Abstract: A leukemia inhibitory factor antagonist, alone or in combination with an endothelin antagonist, may be used for treatment of heart failure. The antagonist(s) are administered in a chronic fashion, in therapeutically effective amounts, to achieve this purpose.

Abstract: A process is described for preparing transfectacons, or particles, of calcium phosphate and a desired nucleic acid comprising admixing calcium divalent cation, phosphate multivalent anion, and the desired nucleic acid to form a precipitation mixture, wherein the precipitation mixture comprises an initial phosphate anion concentration of about 0.2 to 0.5 mM; and incubating the precipitation mixture for about 10 to 60 minutes to form transfectacons comprising calcium phosphate and the desired nucleic acid. A process is also provided for delivering desired nucleic acid to eukaryotic tissue or cells comprising introducing to the tissue or cells the transfectacons so prepared.

Abstract: Compounds are provided that prevent the interaction of an IGF with any one of its binding proteins and not to a human IGF receptor.

Abstract: An assay is provided for determining the presence of contaminating microbial host cells in a culturing vessel containing a microbial host cell strain that utilizes more than one carbohydrate source as a substrate comprising:(a) culturing the microbial host cell strain in the vessel, wherein the strain comprises nucleic acid encoding a polypeptide of interest and is genetically marked so as not to utilize a carbohydrate source as a substrate;(b) plating an isolated sample of culture from step (a) onto culture media supplemented with a carbohydrate source not utilized by the host cell strain as a substrate;(c) incubating the plated cells at a temperature and for a time sufficient for any positive colony to grow to a detectable level; and(d) detecting whether any colonies are growing on the supplemented culture media.

Abstract: An assay is provided for determining the presence of contaminating microbial host cells in a culturing vessel containing a microbial host cell strain that utilizes more than one carbohydrate source as a substrate comprising:(a) culturing the microbial host cell strain in the vessel, wherein the strain comprises nucleic acid encoding a polypeptide of interest and is genetically marked so as not to utilize a carbohydrate source as a substrate;(b) plating an isolated sample of culture from step (a) onto culture media supplemented with a carbohydrate source not utilized by the host cell strain as a substrate;(c) incubating the plated cells at a temperature and for a time sufficient for any positive colony to grow to a detectable level; and(d) detecting whether any colonies are growing on the supplemented culture media.

Abstract: A mammal with congestive heart failure is treated by administering to the mammal an effective amount of growth hormone. Treatment results in increased left ventricular cystolic pressure, increased left ventricular maximum, increased cardiac output, and increased stroke volume index. Treatment also results in reduced left ventricular end-diastolic pressure and reduced systemic vascular resistance. These measurements indicate improvement in cardiac function by increased ventricular contractility and decreased peripheral vascular resistance.

Abstract: A leukemia inhibitory factor antagonist, alone or in combination with an endothelin antagonist, may be used for treatment of heart failure. The antagonist(s) are administered in a chronic fashion, in therapeutically effective amounts, to achieve this purpose.

Abstract: A composition is provided comprising about 0.1 to 15 mg/ml of a polypeptide in a buffer having a pH of about 7-12 comprising about 5-40% (v/v) of an alcoholic or polar aprotic solvent, about 0.2 to 3M of an alkaline earth, alkali metal, or ammonium salt, about 0.1 to 9M of a chaotropic agent, and about 0.01 to 15 .mu.M of a copper or manganese salt. The buffer is suitably used in a method for refolding improperly folded polypeptides.

Abstract: Nucleic acid encoding TGF-.beta. has been isolated and cloned into vectors which are replicated in bacteria and expressed in eukaryotic cells. TGF-.beta. is recovered from transformed cultures for use in known therapeutic modalities. Nucleic acid encoding TGF-.beta. is useful in diagnosis and identification of TGF-.beta. clones.

Abstract: A process is provided for producing a heterologous polypeptide in bacteria. This process comprises, in a first step, culturing bacterial cells that lack their native pstS gene and comprise nucleic acid encoding a PstS variant having an amino acid variation within the phosphate-binding region of the corresponding native PstS, nucleic acid encoding a DsbA or DsbC protein, nucleic acid encoding the heterologous polypeptide, a signal sequence for secretion of both the DsbA or DsbC protein and the heterologous polypeptide, an inducible promoter for the nucleic acid encoding the DsbA or DsbC protein, and an alkaline phosphatase promoter for the nucleic acid encoding the heterologous polypeptide. The nucleic acid encoding a PstS variant is under the transcriptional control of the wild-type pstS gene promoter. The second step of the process involves recovering the heterologous polypeptide from the periplasm or the culture medium.

Abstract: Formulations containing NPH insulin are useful for treating hyperglycemic disorders, such as diabetes, in a mammal in need of treatment. One such formulation, which is preferably administered parenterally, more preferably by injection, comprises IGF-I and NPH insulin, in amounts of from or about 1 to 10 mg IGF-I and from or about 0.2 to 2 mg NPH insulin in a pharmaceutically acceptable carrier. Another such formulation comprises IGF-I and NPH insulin in an acetic acid salt buffer. Still another formulation comprises IGF-I and NPH insulin in a weight ratio of NPH insulin to IGF-I of from or about 10:1 to 1:50 (w/w), from or about 0.05 to 0.3M of an osmolyte, from or about 0.1 to 10 mg/mL of a stabilizer, and from or about 5 to 100 mM of a buffer at from or about pH 5 to 7. A still further composition comprises NPH insulin in an acetic acid salt buffer.

Abstract: Tissue plasminogen activator (t-PA) zymogens and variants are prepared, including a fibrinolytically active variant of t-PA that has an amino acid alteration at a site within the protease domain of t-PA as compared with the corresponding wild-type t-PA, which alteration renders the variant zymogenic in the presence of plasmin-degraded fibrinogen, and/or fibrin (or plasma clot) specific, as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the zymogens and variants, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The zymogens and variants may be used in a pharmaceutical preparation to treat a vascular disease or condition or to prevent fibrin deposition or adhesion formation or reformation in mammals.

Abstract: A composition is provided comprising about 0.1 to 15 mg/mL of a polypeptide in a buffer having a pH of about 7-12 comprising about 5-40% (v/v) of an alcoholic or polar aprotic solvent, about 0.2 to 3M of an alkaline earth, alkali metal, or ammonium salt, about 0.1 to 9M of a chaotropic agent, and about 0.01 to 15 .mu.M of a copper or manganese salt. The buffer is suitably used in a method for refolding improperly folded polypeptides.

Abstract: A method is disclosed that comprises administering insulin-like growth factor-I (IGF-I) to a mammal so as to sustain its biological activity in the mammal comprising administering a therapeutically effective amount of IGF-I to the mammal to provide an exposure to IGF-I for a period of time that stimulates the maximum biological response in the mammal, then discontinuing said administration for a period of time equal to or less than the time period used for administration, and repeating this pattern of administration and discontinuance of administration for a period as long as necessary to achieve or maintain the desired biological response in the mammal.

Abstract: Polypeptides that are cleared from the kidney and do not contain in their original form a Fc region of an IgG are altered so as to comprise a salvage receptor binding epitope of an Fc region of an IgG and thereby have increased circulatory half-life.

Abstract: An acid-labile protein is described that, when incubated with the 53-Kd acid-stable protein occupied by IGF, converts it to a high molecular weight complex, corresponding to the in vivo form of IGF. This protein is called the acid-labile subunit (ALS) of IGF binding protein complex and is provided in biologically pure form. ALS is useful in treating wounds and promoting cellular growth. The nucleic acid encoding ALS, antibodies binding thereto, and fragments thereof are also disclosed.

Abstract: A method is described for isolating an exogenous polypeptide in a non-native conformation from cells, such as an aqueous fermentation broth, in which it is prepared comprising contacting the polypeptide with a chaotropic agent and preferably a reducing agent and with phase-forming species to form multiple aqueous phases, with one of the phases being enriched in the polypeptide and depleted in the biomass solids and nucleic acids originating from the cells. Preferably, the method results in two aqueous phases, with the upper phase being enriched in the polypeptide.

Abstract: Isolated CHF, isolated DNA encoding CHF, recombinant or synthetic methods of preparing CHF, and a method of purifying CHF are disclosed. These CHF molecules are shown to influence hypertrophic activity and neurological activity. Accordingly, these compounds or their antagonists may be used for treatment of heart failure, arrhythmic disorders, inotropic disorders, and neurological disorders.

Abstract: DNA encoding the prepro inhibin .alpha. and .beta. chains has been isolated. This DNA is ligated into expression vectors and used to transform host cells for the preparation of inhibin or activin. Also provided are prohormone domains and other inhibin .alpha. or .beta. chain derivatives having therapeutic or diagnostic interest. The compositions provided herein are useful in the manipulation of fertility in animals.

Abstract: A method is described for isolating an exogenous polypeptide in a non-native conformation from cells, such as an aqueous fermentation broth, in which it is prepared comprising contacting the polypeptide with a chaotropic agent and preferably a reducing agent and with phase-forming species to form multiple aqueous phases, with one of the phases being enriched in the polypeptide and depleted in the biomass solids and nucleic acids originating from the cells. Preferably, the method results in two aqueous phases, with the upper phase being enriched in the polypeptide.