Abstract: A macromolecular contrast agent for magnetic resonance imaging of the vascular system is constructed of a polymeric backbone structure with a plurality of spacer arms bonded to the backbone structure, each spacer arm terminating in at least one paramagnetic complex. The polymeric backbone thus serves as an amplifier by supporting a multitude of paramagnetic complexes, and the spacer arms contribute to the molecular weight. The spacer arms further contribute useful properties to the agent, such as hydrophilicity and the ability to cleave at a relatively rapid rate in blood.

Abstract: Two novel cytokines which are involved in an inflammatory response (inflammatory cytokines) are disclosed. The inflammatory cytokines have been isolated from activated peripheral blood, preferably monocytes adhered to plastic; or peripheral blood leukocytes induced with calcium ionophore and mezerin. The two cytokines are Gro .beta. and .gamma., and their cDNA and amino acid sequences are disclosed. The expression of the genes in various cells is presented. Assay and diagnostic utilities using the cytokines; recombinant materials and procedures; purification procedures; and monoclonal antibodies to the cytokines are also shown.

Abstract: Two novel cytokines which are involved in an inflammatory response (inflammatory cytokines) are disclosed. The inflammatory cytokines have been isolated from activated peripheral blood, preferably monocytes adhered to plastic; or peripheral blood leukocytes induced with calcium ionophore and mezerin. The two cytokines are Gro .beta. and .gamma., and their cDNA and amino acid sequences are disclosed. The expression of the genes in various cells is presented. Assay and diagnostic utilities using the cytokines; recombinant materials and procedures; purification procedures; and monoclonal antibodies to the cytokines are also shown.

Abstract: Two novel cytokines which are involved in an inflammatory response (inflammatory cytokines) are disclosed. The inflammatory cytokines have been isolated from activated peripheral blood, preferably monocytes adhered to plastic; or peripheral blood leukocytes induced with calcium ionophore and mezerin. The two cytokines are Gro .beta. and .gamma., and their cDNA and amino acid sequences are disclosed. The expression of the genes in various cells is presented. Assay and diagnostic utilities using the cytokines; recombinant materials and procedures; purification procedures; and monoclonal antibodies to the cytokines are also shown.

Abstract: Two novel cytokines which are involved in an inflammatory response (inflammatory cytokines) are disclosed. The inflammatory cytokines have been isolated from activated peripheral blood, preferably monocytes adhered to plastic; or peripheral blood leukocytes induced with calcium ionophore and mezerin. The two cytokines are Gro .beta. and .gamma., and their cDNA and amino acid sequences are disclosed. The expression of the genes in various cells is presented. Assay and diagnostic utilities using the cytokines; recombinant materials and procedures; purification procedures; and monoclonal antibodies to the cytokines are also shown.

Abstract: A macromolecular contrast agent for magnetic resonance imaging of the vascular system is constructed of a polymeric backbone structure with a plurality of spacer arms bonded to the backbone structure, each spacer arm terminating in at least one paramagnetic complex. The polymeric backbone thus serves as an amplifier by supporting a multitude of paramagnetic complexes, and the spacer arms contribute to the molecular weight. The spacer arms further contribute useful properties to the agent, such as hydrophilicity and the ability to cleave at a relatively rapid rate in blood.

Abstract: A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials.

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, AIDS and autoimmune diseases.

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, and autoimmune diseases.

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, and autoimmune diseases.

Abstract: The present invention is a process for preparing an activated ester of polyethylene glycol or a polyoxyethylated polyol. After the activated ester is prepared, it can be reacted with a protein to form a polymer/protein conjugate. Conjugation with a polymer can reduce the protein's immunogenicity, increase its solubility, and increase its circulating in vivo half-life. Preferred proteins are IL-2, CSFs, and interferons.

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: ##STR1## 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 from--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --a)wherein each n2 is independently 2-4 and ##STR2## wherein n3 is 2-6. Also claimed are hydrazides, semicarbazides, and thiosemicarbazides of .omega.-mercaptocarboxylic acids which lack SPACER diamine.

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## wherein n=1-6R=CH.sub.3, CF.sub.3, --CO.sub.2 R.sup.IV, ##STR2## R.sup.I, R.sup.II =H, F, CH.sub.3, or ##STR3## R.sup.III =H, ##STR4## or tetrazolyl R.sup.IV =H, or alkyland 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: This invention discloses heterobifunctional coupling agents for making a wide array of molecular conjugates. The agents contain a sterically hindered thiol, linked through a spacer arm to a second group reactive toward nucleophiles such as 1.degree. and 2.degree. amines or reactive thiols that are present on biological and organic materials. The coupling agents are useful for making conjugates containing a sterically hindered linkage.

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: 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: A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.

Abstract: The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase its solubility, and increase its circulating in vivo half-life.

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.