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  • sickle
  • Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. (euvolution.com)
  • Sickle cell disease (SCD) is an inherited hemoglobinopathy that arises from a single-base substitution at codon 6 of the β-globin gene, resulting in the conversion of valine to glutamic acid. (jci.org)
  • In this episode of JCI's Author's Take, Donald Kohn of UCLA describes his group's efforts to develop a method to safely and effectively modify patient bone marrow to treat sickle cell disease. (jci.org)
  • Zulema Romero, Donald Kohn, and colleagues investigated the utility of a lentiviral vector encoding a human b-globin gene engineered to impede sickle hemoglobin polymerization. (jci.org)
  • For example, Linus Pauling and Vernon Ingram's discovery of a structural difference and amino acid variant in the beta‐globin protein, which causes monogenic hemoglobinopathies such as sickle cell disease or thalassemia, issued in the era of molecular medicine (Pauling et al , 1949 ). (embopress.org)
  • In people with conditions where the cells die early (such as sickle cell disease), however, parvovirus infection can lead to severe anemia. (wikipedia.org)
  • Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders. (wikipedia.org)
  • Those who have minor degrees of thalassemia, similar to those with sickle-cell trait, have some protection against malaria, explaining why they are more common in regions of the world where malaria exists. (wikipedia.org)
  • patients
  • Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified and even if he is correct, it's unlikely it produced any significant beneficial effects treating beta-thalassemia. (euvolution.com)
  • As of 2014[update] these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients. (euvolution.com)
  • Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. (jci.org)
  • The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. (jci.org)
  • Patients with SCD are characterized by chronic hemolytic anemia, erythroid hyperplasia in the bone marrow, and reticulocytosis. (jci.org)
  • The vector efficiently transduced bone marrow cells from SCD patients and expressed the engineered globin gene to prevent sickling of red blood cells and the transduced cells were successfully transplanted into immunocompromised mice, indicating that this method could potentially be used to treat SCD. (jci.org)
  • Patients with SCID were among the first to receive bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40 years ago, and HCT is the standard treatment today for this group of diseases. (clinicaltrials.gov)
  • During this time his work has been the first to demonstrate that gene correction could be achieved in human cells at frequencies that were high enough to potentially cure patients and is considered one of the pioneers and founders of the field of genome editing-a field that now encompasses thousands of labs and several new companies throughout the world. (stanford.edu)
  • Clinically, Dr. Porteus attends at the Lucille Packard Children's Hospital where he takes care of pediatric patients undergoing hematopoietic stem cell transplantation. (stanford.edu)
  • It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. (wikipedia.org)
  • Somatic rearrangement of the gamma locus has been observed in T cells derived from patients with T cell leukemia and ataxia telangiectasia. (wikipedia.org)
  • Patients who suffer from RD will now have more stem cells that can differentiate into immune cells. (wikipedia.org)
  • This cure is commonly used in patients who are awaiting bone marrow transplantation. (wikipedia.org)
  • Absent these causes, patients were diagnosed in the World Health Organization's classification as having either 1) Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) if blood or bone marrow blast cells exceeded 2% or 5% of total nucleated cells, respectively, and other criteria were met or 2) idiopathic hypereosinophilic syndrome (HES) if there was evidence of eosinophil-induced tissue damage but no criteria indicating chronic eosinophilic leukemia. (wikipedia.org)
  • Two patients have been cured by bone marrow transplantation. (wikipedia.org)
  • Because macrocytosis usually precedes a low platelet count, patients with typical congenital anomalies associated with FA should be evaluated for an elevated red blood cell mean corpuscular volume. (wikipedia.org)
  • Within the next 10 years, over 50% of patients presenting haematological abnormalities will have developed pancytopenia, defined as abnormalities in two or more blood cell lineages. (wikipedia.org)
  • citation needed] As FA is now known to affect DNA repair, specifically nonhomologous end joining, and given the current knowledge about dynamic cell division in the bone marrow, finding patients are more likely to develop bone marrow failure, myelodysplastic syndromes, and acute myeloid leukemia (AML) is not surprising. (wikipedia.org)
  • Small groups of CGD patients may also be affected by McLeod syndrome because of the proximity of the two genes on the same X-chromosome. (wikipedia.org)
  • SCID
  • Since more than one type of immune cell is affected, this disease is classified as a severe combined immunodeficiency disease (SCID). (wikipedia.org)
  • SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. (wikipedia.org)
  • About half of US states are performing screening for SCID in newborns using real-time quantitative PCR to measure the concentration of T-cell receptor excision circles. (wikipedia.org)
  • Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. (wikipedia.org)
  • defective
  • This is caused by defective expansion of activated T cells required for an efficient immune response to EBV. (embopress.org)
  • Two main approaches were considered replacing or disrupting defective genes. (euvolution.com)
  • Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia who have lost their stem cells after birth. (wikipedia.org)
  • Chronic granulomatous disease (CGD) (also known as Bridges-Good syndrome, chronic granulomatous disorder, and Quie syndrome) is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly the superoxide radical due to defective phagocyte NADPH oxidase) used to kill certain ingested pathogens. (wikipedia.org)
  • Diagnosis
  • Condition follows an autosomal recessive patternThe mutated gene must be inherited from both the mother and father Both males and females must have an equal frequency of inheritance Health professionals must look at a person's history, symptoms, physical exam and laboratory test in order to make a diagnosis. (wikipedia.org)
  • The diagnosis can only be confirmed on bone marrow examination. (wikipedia.org)
  • The following tests aid in determining differential diagnosis for aplastic anemia: Bone marrow aspirate and biospy: to rule out other causes of pancytopenia (i.e. neoplastic infiltration or significant myelofibrosis). (wikipedia.org)
  • Diagnosis is generally based on bone marrow aspiration and specific blood tests. (wikipedia.org)
  • reconstitution
  • In the present study, mobilized PBSC from male mice were transduced with human adenosine desaminase gene (hADA) and were used for reconstitution of lethally irradiated female mice. (bloodjournal.org)
  • At 1 1 2 , 3, 6, 9, and 12 months after reconstitution, the bone marrow cells were repeatedly collected from each mouse under light anesthesia and the number of colony-forming unit-spleen (CFU-S), spleen repopulating ability (SRA), and the integration of human ADA gene were studied in CFU-S-derived colonies by polymerase chain reaction (PCR) and Southern blot hybridization analyses. (bloodjournal.org)
  • The integration of the human ADA gene was observed during 9 months in about 60% of studied CFU-S. The proportion of marked colonies sharply decreased 1 year following reconstitution. (bloodjournal.org)
  • Cytokines
  • 4-7 Cytokines mobilize long-term culture-initiating cells (LTC-IC) and young colony-forming unit-spleen (CFU-S) with high proliferative potential into circulation. (bloodjournal.org)
  • Their innate effector functions include cell lysis and secretion of chemokines and cytokines, while their adaptive immunity functions include B cell help, DC maturation, and provision of memory T cells. (wikipedia.org)
  • It is similar to the ELISA assay in that antibodies bound to plastic wells are used to bind the cytokines secreted by T cells. (wikipedia.org)
  • Cells that have the capacity to release soluble factors such as cytokines, chemokines, and growth factors which act in a paracrine or endocrine manner. (wikipedia.org)
  • immune
  • Macrophages and dendritic cells are bone marrow derived antigen presenting cells (APC) which serve in the first step of the acquired immune responses. (pubmedcentralcanada.ca)
  • Tsonwin Hai and colleagues discuss how the transcription factor ATF3 acts as a key regulator of the host immune response and as a contributor to co-option of the host by cancer cells to promote metastasis. (jci.org)
  • People with Primary Immune Deficiency (PID) may develop severe, life-threatening infections as a result of inherited defects in the genes that normally instruct blood-forming cells to develop and to fight infections. (clinicaltrials.gov)
  • These antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells. (wikipedia.org)
  • Although B cell receptors can also recognize MHCs, immune responses seem to only be elicited by T cells. (wikipedia.org)
  • The recognition of a mature T cell to this self antigen should not induce an immune response. (wikipedia.org)
  • The significance of MiHAs in an immune response was recognized following transplantation. (wikipedia.org)
  • There is a hypothesis that γδ T cells process these pathogenic antigens, transport them to draining lymph nodes, and then present the antigens to activate αβ T cells and other immune effectors. (wikipedia.org)
  • These Vδ2+ T cells have been reported to connect the innate and adaptive immune systems. (wikipedia.org)
  • The immune system consists of specialized cells that work together to fight off bacteria, fungi and viruses. (wikipedia.org)
  • These cells include T lymphocytes (T cells), that primarily mediate the immune system, B lymphocytes (B cells) and Natural Killer cells. (wikipedia.org)
  • B cell immune responses are measured by analyzing antibodies produced through the humoral immune response. (wikipedia.org)
  • Ionizing radiation kills lymphoid cells while leaving other tissues of the body intact, and this eliminates immune function. (wikipedia.org)
  • Though early research on hematopoietic stem cell transplantation was equivocal, later research has shown it to improve immune function. (wikipedia.org)
  • The paracrine soluble factors produced by stem cells, known as the stem cell secretome, has been found to be the predominant mechanism by which stem cell-based therapies mediate their effects in degenerative, auto-immune and inflammatory diseases. (wikipedia.org)
  • Consequently, both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes. (wikipedia.org)
  • tumor
  • Finally, CDA gene silencing inhibited tumor growth. (springer.com)
  • By delivering a 'suicide' gene, we selectively eliminated the TEM cells and achieved substantial inhibition of angiogenesis and slower tumor growth without systemic toxicity. (epfl.ch)
  • See commentary " A Catalytic Role for Proangiogenic Marrow-Derived Cells in Tumor Neovascularization " in Cancer Cell , volume 13 on page 181. (pubmedcentralcanada.ca)
  • Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and bone marrow (BM)-derived circulating cells (vasculogenesis). (pubmedcentralcanada.ca)
  • Rather, CD11b positive myelomonocytic cells from the transplanted BM were responsible for tumor growth and the development of immature blood vessels in MMP-9 knockout mice receiving wild-type BM. (pubmedcentralcanada.ca)
  • Overall, these studies indicate that BM-derived myelomonocytic cells play an important role in tumor vasculogenesis. (pubmedcentralcanada.ca)
  • In addition, the gene encoding CD117 is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon. (wikipedia.org)
  • Blood
  • In CEP, there is a defect in the synthesis of heme within the red blood cells of bone marrow. (nih.gov)
  • Blood transfusions or spleen removal may also reduce the amount of porphyrin produced by the bone marrow. (nih.gov)
  • Donors will undergo an initial apheresis procedure to donate white blood cells. (clinicaltrials.gov)
  • After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood. (clinicaltrials.gov)
  • After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood. (clinicaltrials.gov)
  • Recipients will provide an initial donation of white blood cells to be used for research purposes only. (clinicaltrials.gov)
  • The reduction in CD11b+ macrophages and IFN-γ-producing T cells was due to reduced proliferative expansion and not to enhanced apoptosis or to altered distribution of these cells between spleen, blood, and the lymphatic system. (jci.org)
  • Biospecimens may include blood, other tissues (e.g., buccal swab or brushing), and/or bone marrow. (clinicaltrials.gov)
  • The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. (wikipedia.org)
  • Hematopoietic stem cells give rise to blood cells. (wikipedia.org)
  • GM-CSF stimulates production of white blood cells. (wikipedia.org)
  • Stem cells are taken from an affected child's blood or bone marrow. (wikipedia.org)
  • Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. (wikipedia.org)
  • The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs. (wikipedia.org)
  • Some hematological malignancies exhibit increased numbers of circulating blood eosinophils, increased numbers of bone marrow eosinophils, and/or eosinophil infiltrations into otherwise normal tissues. (wikipedia.org)
  • Hematopoietic progenitor cells are normally present in the blood at low levels. (wikipedia.org)
  • CD34+ cells may be isolated from blood samples using immunomagnetic or immunofluorescent methods. (wikipedia.org)
  • Other treatments used in DOCK8 deficiency include sodium cromoglycate, which improves white blood cell function, and isotretinoin, which improves skin condition. (wikipedia.org)
  • This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). (wikipedia.org)
  • Aplastic refers to inability of the stem cells to generate mature blood cells. (wikipedia.org)
  • Low white blood cell counts (leukocytopenia) if present leads to an increased risk of infections which can be severe. (wikipedia.org)
  • One known cause is an autoimmune disorder in which white blood cells attack the bone marrow. (wikipedia.org)
  • Because it infects red blood cells as a result of the affinity for the P antigen, Parvovirus causes complete cessation of red blood cell production. (wikipedia.org)
  • In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating red blood cells. (wikipedia.org)
  • citation needed] More frequently parvovirus B19 is associated with aplastic crisis which involves only the red blood cells ( despite the name). (wikipedia.org)
  • Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells. (wikipedia.org)
  • Play media Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukemic cells. (wikipedia.org)
  • A drop in red blood cell count (anemia) can cause fatigue, paleness, and shortness of breath. (wikipedia.org)
  • Because of the failure of hematologic components to develop-white blood cells, red blood cells, and platelets-the body's capabilities to fight infection, deliver oxygen, and form clots are all diminished. (wikipedia.org)
  • While at birth, blood count is usually normal, macrocytosis/megaloblastic anemia, defined as unusually large red blood cells, is the first detected abnormality, often within the first decade of life (median age of onset is 7 years). (wikipedia.org)
  • Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. (wikipedia.org)
  • It may also be used to increase white blood cells for gathering during leukapheresis. (wikipedia.org)
  • Filgrastim is also used to increase the number of hematopoietic stem cells in the blood before collection by leukapheresis for use in hematopoietic stem cell transplantation. (wikipedia.org)
  • Often there is mild to severe anemia (low red blood cells). (wikipedia.org)
  • Enlarged spleen: The spleen aids in fighting infection and filters unwanted material, such as old or damaged blood cells. (wikipedia.org)
  • Thalassemia is often accompanied by the destruction of a large number of red blood cells and the task of removing these cells causes the spleen to enlarge. (wikipedia.org)
  • Splenomegaly can make anemia worse, and it can reduce the life of transfused red blood cells. (wikipedia.org)
  • Researchers collected samples of DeSilva's blood, isolated some of her white blood cells, and used a retrovirus to insert a healthy adenosine deaminase (ADA) gene into them. (wikipedia.org)
  • Bernard Babior made key contributions in linking the defect of superoxide production of white blood cells, to the cause of the disease. (wikipedia.org)
  • Viral
  • Opportunistic infections with viral, fungal, or protozoan pathogens suggest concomitant T-cell deficiency, although some of these pathogens can occasionally cause infections with CVID and XLA. (medscape.com)
  • transduction
  • When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. (wikipedia.org)
  • proteins
  • Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. (wikipedia.org)
  • In contrast, proteins from outside cell is internalized and then binds to MHC class II molecule. (wikipedia.org)
  • The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. (wikipedia.org)
  • genetically
  • This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell. (wikipedia.org)