta and subsequent Northern blots confirming the mRNA expression also in human parathyroid and kidney tubule cells. Close sequence similarity is demonstrated with the rat Heymann nephritis antigen, a glycoprotein of the kidney tubule brush border with calcium binding ability. Immunohistochemistry substantiates a tissue distribution of the calcium sensor protein similar to that previously described for the Heymann antigen. It is proposed that the identified calcium sensor protein constitutes a universal sensor for recognition of variation in extracellular calcium, and that it plays a key role for calcium regulation via different organ systems. The calcium sensor protein belongs to the LDL-superfamily of glycoproteins, claimed to function primarily as protein receptors, but with functionally important calcium binding capacity.

Abstract: Devices, processes and compositions are provided for effective separation of cells from a mixture of cells, where depletion or positive selection may be employed to provide a cellular population of interest. Of particular utility is the separation of cells from peripheral blood mononuclear cells, where members of the lymphoid or myeloid lineages may be isolated and used for research, diagnosis or therapy. Also of interest are cellular separation from bone marrow, tumor suspensions or lymphoid tissue suspensions, where cells can be isolated and used for a variety of purposes. The separated cells may be homogeneous, free of exogenous biologicals, viable, capable of replication and exhibit their full complement of biological activities. Multiple phenotypes can be captured simultaneously. Captured cells can be specifically activated with cytokines and antigens to provide cells which are MHC restricted and have antigen-specific effector functions.

Abstract: This invention is directed to methods for stereospecifically preparing [(1-optionally substituted aryl)- or (1-optionally substituted heteroaryl)]-2-substituted ethyl-2-amines, having chirality at the 2-position, and to intermediates to the substituted ethyl-2-amines.

Abstract: This invention is directed to compounds of formula I: ##STR1## wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase.

Abstract: The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.

Abstract: The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.

Abstract: The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.

Abstract: The complete cDNA cloning of two human genes previously designated flg and bek is disclosed. These genes encode for two similar but distinct surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH-3T3 cells led to the biosynthesis of proteins of 150 kDa and 135 kDa for flg and bek respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF), basic FGF (bFGF), or kFGF inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind aFGF, bFGF, or kFGF with dissociation constants of (2-15).times.10.sup.-11 M. The high affinity binding of three distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor/receptor interactions.

Abstract: A composition for genetic manipulation which comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises a terminal repeat of the AAV genome. Methods are disclosed for introducing genetic material into cells by use of AAV liposomes. Accordingly, genetic material was introduced and integrated into stem cells, T cells, primary tumor cells, or tumor cell lines.

Abstract: A composition for genetic manipulation which comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises a terminal repeat of the AAV genome. Methods are disclosed for introducing genetic material into cells by use of AAV liposomes. Accordingly, genetic material was introduced and integrated into stem cells, T cells, primary tumor cells, or tumor cell lines.

Abstract: The present invention is directed to DNA encoding human endothelial cell growth factors, and to plasmids comprising said DNA. In particular, the invention relates to DNA encoding a cleavable signal peptide and an endothelial cell growth factor, wherein removal of said signal peptide yields a mature form of the growth factor.

Abstract: A composition for genetic manipulation which comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises a terminal repeat of the AAV genome. Methods are disclosed for introducing genetic material into cells by use of AAV liposomes. Accordingly, genetic material was introduced and integrated into stem cells, T cells, primary tumor cells, or tumor cell lines.

Abstract: The present invention is directed to compositions comprising endothelial cell growth factor, an acceptable carrier and, optionally, an extracellular matrix protein, a glycosaminoglycan or serum albumin. The compositions are useful for wound repair.

Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.

Abstract: Simplified methods to produce recombinant adeno-associated virus (rAAV) vectors are described. The methods involve the use of chimeric plasmids which incorporate the Epstein Barr nuclear antigen (EBNA) gene, the latent origin of replication of Epstein Barr virus (oriP), and a rAAV genome. The chimeric plasmids themselves are also a part of the present invention. These plasmids are maintained as multicopy extra-chromosomal elements in cells, such as human 293 cells. Permanent cell lines carrying these EBV/AAV plasmids are induced to produce large amounts of rAAV upon addition of wild-type, adeno-associated virus helper functions. Vectors produced in this manner are capable of transducing exogenous genes into other human cell lines and exhibit the attributes of viral elements produced by conventional methods.

Abstract: The invention is directed to a non-hygroscopic stable crystalline form of the antithrombotic compound N-?N-?N-(4-piperdin-4-yl)butanoyl)-N-ethylglycyl!-(L)-aspartyl!-(L)-.beta. -cyclohexyl-alanine amide, to processes for preparing said stable crystalline form, to a pharmaceutical composition thereof, and intermediates thereof, and the invention is directed also to processes for preparing a compound of the formula ##STR1## wherein: A, B, Z, E.sup.1, E.sup.2, G, R, m, n, and p are as defined herein.

Abstract: Compounds of the Formula ##STR1## wherein: K is N or N.fwdarw.O; Q is CH.sub.2 or O; T is ##STR2## or R.sub.3 O--CH.sub.2 ; X is a straight or branched chain alkylene, cycloalkylene or cycloalkenylene group, each of which is optionally substituted by at least one CH.sub.3, CH.sub.3 CH.sub.2, Cl, F, CF.sub.3 or CH.sub.3 O; Y is NR.sub.4, O or S; a=0 or 1; Z is of the formula ##STR3## Z.sub.1 is N, CR.sub.5, (CH).sub.m --CR.sub.5 or (CH).sub.m --N, m being 1 or 2; Z.sub.2 is N, NR.sub.6, O or S, n being 0 or 1; R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently H, alkyl, aryl or heterocyclyl; R.sub.a and R.sub.

Abstract: The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.

Abstract: This invention provides a composition, device and method for the removal of selected factors, such as cytokines or pharmaceuticals, from a substance such as whole blood or plasma. Advantageously, the invention provides for the treatment or prevention of septic shock syndrome or other conditions evidenced by the presence of cytokines in a patient by contacting the patient's whole blood with a composition comprising silica and a surface treatment material, such as heparin, but preferably human serum albumin (HSA). The treatment lowers the cytokine concentration of the blood. Pharmaceuticals can be removed from an individual's whole blood or plasma, such as for use in treating drug overdosage.

Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.