Abstract: A method and means for protecting cells and transplanted organs for the effects of activated complement proteins generated in blood serum or plasma by introducing the gene for CD59 into the cells to be protected is described. In an example of the method, protection against the pore-forming activity of the human C5b-9 proteins was conferred on CHO cells by transfection with cDNA encoding the human complement regulatory protein CD59.

Abstract: A method for using thiazine dyes, especially methylene blue, alone or in combination with low levels of light, to selectively inactivate or inhibit intracellular replication of specific viruses, especially human immunodeficiency virus in vitro and in vivo. Examples of useful thiazine dyes are methylene blue, azure A, azure C, toluidine blue O, and thionine. The preferred dye at this time is methylene blue. Methylene blue is FDA approved for topical, i.v., and oral administration, and has minimal side effects. Since methylene blue absorbs in the red wavelengths, i.e., approximately 670 nm, which penetrates tissue much better than other lower wavelengths, light penetrating the skin to the capillaries at the surface can be used to enhance the activity of the dye.

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: This invention relates to an improved process for the synthesis of 4-alkoxy-N-acetylneuraminic acids. According to the process of the invention, N-acetylneuraminic acid is first alkylated at C-1 and C-2 and then the vicinal hydroxyl groups at C-8 and C-9 are protected through the formation of a ketal. The resulting protected alkyl ester alkyl ketoside is then alkylated at the C-4 position whereby the hydrogen of the C-4 hydroxyl group is replaced with an alkyl group to form an alkoxy group. Deprotection is accomplished through the removal of the ketal group at C-8 and C-9 and removal of the alkyl groups at C-1 and C-2, thereby producing the 4-alkoxy-N-acetylneuraminic acid.

Abstract: Based on the discovery that normal pregnant mice have a striking reduction in committed precursors of B lymphocytes, which could be documented in mice as early as day 6 of gestation, when IL-7 responding colony forming cells were reduced as much as two-thirds of normal levels, it has been determined that estrogen and other hormones elevated in pregnancy induce a specific modulation of lymphocyte formation during pregnancy and lactation. It is therefore possible to immunomodulate in a specific manner an animal by administration of hormones elevated during pregnancy, such as estrogen and estrogen-like compounds, or antagonists of estrogen. This has potential in the treatment of a number of disorders, especially those found in very high percentages of women as compared with men, such as many of the autoimmune disorders, as well as in immune tolerance during pregnancy, cyclic neutropenia, and osteoporosis.

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, 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. Further, immune disease states can be treated by administering an effective amount of a C5b-9 inhibitor to suppress C5b-9 mediated platelet activation in vivo.

Abstract: The invention is the use of nitronyl substituted hindered phenols as antioxidants in therapeutic applications. In the preferred embodiment the compositions have the general formula: ##STR1## Wherein R1 is hydrogen, an alkyl or an aryl and R2 is an alkyl or an aryl; R.sub.3 is an alkyl; and R.sub.4 is an alkyl. Further, the invention relates to novel compositions useful as antioxidants. The novel compounds include: 2,6-di-tert-butyl-4-(N-tert-octyl) nitronyl phenol (DBONP); 2,6-dimethyl-4-(N-tert-octyl) nitronyl phenol (DMONP); N-tert -octylC-phenyl nitrone (OPN).

Abstract: The invention is the use of nitronyl substituted hindered phenols as antioxidants in therapeutic applications. In the preferred embodiment the compositions have the general formula: ##STR1## Wherein R1 is hydrogen, an alkyl or an aryl and R2 is an alkyl or an aryl; R.sub.3 is an alkyl; and R.sub.4 is an alkyl. Further, the invention relates to novel compositions useful as antioxidants. The novel compounds include: 2,6-di-tert-butyl-4-(N-tert-octyl) nitronyl phenol (DBONP); 2,6-dimethyl-4-(N-tert-octyl) nitronyl phenol (DMONP); N-tert-octylC-phenyl nitrone (OPN).

Abstract: 2,4-disulfonyl .alpha.-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

Abstract: It has been discovered that it is possible to administer truncated tissue factor, not having the transmembrane region (tTF) in combination with factor VIIa (FVIIa) to treat bleeding disorders such as those resulting from hemophilia or cirrhosis of the liver. Preferably, the tTF is administered to produce up to 10 .mu.g tTF/ml of plasma. The FVIIa is administered to produce levels of between 40 ng FVIIa/ml and 4 .mu.g FVIIa/ml of plasma. The effective dosages of both tTF and FVIIa are significantly and surprisingly less than the administration of either alone to stop bleeding. Examples demonstrate safety and efficacy in normal and hemophilic dogs.

Abstract: It has been discovered that it is possible to administer truncated tissue factor (not having the transmembrane region) (tTF) in combination with factor VIIa (FVIIa) or an activator of endogenous factor VII to treat bleeding disorders such as those resulting from hemophilia or cirrhosis of the liver. The tTF is administered to produce up to 10 .mu.g tTF/ml of plasma. The FVIIa or FVII activator is administered to produce levels of between 40 ng FVIIa/ml and 700 ng FVIIa/ml of plasma. The effective dosages of both tTF and FVIIa/factor VII activator are significantly and surprisingly less than the administration of either alone to stop bleeding. Examples demonstrate safety and efficacy in normal and hemophilic dogs.

Abstract: It has been determined that estrogen and other hormones elevated in pregnancy induce a specific modulation of lymphocyte precursor cell production. The immune system of an animal or bone marrow cells in culture can therefore be modulated in a specific manner by administration of hormones elevated during pregnancy, such as estrogen and estrogen-like compounds or compounds that interfere with the synthesis or activity of these hormones, to increase or decrease production of B lymphocyte precursor cells.

Abstract: 2,4-disulfonyl .alpha.-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss.

Abstract: 2,4-disulfonyl .alpha.-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

Abstract: An assay for activated factor VII (factor VIIa) has been developed using truncated tissue factor (tTF), a soluble mutant form of (tTF) that retains the cofactor function of TF toward factor VIIa. Unlike full-length TF, however, tTF appears not to support the conversion of factor VII to VIIa. As a result, the tTF assay for factor VIIa is free from interference from factor VII in the plasma and is therefore specific for factor VIIa. The assay is much simpler than existing assays, because it is a single-stage clotting assay performed almost identically to a prothrombin time assay. It is also considerably more sensitive than current assays for factor VIIa in plasma. Since the tTF assay is calibrated against a factor VIIa standard, it yields an absolute concentration of factor VIIa in ng/ml.

Abstract: An assay useful for detecting the propensity of patients for thrombotic disease, especially patients having the lupus anticoagulant or antiphospholipid antibodies, is described. The assay is conducted on patient and control plasma in the presence and absence of exogenous Protein C with a membrane source comprising phosphatidylethanolamine and phosphatidylserine. Patients at risk exhibit test results indicating activated Protein C function is inhibited.

Abstract: The invention is the use of nitronyl substituted hindered phenols as antioxidants in therapeutic applications. In the preferred embodiment the compositions have the general formula: ##STR1## Wherein R1 is hydrogen, an alkyl or an aryl and R2 is an alkyl or an aryl; R.sub.3 is an alkyl; and R.sub.4 is an alkyl. Further, the invention relates to novel compositions useful as antioxidants. The novel compounds include: 2,6-di-tert-butyl-4-(N-tert-octyl)nitronyl phenol (DBONP); 2,6-dimethyl-4-(N-tert-octyl)nitronyl phenol (DMONP); N-tert-octyl-C-phenyl nitrone (OPN).

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 preventin 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 for treating tissue damage from ischemia contain PBN, or active derivatives thereof, which are active during ischemia in preventing ATP depletion of the cells which predisposes them to subsequent injury during reperfusion, and which are active during reperfusion as oxygen radical scavengers, in a suitable pharmaceutical carrier for systemic or local administration, especially to the CNS, spinal column and eyes. Based on animal studies, the dosage for treating damage due to stroke is in the range of 10 to 300 mg/kg. Similar dosages are useful in treating damage resulting from free radical generation during inflammation, either as a product of infection or exposure to inflammatory agents or abusive agents, including drugs and alcohol.

Abstract: Compositions containing PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient, are disclosed for treating or preventing gastric ulceration caused by ingestion of non-steroidal anti-inflammatories. Based on animal studies, the dosage is in the range of 3 to 300 mg/kg and is administered prior to, simultaneously, or shortly after ingestion of the NSAID compounds(s). In the preferred embodiment, the range is between 10 and 30 mg/kg, depending on the dosage unit required to protect the mucosa. The preferred method of administration is orally, alone or in combination with the non-steroidal anti-inflammatory. It is believed that the PBN is also useful alone for treatment or prevention of ulcers, aspects of diarrhea, gastritis, esophagitis, ileitis, and as an analgesic.