Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen but not to native triple helical forms of the collagen. Antagonists of the invention can target, for example, denatured collagens type-I, type-II, type-III, type-IV, type-V and combinations thereof. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. Antagonists include monoclonal antibodies referred to as HUI77, HUIV26, and XL313.

Abstract: Novel products comprising conditioned cell culture medium compositions and methods of use are described. The conditioned cell medium compositions of the invention may be comprised of any known defined or undefined medium and may be conditioned using any eukaryotic cell type. The medium may be conditioned by stromal cells, parenchymal cells, mesenchymal stem cells, liver reserve cells, neural stem cells, pancreatic stem cells and/or embryonic stem cells. Additionally, the cells may be genetically modified. A three-dimensional tissue construct is preferred. Once the cell medium of the invention is conditioned, it may be used in any state. Physical embodiments of the conditioned medium include, but are not limited to, liquid or solid, frozen, lyophilized or dried into a powder.

Abstract: The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic or diagnostic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in improved utility for agents such as oligonucleotides and polynucleotides which are plagued with problems with biodistribution.

Abstract: The invention relates to antioxidants that make effective use of acerola seeds, which have conventionally been discarded, that have high safety and excellent antioxidative effect in skin preparations for external use, cosmetics, and food, and that contain acerola seed extract as an active component. The invention also relates to skin preparations for external use, cosmetics, and food containing the antioxidant.

Abstract: A labile disulfide-containing compound under physiological conditions containing a labile disulfide bond and a transduction signal.

Abstract: The present invention relates to a composition comprising factor VII or a factor VII-related polypeptide and alpha2-antiplasmin or an alpha2-antiplasmin-related polypeptide, and the use thereof for treating bleeding episodes.

Abstract: A method to enhance the cytotoxic activity of an antineoplastic drug comprising administering an effective amount of the antineoplastic drug to a host exhibiting abnormal cell proliferation in combination with an effective cytotoxicity-increasing amount of an antioxidant. The invention also includes a method to decrease the toxicity to an antineoplastic agent or increase the therapeutic index of an antineoplastic agent administered for the treatment of a solid growth of abnormally proliferating cells, comprising administering an antioxidant prior to, with, or following the antineoplastic treatment.

Abstract: The present invention relates to novel methods for monitoring and guiding therapeutic suppression of parathyroid hormone in renal patients having secondary hyperparathyroidism. One determines and monitors the level of parathyroid hormone agonist and parathyroid hormone antagonist in the renal patient. The parathyroid hormone suppressing therapeutic is administered to the patient so as to minimize the level of parathyroid hormone antagonist.

Abstract: The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin ?v?5 antagonists. The ?v?5-mediated angiogenesis is correlated with exposure to cytokines including vascular endothelial growth factor, transforming growth factor-? and epidermal growth factor. Inhibition of ?v?5-mediated angiogenesis is particularly preferred in vascular endothelial ocular neovascular diseases, in tumor growth and in inflammatory conditions, using therapeutic compositions containing ?v?5 antagonists.

Abstract: The present invention provides methods of effecting a change in the core circadian clock by modulating retinoid nuclear receptors.

Abstract: An isolated polypeptide comprising a peptide which consists of a legless homology domain (HD); wherein the peptide inhibits Lgs function in colon cancer cells; and a composition comprising the same, are disclosed.

Abstract: This invention provides methods for screening a modulating agent which when combined with antitumor therapeutic agent increases apoptosis in tumor cells. This invention also provides methods for screening antitumor therapeutic agents suitable for combination therapy with a protein kinase C inhibitors capable of potentiating apoptosis in tumor cells. This invention further provides different combination therapies comprising the specific protein kinase C inhibitors and the antitumor therapeutic agents.

Abstract: A method of treatment of neurodegenerative diseases using neuronal cell transplants is provided. The growth, survival and integration of the transplanted neuronal cells is enhanced by a method of culturing the neuronal cells with drugs having an affinity for immunophilins. Immunophilin binding drugs are optionally administered to the patient during transplantation and/or post-operatively. Neurotrophic factors can also be administered to the neuronal cells in vitro, or to the patient during the transplantation procedure and/or post-operatively.

Abstract: Disclosed is a phage display system in which the molecules to be displayed (i.e., molecules of interest) are bound to dispensable capsid polypeptides such as SOC (small outer capsid) and HOC (highly antigenic outer capsid) polypeptides that are, in turn, bound to a surface lattice protein, such as those on the surface of a virion or polyhead. Also disclosed are methods of displaying a molecule of interest, methods of immunizing a patient by administering a displayed antigen, and methods of treating a patient who has a disorder associated with aberrent expression or activity of a biological molecule. In the latter instance, the method includes administering a displayed polypeptide, such as an immunoglobulin molecule or an enzyme, that is capable of specifically interacting with the aberrent biological molecule.

Abstract: A compound which comprises a backbone having a plurality of chiral carbon atoms, the backbone bearing a plurality of ligands each being individually bound to a chiral carbon atom of the plurality of chiral carbon atoms, the ligands including one or more pair(s) of adjacent ligands each containing a moiety selected from the group consisting of a naturally occurring nucleobase and a nucleobase binding group, wherein moieties of the one or more pair(s) are directly linked to one another via a linker chain; building blocks for synthesizing the compound; and rises of the compound, particularly in antisense therapy.

Abstract: Formulations, methods and devices for producing formulations and methods for nebulizer delivery of formulations of water-insoluble drugs are provided. Also provided are methods for minimizing wastage of drugs administered by nebulizer, and for the achievement of quantitative dosing with diluent from a mass marketed formulations, which because of the mass market is much less costly per dose than formulations manufactured specifically for much lower volume medical use.

Abstract: This invention relates to proteins or peptides that elicit T cell mediated immunity, and to cancer vaccines and compositions for anti-cancer treatment comprising such proteins or peptide fragments. This invention also relates to pharmaceutical compositions comprising the proteins or peptides and methods for generating T lymphocytes capable of recognizing and destroying tumor cells in a mammal. More specifically, a telomerase protein or peptide for use in a method of treatment or prophylaxis of cancer is provided. In a preferred embodiment, the method comprises generating a T cell response against telomerase.

Abstract: The present invention relates to a 5-amidino-N-(2-aminophenethyl)-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or a lower alkyl group; R2 represents a hydrogen atom, an optionally substituted lower alkyl group, etc.; R3 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group, etc., or a pharmaceutically acceptable salt thereof, which exerts a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

Abstract: Disclosed are methods of selectively delivering a medicant to an abnormal brain region and/or to a malignant tumor in a mammalian subject, including a human. A medicant is administered simultaneously or substantially simultaneously with a potassium channel agonist (other than bradykinin or a bradykinin analog), such as NS-1619,1-EBIO, a guanylyl cyclase activator, a guanylyl cyclase activating protein, minoxidil, pinacidil, cromakalim, or levcromakalim, whereby the medicant is delivered selectively to the cells of the abnormal brain region and/or to the tumor, compared to normal tissues. Thus, among the disclosures is a method of treating a malignant tumor in a human subject. Also disclosed are pharmaceutical compositions that combine a potassium channel agonist together with a medicant and a kit for enhancing the delivery of a medicant to an abnormal brain region and/or to a malignant tumor.

Abstract: The present invention relates to the finding that cyclin D1 interacts in a ligand-independent fashion with coactivators of the SRC-1 family. The direct interaction of cyclin D1 enhances estrogen receptor (ER) mediated transcription and provides a novel target for the development of assays for substances which modulate the cell cycle. The invention provides assay methods for the prevention of growth of tumors, for assays for compounds useful in the prevention of tumors and compounds obtainable by such assays.

Abstract: The present invention provides a medicinal composition comprising (1) a pharmacologically active substance, (2) a drug absorbefacient and (3) a taurine compound or a polyamine. A taurine compound has an efect of suppressing or preventing damage of the intestinal mucous membrane, and therefore adding the taurine compound to a medicinal composition containing a pharmacologically active substance and a drug absorbefacient makes it possible to suppress or prevent damage of the intestinal mucosa. A polyamine improves the absorbability of pharmacologically active substances, and therefore adding the polyamine to a medicinal composition containing a pharmacologically active substance and a drug absorbefacient makes it possible to decrease the dose of the drug absorbefacient, thereby suppressing or preventing damage of the intestinal mucosa.

Abstract: The present invention relates to pharmaceutical compositions comprising at least one fragment of a polynucleotide, preferably at least one antigen, and optionally a pharmaceutically acceptable carrier and/or diluent. In accordance with the present invention was found that the introduction of the pharmaceutical composition into vertebrates will achieve regulation of growth, induction of cellular transcription and translation, protein synthesis, protein expression or protein secretion. The pharmaceutical compositions are useful in vaccination protocols but also in any other therapeutic situation in which immunomodulation is of benefit, such as sub-optimal immune responses, reaction to pathogens, tolerance or autoimmunity.

Abstract: A new chromotropic compound, compositions containing such a compound and methods of using such compound, such as in a test method for identifying the presence of free radicals, are disclosed.

Abstract: The present invention discloses that DARPP-32 is substrate for the cyclin dependent kinase Cdk5. The phosphorylation takes place at a specific threonine residue of DARPP-32 (Threonine 75). The Cdk5 catalyzed phosphorylation of DARPP-32 converts this protein into an inhibitor of the cAMP dependent protein kinase (PKA) and furthermore prevents it from being converted to an inhibitor of protein phosphatase 1 (PP1). Methods of identifying agents that modulate the phosphorylation of DARPP-32 by Cdk5 are disclosed. Methods of treating dopamine dysfunction in animal subjects are also provided.

Abstract: The use of screening assays based on the role of human stearoyl-CoA desaturase-1 (“hSCD1”) in human diseases, disorders or conditions relating to serum levels of triglyceride, VLDL, HDL, LDL, total cholesterol, or production of secretions from mucous membranes, monounsaturated fatty acids, wax esters, and the like, is disclosed. Also disclosed are conventions useful in the prevention and/or treatment of such diseases.

Abstract: Methods and pharmaceuticals for inhibiting or preventing metastasis formation in animals, including humans, having primary tumors, through the administration of phosphorothioates including their thiol and disulfide metabolites are disclosed. These compounds stimulate angiostatin levels, inhibit matrix metalloproteinases (MMPs), and stimulate manganese superoxidase dismutase (MnSOD). Phosphorothioates, of which amifostine is an example, can be administered as a combination therapy with traditional cancer therapies, including chemotherapy, radiotherapy, surgery, immunotherapy, hormone therapy and gene-therapy. Inhibition or prevention of metastasis by phosphorothioates is independent of tumor type, including adenocarcinomas and sarcomas.

Abstract: A new chemical compound for treating human inflammatory diseases, tissue damage, stroke, septic shock and cancer. This chemical compound is produced from a process including the following steps: (a) washing human foreskin fibroblasts with a fresh DMEM medium then incubated in a fresh medium containing 2.5%-10% fetal bovine serum for at least 8 hours to form a proliferating phase medium (PPM); (b) subjecting the proliferating phase medium to a 10-kDa ultrafiltration membrane to separate the proliferating phase medium into a <10 kDa fraction, which passes through the 10-kDa ultrafiltration membrane, and a >10 kDa fraction, which is retained by the 10-kDa ultrafiltration membrane; (c) Chromatographing the <10 kDa fraction on a Superdex 30 column by FPLC to separate the <10 kDa fraction into five post-FPLC fractions; (d) Injecting the second post-FPLC fraction into a C18 column in a HPLC system with a gradient elute from 10% to 50% acetonitrile and water containing 0.

Abstract: The present invention relates generally to oligonucleotide analogues that include novel protein nucleic acid molecules (PNAs), particularly monomers, dimers, oligomers thereof and methods of making and using these oligonucleotide analogues. The PNAs of the present invention are characterized as including a variety of classes of molecules, such as, for example, hydroxyproline peptide nucleic acids (HypNA), and serine peptide nucleic acids (SerNA). The invention includes monomers, homodimers, heterodimers, homopolymers and heteropolymers of these and other oligonucleotide analogues. The present invention includes methods of using these oligonucleotide analogues in the detection and separating of nucleic acid molecules, including uses that include the utilization of oligonucleotide analogues on a solid support. The present invention also includes methods for purifying or separating nucleic acids, such as mRNA molecules, by hybridization with the oligonucleotides of the present invention.

Abstract: Disclosed are compounds having the formula: where R1=H, C1-C6 alkyl, cycloalkyl, R2=H, C1-C6 alkyl, cycloalkyl W=CnH2n-m—NH (n=1-6, m=0, 2, or 4), X= R3= Y= Z=CONR8(CH2)n, CONR8(CH2)nCO, P(CH3)OCHR8OCOR9, SO2, SO2(CH2)n, SO2(CH2)nCO, SO2NR8(CH2)n, SO2NR8(CH2)nCO, n=1-4 R4=H, (CH2)nOH, (CH2)nOCOR10, (CH2)nNR10R11, (CH2)nCONR10R11, n=0-4 R5=H, (CH2)nNR12R13, n=0-4 R6=H, (CH2)nNR14R15, n=0-4 R7=H, C1-C6 alkyl, cycloalkyl; R8=H, C1-C6 alkyl, cycloalkyl; R9=H, C1-C6 alkyl, cycloalkyl; R10=H, C1-C6 alkyl, cycloalkyl; R11=H, C1-C6 alkyl, cycloalkyl; R12=H, C1-C6 alkyl, cycloalkyl; R13=H, C1-C6 alkyl, cycloalkyl; R14=H, C1-C6 alkyl, cycloalkyl; R15=H, C1-C6 alkyl, cycloalkyl. Dashed lines: optional; conformational constraint by (CH2)n, n=1-3, R?=H or O(?) as well as pharmaceuticals compositions and methods for the treatment of opiate addiction, opiate dependence, opiate tolerance, opiate related abstinence syndrome, nicotine addition and obesity based thereon.

Abstract: The present invention relates to methods for screening for anti-obesity agents using the ciliary neutrophic factor receptor.

Abstract: A compound of formula: in which L is sulfur, sulfoxide, oxygen or methylene, and a compound of formula: in which (i) aa1 is Adi and aa4 is Glu or (ii) each of aa1 and aa4 is Adi, L is sulfur, sulfoxide, oxygen or methylene, which compounds (and their conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, are non-phosphorylated, are redox-stable in vivo, are characterized by an IC50 in vivo of less than about 4.0 ?M with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, have a turn conformation.

Abstract: A composition comprising at least one liquid fatty phase structured by at least one semi-crystalline polymer having a low melting point and an organic structure, wherein said polymer is solid at ambient temperature, has a melting temperature of less than 50° C., and comprises a) a polymer backbone and b) at least one crystallizable organic side chain and/or one crystallizable organic block that forms part of the polymer backbone of said polymer, wherein said polymer has a number-average molecular mass of greater than 2000, and wherein the liquid fatty phase and the polymer form a physiologically acceptable medium. This composition is provided in the form of a stick, for example, which deposits, on keratinous substances such as the lips, a glossy, nonsticky and covering film.

Abstract: Disclosed are bilayer matrices of a polysaccharide such as collagen (COL) and another polysaccharide such as hyaluronic acid (HA) with various COL/HA ratios. Each layer has a porous structure. These materials are useful for tissue regeneration, particularly when used with orthopedic implants and drug delivery.

Abstract: The present invention generally provides methods and vaccines for the prevention of diseases caused by Neisseria meningitidis bacteria, particularly serogroup B strains.

Abstract: Disclosed are bilayer matrices of a polysaccharide such as collagen (COL) and another polysaccharide such as hyaluronic acid (HA) with various COL/HA ratios. Each layer has a porous structure. These materials are useful for tissue regeneration, particularly when used with orthopedic implants and drug delivery.

Abstract: The present invention relates to the use of ?1aAR-selective and/or ?1a/?1d-selective antagonists in a method of preventing restenosis after myocardial infarction and re-perfusion. The invention further relates to a method of identifying agents suitable for us in such a method.

Abstract: Methods for inhibiting the growth of tumor cells by combination treatment with a selenium-containing prodrug and an enzyme for which it is a substrate are described. The treatment also enhances the effect of anti-tumor agents.

Abstract: Disclosed are osteoprotegerin-like polypeptides, nucleic acids encoding osteoprotegerin-like polypeptides, and methods of using these molecules. The osteoprotegerin-like polypeptides sequence homology to osteoprotegerin and tumor necrosis factor receptor molecules.

Abstract: Methods of using a complex (scuPA/suPAR) which has thrombolytic activity under physiological conditions and in the presence of IgG, or of at least one IgG-derived peptide, which complex comprises a single chain urokinase type plasminogen activator (scuPA) and a soluble urokinase plasminogen activator receptor (suPAR), for the treatment and/or prevention of thromboembolic disorders associated with the formation of fibrin clots are disclosed.

Abstract: A class of 2?-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer.

Abstract: Preventives and remedies for diffuse lung diseases whereby apoptosis can be inhibited and thus favorable preventive/therapeutic effects can be established. These drugs contain apoptosis-inhibiting substances as the active ingredient. The above apoptosis-inhibiting substances include Fas antagonists and Fas/Fas ligand binding inhibitors such as Fas derivatives and anti-Fas ligand antibodies.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, antherosclerosis. AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The perioperative multivitamin protein bar for promoting an anabolic state in a person is made of from about 250 mg to about 2500 mg of a digestive enzyme, such as bromelain, pepsin, amylase, protease, lipase, cellulase, lactase, alpha-g, glucoamylase, invertase, malt diastase, pectinase, xylanase, bromelain, betain, trypsin, or combinations thereof; from about 50 mg to about 2500 mg of an amino acid; from about 200 mg to about 2000 mg of a sea plant; from about 10 mg to about 8000 mg of a flavoring; from about 100 mg to about 2500 mg of Vitamin A, Vitamin B, Vitamin D, Vitamin E, Vitamin K, calcium, complexes thereof, or combinations thereof; and from about 1000 mg to about 9000 mg of a fiber.

Abstract: The invention comprises lipid derivatives that rapidly degrade in the pH range from 4.0 to 7.0 and lipidic delivery systems that contain them. These lipid derivatives can be used to modify the delivery properties of the lipidic delivery systems to enable prolonged circulation times or more rapid drug unloading in the target tissue. The lipid derivatives are amphipathic compounds comprising a hydrophilic head group joined to a hydrophobic group by an acid-labile ortho ester linkage. The delivery systems of the invention exhibit degradation of less than 10% within 3 hours at a pH of 7.4 and degradation greater than 50% within 60 min at a pH of 5.0.

Abstract: Disclosed are bilayer matrices of a polysaccharide such as collagen (COL) and another polysaccharide such as hyaluronic acid (HA) with various COL/HA ratios. Each layer has a porous structure. These materials are useful for tissue regeneration, particularly when used with orthopedic implants and drug delivery.

Abstract: This invention concerns methods for identifying A2B adenosine receptor agonists and antagonists as well as methods for using A2B adenosine receptor antagonists to treat cell proliferation orders mediated by the A2B adenosine receptor.

Abstract: Bifunctional molecules and methods for their use are provided. The subject bifunctional molecules are conjugates of a drug moiety and a pharmacokinetic modulating moiety, where these two moieties are optionally joined by a linking group. The bifunctional molecules are further characterized in that they exhibit at least one modulated pharmacokinetic property upon administration to a host as compared to a free drug control. The subject bifunctional molecules find use in a variety of therapeutic applications.

Abstract: The present invention provides a medicinal composition comprising (1) a pharmacologically active substance, (2) a drug absorbefacient and (3) a taurine compound or a polyamine. A taurine compound has an efect of suppressing or preventing damage of the intestinal mucous membrane, and therefore adding the taurine compound to a medicinal composition containing a pharmacologically active substance and a drug absorbefacient makes it possible to suppress or prevent damage of the intestinal mucosa. A polyamine improves the absorbability of pharmacologically active substances, and therefore adding the polyamine to a medicinal composition containing a pharmacologically active substance and a drug absorbefacient makes it possible to decrease the dose of the drug absorbefacient, thereby suppressing or preventing damage of the intestinal mucosa.

Abstract: Methods are provided relating to the enhanced cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes under conditions of high extracellular pH. Furthermore, the methods relate to the unexpected synergistic effects of high extracellular pH and disrupted cellular efflux mechanisms on the cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes. Methods are also provided for increasing the therapeutic potency of amphipathic weakly basic or amphipathic cationic compounds, e.g. antiseptics and disinfectants by using the antiseptic or disinfectant in the presence of a multiple drug resistance inhibitor such as reserpine. Finally, methods also relate to the exploitation of the aforementioned discoveries in the screening of small molecules, and libraries thereof, for biological activity in prokaryotes and eukaryotes.