1817 results about "Endogeny" patented technology

Methods and apparatus for direct coronary revascularization wherein a transmyocardial passageway is formed between a chamber of the heart and a coronary blood vessel to permit blood to flow therebetween. In some embodiments, the transmyocardial passageway is formed between a chamber of the heart and a coronary vein. The invention includes unstented transmyocardial passageways, as well as transmyocardial passageways wherein protrusive stent devices extend from the transmyocardial passageway into an adjacent coronary vessel or chamber of the heart. The apparatus of the present invention include protrusive stent devices for stenting of transmyocardial passageways, intraluminal valving devices for valving of transmyocardial passageways, intracardiac valving devices for valving of transmyocardial passageways, endogenous tissue valves for valving of transmyocardial passageways, and ancillary apparatus for use in conjunction therewith.

The present invention includes systems and methods for monitoring endogenous compound concentration in blood by detecting markers, such as odors, upon exhalation by a patient, wherein such markers are the endogenous compound itself or result from the endogenous compound. In the case of olfactory markers, the invention preferably utilizes electronic sensor technology, such as the commercial devices referred to as “artificial” or “electronic” noses or tongues, to non-invasively monitor endogenous compound levels in blood. The invention further includes a reporting system capable of tracking endogenous compound concentrations in blood (remote or proximate locations) and providing the necessary alerts with regard to emergent or harmful conditions in a patient.

Delivery of large enzymes to the brain via transport across the blood-brain barrier (BBB) utilizing conjugates, or fusion proteins, which are composed of a therapeutic enzyme and a BBB targeting agent (molecular Trojan horse). The enzyme is missing in the brain, and does not cross the BBB. The molecular Trojan horse is a receptor-specific endogenous peptide, or peptidomimetic monoclonal antibody (MAb), that undergoes receptor-mediated transport across the BBB, thereby carrying into brain the attached enzyme.

Methods and apparatus for direct coronary revascularization wherein a transmyocardial passageway is formed between a chamber of the heart and a coronary blood vessel to permit blood to flow therebetween. In some embodiments, the transmyocardial passageway is formed between a chamber of the heart and a coronary vein. The invention includes unstented transmyocardial passageways, as well as transmyocardial passageways wherein protrusive stent devices extend from the transmyocardial passageway into an adjacent coronary vessel or chamber of the heart. The apparatus of the present invention include protrusive stent devices for stenting of transmyocardial passageways, intraluminal valving devices for valving of transmyocardial passageways, intracardiac valving devices for valving of transmyocardial passageways, endogenous tissue valves for valving of transmyocardial passageways, and ancillary apparatus for use in conjunction therewith.

This invention relates to a method for prevention and treatment of aging and age-related disorders including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging and age-related disorders including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and / or inhibition of the signal transduction pathway.

The present invention is based, in part, on the discovery that endogenous mRNAs can be recruited for translational repression of target mRNAs. The RNA-silencing agents and the methods described herein, thereby provide a means by which to treat genetic (e.g., genetic neurodegenerative diseases such as Huntington's Disease) or non-genetic diseases by, for example, blocking the synthesis of proteins that contribute to the diseases. Accordingly the RNA-silencing agents of the present invention have an mRNA targeting moiety, a linking moiety, and an mRNA recruiting moiety.

The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and / or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and / or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

This invention relates to a method for prevention and treatment of Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, and age-related disorders including Osteoporosis, Arthritis, Type II Diabetes, Dementia and Alzheimer's disease in a subject comprising administering to said subject a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging and age-related disorders including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway including interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and inhibition of the signal transduction pathway.

The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

The present invention relates, inter alia, to compounds having the general formula: in which: R1 is a member selected from the group consisting of —OCH3, —SCH3, —N(CH3)2, —NHCH3, —NC4H8, —NC5H10, —NC4H8O, —CHO, —CH(OH)CH3, —C(O)CH3, —O(CH2)2N(CH3)2, and —O(CH2)2NC5H10; R2 is a member selected from the group consisting of hydrogen, halogen, alkyl, acyl, hydroxy, alkoxy (e.g., methoxy, ethoxy, vinyloxy, ethynyloxy, cyclopropyloxy, etc.), acyloxy (e.g., acetoxy, glycinate, etc.), alkylcarbonate, cypionyloxy, S-alkyl, —SCN, S-acyl and —OC(O)R6, wherein R6 is a functional group including, but not limited to, alkyl (e.g., methyl, ethyl, etc.), alkoxy ester (e.g., —CH2OCH3) and alkoxy (—OCH3); R3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R4 is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl.In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.

A pharmaceutical composition for oral administration comprising PTH, wherein the in vitro release of PTH-when tested in a dissolution test of pharmacopoeia standard-is delayed with at least 2 hours and once the release starts, at least 90% w / w such as, e.g., at least 95% or at least 99% of all PTH contained in the composition is released within at the most 2 hours. The composition may also comprises a calcium containing compound and / or a vitamin, D. In particular, PTH is administered in combination with a calcium-containing compound for the treatment or prevention of bone-related diseases, so that I) an effective amount of a calcium-containing compound is administered to lower the plasma level of endogenous PTH, and II) an effective amount of PTH is administered to obtain a peak concentration of Pm once the endogeneous PTH level is lowered. This present a potential therapeutic or prophylactic regimen for bone-related disorders including osteoporosis.

The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

T cell responses are often diminished in humans with a compromised immune system. We have developed a method to isolate, stimulate and expand naïve cytotoxic T lymphocyte precursors (CTLp) to antigen-specific effectors, capable of lysing tumor cells in vivo. This ex vivo protocol produces fully functional effectors. Artificial antigen presenting cells (AAPCs; Drosophila melanogaster) transfected with human HLA class I and defined accessory molecules, are used to stimulate CD8+ T cells from both normal donors and cancer patients. The class I molecules expressed to a high density on the surface of the Drosophila cells are empty, allowing for efficient loading of multiple peptides that results in the generation of polyclonal responses recognizing tumor cells endogenously expressing the specific peptides. The responses generated are robust, antigen-specific and reproducible if the peptide epitope is a defined immunogen. This artificial antigen expression system can be adapted to treat most cancers in a significant majority of the population.

PROBLEMThere are provided induced malignant stem cells capable of in vitro proliferation that are useful in cancer research and drug discovery for cancer therapy, as well as processes for production thereof, cancer cells derived from these cells, and applications of these cells.MEANS FOR SOLVINGAn induced malignant stem cell capable of in vitro proliferation are characterized by satisfying the following two requirements:(1) having at least one aberration selected from among (a) an aberration of methylation (high or low degree of methylation) in a tumor suppressor gene or a cancer-related genetic region in endogenous genomic DNA, (b) a somatic mutation of a tumor suppressor gene or a somatic mutation of an endogenous cancer-related gene in endogenous genomic DNA, (c) abnormal expression (increased or reduced / lost expression) of an endogenous oncogene or an endogenous tumor suppressor gene, (d) abnormal expression (increased or reduced / lost expression) of a noncoding RNA such as an endogenous cancer-related microRNA, (e) abnormal expression of an endogenous cancer-related protein, (f) an aberration of endogenous cancer-related metabolism (hypermetabolism or hypometabolism), (g) an aberration of endogenous cancer-related sugar chain, (h) an aberration of copy number variations in endogenous genomic DNA, and (i) instability of microsatellites in endogenous genomic DNA in an induced malignant stem cell; and(2) expressing genes including POU5F1 gene, NANOG gene, SOX2 gene, and ZFP42 gene.

The present invention consists of an implantable structural element for in vivo controlled delivery of bioactive active agents to a situs in a body. The implantable structural element may be configured as an implantable prosthesis, such as an endoluminal stent, cardiac valve, osteal implant or the like, which serves a dual function of being prosthetic and a carrier for a bioactive agent. Control over elution of the bioactive agents occurs through a plurality of cantilever-like cover members which prevent drug elution until an endogenous or exogenous stimulus causes the cover members to open and permit drug elution.

All or a portion of a surface of an implantable sensor is covered with a biocompatible coating formed at least partially of a biomaterial matrix having properties that promote a substantially even growth of tissue cells over the surface of the coating. Additional materials, such as growth factors, agents that recruit endogenous stem cells, and cell adhesion motif arginine, glycine, aspartic acid may be included in the coating. Autologous cells may be added to the coating prior to implantation. The sensor surface may also be textured, by etching or abrading, in order to promote even tissue growth. Alternatively, the sensor surface may be covered with a coating having properties that inhibit the growth of tissue. These coatings may include a biomaterial, a biomaterial matrix having a drug, such as a sirolimus or a steroid, an active component, or a self assembled monolayer.

The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue.

An apparatus and method according to the present invention can be provided, e.g., for a cell specific laser therapy of atherosclerotic plaques, particularly to systems and methods for targeting endogenous light absorbers present within plaque macrophages and exogenous nanoparticle targeting. In one exemplary embodiment, an electro-magnetic radiation can be forwarded to an anatomical structure. The electromagnetic radiation may have at least one property configured to (a) modify at least one characteristic of at least one first cell, and (b) minimize any modification of and / or modify at least one characteristic of at least second cell. The first and second cells may be different from one another, the characteristics of the first and second cells can be different from one another, and the first cell and / or the second cell may have at least one macrophage feature, and the characteristic of the at least one first cell and / or the at least one second cell can be temperature. According to still another exemplary embodiment, a location associated with the first cell and the second cell can be determined. For example, the electromagnetic radiation can be forwarded in a vicinity of the location.

Disclosed herein are antibodies that bind with high specificity to soluble oligomers of amyloid β (Abeta) and methods of employing those antibodies. The antibodies are able to distinguish between Alzheimer's Disease (AD) and control human brain extracts. The antibodies identify endogenous Abeta oligomers in AD brain slices and also bind to Abeta oligomers on cultured hippocampal cells. The antibodies neutralize endogenous Abeta oligomers and Abeta oligomers produced in solution.

The present invention provides methods for the production of cysteine or derivates thereof by culturing a microorganism having reduced activity of endogenous phosphoserine phosphatase. The O-phosphoserine produced by such an organism can then be reacted with a sulfide in the presence of a sulfydrylase or a microorganism expressing a sulfhydrylase to produce cysteine or a derivative thereof. Microorganisms having the properties noted above are also provided herein.

The present invention relates to methods and compositions for reducing Distress Dysfunction by restoring and maintaining homeostatic balance in the neurotransmitter systems underlying the Stress Response and the experience of distress and hedonic tone. Distress Dysfunction refers to the experience of dysfunctional emotional and physical distress that interferes with the individual's quality of life and functioning. A novel understanding of the bimodal opioid modulation of pain, and its impact, through serotonergic, dopaminergic, epinephrinergic, and norepinephrinergic processes, on hedonic tone, leads directly to new generation pharmaceutical formulations that are remarkably safe and effective for the treatment of a wide variety of Distress Dysfunctions, including anxiety, depression, anger, insomnia, mood disorders, eating disorders, sexual problems, pain, substance and behavioral addictions, gastrointestinal disorders, autistic spectrum disorders, attention-deficit and hyperactivity disorders, and other emotional and physical distress disorders. The foundation of this discovery is the power of Receptor Switchers, such as ultra-low-dose and very-low-dose opioid antagonists and GM1 ganglioside attenuators, in blocking acute and protracted excitatory opioid receptor signaling. Co-administration of Receptor Switchers with Endorphin Enhancers, such as specific cAMP PDE inhibitors and excitatory amino acids, is an excellent formulation for restoring healthy homeostatic balance to the endogenous opioid system, using the body's endorphins to reduce emotional and physical distress, and through synergistic and homeostatic processes, restoring positive hedonic tone. The addition of Synergistic Enhancers, such as amino acids, SSRI and SNRI agents, and non-opioid analgesics, as well as Exogenous Opioids, enhances and prolongs these therapeutic benefits. The novel principles discovered by this invention also teach a new generation of safe and effective formulations for the treatment of respiratory conditions, neuropathy, and nociceptive pain.

There are provided compositions and methods for activating expression of an exogenous polynucleotide of interest only in the presence of a specific endogenous miRNA in a cell. Further provided are uses for the compositions in treatment and diagnosis of various conditions and disorders, for example by selectively activating expression of a toxin only in target cell populations.

Apparatus and methods for spatially resolved Raman detection of molecules indicative of the borders of lesions with normal tissue are disclosed. A region of biological tissue was illuminated with monochromatic light. A Raman shifted light signal is detected from endogenous molecules in the region, the molecules being spatially organized in a localized first area of the region. These molecules are indicative of a border between normal tissue and a lesion. The Raman shifted light signal is then spatially resolved in at least one direction.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a rodent (e.g., a mouse), wherein the non-human animals rearrange human immunoglobulin light chain gene segments in the context of heavy chain constant regions and express immunoglobulin-like molecules comprising human immunoglobulin light chain variable domains fused to heavy chain constant domains that are cognate with human immunoglobulin light chain variable domains fused to light chain constant domains.

Methods of treating mitochondrial disorders that are not respiratory chain disorders using compositions comprising EPO mimetic compounds or compounds capable of increasing endogenous EPO levels or stimulating erythropoiesis are disclosed. Methods of treating Friedreich's ataxia, Leigh's syndrome, or other disorders by increasing the expression of frataxin with an EPO mimetic compound or a compound capable of increasing endogenous EPO levels or stimulating erythropoiesis are also disclosed.

The invention provides DNA molecules encoding a chimeric polypeptide comprising (a) a component of a MHC molecule capable of association on a cell surface with an endogenous MHC molecule component of the same class, and (b) an intracellular region of a signal transduction element capable of activating T cells. Component (a) may be a monomorphic component and is preferably beta 2-microglobulin, or a polymorphic class I or class II component. The signal transduction element (b) capable of activating T cells may be a component of T-cell receptor CD3, preferably the CD3 zeta (zeta) polypeptide, a B cell receptor polypeptide or an Fc receptor polypeptide. Immune cells such as a CTLs expressing said chimeric MHC molecules specifically eliminate or inactivate harmful T cells and are useful for treating graft rejection and autoimmune diseases.

The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.