850 results about "Granulocytic cells" patented technology

The present invention relates to methods of modulating mammalian stem cell and progenitor cell differentiation. The methods of the invention can be employed to regulate and control the differentiation and maturation of mammalian, particularly human stem cells along specific cell and tissue lineages. The methods of the invention relate to the use of certain small organic molecules to modulate the differentiation of stem or progenitor cell populations along specific cell and tissue lineages, and in particular, to the differentiation of embryonic-like stem cells originating from a postpartum placenta or for the differentiation of early progenitor cells to a granulocytic lineage. Finally, the invention relates to the use of such differentiated stem or progenitor cells in transplantation and other medical treatments.

The present invention relates to a pharmaceutical composition containing blood cells or haemopoietic cells, e.g. red blood cells (erythrocytes), granulocytes, mononuclear cells (PBMCs) and / or blood platelets, in combination with a pharmaceutically acceptable excipient and / or vehicle, wherein the cells are transfected with at least one mRNA comprising at least one region coding for at least one antigen. The invention further discloses a method of preparing the aforesaid pharmaceutical composition and the use of blood cells transfected in this way for the preparation of drugs or pharmaceutical compositions for immune stimulation against the antigens encoded by the mRNA. The subjects according to the invention are used especially for the therapy and / or prophylaxis of carcinoses or infectious diseases and can also be employed in gene therapy.

The present invention relates to a pharmaceutical composition containing blood cells or haemopoietic cells, e.g. red blood cells (erythrocytes), granulocytes, mononuclear cells (PBMCs) and / or blood platelets, in combination with a pharmaceutically acceptable excipient and / or vehicle, wherein the cells are transfected with at least one mRNA comprising at least one region coding for at least one antigen. The invention further discloses a method of preparing the aforesaid pharmaceutical composition and the use of blood cells transfected in this way for the preparation of drugs or pharmaceutical compositions for immune stimulation against the antigens encoded by the mRNA. The subjects according to the invention are used especially for the therapy and / or prophylaxis of carcinoses or infectious diseases and can also be employed in gene therapy.

The present invention comprises a method to identify granulocytic cell genes that are differentially expressed upon exposure to a pathogen or in a sterile inflammatory disease by preparing a gene expression profile of a granulocytic cell population exposed to a pathogen or isolated from a subject having a sterile inflammatory disease and comparing that profile to a profile prepared from quiescent granulocytic cells. The present invention is particularly useful for identifying cytokine genes, genes encoding cell surface receptors and genes encoding intermediary signaling molecules. The invention also includes methods to identify a therapeutic agent that modulates the expression of at least one gene in a granulocytic population. Genes which are differentially expressed during neutrophil contact with a pathogen, such as a virulent bacteria, or that are differentially expressed in a subject having a sterile inflammatory disease are of particular importance.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-beta. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

The present invention provides methods and compositions for the production of hematopoietic progenitor cells or endothelial progenitor cells from human pluripotent stem cells using a defined cell culture medium without the need to utilize feeder cells or serum. In some embodiments, differentiation is accomplished using hypoxic atmospheric conditions. The defined medium of the present invention may contain growth factors and a matrix component. The hematopoietic progenitor cells may be further differentiated into cell lineages including red blood cells, macrophages, granulocytes, and megakaryocytes. The endothelial progenitor cells may be further differentiated into endothelial cells. Also disclosed are screening assays for identification of candidate substances that affect differentiation of pluripotent stem cells into progenitor cells.

The present invention relates to a method of reducing the numbers of eosinophils in a human subject comprising administration to a subject an IL-5R binding molecule that comprises (a) a region that specifically binds to the IL-5R and (b) an immunoglobulin Fc region. In a specific embodiment, a method of the invention reduces the number of eosinophils in blood, bone marrow, gastrointestinal tract (e g, esophagus, stomach, small intestine and colon), or lung.

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.

Novel site-specific mono-conjugates of Granulocyte Colony Stimulating Factor (G-CSF) are hereby described, with analogues and derivatives thereof, which stimulate proliferation and differentiation of progenitor cells to mature neutrophiles. These conjugates have been obtained using transglutaminase to covalently and site-specifically bind a hydrophilic, non-immunogenic polymer to a single glutamine residue of the human G-CSF native sequence and analogues thereof. These novel site-specific mono-conjugated derivatives are recommended for therapeutic use since they are stable in solution and exhibit significant biological activity in vitro and a longer bloodstream half-life, as compared to the non-conjugated protein, with a consequent prolonged pharmacological activity.

Methods and compositions are provided for reducing the level of expression of a target polynucleotide in an organism. The methods and compositions selectively silence the target polynucleotide through the expression of a chimeric polynucleotide comprising the target for a sRNA (the trigger sequence) operably linked to a sequence corresponding to all or part of the gene or genes to be silenced. In this manner, the final target of silencing is an endogenous gene in the organism in which the chimeric polynucleotide is expressed. In a further embodiment, the miRNA target is that of a heterologous miRNA or siRNA, the latter of which is coexpressed in the cells at the appropriate developmental stage to provide silencing of the final target when and where desired. In a further embodiment, the final target may be a gene in a second organism, such as a plant pest, that feeds upon the organism containing the chimeric gene or genes. Compositions further comprise vectors, seeds, grain, cells, and organisms, including plants and plant cells, comprising the chimeric polynucleotide of the invention.

Immunostimulatory compositions described as CpG-like nucleic acids are provided, including nucleic acids having immunostimulatory characteristics of CpG nucleic acid, despite certain substitutions of C, G, or C and G of the CpG dinucleotide. The substitutions can include, among others, exchange of methylated C for C, inosine for G, and ZpY for CpG, where Z is cytosine or dSpacer and Y is inosine, 2-aminopurine, nebularine, or dSpacer. Also provided are methods for inducing an immune response in a subject using the CpG-like nucleic acids. The methods are useful in the treatment of a subject that has or is at risk of developing an infectious disease, allergy, asthma, cancer, anemia, thrombocytopenia, or neutropenia.

The present invention relates to methods of using granulocyte colony stimulating factor (G-CSF) polypeptide, alone and in conjunction with stromal cell derived factor (SDF-1) polypeptide, to increase the mobilization of c-Kit+ stem cells in the blood, bone marrow, tissue, heart or other organs for the subsequent production of embryoid body-like cell clusters. These embryoid body-like cell clusters can be used for cell replacement therapy, for the treatment of cardiac myopathy and other diseases and disorders, and for screening agents that drive or inhibit differentiation and proliferation.

A method for administering a therapeutic or diagnostic agent to a subject is described. The method includes providing a suspension of liposomes comprised of one or more of vesicle-forming lipids selected from (i) a vesicle-forming lipid derivatized with a hydrophilic polymer and (ii) a neutral lipopolymer, said liposomes being associated with said therapeutic or diagnostic agent, forming an aerosol of said liposome suspension; and administering the aerosol to the subject by inhalation. The liposome formulation delivers intact liposomal particles to the respiratory tract of said subject to form a depot of therapeutic agent therein with no observable provocation of an immune response, as measured by neutrophil or macrophage cell count in the lung after administration.

Blood cells of interest are readily distinguishable from other blood cells and look-a-like particles found in a blood sample by their back-scatter signature. A preferred method for differentiating platelets in a blood sample is to irradiate the cells and particles, one at a time, with a beam of radiation, and to detect back-scattered (reflected) radiation using a plurality of optical fibers to transmit the back-scattered radiation to a high-gain photodetector, e.g. a photomultiplier tube. Preferably, the back-scatter signal so obtained is combined with a second signal representing, for example, either the level of forward-scatter within a prescribed, relatively narrow angular range, or the level of side-scattered radiation, or the level of attenuation of the cell-irradiating beam caused by the presence of the irradiated cell or particle in the beam, or the electrical impedance of the irradiated cell or particle, to differentiate the cells of interest. The method and apparatus of the invention are particularly useful in differentiating platelets and basophils in a blood sample.

Provided herein are methods for treating gastrointestinal inflammation, for example, esophageal inflammation, or reduction of eosinophilic infiltration of the esophagus and / or reducing local and systemic exposure and / or side effects resulting therefrom. Provided herein are methods for diagnosing gastrointestinal inflammation, for example, esophageal inflammation, or reduction of eosinophilic infiltration of the esophagus. Also provided herein are methods for inducing remission of eosinophilic infiltration of the esophagus

A particle / cell separation device is described which is particularly adapted for neutrophil depletion from a preparation of whole blood or platelet-rich plasma. Also described are blood and platelet rich plasma compositions produced using the device which are neutrophil-depleted.

Disclosed are compositions and methods for the inhibition of biofilm formation or reduction of existing or developing biofilms in a patient. These methods also inhibit the aggregation of bacteria that form biofilms in the airways. The methods include administering to a subject that has or is at risk of developing biofilms a compound or formulation that inhibits the formation or polymerization of actin microfilaments or depolymerizes actin microfilaments at or proximal to the site of biofilm formation. Such a compound can be administered in combination with a compound or formulation that inhibits the accumulation or activity of cells that are likely to undergo necrosis at or proximal to the site of biofilm formation (i.e., neutrophils). The methods and compositions can further include the use of anti-DNA and / or anti-mucin compounds, as well as other therapeutic compounds and compositions.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The present invention provides an absorbent which can remove cells present in blood including activated leukocytes such as granulocytes and monocytes, and cancer cells as well as can remove cytokines which facilitate the activation of the remaining cells, and further has no concern for pressure loss and has high configuration stability. That is, the present invention provides an absorbent which absorbs the granulocytes and the monocytes in blood, an absorbent for cancer therapy which absorbs an immunosuppressive protein and an absorbent having a bilayer structure of a net and a nonwoven fabric, having a zeta potential of −20 mV or more, as well as a blood circulation column containing any of the absorbents filled therein.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a plurality of assays, one or more of which is configured to detect a kidney injury marker selected from the group consisting of metalloproteinase inhibitor 2, soluble oxidized low-density lipoprotein receptor 1, interleukin-2, von Willebrand factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor receptor superfamily member 11B, neutrophil elastase, interleukin-1 beta, heart-type fatty acid-binding protein, beta-2-glycoprotein 1, soluble CD40 ligand, coagulation factor VII, C—C motif chemokine 2, IgM, CA 19-9, IL-10, TNF-α, and myoglobin as diagnostic and prognostic biomarkers in renal injuries.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m / II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

This invention relates to a method of inhibiting the overactivity of phagocytes or lymphocytes in an individual by administering to said individual an effective amount of a lignan, wherein i) the phagocytes are neutrophils and the lignan is hydroxymatairesinol or matairesinol or mixtures thereof, or ii) the phagocytes are cells of myeloid origin and the lignan is enterolactone or hydroxymatairesinol or mixtures thereof, or iii) the lymphocytes are T-lymphocytes and the lignan is hydroxymatairesinol, matairesinol or enterolactone or mixtures thereof. Furthermore, this invention concerns a method of treating or preventing an acute ischemia-reperfusion injury or a chronic condition, caused by overactivity of phagocytes or lymphocytes in an individual, said method comprising decreasing the activity of phagocytes in an individual by administering to said individual an effective amount of a lignan.

A method for classifying and counting leukocytes comprises the steps of: (1) adding to a hematological sample the following fluorescence-labeled antibodies labeled with fluorescent dyes which emit fluorescences distinguishable from each other; (a) a first fluorescence-labeled antibody (1st antibody) which bonds specifically to leukocytes, (b) a second fluorescence-labeled antibody (2nd antibody) which bonds to at least one kind of neutrophilic cells, and (c) a third fluorescence-labeled antibody (3rd antibody) which bonds to at least one kind of immature granulocytic cells, in order to stain leukocytic cells in the sample, and removing erythrocytes from the sample; (2) analyzing the resulting sample using a flow cytometer to measure at least one scattered light signal and three separate fluorescence signals; (3) defining a group of granulocytic cells on the basis of intensity of the scattered light and intensity of fluorescence from the 1st antibody; (4) defining neutrophilic cells in the defined group of granulocylic cells on the basis of the intensity of the fluorescence from the 1st antibody and intensity of fluorescence from the 2nd or 3rd antibody; (5) classifying the defined group of the neutrophilic cells into groups of neutrophilic cells different in degree of maturity on the basis of the intensity of the fluorescence from the 2nd antibody and the intensity of the fluorescence from the 3rd antibody, and counting the number of cells in each of the groups.

The present invention relates to methods and immunonutritional compositions for preventing the impairment of the immune function during anti-cancer therapy, thereby attaining a better efficacy of the treatment. More particularly, the present invention relates to methods and immunonutritional compositions that can transiently preventing or moderating, bone marrow paralysis or neutropenia of a subject undergoing anti-cancer therapy-induced apoptosis or necrosis or other cell damage such that the innate and adaptive immune functions and normal physiology of the bone marrow are preserved, at least in part, which, in turn, lead to (i) a better tolerance and increased efficacy to anti-cancer therapy; (ii) transient augmentation or enhancement of immunocompetence of the immune cell; and (iii) optimization of the effects of and increase of immunocompetence of the immune cell weakened by anti-cancer therapy.

Methods for detecting nonactivated basophils in a whole blood sample obtained from a normal healthy subject, methods for determining a subject's susceptibility to an allergic reaction to an allergen, where the subject has no known allergy to the allergen, methods for measuring a response to challenge with a potential allergen in a whole blood sample obtained from a subject with known allergic reactivity to allergens other than the potential allergen; and an in vitro system for reliable detection or quantification of a specific white blood cell population in a whole blood sample are described.

An object of the present invention is to provide a compound having a novel structure for overcoming the defects of conventional steroid agents and NSAIDs. It is found that the particular dihydroxy bodies of eicosapentaenoic acid and docosahexaenoic acid, which have not conventionally been known (11,18-dihydroxy eicosapentaenoic acid (11,18-diHEPE), 17,18-dihydroxy eicosapentaenoic acid (17,18-diHEPE) etc.), have activity of inhibiting neutrophil, thereby solving the object. The present invention unexpectedly remarkably inhibits infiltration into a tissue of, and activation of neutrophil found out at acute inflammation. The compound of the present invention is a compound which has not conventionally been known. Therefore, utility as a new therapeutic is provided.

The invention provides preparation of mesothelin chimeric antigen receptor modified T cells and application of the T cells in pancreatic cancer treatment, discloses a chimeric antigen receptor, particularly relates to a chimeric antigen receptor which serves as a guiding sequence by combining a granulocyte-macrophage cluster stimulating factor receptor, and further relates to the T cells expressing the chimeric antigen receptor. The T cells can kill tumor cells highly expressing mesothelin in a targeted mode and have the application of preparing drugs for treating pancreatic cancer malignant tumors and virus infective diseases.