Abstract: The use of agonists or antagonists of Mullerian Inhibiting Substance to suppress or treat respiratory distress syndrom. The treatment can be accomplished by providing an effective amount of the agonist or antagonist to a neonatal or prenatal individual.

Abstract: Disclosed are (1) a stabilized FGF protein composition which comprises an FGF protein and water-insoluble hydroxypropyl cellulose; (2) a method for preparing a stabilized FGF protein composition, which comprises admixing an FGF protein with a water-insoluble hydroxypropyl cellulose; and (3) a method for stabilizing an FGF protein which comprises admixing an FGF protein with a water-insoluble hydroxypropyl cellulose, whereby the stabilized FGF protein can be provided. The composition is obtained in a solid state which has improved stability.

Abstract: The invention provides recombinant native and mutein forms of human reproductive hormones with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern and activity. Modified forms of LH and FSH beta subunits which enhance the rate of dimerization and secretion of the dimers or individual chains are also disclosed.

Abstract: At least seven genes have been identified which encode proteins generally identified as pregnancy specific protein (SP1), also known as pregnancy specific beta glycoprotein (PSBG). These genes have been found using human placental SP1 labelled cDNA in a number of mammalian species, including human, baboon, cow, sheep, goat, pig and rat, and non-mammalian species, including fish and bird. The genes are classified on the basis of their nucleotide sequence, structure, glycosylation sites, restriction enzyme mapping, and tissue of origin. Genes have been found in cells of human placenta origin (three groups); in intestinal cells; in cells of both testis and placental origin; in tissue of testis origin; and in HeLa cells. One clone encodes a SP1-like protein which is specifically found in placenta aThe United States Government has rights in this invention by virtue of National Institute of Health funding Grant No. HD21793.

Abstract: A method is provided for increasing fertility in a male mammal exhibiting germinal epithelium failure comprising administering to the mammal an effective amount of activin. Preferably, the administration is to the testis of the mammal.

Abstract: A targetable gene delivery system is provided for introducing foreign genes into mammalian cells. The system employs a soluble targetable DNA complex and utilizes receptor-mediated endocytosis to endow cell specificity. The soluble DNA-carrying complex is formed by non-covalently binding a ligand conjugate with the foreign gene. The conjugate, in turn, is formed by bonding receptor-specific ligands such as asialoglycoproteins to polycations such as polylysine through covalent bonds such as disulfide bonds. The system exhibits a high degree of cell specificity and offers potential for the treatment of inherited genetic disorders.

Abstract: The invention relates to the purification and characterization of growth stimulatory and inhibitory protein factors produced by various organs which appear to play a role in the successful formation of metastatic colonies of tumor cells. In particular, it has been found that syngeneic organs secrete protein growth stimulatory and inhibitory factors which can, at low concentrations, affect metastatic tumor cells. The ability of a malignant cell to respond to these factors is believed to be related to tumor cell metastasis to specific body organs. In particular a lung growth stimulatory glycoprotein having a molecular weight of approximately 66,000 daltons has been found to stimulate growth of lung-metastatic rat and human mammary tumor cells in serum deprived medium.

Abstract: Polypeptide compositions are provided having a binding site specific for a particular target ligand and further having an active functionality proximate the binding site. The active functionality may be a reporter molecule, in which case the polypeptide compositions are useful in performing assays for the target ligand. Alternatively, the active functionality may be a chemotherapeutic agent, in which case the polypeptide compositions are useful for therapeutic treatment of various diseased states. A novel method for preparing such polypeptides having active functionalities proximate their binding site comprises combining the polypeptide specific for the target ligand with an affinity label including ligand having a reactive group attached thereto. The reactive group is then covalently attached to an amino acid side chain proximate the binding site and cleaved from the substrate. The substrate is eluted, leaving a moiety of the reactive group covalently attached to the polypeptide.

Abstract: The present invention relates to a process for solubilization and naturation of somatotropins utilizing a combination of sulfolane and an aqueous alkaline solution. By utilizing the process of the present invention, enhanced yields of end product result.

Abstract: The present invention is directed to genes, termed Rpt-1 (regulatory protein T lymphocyte-1), which are expressed at higher levels by resting CD4.sup.+ helper/inducer T cells relative to activated CD4.sup.+ cells. The invention also relates to the proteins encoded by such genes, termed rpt-1 proteins, which regulate gene expression directed by the promoter region of the interleukin-2 receptor (IL-2r) alpha chain gene or by the promoter region of the long terminal repeat of human lymphotropic retroviruses such as the human immunodeficiency virus type 1 (HIV-1), human T cell leukemia virus (HTLV-I, and HTLV-II. In particular, rpt-1 proteins down-regulate gene expression controlled by the promoter of the IL-2r alpha chain gene or by the promoter of the long terminal repeat of HIV-1. The proteins and nucleic acids of the invention have value in diagnosis and therapy of immune disorders such as AIDS.

Abstract: Method for oxidative folding of peptide and protein substrates to form disulfide bonds using dimethyl sulfoxide and other equivalent sulfoxides as mild oxidizing agents.

Abstract: This invention relates to a method of isolating and purifying proteins such as fibroblast growth factor using metal chelate affinity column chromatography and without the use of heparin. Also disclosed is a method of recovering bFGF multimers and purifying bFGF using metal chelate affinity column chromatography in the absence of heparin.

Abstract: Inducible nitric oxide (NO) synthase flavoprotein purified to an activity more than 400-fold from activated mouse macrophage cell line is water soluble, has a denatured molecular mass as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions ranging from 125 to 135 kDa, has a molecular mass in catalytically active form of about 250 kDa, does not require added calcium ions or calmodulin for activity, and on heat denaturation releases flavin adenine dinucleotide in an amount of 1.1.+-.0.1 mol per mol of 130 kDa polypeptide subunit of the purified flavoprotein and flavin mononucleotide in an amount of at least 0.55.+-.0.04 mol per mol of 130 kDa polypeptide subunit of the purified flavoprotein.

Abstract: Purification of human FSH from post-menopausal urine gonadotropin using immunoaffinity chromatography with elution at high pH and reverse-phase HPLC steps yields a biologically active hormone which is free from detectable traces of luteinizing hormone and other urinary proteins.

Abstract: The present invention provides for a new polypeptide and a method for producing the same. The polypeptide has a molecular weight of approximately 30,000 daltons as a dimer and a monomer molecular weight of about 15,000 daltons, an isoelectric pH of about 4.47 and an activity of at least 21,000 units per milligram of protein in the monomer or dimer state. The preferred method comprises chromatographing a crude polypeptide-containing medium on a dextran derived chromatography column; precipitating the eluate in a water-ethanol solution; electrophoresing the precipitate in a polyacrylamide gel; and chromatographing the extract on a reverse phase-high performance liquid chromatography column.

Abstract: A method for purifying two distinct insulin mediators to substantial homogeneity, and relative purity values above 80%, comprises adsorption on first anion exchange resin and subsequently on a chelex cation exchange resin column. The chelex resin ion exchange column substantially increases the activity of the recovered mediator. Following purification, the already treated fraction is subjected to three successive thin layer chromatography purification steps, the last giving, in the presence of ninhydrin stain, a characteristic salmon-color spot, which is indicative of the presence of the mediator. This process can also be used as a screening process, the absence of the salmon-colored spot being indicative of the diabetic state. Structure information on the insulin mediators obtained is given.

Abstract: A method for the prophylaxis or direct treatment of inflammation in a mammal which comprises administering an effective amount of alpha 1-antichymotrypsin, its salts or derivatives, and compositions thereof.

Abstract: A method for the solubilization and naturation of somatotropin from refractile bodies produced by r-DNA technology wherein the refractile bodies are dissolved in an aqueous solution comprising a chaotropic agent such as urea or guanidine hydrochloride and a soluble organic alcohol such as isopropanol or benzyl alcohol. The solubilized protein is exposed to mild oxidation for a time sufficient to allow the protein to form disulfide bonds and refold to its native conformation. The presence of the alcohol suppresses the formation of somatotropin dimers and aggregates and results in higher yields of the desirable monomeric form of the protein.

Abstract: Glycoprotein which inactivates ribosomes (GPIR) having the ribosome-inhibiting activity of the native GPIR and having a prolonged-action in vivo which is obtained by oxidation of its osidic units by the action of periodate ions, and simultaneous reduction with cyanoborohydride ions. Said modified glycoprotein may be coupled to an antibody or a fragment thereof in order to form an immunotoxin having a prolonged-action in vivo.

Abstract: Glycoprotein which inactivates ribosomes (GPIR) the ribosome-inhibiting activity of the native GPIR and having a prolonged-action in vivo which is obtained by oxidation of its osidic units by the action of periodate ions, and simultaneous blocking of the oxidation product by formation of a Schiff's base with a suitable primary amine. Said modified glycoprotein may be coupled to an antibody or a fragment thereof in order to form an immunotoxin.

Abstract: A protein which satisfies all the biological criteria which are characteristic of inhibin has been isolated from a gonadal source. The purification and characterization of inhibin and the use of the purified material to raise antibodies, the use of inhibin and said antisera in a quantative radioimmunoassay, and applications in vitro and in vivo of inhibin and antibody to inhibin, are described.There is provided a purified protein, inhibin, characterised in thata. the apparent molecular weight as determined by SDS-PAGE is 56,000.+-.1,000b. the isoelectric point is in the range 6.9-7.3c. the protein can bind specifically to Concanavalin A-Sepharosed the protein consists of two sub-units, characterized in thati. their apparent molecular weights as determined by SDS-PAGE are 44,000.+-.3,000 and 14,000.+-.2,000 respectively.ii. the isoelectric point of the 44,000 molecular weight sub-unit is in the range 6.0-7.0iii. the N-terminal amino acid sequences of the two sub-units are as described hereine.

Abstract: The invention relates to a process for the production of thyroglobulin, which is used in the treatment of hypothyroidism, from hog thyroid glands. Ground hog thyroid glands are subjected to saline digestion to produce a thyroglobulin extract. The extract is precipitated by pH adjustment and then heated to a denaturing temperature. The denatured precipitated thyroglobulin solution is subjected to a separation step to produce crude wet thyroglobulin solids. The crude thyroglobulin solids are defatted and dewatered by solvent extraction. The resultant defatted thyroglobulin product can then be further worked up, for example, by drying, milling, and screening, to produce a powdered product. In order to achieve a final product having a T.sub.4 /T.sub.3 ratio of 2.6-3.4 and upon proteolysis a minimum of 0.7 .mu.g/mg of levothyronine and 2.1 .mu.g/mg of liothyronine, the time periods for the precipitating, denaturing, and/or defatting steps are carefully controlled so that the T.sub.4 /T.sub.

Abstract: A method for treating pulmonary inflammation and alpha-1-antitrypsin deficiencies by the administration of an effective amount of microcrystalline alpha-1-antitrypsin, its salt or derivative by inhalation, alone or with other serine protease inhibitors, and the pharmaceutical compositions thereof.

Abstract: The invention provides DNA sequences encoding a human preproinsulin-like growth factor I protein and novel extension peptides. A novel preproinsulin-like growth factor I protein and novel extension peptides are also provided. The present invention further provides a human IGF-I gene which has been sequenced and which encodes at least two preproinsulin-like growth factor-I proteins. Various genes and DNA sequences useful in producing essentially pure mature IGF-I, preproinsulin-like growth factor I proteins and IGF-I gene related proteins are also provided.

Abstract: Crosslinking reagents for amino group-containing compounds are provided, which crosslinkers can be cleaved under mildly acidic conditions. The crosslinkers can be used to crosslink biologically active substances to be delivered to the cells, wherein the crosslinker will be cleaved in the mildly acidic conditions within the cell.

Abstract: Methods and compositions are provided for the treatment or prophylaxis of septic shock caused by bacteremic infection. Therapeutically and prophylactically effective doses of transforming growth factor-beta are administered to patients, either alone or in combination with another therapeutic or prophylactic agent for treating this pathologic condition. Preferably, the transforming growth factor-beta is human transforming growth factor-beta, and most preferably TGF-.beta..sub.1, TGF-.beta..sub.2, or TGF-.beta..sub.3.

Abstract: Nucleic acid encoding lecithin:cholesterol acyltransferase is ligated into expression vectors and used to transform host cells for the synthesis of lecithin:cholesterol acyltransferase in recombinant cell culture. Lecithin:cholesterol acyltransferase amino acid sequence variants are described for enhancing the properties of lecithin:cholesterol acyltransferase. Lecithin:cholesterol acyltransferase and its variants are employed in the therapy of conditions characterized by hypercholesterolemia and for the mobilization of cholesterol in vivo.

Abstract: Thrombin-binding substances are obtained by fractionating human urine by ion-exchange chromatography, affinity chromatography using a thrombin-bound carrier, immune adsorption column chromatography, gel filtration, and/or molecular-weight fractionation. One of the substances has a molecular weight of 46,500.+-.6,000 in reduced condition and 39,000.+-.10,000 in unreduced condition by SDS PAGE and an isoelectric point at pH 5.0-5.3, while the other has a molecular weight of 40,000.+-.8,000 in reduced condition and 31,000.+-.10,000 in unreduced condition by SDS PAGE and an isoelectric point at pH 4.9-5.7. They have strong affinity to thrombin. They are capable of promoting the thrombin catalyzed activation of protein C and prolong clotting time. They are stable to denaturing agents (urea and sodium dodecylsulfate).

Abstract: Two follistatin proteins with inhibin-like activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then six steps of high-performance liquid chromatography. Each isolated molecule is a monomer having a molecular weight of at least about 32,000 daltons. Microsequencing revealed the NH.sub.2 -terminal portions both to be Gly-Asn-Cys-Trp-Leu-Arg-Gln-Ala-Lys-Asn-Gly-Arg-Cys-Gln-Val-Leu. The larger protein has 315 residues and is believed to be glycosylated. The smaller protein is a 288-residue, C-terminally shortened version thereof. These proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The Half-maximal effective dose for both is 2.5-6.0 ng/ml.

Abstract: A dimeric protein with inhibin activity is isolated from ram reta testis fluid using reverse-phase high-performance liquid chromatography and gel filtration. The isolated molecule is composed of two chains having apparent molecular weights of about 18,000 and about 16,500 to 14,500 Daltons, as measured by gel electrophoresis, which are bound together by disulfide bonding and the longer of which is likely glycosylated. Microsequencing revealed the NH.sub.2 -terminal portion of the longer chain to be Ser- Thr-Pro-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Gln-Arg-Pro-Pr o- Glu-Glu-Pro-Ala-Ala-His-Ala-Asp-Cys and of the shorther chain to by Gly-Leu-Glu-Cys-Asp-Gly-Lys-Val-Asn-Ile-Cys-Cys-Lys-Lys-Gln-Phe. This dimeric protein specifically inhibits basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system, exhibiting a half-maximal effective dose of about 0.1 to 0.3 ng/ml.

Abstract: A process is described for the purification of plasminogen activator (PA), wherein a solution containing such as plasminogen activator is brought into contact with a carrier-bound polysulfate of a saccharide or sulfated sugar, the liquid is removed, and the PA bound by this material is eluted.

Abstract: Purified Mullerian inhibiting substance (MIS) is obtained from testicular tissue by extraction, density gradient sedimentation and chromatography. The purified MIS has selective activity for inhibiting the growth of human ovarian cancer cells.

Abstract: A method for the preparation of a protein in a physiologically active or native form, which method includesproviding a source of protein in a solubilized form,and a cationic exchange medium;contacting the source of protein and cationic exchange medium; andrecovering the protein in a physiologically active form.

Abstract: A method for separating and purifying lactoferrin from milk is disclosed, which method comprises the steps of bringing raw milk containing lactoferrin into contact with a sulfuric ester of a crosslinked polysaccharide so that lactoferrin may be adsorbed by the sulfuric ester, and then eluting the adsorbed lactoferrin. The elution of the adsorbed lactoferrin is preferably conducted by the use of a buffer solution containing a 0.4-1.5 M aqueous sodium chloride solution.

Abstract: A method for recovering a recombinant protein from a protein solution containing high molecular weight contaminating proteins by directly adding Group IIA metal salts to the solution in amounts sufficient to selectively precipitate the high molecular weight protein contaminants is disclosed.The high molecular weight precipitates are removed and the solution is further processed to remove low molecular weight contaminating proteins and other non-protein contaminants. The recombinant protein is subsequently recovered and further processed to produce a protein composition suitable for its intended use.

Abstract: A method for treating anemia comprises administering an atrial natriuretic factor (ANF) alone or in combination with erythropoietin (Epo). The ANF potentiates the activity of Epo and causes production of erythroid progenitors, BFU-E and CFU-E, and as a consequence red blood cell production at greater levels than if Epo alone is present in the blood stream.

Abstract: Purified cytotoxic proteins for use within therapeutic compositions are disclosed. The proteins inhibit protein synthesis in vitro, exhibit abortifacient activity in mice, and contain proline residues with equivalent positions at residue 43 and residue 46 in ricin A-chain. A method for preparing such a cytotoxic protein from the tissue of Trichosanthes kirilowii is also disclosed. The proteins may also be used within a method for inhibiting protein synthesis in selected cells.

Abstract: Synthetic peptides corresponding to .alpha.-subunit of human glycoprotein hormone amino acid regions .alpha.31-45, .alpha.21-35, .alpha.26-46 and .alpha.81-92; were found to inhibit binding of 125.sub.I-bTSH to human thyroid. Peptides corresponding to regions .alpha.26-46 and .alpha.31-45 were also found to potently inhibit the stimulation of adenylate cyclase activity by bTSH in a TSH bioassay using FRTL-5 cells and block the action of thyroid stimulating immunoglobulin.

Abstract: Conjugates comprising recombinant ricin toxin A chain and a binding moiety which may be an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of monoclonal or polyclonal antibodies, hormones, lectins or other compounds that are recognized by cell receptors, are described and claimed.

Abstract: Proteins having therapeutic potential as both anticoagulants and as anti-inflammatory agents are disclosed. The present invention also discloses the use of lipocortins in reducing blood coagulation in warm-blooded animals.

Abstract: A method for treating pulmonary and/or bowel inflammation in mammals by the administration of an effective amount of alpha 1-antichymotrypsin, its salt or derivative, and the pharmaceutical compositions therefor.

Abstract: A homogeneously modified protein is provided having one or more selected naturally occurring lysine residues replaced by a suitable amino acid, or having one or more lysine residues substituted for other amino acids or inserted into a polypeptide sequence, leaving selected lysine residues having .epsilon.-amino groups in the protein and coupling amine reactive compounds to selected lysine residues. Methods for producing the selected homogeneously modified proteins and pharmaceutical compositions containing such proteins are provided.

Abstract: A method to obtain a substantially pure and stable hLH-hCG receptor from gonadal cells is disclosed. The characteristics of the purified receptor are disclosed. The receptor, in addition to being used as receptor in an enzyme- or dye-receptor assay for hLH and/or hCG, can be used to purify hLH or hCG used in the preparation of standard dye-hormone or enzyme-hormone complexes. These complexes can be used in enzyme- or dye-immunoassays, as well as the receptor assay.

Abstract: A new glycoprotein ZP-0 originating from the oviduct of a mammal having a molecular weight of about 200,000 to 240,000, as determined by SDS-polyacrylamide gel density-gradient electrophoresis having an isoelectric point of about 4 to 6.2, as determined by isoelectric focusing, containing no sub-fragments, as determined by SDS-disk electrophoresis, forming a carbamylation train in two-dimensional electrophoresis (isoelectric focusing, and SDS-polyacrylamide gel density-gradient electrophoresis, and facilitating species-specific bonding of sperm to zonae pellucidae; and a process for production of the above-mentioned glycoprotein comprising, preparing oviduct from a mammal, homogenating the oviduct optionally with a buffer, to obtain a homogenate, obtaining a liquid containing the glycoprotein from the homogenate, adsorbing the glycoprotein onto lectin immobilized on an insoluble support, liberating the glycoprotein from the support, and recovering the glycoprotein.

Abstract: An insulin activity messenger material and its precursor material are disclosed which have been isolated from hapatic plasma membrane cells that have been incubated with an enzyme known as a phosphatidylinositol-specific phospholipase C. The messenger material comprises a carbohydrate-based compound that exhibits the ability to modulate the activity of the insulin-sensitive enzymes pyruvate dehydrogenase, adenylate cyclase, acetyl CoA carboxylase, and low Km cAMP phosphodiesterase, and thereby effectuate the activity of insulin on the cellular level. The precursor material comprises an inositol containing glycolipid capable of phosphodiesteractic cleavage by a phosphatidylinositol-specific phospholipase C. The enzyme phosphatidylinositol-glycan specific phospholipase C has also been purified and found to participate in many of the activities identified with respect to the messenger and its precursor.

Abstract: This application discloses a process for reducing methionine sulfoxide residues in peptides and proteins to methionine residues. The process comprises subjecting said peptide or protein to a substantially anhydrous trifluoroacetic acid reaction medium containing from about 0.01M to about 3M of an organic sulfide and from about 0.01M to about 3M of a haloacid selected from the group consisting of hydrochloric acid, hydrobromic acid, and hydroiodic acid.

Abstract: A new improved glycoprotein having erythropoietin-type activity is disclosed. The substrate is characterized by amino acid sequence substantially identical to the amino acid sequence of native human erythropoietin wherein the methionine-54 is replaced with leucine. DNA encoding for the EPO-substance and expression vectors incorporating the same are disclosed. Therapeutic compositions and methods for treatment of anemic conditions are described.

Abstract: Growth hormones are admixed with various stabilizers to provide for the decreased formation of insolubles and preservation of the soluble bioactivity of the growth hormone in aqueous environments. Examples of such stabilizers include certain polyols, amino acids, polymers of amino acids having a charged side group at physiological PH, and choline salts.

Abstract: Macromolecular conjugates of muramylpeptides useful as a stimulant of the cellular immune systems have the formula (R--X).sub.m --(LAM) wherein R is an N-acetylmuramylpeptidyl group or a derivative thereof; (LAM) is a neoglycoprotein having affinity for macrophages or monocytes, consisting of a protein covalently substituted by more than five glycidic chains, each having at least five osidic units, X is a covalent bond between a functional group of the peptidic part of R and a functional group of (LAM) or X is the residue of a conventional bifunctional coupling agent capable of bonding to R and (LAM) by formation of covalent bonds; and m is a number greater than or equal to 1.