Abstract: Compounds related to BNP have reduced binding affinity for the natriuretic peptide receptor-C but possess improved or equivalent affinity to the wild type BNP for natriuretic peptide receptor-A. The BNP related compounds are suitable for use in the treatment or prophylaxis of various pathological conditions associated with water or electrolyte imbalance.

Abstract: A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.

Abstract: The protein tyrosine kinase receptors, designated Rse and HPTK6, have been purified from human and/or murine cell tissues. Rse and HPTK6 have been cloned from a cDNA library of a human liver carcinoma cell line (i.e., Hep 3B) using PCR amplification. Provided herein are nucleic acid sequences encoding Rse and HPTK6 useful as diagnostics and in the recombinant preparation of Rse and HPTK6. Rse and HPTK6 are used in the preparation and purification of antibodies thereto and in diagnostic assays.

Abstract: A pharmaceutical composition is provided wherein human relaxin is formulated at an acidic pH of about 4 to less than about 7. The composition, useful for effecting parturition and inhibiting premature delivery, includes a buffer capable of maintaining the pH of the composition within a desired range, and may also include an agent to make the composition isotonic, and a stabilizing agent, if necessary. A specific example is human relaxin formulated in a citrate buffer, pH about 5.0, in the presence of sodium chloride, at an ionic strength of about 0.15 .mu..

Abstract: The invention concerns hepatocyte growth factor (HGF) variants that compise an amino acid alteration at a site within the protease domain of HGF and retaining substantially full receptor binding affinity of the corresponding wild-type HGF.

Abstract: cDNAs encoding a class of receptors, including the IL-8 receptors, have been identified in human tissue. Recombinantly produced PF4ARs are used in the preparation and purification of antibodies capable of binding to the receptors, and in diagnostic assays. The antibodies are advantageously used in the prevention and treatment of inflammatory conditions.

Abstract: The invention concerns new tumor necrosis factor receptor associated factors, designated TRAF. The new factors are capable of specific association with the intracellular domain of the type 2 TNF receptor (TNF-R2), and are involved in the mediation of TNF biological activities.

Abstract: Methods for making unclipped HIV env proteins are provided. According to the methods, a genetically engineered cell line comprising an nucleic acid sequence encoding an HIV env protein is cultured to produce unclipped HIV env protein, which is recovered from the cell culture.

Abstract: A method for enhancing the survival and/or proliferation of Schwann cells (especially human Schwann cells) in cell culture is disclosed which involves culturing the cells in serum free culture medium comprising gas6 and other mitogenic agents, such as heregulin and forskolin. The culturing step is generally preceded by a pre-incubation period wherein nerve tissue comprising the Schwann cells is cultured under appropriate conditions and for a period of time such that demyelination occurs. The isolated Schwann cells can be used as cellular prostheses to treat patients with nervous system injuries. The invention also provides a cell culture medium for culturing Schwann cells.

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: The instant invention discloses the unexpected result that mutant signal sequences with reduced translational strength provided essentially complete processing and high levels of expression of a polypeptide of interest as compared to wild type signal sequences, and that many mammalian polypeptides require a narrow range of translation levels to achieve maximum secretion. A set of signal sequence vectors provides a range of translational strengths for optimizing expression of a polypeptide of interest.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine).

Abstract: Provided are nucleic acids encoding AL-1 protein, as well as AL-1 protein produced by recombinant DNA methods. Such AL-1 protein is useful in preparing antibodies and in diagnosing and treating various neuronal disorders. The present invention provides methods to preferentially detect or amplify AL-1 nucleic acid in a sample using AL-1 nucleotide sequence probes.

Abstract: Human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.

Abstract: The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide.

Abstract: DNA isolates coding for a vascular endothelial cell growth factor may be used to produce the protein via recombinant expression systems. Such protein is useful therapeutically to treat conditions in which a selective action on the vascular endothelial cells, in the absence of excessive connective tissue proliferation, is desirable.

Abstract: A tissue plasminogen activator (t-PA) variant is prepared that has an amino acid deletion at positions 466 to 470 of the corresponding wild-type t-PA. This alteration renders the variant fibrin (and plasma clot) specific as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the variant, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The variant 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: Sequential degradation of peptides for sequencing purposes by successive cleavage of amino acids from one end of the peptide chain is performed in an adsorption column with flows of the degradation reagents and wash liquids passing through the column in both directions. Migration of the peptide in one direction is thereby compensated by a subsequent migration in the other, and loss of peptide from the column over repeated cleavages is avoided. In preferred embodiments, the column contains two serially arranged adsorbent zones with differing adsorption characteristics, and the directions of flow of the various system components through the column are selected with a view toward a difference in peptide partitioning between the stationary and mobile phases in one zone vs. the other. The result is that any migration of the peptide occurring at any stage of a given cycle of the procedure occurs at a greater rate toward the zone interface than away from it.

Abstract: A process for the preparation of 2-keto-L-gulonic acid (2-KLG) from 2,5-diketo-D-gluconic acid (2,5-DKG) using a DNA sequence encoding 2,5-DKG reductase. The 2-KLG is a precursor for the synthesis of ascorbic acid (Vitamin C).

Abstract: Production of human relaxin or novel human relaxin analogs by combination of a human relaxin A-chain and B-chain comprises combining the reduced form of the human relaxin A-chain and the reduced form of the human relaxin B-chain in an aqueous medium having a pH of about 7.0 to 12 at room temperature, under conditions that are mildly denaturing for the relaxin B-chain such that the human relaxin or novel human relaxin analog can be formed.