Abstract: A recombinant melusin fusion protein having an improved stability and a capability to reach intracellular compartments as compared to recombinant melusin in vivo, wherein said protein comprises i) a human melusin protein having the amino acid sequence as defined in SEQ ID No.:1, or a homologue thereof having at least 60%, preferably at least 80%, more preferably at least 90% sequence identity to SEQ ID No.:1 and having the function of native melusin protein or a human melusin portion derived from SEQ ID No.:1 or homologue thereof having at least 60%, preferably at least 80%, more preferably at least 90% sequence identity of the melusin portion derived from SEQ ID No.:1 and having the function of native melusin protein and ii) a cell penetrating polypeptide.

Abstract: The present invention relates to improved therapies for the treatment of heart disease, particularly the improved delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method comprising, identifying a mammal in need of treatment or prevention of heart disease, and supplying NO to the coronary circulation prior to, and/or during the infusion of a therapeutic polynucleotide into a blood vessel of the coronary circulation in vivo.

Abstract: Compositions and methods for inducing the deposition of elastin by administering compositions including a mineralocorticoid, such as, for example, aldosterone and, optionally, a secondary active agent for enhancing or modulating the effect of the mineralocorticoid are described herein.

Abstract: We found that FIZZ1/RELM? is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM? was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM? protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Abstract: We found that FIZZ1/RELM? is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM? was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM? protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Abstract: The present invention relates to improved therapies for the treatment of heart disease, particularly the improved delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method of treating or preventing a cardiovascular disease by transfecting cardiac cells of a large mammal, the method comprising, identifying a mammal in need of treatment or prevention of heart disease, supplying NO to the coronary circulation prior to, and/or during the infusion of a therapeutic polynucleotide into a blood vessel of the coronary circulation in vivo, where the therapeutic polynucleotide is infused into the blood vessel over a period of at least about three minutes, where the coronary circulation is not isolated or substantially isolated from the systemic circulation of the mammal; and where the therapeutic polynucleotide transfects cardiac cells of the animal resulting in the treatment or prevention of the heart disease.

Abstract: The invention provides LTBP2, which is associated with cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of LTBP2 as well as pharmaceutical compositions comprising such compounds. The invention also provides LTBP2 as a biomarker for diseases such as cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases.

Abstract: The present invention relates to the polypeptides known as muscle calcineurin interacting proteins (MCIPs). These molecules binding to calcineurin and, in so doing, modulate its functions, which includes phosphate removal as part of a pathway coupling Ca2+ to cellular responses in muscle. MCIPs form a physical complex with the catalytic subunit of calcineurin, and increased levels of MCIPs correspond to a reduced ability of calcineurin to stimulate transcription of certain target genes. Methods to exploit these observation are provided and include screening for modulators of MCIP expression and binding to calcineurin, methods of diagnosis of MCIP defects, and methods for treating cardiomyopathies, including cardiac hypertrophy.

Abstract: The present provides nuclear localization signaling (NLS) sequences derived from titin, comprised of amino acids 181-220: SVGRATSTAE LLVQGEEEVP AKKTKTIVST AQISESRQTR and fragments thereof, such as amino acids 193-208: VQGEEEVP AKKTKTIV; amino acids 199-208: VPAKKTKTIV; and amino acids 200-206: PAKKTKT. The NLS sequences can be linked to agents, such as peptides, proteins or nucleotides, for transporting the agents into the nucleus of cells, and the NLS-agent complex can be further linked to antibodies or ligands for specific binding to cells. Also provided is a method for constructing cDNAs comprising combining a NLS sequence with a nucleic acid sequence for a target protein for expression and entry of the target protein into the nucleus of cells, which then can perform specific functions therein.

Abstract: Disclosed are modified naturally occurring biocompatible biopolymers of plant and animal origin made by subjecting same to ionizing radiation in the presence of a mediating gas, typically acetylene to enable one to selectively enhance and modify one or more of the physiochemical properties of the starting materials which have a wide range of uses in medicine, food technology and other industrial applications. Notwithstanding the modifications, the biocompatibility of the biopolymer remains unchanged and no new or additional functional groups are introduced into the starting biopolymer.

Abstract: A method to facilitate recovery troponin I and/or troponin T from a sample comprising addition of troponin C to the sample or to a surface from which the troponin I and/or troponin T are recovered.

Abstract: A method for purifying bone-derived TGF-&bgr; proteins including an anion exchange process, a cation exchange process, and a reverse phase HPLC process, and optionally, a filtration process, a Heparin-Sepharose process, and/or a reverse phase HPLC desalting process. The filtration process preferably selects proteins having a nominal molecular weight between approximately 10 kilodaltons and approximately 100 kilodaltons. Preferably, the anion exchange process uses a strongly cationic resin having quaternary amine functional groups. Preferably, the cation exchange process uses a strongly anionic resin having sulfonic acid functional groups. The TGF-&bgr; proteins can be eluted from the reverse phase HPLC column with an acetonitrile solution in combination with aqueous trifluoracetic acid. The purification processes yield highly enriched TGF-&bgr;1 and TGF-&bgr;2 proteins.

Abstract: A cardiogenic composition comprising a purified mixture of a transforming growth factor-&bgr; protein and a fibroblast growth factor is disclosed. In another embodiment, the present invention is a method of inducing cardiogenesis in cells of a non-cardiac lineage comprising the steps of exposing cells to the composition and observing the development of cardiac cells.

Abstract: The present invention relates to an isolated fragment of human cardiac troponin I (TnI) comprising the following sequence X-A-B-Y wherein X comprises any of amino acid residues 1-27 of SEQ ID NO: 2; A comprises amino acid residues 28-69 of SEQ ID NO: 2; B comprises amino acid residues 70-90 of SEQ ID NO: 2; and Y comprises any of amino acid residues 91-170 of SEQ ID NO: 2. The present invention further relates to fragments of TnI wherein the fragment has a greater immunologic reactivity than intact cTnI when the fragment and intact cTnI are reacted with a monoclonal antibody, which has an epitopic site on the fragment.

Abstract: The present invention provides reagents and assays for the quantification of hBNP in biological fluid samples such as plasma or serum. Antibodies are provided which are monospecific to epitopes comprising the amino acid sequences 5-13, 1-10 and 15-25 of hBNP. These antibodies, and peptide fragments containing these sequences, can be employed in the assays of the invention, which may be carried out in a sandwich format or a competition format.

Abstract: The invention relates to synthetic calibrators for immunological tests, analyte-specific epitopes being coupled to other proteins or to synthetic carriers.

Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the individual subunit in its native conformation in liquid medium, which in turn acts to stabilize its biological activity.

Abstract: Provided herein are human proteins or xenogeneic homologs thereof, which are predictive markers for acute allograft rejection, processes for obtaining the proteins of the invention, nucleotide sequences which encode the proteins, and antibodies to the proteins. Also provided are methods of assaying biological samples for the presence, and optionally the amounts of proteins of the invention, a kit for assaying such proteins in a bodily sample, and a method and kit related to diagnosis and prognosis of organ rejection in a subject.

Abstract: The breakpoints of the pericentric inversion of chromosome 16 have been cloned. Two genes, one at each breakpoint, have also been identified, as well as several forms of the inversion 16 fusion gene. Diagnostic applications for chromosome 16 abnormalities and, particularly acute myeloid leukemia are also within the scope of the present invention.

Abstract: Biodegradation additive characterized in that it consists of a mixture of (i) at least one assimilable nitrogen source composed of at least one unsubstituted or substituted amino acid; (ii) at least one phosphorus source, the ratio of nitrogen to phosphorus ranging from 2 to 100, said additive being subjected to a treatment to make it oleophilic. The invention also concerns an additive in accordance with any of the foregoing claims for the biodegradation of hydrocarbons.

Abstract: Stabilized composition of troponin I or T for immunoassays, comprising an aqueous solution containing troponin I or troponin T, 1 to 10 molar equivalents of troponin C per molar equivalent of troponin I or T, and Mg.sup.++ and/or Ca.sup.++ ions, as well as a process for stabilizing a composition of troponin I or T for immunoassays consisting in adding from 1 to 10 molar equivalents or troponin C per molar equivalent of troponin I or T.

Abstract: A monoclonal antibody having high affinity to human cardiac myoglobin, which has undergone a conformational change resulting from the binding of the molecule to another molecule is described. This monoclonal antibody can be used in a rapid format double antibody immunoassay system to identify blood, serum or plasma levels of cardiac myoglobin. Such an immunoassay system can be used for diagnosing and quantifying myocardial necrosis and infarction.

Abstract: A formulated biological adhesive composition utilizes tissue transglutaminase in a pharmaceutically acceptable aqueous carrier. The tissue transglutaminase is used in an effective catalytic amount to promote adhesion between tissue surfaces upon treatment thereof by catalyzing the reaction between glutaminyl residues and amine donors of the tissue and/or the enzyme. The carrier contains a divalent metal ion such as calcium to promote said reaction.

Abstract: A biochemically pure polypeptide(s), termed osteogenic growth polypeptide (OGP), which exhibits stimulatory effects on osteoblastic cells, in vivo bone formation and hemopoietic reconstruction. OGP, identified from regenerating bone marrow, has an amino acid sequence ofAla-Leu-Lys-Arg-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-Gly-Gly.

Abstract: A process is disclosed which makes possible the isolation of the luminal endothelial cell membrane from associated tissue. It is particularly applicable to vasculature, but broadly is applicable to all tissue cavities which are accessible from adjacent perfusable lumens. The method involves the identification of characteristic molecules (primarily proteins and lipids) associated with the luminal surface of the any endothelial membrane in situ by utilizing a novel membrane-isolation scheme to separate the endothelium from associated tissue. In this method, the endothelial luminal plasmalemma of a given organ is coated with colloidal silica by perfusion, a pellicle is formed, the coated area of tissue is excised and the coated plasmalemma fragments are isolated from the cognate homogenate by centrifugation. The isolated plasmalemma attached to the pellicle can then be subjected to biochemical analysis to identify and catalogue molecules characteristic of the endothelial membrane.

Abstract: A factor isolable from muscle tissue or muscle cell culture inhibits proliferation of tumor cells, such as ESB, HT-29 and B-16 F1 cell lines, as well as the peripheral white blood cells of a patient with chronic myeloid leukemia. The active fraction has a molecular weight in the range of 25-30,000 daltons.

Abstract: The present invention is based on the discovery that amyotrophic lateral sclerosis (ALS), Parkinson disease and Alzheimer disease are due to lack of disorder-specific neurotrophic factors. Specific neurotrophic factors of .about.20-22 kD and .about.16-18 kD have been isolated from rat and human skeletal motor neurons, respectively, and purified. With tissue culture, the presence or absence of the specific neurotrophic factors provided herein can be assessed in ALS. If there is a deficiency, extracted and purified neurotrophic factors specific to the motor neuronal network or system can be administered to ALS-affected individuals.

Abstract: A channel protein has a molecular weight of approximately 280 kD and is capable of affecting K.sup.+ and Cl.sup.- membrane transport. Furosemide and quinine derivatives, and polysaccharide or monosaccharide gels incorporating such derivatives, are useful in treating membrane transport, cellular volume and cellular pressure disorders and in producing the channel protein. The channel protein is used in diagnostic assays and screening assays is described.

Abstract: Two proteins that are found in bone and that have in vivo chondrogenic/osteogenic activity in combination with a co-factor are described. Both proteins also were active in combination with EGF in the in vitro TGF-.beta. assay. Each has a molecular weight of approximately 26,000 daltons by SDS-PAGE. Each is reduced to a single polypeptide indicating that the proteins are probably homodimers. One has an N-terminal sequence identical to that of human placenta-derived TGF-.beta. whereas the other has an N-terminal sequence that is different from that of TGF-.beta. derived from human placenta. The two proteins may be purified to hmogeneity using RP-HPLC or acetic acid-urea gel electrophoresis.

Abstract: Two proteins that are found is bone and that have in vivo chondrogenic/osteogenic activity in combination with a co-factor are described. Both proteins also were active in combination with EGF in the in vitro TGF-.beta. assay. Each has a molecular weight of approximately 26,000 daltons by SDS-PAGE. Each is reduced to a single polypeptide indicating that the proteins are probably homodimers. One has an N-terminal sequence identical to that of human placenta-derived TGF-.beta. whereas the other has an N-terminal sequence that is different from that of TGF-.beta. derived from human placenta. The two proteins may be purified to homogeneity using RP-HPLC or acetic acid-urea gel electrophoresis.

Abstract: A method of isolating cell surface receptors utilizing a short peptide sequence bound to an affinity column. Cell surface receptors which bind selectively to the short peptide and which are specific to various adhesion proteins may be isolated therewith from various cell preparations. These receptors, whose functional integrity has been maintained by the presence of the peptide ligand, are incorporated into liposomes and used to deliver specific compounds inside the liposomes to select tissues containing the specific adhesion proteins.

Abstract: There is described a new peptide hormone (cardiodilatin) and a process for its preparation, with the amino acid sequence: Asn-Pro-Val-Tyr-Gly-Ser-Val-Ser-Asn-Ala-Asp-Leu-Met-Asp-Phe-Lys-Asn-Leu-Le u-Asp-His-Leu-Glu-Asp-Lys-Met-Pro-Leu-Glu-Asp-Glu-Ala-Met-Pro-Pro-Gln-Val-L eu-Ser-Glu-Gln-Asp-Glu-Glu-Val-Gly-Ala-Pro-Leu-Pro-Leu-Leu-Glu-Glu-Val-Pro- Pro-Trp-Thr-Gly-Glu-Val-A n-Pro of the composition Asp/Asn 14, Thr 3, Ser 15, Glu/Gln 12, Pro 10, Gly 12, Ala 10, Val 7, Met 4, Ile 1, Leu 15, Tyr 2, Phe 3, Lys 4, His 2, Arg 10, Trp 2, a molecular weight of 13000 Dalton and an isoelectric point I.P. of 6 to 6.5.The peptide hormone, as well as its C-terminal fragments obtained after partial cyanogen bromide fission between and behind Met groups, possess a high relaxing action on the smooth bloodvessel musculature.

Abstract: Two proteins that are found is bone and that have in vivo chondrogenic/osteogenic activity in combination with a co-factor are described. Both proteins also were active in combination with EGF in the in vitro TGF-.beta. assay. Each has a molecular weight of approximately 26,000 daltons by SDS-PAGE. Each is reduced to a single polypeptide indicating that the proteins are probably homodimers. One has an N-terminal sequence identical to that of human placenta-derived TGF-.beta. whereas the other has an N-terminal sequence that is different from that of TGF-.beta. derived from human placenta. The two proteins may be purified to homogeneity using RP-HPLC or acetic acid-urea gel electrophoresis.

Abstract: Two proteins that are found in bone and that have in vivo chondrogenic/osteogenic activity in combination with a co-factor are described. Both proteins also were active in combination with EGF in the in vitro TGF-.beta. assay. Each has a molecular weight of approximately 26,000 daltons by SDS-PAGE. Each is reduced to a single polypeptide indicating that the proteins are probably homodimers. One has an N-terminal sequence identical to that of human placenta-derived TGF-.beta. whereas the other has an N-terminal sequence that is different from that of TGF-.beta. derived from human placenta. The two proteins may be purified to homogeneity using RP-HPLC or acetic acid-urea gel electrophoresis.