Abstract: In accordance with the present invention, ELISA methods for the measurement of NO levels in mammalian body fluids utilizing monoclonal antibodies directed against dithiocarbamates and related iron complexes are described. It has been found that conjugation of dithiocarbamates to a macromolecule produces immunogenic dithiocarbamate-macromolecule derivatives. Such derivatives can be used for the production (e.g., in rodents) of monoclonal antibodies directed against different forms of dithiocarbamates (e.g., free dithiocarbamates, as well as complexes thereof with iron and, optionally, nitric oxide). In contrast, non-derivatized dithiocarbamates alone are not immunogenic. The simple, easy and non-invasive ELISA methods for measurement of NO levels in body fluids will find a variety of uses, e.g., for diagnosis and monitoring of NO overproduction that has been associated with many inflammatory and infectious diseases.

Abstract: When measurement by a 1 step sandwich method is performed, a signal corresponding to a quantity of labeled antibodies A is sampled, the labeled antibodies being constrained in the vicinity of a surface of an optical waveguide (D) by an antigen-antibody reaction. A differential value by time at the beginning of the measurement and a signal corresponding to an extent of an immunological reaction at a time at which the signal becomes nearly stable are obtained based upon the sampled signals. The extent of the immunological reaction is then uniquely determined based upon the differential value by time and the signal corresponding to the extent of the immunological reaction.

Abstract: A novel hepatoma transmembrane kinase receptor ligand (Htk ligand) which binds to, and activates, the Htk receptor is disclosed. As examples, mouse and human Htk ligands have been identified in a variety of tissues using a soluble Htk-Fc fusion protein. The ligands have been cloned and sequenced. The invention also relates to nucleic acids encoding the ligand, methods for production and use of the ligand, and antibodies directed thereto.

Abstract: Disclosed are DNA and amino acid sequences for a novel polypeptide termed Neuritin which is expressed primarily in selected regions of the brain.

Abstract: The invention relates to new compounds with the general formula I for use as a tool to introduce macromolecules into cells. The invention further relates to compositions for introducing macromolecules into cells, comprising vesicles formed by at least one compound in a solvent. The macromolecule can be incorporated in the vesicles and/or bound to the vesicles or another aggregate of the new compounds. In a preferred embodiment at least one targeting molecule, for instance a (labelled) antibody, may further be attached to the vesicles.

Abstract: The invention relates to a sequence of nucleotides, characterized in that it comprises at least a part of a sequence coding for a protein with urease activity such as that expressed by C. pylori.Another subject of the invention is the uses of this sequence, in particular for the in vitro diagnosis of diseases associated with the presence of Campylobacter pylori in the organism of an individual.

Abstract: The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4.sup.+ T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4.sup.+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C' loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

Abstract: An improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is allowed to the substrate, it is capable of penetrating through each such region during the course of said binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Abstract: A method, device and a kit for determining total nucleic acid concentration in a nucleic acid solution, which comprises applying the nucleic acid solution to a nucleic acid-support capable of retaining the total nucleic acid in the form of a nucleic acid spot having a size that is proportional to the nucleic acid concentration; measuring the size of the nucleic acid spot produced on the nucleic-support; and comparing the size of the nucleic acid spot with a standard.

Abstract: Vitamin B.sub.12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B.sub.12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solublizing linker.

Abstract: Specific netrin proteins, nucleic acids which encode netrin proteins and hybridization reagents, probes and primers capable of hybridizing with netrin genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant netrin protein, a natural intracellular netrin protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said netrin protein selectively binds said binding target; and detecting the presence or absence of specific binding of said netrin protein to said binding target.

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: Disclosed are DNA and amino acid sequences for a novel polypeptide termed Neuritin which is expressed primarily in selected regions of the brain.

Abstract: The molecular cloning, expression, and biological characteristics of a novel receptor tyrosine kinase related to the epidermal growth factor receptor, termed HER4/p180.sup.erbB4, are described. Antibodies to HER4 are disclosed. A HER4 ligand capable of inducing cellular differentiation of breast cancer cells is also disclosed. In view of the expression of HER4 in several human cancers and in certain tissues of neuronal and muscular origin, various diagnostic and therapeutic uses of HER4-derived and HER4-related biological compositions are provided.

Abstract: METHOD OF SCREENING PHYSIOLOGICAL SAMPLES for elevated levels of heat shock proteins due to chronic exposure to sublethal levels of stressors, and kits for carrying out the method, are disclosed.

Abstract: There is disclosed an assay method of screening and identification of anti-amebic drugs which utilizes the ability to inhibit anaerobic growth of a novel bacterial mutant that expresses the EhADH2 gene and which bypasses the conventional need for a parasitic culture. The novel mutant, designated E. coli/EhADH2, is cultured under anaerobic conditions, a predetermined or known quantity of the agent to be tested or target compound is combined with the cell culture, and the combination is then monitored to determine the inhibitory effect upon the anaerobic growth of the E. coli/EhADH2 cell mutant.

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: The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.

Abstract: The invention is directed to synthetic receptor(s) which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and may independently be straight chain or branched. The template may be linked to an identifier which uniquely defines the synthetic receptor. The identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels or may be an oligonucleotide. In an preferred embodiment, the template is covalently linked to a solid support which is linked to an identifier.

Abstract: The present invention relates to phospholipid-polysaccharide adjuvant compositions and to vaccine formulations comprising same, as well as to methods of making and using such adjuvants and vaccines.