Abstract: Compounds of the formulas ##STR1## wherein R.sup.1 is H and R.sup.2 is alkyl (3-8C) or wherein R.sup.1 and R.sup.2 taken together are --(CH.sub.2).sub.n -- wherein n=3-5;R.sup.3 is H or alkyl (1-4C);R.sup.4 is a substituted or unsubstituted fused or conjugated bicycloaryl methylene;X is OR.sup.5 or NHR.sup.5, wherein R.sup.5 is H or substituted or unsubstituted alkyl (1-12C), aryl (6-12C), aryl alkyl (6-16C); orX is an amino acid residue or amide thereof; orX is the residue of a cyclic amine or heterocyclic amineare useful for treating conditions which are characterized by unwanted matrix metalloprotease activities.

Abstract: Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.

Abstract: Murine monoclonal antibodies, or fragments thereof, that bind selectively to human breast cancer cells, are IgGs or IgMs, and when conjugated to ricin A chain, exhibit a TCID 50% against at least one of MCF-7, CAMA-1, SKBR-3, or BT-20 cells of less than about 10 nM. Methods for diagnosing, monitoring, and treating human breast cancer with the antibodies or immunotoxins made therefrom are described.

Abstract: This invention is in the field of cell and/or tissue culture. In particular, this invention relates to methods which adapt cells to a desired phenotype by exposing the cells to high levels of ammonia in culture, and subsequently transferring the adapted cells to a new culture medium in which there is no initial level of ammonia or the initial level of ammonia is below the level to which cells have been exposed to during the adaptation process. In this new culture medium, the adapted cells express the desired phenotype of growing to a higher viable cell density, and/or remaining viable for a longer period of time, and/or producing more of a desired cell product than their non-adapted counterparts grown in the same medium. This invention includes the adapted cells produced thereby and their cell products.

Abstract: This invention is in the area of immunology, and specifically relates to immunopharmacology as applied to the development of immunosuppressive compositions and methods of use thereof for treating a wide variety of diseases arising from abnormal or undesirable normal immune responses. Compositions and methods of using the same that are particularly useful in treating autoimmune diseases are shown.

Abstract: Separation of anionic oligosaccharides on a preparative scale with high resolution can be achieved by anionic exchange chromatography using PEI-derivatized supports.

Abstract: Ligands in the form of N-acetyllactosamines which bind to endothelial leukocyte adhesion molecule-1 (ELAM-1) are disclosed. The ligand compounds can be formulated into pharmaceutical compositions and/or assay compositions used to alleviate inflammation and assay for the presence of (qualitative) and amount of (quantitative) ELAM-1 and thereby determine the presence, location and degree of inflammation. The ligands are encompassed by general structural formula I as follows: ##STR1## wherein one of A and B is hydrogen and one is an N-acetyl neuraminic acid residue; D and E are each independently hydrogen or a fucose residue; n is an integer of from 0 to 10 with the proviso that if n is 0, E is a fucose residue; F is hydrogen, a lactosylceramide residue or a linking group; and molecules equivalent to a compound of formula I regarding its ability to bind to an ELAM-1 receptor to the same degree as a compound of formula I.

Abstract: A novel a selectable fusion protein having aminoglycoside phosphotransferase activity is disclosed. The marker comprises the coding sequences for aminoglycoside phosphotransferase I (APH-I) which has been modified and truncated so as to render its use in recombinant vectors more convenient. The modified, truncated sequence (mtAPH-I) gene is capable, upon expression, of conferring resistance to a number of antibiotics on the host. One of these antibiotics, G418, is toxic to eucaryotic as well as procaryotic hosts. Also disclosed are methods of constructing fusion proteins having N-terminal sequences corresponding to a desired peptide sequence, and C-terminal sequences comprising the amino acids encoded by mtAPH-I. The preferred N-terminal sequences are the first 11 amino acids of .beta.-isopropyl malate dehydrogenase, and the first 7 amino acids of yeast enolase.

Abstract: Compositions useful for detecting ras gene proteins are described consisting of GTP and a protein having an apparent reduced molecular weight of about 115,000-120,000 daltons, or fragments derived therefrom, that stimulate ras protein guanosine triphosphatase activity. Also described are methods whereby the compositions are used to identify cancer therapeutics.

Abstract: Anti-tumor activity in mammals can be augmented by administering to the mammalian host a synergistically effective amount of TNF and IL-2 or of TNF and IFN-.beta., or of TNF, IL-2 and IFN-.beta. in combination. The composition of TNF and IL-2 and/or IFN-.beta. may be prepared in vitro or administered separately to the host. If the TNF and IL-2 are administered sequentially, the TNF must be administered prior to the IL-2 to obtain synergy. The composition is useful for treating such cancers as mastocytoma, melanoma, leukemia, lymphoma, mammary adenocarcinoma, and pharyngeal squamous cell carcinoma.

Abstract: This invention relates generally to the field of cell culture. The invention presents pH based methods for controlling the glycosylation patterns of cell products, particularly proteins produced by cells in vitro, preferably via a multi-level pH control strategy. Preferably, this invention is applied to manage the effect of high level of ammonia on the glycosylation of cell products. The glycosylation affected is preferably that of terminal sialylations of the oligosaccharide of glycoproteins.

Abstract: Ricin B muteins, ricin and ricin precursors having at least one amino acid of at least one galactoside binding site altered to decrease the binding of ricin B to galactosides are claimed. DNA sequences encoding the ricin B muteins, ricin and ricin precursor in which the B chain thereof is the ricin B mutein are claimed. Recombinant expression vectors effective in expressing the DNA sequences of the ricin B muteins, ricin and ricin precursors are claimed. Host cells transformed with the foregoing expression vectors are also claimed. Conjugates comprising binding moieties such as antibodies, hormones, and lymphokines bound to the ricin B mutein and ricin wherein the B chain thereof is the mutein is also claimed.

Abstract: Bifunctional chemicals useful for linking aldehyde containing moieties to moieties containing functionalities which are or can be reactive with sulfhydryl are claimed and have the formula:L--S--(CH.sub.2).sub.n1 --CONH--SPACER--NH--XwhereinL is a leaving group selected from --H or --S--Ar, wherein Ar represents optionally substituted phenyl or pyridyl;n.sub.1 =2-4;X is selected from: --CO--Y--CONHNH.sub.2, a hydrazide; ##STR1## a hydrazine; ##STR2## a hydrazine; --CO--Y--NH--CONHNH.sub.2, a semicarbazide; and --CO--Z--NH--CSNHNH.sub.2, a thiosemicarbazide;wherein Y is alkylene or oxaalkylene and Z is alkylene or a polypeptide residue briding the N-terminal amino group and C-terminal carboxy group thereof;the SPACER is oxaalkylene or oxaalkylene substituted with hydroxyl and specifically includes residues having formulas selected froma) --(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 -- wherein each n2 is independently 2-4 andb) ##STR3## wherein n3 is 2-6.

Abstract: Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.

Abstract: A stable, continuous human cell line or progeny thereof is produced that is resistant to 6-thioguanine and ouabain, secretes less than 40 ng/ml of endogenous IgM antibodies, and grows with a doubling time of about 18 hours. The cell line, which preferably is adapted to serum-free medium, may be used as a fusion partner with an antibody-producing cell line so as to generate antibodies. In addition, it may be electroporated with a vector containing a gene of interest to produce a transformed cell line which generates a protein encoded by the gene, such as an IgG or IgM antibody.

Abstract: The invention discloses modified signal peptides derived from wild-type signal peptides of the type that are capable of forming membrane-bound lipoproteins and methods for making such modified signal peptides and DNA sequences encoding them. Modified signal peptides of the invention and DNA sequences encoding them are useful for increasing the secretion of heterologous gene products produced by transformed host organisms. The invention further discloses a method for producing recombinant DNA sequences in vivo.

Abstract: Damage to cells, tissue and other body parts in a mammalian host may be treated by using a lymphokine or cytotoxin in conjunction with at least one biological modifier, which may be a free radical scavenger or a metabolic inhibitor. The lymphokine or cytotoxin is preferably tumor necrosis factor and the biological modifier is preferably uric acid, buthionine sulphoximine, vitamin C, aspirin, or nordihydroguaiaretic acid. Such a combination may be used to treat, for example, cancer, infectious diseases, and damage caused by radiation therapy, high oxygen tension, and chemotherapy.

Abstract: The invention herein is directed to methods using Procion dyes to perform separations of interest in manipulating the NAD.sup.+ -independent ribotoxins. The methods are useful for preparing therapeutic agents containing these ribotoxins or their A polypeptide components. This separation method has been applied in particular to preparing hybrid toxins containing ricin toxins, both for purifying the resulting products and also for separating the components intended to be used in the preparation of these end products. In addition, a novel ricin isotoxin prepared using the method of the invention is disclosed.

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: Immunotoxins comprising a cytotoxic moiety and monoclonal antibodies which bind to human ovarian cancer tissue having at least one of the following capabilities are claimed: cytotoxic ID.sub.50 of 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens to which the monoclonal antibody of the immunotoxin bind are identified and characterize the immunotoxins. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals or extending the survival of mammals carrying human ovarian cancer tumors are claimed.