Abstract: Antibodies directed against idiotypes on naturally occurring human anti-animal antibodies are disclosed for use in inhibiting xenograft rejection in human patients. An effective quantity of these anti-idiotypic antibodies is injected into the actual or potential xenograft recipient in order to bind to the idiotypes expressed on anti-animal antibodies as well as subpopulations of B lymphocytes, to inhibit hyperacute rejection of transplanted animal tissues or organs by the human patient. Alternatively, anti-idiotypic antibodies are used in the form of immunoaffinity columns to deplete anti-animal antibodies from the recipient's serum. Methods of making mouse monoclonal, mouse recombinant, and human recombinant anti-idiotypic antibodies are described, as well as immunoaffinity columns containing immobilized anti-idiotypic antibodies.

Abstract: The present invention relates to a 1.9 kb cDNA and new tissue transglutaminase protein encoded thereby. The cDNA was obtained from reverse transcription of mRNA isolated from retinoic-acid treated HEL cells. The invention also relates to vectors and expression systems to produce the new tissue transglutaminase as well as the recombinantly-produced enzyme protein.

Abstract: It has been determined that HLA B27 is related to proteins of the Gram negative enteric bacteria. The hypervariable regions of the HLA B alleles were compared to the known sequenced proteins for short consecutive amino acid identities. It was found that, unique to the HLA B alleles,, HLA B27 shares an unexpected number of hexapeptides and pentapeptides with Gram negative bacteria proteins. The proteins from enteric organisms that share sequence with B27 tend to have sequences that satisfy protein sequence motifs which are thought to predict binding to B27. In addition, there is a sequence in B27, LRRYLENGK, which is predicted to bind as a peptide to B27. Binding of this peptide to B27 has been demonstrated. The disclosed peptides are useful for diagnostic and therapeutic purposes and can be used to design additional peptides from Gram negative enteric organisms can be identified to be important in the spondyloarthropathies.

Abstract: Chromogenic and fluorogenic 4,7-dialkoxy-N-acetylneuraminic acid substrates of the general formula ##STR1## are provided wherein R.sub.1 and R.sub.2 are alkyl groups containing 1 to 4 carbon atoms and R.sub.3 is a chromogenic or fluorogenic group. These substrates can be used to detect influenza types A and B in clinical samples or specimens. More particularly, these 4,7-dialkoxy-N-acetylneuraminic acid substrates can be used to distinguish between various viruses having neuraminidase reactivity. Thus, influenza type A and B viruses can be distinguished from parainfluenza type 1, 2, 3, and 4, and mumps using the 4,7-dialkoxy-N-acetylneuraminic acid derivatives of this invention. Diagnostic methods employing these substrates are provided to identify influenza type A and B viruses in clinical specimens and to distinguish from other viruses having neuraminidase reactivity.

Abstract: Genetically engineered cells are provided which can serve as universal donor cells in such applications as reconstruction of vascular linings or the administration of therapeutic agents. The cells include a coding region which provides protection against complement-based lysis, i.e., hyperacute rejection. In addition, the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface. In this way, attack by T-cells is avoided. Optionally, the cells can include a self-destruction mechanism so that they can be removed from the host when no longer needed.

Abstract: A method of treating patients to inhibit inflammation is disclosed. In the method, an effective amount of calmodulin, a calmodulin analogue or calmodulin receptor agonist is administered to a patient to inhibit production of tumor necrosis factor and/or augment elastase. In another method, an effective amount of calmodulin antagonist is administered to a patient to stimulate immune response or inhibit elastase release. In another embodiment, a diagnostic test is disclosed to be used on patient blood samples to determine individual propensity to regulate tumor necrosis factor and/or elastase by calmodulin, its analogues or receptor agonists.

Abstract: Compositions including all or a portion and chemically or recombinantly synthesized analogues of the carboxy terminal region of bile salt-activated lipase (BAL) are described, which, when orally ingested, compete with native BAL in binding to the intestinal surface and thus reduce the amount of cholesterol taken into the blood stream.

Abstract: Human protein C and activated protein C were shown to bind to endothelium specifically, selectively and saturably (Kd=30 nM, 7000 sites per cell) in a Ca.sup.2+ dependent fashion. Expression cloning revealed a 1.3 kb CDNA that coded for a novel type I transmembrane glycoprotein capable of binding protein C. This protein appears to be a member of the CD1/MHC superfamily. Like thrombomodulin, the receptor involved in protein C activation, the endothelial cell protein C receptor (EPCR) function and message are both down regulated by exposure of endothelium to TNF. Identification of EPCR as a member of the CD1/MHC superfamily provides insights into the role of protein C in regulating the inflammatory response, and determination of methods for pharmaceutical use in manipulating the inflammatory response.

Abstract: Compositions containing as the active ingredient a spin-trapping reagent, preferably .alpha.-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or .alpha.-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, cardiovascular system, and lymphatic system.

Abstract: Compositions derived from all or a portion of the carboxy terminal region of human bile salt-activated lipase (BAL) are described, which, when orally ingested, compete with native BAL in binding to the intestinal surface, thus reducing the physiological role of BAL in mediating the transfer of cholesterol into the intestinal cells, and, as a result, reducing the amount of cholesterol absorbed from the intestine into the blood stream. Useful derivatives of the carboxy terminal region of BAL are derived from all or portion of the region containing amino acid residues 539 to 722, and have a mucin-like structure containing at least three of the repeating proline-rich units of eleven amino acid residues each.

Abstract: Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia (DMPO include 5,5-dimethyl pyrroline N-oxide (DMPO), and spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Many different disorders can be treated using these compounds, including diseases or disorders of the central and peripheral nervous systems, and disorders arising from ischemia, infection, inflammation, oxidation from exposure to radiation or cytotoxic compounds, as well as due to naturally occurring processes such as aging.

Abstract: Assays that are prognostic for patients that will develop nephritis have been developed where patient serum is screened for the presence of anti-dsDNA antibodies that are cross reactive with A and D SnRNP proteins. The assays are based on the use of either peptides containing epitopes bound by the anti-dsDNA antibodies, or the antigens for the antibodies, A and D SnRNP proteins. Therapeutic compositions have also been developed using either antibodies that block the pathogenicity of the anti-dsDNA antibodies, such as the naturally occurring anti-La/SSB and anti-U.sub.1 RNP antibodies that are cross reactive with the anti-dsDNA or using the peptides or A and D proteins to induce tolerance.

Abstract: Chromogenic derivatives of N-acetylneuraminic acid modified in the 4-position to contain a hydrogen atom, a fluorine atom, a methoxy group, or an ethoxy group are used as substrates in colorimetric assays for human influenza neuraminidase activity in clinical specimens for the purpose of selectively diagnosing influenza infection. The substrates may exhibit different reactivity with the different types of influenza neuraminidases, thus enabling one to discern the specific type of influenza infection and prescribe appropriate treatment and/or supportive therapy therefor.

Abstract: A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, a 37 kDa protein found on the surface of human platelets, a 37 kDa protein found on the surface of human endothelial cells, active derivatives or fragments thereof which act to inhibit the activity of C5b-9, anti-idiotypic antibodies mimicking the action of the inhibitor proteins or antibodies against C7 or C9 which block the formation of the C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and vascular endothelium of perfused organs and tissues, thereby preventing the C5b-9 initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage.

Abstract: N-L-.alpha.-aspartyl-L-phenylalanine 1-methyl ester and/or its derivatives has been found to have analgesic pain relieving properties. It has been found to be especially effective in relieving pain associated with osteoarthritis and multiple sclerosis. It can be administered by itself or in combination with other analgesics. When given in combination with other analgesics, N-L-.alpha.-aspartyl-L-phenylalanine 1-methyl ester and/or its derivatives helps to alleviate the detrimental side effects of other analgesic medications by lowering the dosage requirements for pain relief.

Abstract: A novel method of detecting antibodies to thrombomodulin in plasma or serum as an indication of an individual's propensity to thrombosis or inflammation is disclosed. A method for identifiying patients at risks of thrombosis or glomerular nephritis by monitoring autoantibodies to truncated soluble thrombomodulin is revealed. A preferred method is an ELISA assay to detect antibodies to thrombomodulin.

Abstract: A specific method has been developed to identify the etiologic or immunogenic agent responsible for the production of autoantibodies characteristic of a particular disorder or immune response. The antigen is first isolated, then divided into overlapping short amino acid sequences. The sequences having the greatest reactivity with the autoantibodies are identified and compared with all known amino acids sequences using the available computer data bases. The protein having the maximum number of sequences homologous to the sequences of greatest reactivity with the autoantibodies is the likeliest candidate for the etiological agent. Applying this method, it has been determined that the etiological agent for the production of anti-Ro/SSA autoantibodies characteristic of numerous autoimmune diseases such as SLE appears to be a virus highly homologous to the Indiana strain of the vesicular stomatitis virus.

Abstract: Compositions and methods for use thereof relating to monoclonal antibodies, and fragments thereof, having inhibitory activity towards the cell-activating function of the complement C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and/or endothelial cells, thereby preventing C5b-9-initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, disease states can be treated by administering to platelets and/or endothelial cells in vivo an effective amount of a monoclonal antibody, or fragment thereof, which has inhibitory activity towards the cell-activating function of the C5b-9 complex, in a pharmaceutically acceptable carrier.

Abstract: Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Many different disorders can be treated using these compounds, including diseases or disorders of the central and peripheral nervous systems, and disorders arising from ischemia, infection, inflammation, oxidation from exposure to radiation or cytotoxic compounds, as well as due to naturally occurring processes such as aging.

Abstract: Compositions containing as the active ingredient a spin-trapping reagent, preferably .alpha.-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or .alpha.-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, cardiovascular system, and lymphatic system.