paroxysmal hemoglobinuria

Summary

Summary: Disorder characterized by intravascular hemolysis and hemoglobinuria. Some cases occur on exposure to cold and are due to the presence of an autohemolysin in the serum. Other cases are more marked during or immediately after sleep and are considered to be due to an acquired intracorpuscular defect.

Top Publications

  1. ncbi [Acute myocardial infarction in nocturnal paroxysmal hemoglobinuria]
    I Antorrena

    Rev Esp Cardiol 54:117-9. 2001
  2. ncbi Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria
    J Takeda
    Department of Immunoregulation, Osaka University, Japan
    Cell 73:703-11. 1993
  3. pmc Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion
    V Rosti
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, Molecular Biology and Cell Biology Programs, Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    J Clin Invest 100:1028-36. 1997
  4. ncbi Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene
    G Tremml
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 94:2945-54. 1999
  5. pmc X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation
    P Keller
    Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:7479-83. 1999
  6. ncbi Glycosylphosphatidylinositol-anchor-deficient mice: implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria
    K Kawagoe
    Department of Immunoregulation, Osaka University, Japan
    Blood 87:3600-6. 1996
  7. pmc Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene
    M Bessler
    Department of Haematology, Hammersmith Hospital, Royal Postgraduate Medical School, London, UK
    EMBO J 13:110-7. 1994
  8. ncbi Immune pathogenesis of paroxysmal nocturnal hemoglobinuria
    Ramon Tiu
    Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Int J Hematol 84:113-7. 2006
  9. ncbi Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure
    Shinji Nakao
    Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
    Int J Hematol 84:118-22. 2006
  10. ncbi [Paroxysmal nocturnal hemoglobinuria (PNH) as a hematopoietic stem cell disorder--long-term support of hematopoiesis by a single stem cell clone in patients with PNH]
    Toshiyuki Hirota
    Rinsho Ketsueki 43:215-22. 2002

Detail Information

Publications187 found, 100 shown here

  1. ncbi [Acute myocardial infarction in nocturnal paroxysmal hemoglobinuria]
    I Antorrena

    Rev Esp Cardiol 54:117-9. 2001
    ..The patient presented cardiac tamponade and died. The role of hematologic disease in acute myocardial infarction and the treatment and evolution of the coronary syndrome in the context of the disease are discussed...
  2. ncbi Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria
    J Takeda
    Department of Immunoregulation, Osaka University, Japan
    Cell 73:703-11. 1993
    ..We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized...
  3. pmc Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion
    V Rosti
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, Molecular Biology and Cell Biology Programs, Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    J Clin Invest 100:1028-36. 1997
    ..This provides direct evidence for the notion that some additional factor(s) are needed for the expansion of the mutant clone in patients with PNH...
  4. ncbi Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene
    G Tremml
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 94:2945-54. 1999
    ..However, during the 12-month follow-up, the PIGA(-) cell population did not increase, clearly showing that a Piga gene mutation is not sufficient to cause the human disease, PNH...
  5. pmc X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation
    P Keller
    Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:7479-83. 1999
    ..PIGA(-) cells had no growth advantage, suggesting that other factors are needed for their clonal dominance in patients with paroxysmal nocturnal hemoglobinuria...
  6. ncbi Glycosylphosphatidylinositol-anchor-deficient mice: implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria
    K Kawagoe
    Department of Immunoregulation, Osaka University, Japan
    Blood 87:3600-6. 1996
    ....
  7. pmc Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene
    M Bessler
    Department of Haematology, Hammersmith Hospital, Royal Postgraduate Medical School, London, UK
    EMBO J 13:110-7. 1994
    ..These data prove that PNH is caused in most patients by a single mutation in the PIG-A gene. The nature of the mutation can vary and most likely occurs on the active X-chromosome in an early haematopoietic stem cell...
  8. ncbi Immune pathogenesis of paroxysmal nocturnal hemoglobinuria
    Ramon Tiu
    Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Int J Hematol 84:113-7. 2006
    ..Elucidation of the pathogenesis of PNH may provide key information about the causes of idiopathic AA and help understand the regulation of the hematopoietic stem cell compartment...
  9. ncbi Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure
    Shinji Nakao
    Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
    Int J Hematol 84:118-22. 2006
    ..A sensitive flow cytometric analysis for detection of a small population of PNH-type cells in peripheral blood cells is one of the most important examinations in the management of bone marrow failure...
  10. ncbi [Paroxysmal nocturnal hemoglobinuria (PNH) as a hematopoietic stem cell disorder--long-term support of hematopoiesis by a single stem cell clone in patients with PNH]
    Toshiyuki Hirota
    Rinsho Ketsueki 43:215-22. 2002
  11. ncbi Differential apoptosis and Fas expression on GPI-negative and GPI-positive stem cells: a mechanism for the evolution of paroxysmal nocturnal haemoglobinuria
    Medhat M Ismail
    Department of Cellular and Molecular Medicine, St George s Hospital Medical School, London, UK
    Br J Haematol 123:545-51. 2003
    ....
  12. ncbi [Physiopathology of and therapy for aplastic anemia]
    Shinji Nakao
    Nihon Naika Gakkai Zasshi 95:1851-7. 2006
  13. ncbi Relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria
    Taroh Kinoshita
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    Int J Hematol 75:117-22. 2002
    ..Survival of PNH clones in pathologic bone marrow may account for limited expansion of PNH clones; however, additional genetic change(s) that confers cells with growth phenotype may be required for the full development of PNH...
  14. ncbi Phenotypes and phosphatidylinositol glycan-class A gene abnormalities during cell differentiation and maturation from precursor cells to mature granulocytes in patients with paroxysmal nocturnal hemoglobinuria
    Tatsuyuki Kai
    First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan
    Blood 100:3812-8. 2002
    ..In conclusion, our findings suggest that PNH clones might contribute qualitatively and quantitatively differentially to specific blood cell lineages during differentiation and maturation of hematopoietic stem cells...
  15. ncbi Differential usefulness of various markers in the flow cytometric detection of paroxysmal nocturnal hemoglobinuria in blood and bone marrow
    Horatiu Olteanu
    Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, TX 75390 9073, USA
    Am J Clin Pathol 126:781-8. 2006
    ....
  16. ncbi A SIN lentiviral vector containing PIGA cDNA allows long-term phenotypic correction of CD34+-derived cells from patients with paroxysmal nocturnal hemoglobinuria
    David Robert
    INSERM E 0217, Laboratoire de Pathologie Moléculaire et Thérapie Génique, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France
    Mol Ther 7:304-16. 2003
    ..This expression was stable during erythroid, myeloid, and megakaryocytic liquid culture differentiation. CD59 surface cell expression was fully restored during 5 weeks of long-term culture...
  17. ncbi [Molecular pathogenesis and clinical profile of paroxysmal nocturnal hemoglobinuria (PNH)]
    Hideki Nakakuma
    Rinsho Ketsueki 47:1329-39. 2006
  18. ncbi Multilineage glycosylphosphatidylinositol anchor-deficient haematopoiesis in untreated aplastic anaemia
    G L Mukhina
    Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA
    Br J Haematol 115:476-82. 2001
    ..These studies demonstrate that aerolysin-based assays can reveal previously undetectable multilineage PNH cells in patients with untreated aplastic anaemia. Thus, clonality appears to be an early feature of aplastic anaemia...
  19. ncbi Recent advances in biological and clinical aspects of paroxysmal nocturnal hemoglobinuria
    Lucio Luzzatto
    Department of Haematology, University of Genova and Istituto Toscano Tumori, Firenze, Italy
    Int J Hematol 84:104-12. 2006
    ..This process of somatic cell selection may have an autoimmune basis, and the most likely agents are cells belonging to the natural killer-like subset of T-cells...
  20. ncbi PIG-A mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis
    Robert A Brodsky
    Johns Hopkins University School of Medicine, Division of Hematology, Baltimore, MD, USA
    Leuk Lymphoma 47:1215-21. 2006
    ..This review examines the clinical and biological relevance of PIG-A mutations in PNH, aplastic anemia and healthy controls...
  21. ncbi Screening for paroxysmal nocturnal hemoglobinuria (PNH) clone in Egyptian children with aplastic anemia
    S Rizk
    Department of Clinical Pathology, School of Medicine, Cairo University, Egypt
    J Trop Pediatr 48:132-7. 2002
    ..Thrombotic complications should be anticipated in cases with aplastic anemia having a PNH clone...
  22. ncbi CD34+ cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of cellular prion protein (PrPc)
    Antonio M Risitano
    Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    Exp Hematol 31:65-72. 2003
    ..Conversely, PrP(c) is a good model to elucidate the fate of GPI-AP in PIG-A-deficient cells...
  23. ncbi Anti-thymocyte globulin treatment of marrow aplasia associated with paroxysmal nocturnal haemoglobinuria (PNH) resulted in haematological improvement due to an expansion of the PNH clone
    W C Cheung
    University Department of Medicine, Queen Mary Hospital, Hong Kong
    Br J Haematol 120:325-8. 2003
    ..PIG-A gene analysis showed that the same PNH clone had waned and waxed in the clinical course. Our results suggest that the PNH clone might rarely be an immune target as well...
  24. ncbi Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy
    Anita Hill
    Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals National Health Service Trust, Algernon Firth Building, Great George Street, Leeds, United Kingdom, LS1 3EX
    Blood 107:2131-7. 2006
    ..Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH...
  25. ncbi Severe telomere shortening in patients with paroxysmal nocturnal hemoglobinuria affects both GPI- and GPI+ hematopoiesis
    Anastasios Karadimitris
    Memorial Sloan Kettering Cancer Center, Department of Human Genetics, New York, NY, USA
    Blood 102:514-6. 2003
    ..The short telomeres of the GPI+ cells indicate that the residual hematopoiesis contributed by these cells is not normal. This epigenetic change is an additional feature shared by PNH and aplastic anemia...
  26. ncbi Normal patterns of expression of glycosylphosphatidylinositol-anchored proteins on different subsets of peripheral blood cells: a frame of reference for the diagnosis of paroxysmal nocturnal hemoglobinuria
    Pilar María Hernández-Campo
    Servicio General de Citometria, Centro de Investigacion del Cancer, Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain
    Cytometry B Clin Cytom 70:71-81. 2006
    ....
  27. ncbi A cohort study of the nature of paroxysmal nocturnal hemoglobinuria clones and PIG-A mutations in patients with aplastic anemia
    Wanchai Wanachiwanawin
    Division of Hematology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Eur J Haematol 76:502-9. 2006
    ..As PNH frequently occurs during the clinical course of acquired aplastic anemia (AA), it is likely that a process inducing bone marrow failure in AA is responsible for the selection of GPI-AP deficient blood cells or PNH clone...
  28. ncbi The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot
    Yousef Mortazavi
    Department of Haematology, St George s Hospital Medical School, London, United Kingdom
    Blood 101:2833-41. 2003
    ..Our results suggest that the large majority of AA/PNH patients have multiple mutations. These data may suggest a process of hypermutation in the PIG-A gene in AA stem cells...
  29. ncbi Mean fluorescence intensity rate is a useful marker in the detection of paroxysmal nocturnal hemoglobinuria clones
    Zsuzsa Hevessy
    Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, Debrecen, Hungary
    Clin Chem Lab Med 43:919-23. 2005
    ..021-0.34). Thus, CD14 on monocytes seems to be the most reliable marker for establishing the PNH clone size and the severity of antigen deficiency...
  30. ncbi Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial
    John F Tisdale
    Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 100:4668-70. 2002
    ..Bone marrow cytogenetic abnormalities have been observed among surviving patients in both arms (2 of 14 ATG versus 1 of 12 Cy, P =.70). High-dose Cy does not prevent relapse or clonal evolution in SAA...
  31. ncbi Diagnosis of paroxysmal nocturnal hemoglobinuria by fluorescent clostridium septicum alpha toxin
    Dong Jun Shin
    Genomic Research Center for Enteropathogenic Bacteria and Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea
    J Mol Microbiol Biotechnol 11:20-7. 2006
    ..Therefore, nontoxic EGFP-conjugated C. septicum alpha toxin could be used clinically for PNH diagnosis...
  32. ncbi Placental expression of glycophosphatidylinositol (GPI)-anchored proteins in paroxysmal nocturnal haemoglobinuria
    E K Kristoffersen
    The Gade Institute, Department of Microbiology and Immunology, University of Bergen and Haukeland University Hospital, Bergen, Norway
    Scand J Immunol 64:140-4. 2006
    ..These findings show that fetally derived cells in the PNH placenta expressed GPI-linked molecules that are known to be of importance for a successful pregnancy outcome...
  33. ncbi A prospective comparison of four techniques for diagnosis of paroxysmal nocturnal hemoglobinuria
    R Gupta
    Department of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
    Int J Lab Hematol 29:119-26. 2007
    ..The GCT is a useful screening tool as it is fairly sensitive, easy to perform and interpret. Well-standardized lytic tests are fairly reliable as screening tests...
  34. ncbi Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria
    Stephen J Richards
    Haematological Malignancy Diagnostic Service, Department of Haematology, Leeds Teaching Hospitals NHS Trust, The Algernon Firth Building, Leeds General Infirmary, Leeds, LS1 3EX, United Kingdom
    Cytometry B Clin Cytom 72:291-8. 2007
    ..In both these developments, flow cytometry played a critical role. In the first instance, in monitoring direct response to a new therapeutic agent; second, in demonstrating the phenotypic/genotypic link in a new form of GPI deficiency...
  35. ncbi Identification of unsuspected PNH-type cells in flow cytometric immunophenotypic analysis of peripheral blood and bone marrow
    Ronald W Thomason
    Section of Hematopathology, Esoterix Oncology, Brentwood, TN 37027, USA
    Am J Clin Pathol 122:128-34. 2004
    ..Recognition of abnormal patterns of CD14 and CD16 expression might permit the identification of clinically unsuspected PNH by routine flow cytometric analysis...
  36. ncbi [Expression of three kinds of GPI-anchor proteins in paroxysmal nocturnal hemoglobinuria, aplastic anemia and myelodysplastic syndromes patients and their clinical implications]
    Xiao Yuan Dong
    Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
    Zhonghua Xue Ye Xue Za Zhi 25:198-201. 2004
    ....
  37. ncbi A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol-linked proteins
    Marek Jasinski
    Division of Hematology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 103:2827-34. 2004
    ..Future investigations will show whether this novel pathway of PIGA- RBC destruction identified in mice may also operate in patients with PNH...
  38. ncbi Assessing donor chimerism using flow cytometry in paroxysmal nocturnal haemoglobinuria after stem cell transplantation--a case report
    R Z Azma
    Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
    Malays J Pathol 28:107-12. 2006
    ..Engrafted patients will show the presence of CD 55 and CD 59 on their red cells and white cells. We describe here the usefulness of flow cytometry in the assessment of donor chimerism following allogeneic PBSCT, in a case of PNH...
  39. doi Immunophenotypic analysis of PNH cells
    Stephen J Richards
    Haematological Malignancy Diagnostic Service, Leeds, United Kingdom
    Curr Protoc Cytom . 2002
    ....
  40. pmc Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting
    X Sun
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 96:628-33. 1999
    ....
  41. ncbi [Estimation of expression of glycosylphosphatidylinositol-anchored protein in B lymphocytes for diagnosis of paroxysmal nocturnal hemoglobinuria]
    Wei Cui
    Department of Clinical Laboratory, PUMC Hospital, CAMS and PUMC, Beijing 100730, China
    Zhongguo Yi Xue Ke Xue Yuan Xue Bao 25:599-602. 2003
    ..To estimate whether the expression of glycosylphosphatidylinositol (GPI)-anchored protein in B lymphocytes could be an indicator for detecting paroxysmal nocturnal hemoglobinuria (PNH)...
  42. ncbi Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan
    Jun ichi Nishimura
    PNH Research Committee, Duke University Medical Center, Durham, North Carolina 27710, USA
    Medicine (Baltimore) 83:193-207. 2004
    ..These data identify important differences between white and Asian patients with PNH. Identification of prognostic factors will help the design of prospective clinical trials for PNH...
  43. ncbi [Spontaneous recovery from pancytopenia in a young female patient with paroxysmal nocturnal hemoglobinuria(PNH): changes in the GPI-anchor expression on peripheral blood cells]
    Takeshi Inukai
    Department of Pediatrics, Faculty of Medicine, University of Yamanashi
    Rinsho Ketsueki 45:238-42. 2004
    ....
  44. ncbi A new aspect of the molecular pathogenesis of paroxysmal nocturnal hemoglobinuria
    Tsutomu Shichishima
    First Department of Internal Medicine, Fukushima Medical University, 1 Hikariga oka, Fukushima 960 1295, Japan
    Hematology 7:211-27. 2002
    ..To elucidate this problem, it is important to know the pathophysiology of bone marrow failure in detail and how bone marrow failure affects hematopoietic stem cells and immune mechanisms in bone marrow failure syndromes...
  45. ncbi Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice
    N Iwamoto
    Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan
    Blood 87:4944-8. 1996
    ..This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone...
  46. ncbi Recent insights into the pathophysiology of paroxysmal nocturnal hemoglobinuria
    John Meletis
    1st Department of Internal Medicine, University of Athens, School of Medicine, Laikon General Hospital, Athens, Greece
    Med Sci Monit 9:RA161-72. 2003
    ....
  47. ncbi Detection of CD55- and/or CD59-deficient red cell populations in patients with plasma cell dyscrasias
    John Meletis
    First Department of Internal Medicine, University of Athens School of Medicine, Laiko General Hospital, Greece
    Int J Hematol 75:40-4. 2002
    ..These findings illustrate the existence of the PNH phenotype in the red cells of patients with PCD; further investigation is needed into the mechanisms and significance of this phenotype...
  48. ncbi On the origin of multiple mutant clones in paroxysmal nocturnal hemoglobinuria
    Arne Traulsen
    Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA
    Stem Cells 25:3081-4. 2007
    ..Disclosure of potential conflicts of interest is found at the end of this article...
  49. ncbi Clinical paroxysmal nocturnal hemoglobinuria is the result of expansion of glycosyl-phosphatidyl-inositol-anchored protein-deficient clone in the condition of deficient hematopoiesis
    K Pakdeesuwan
    Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Int J Hematol 73:64-70. 2001
    ..All of the findings suggest that in the condition of deficient hematopoiesis, the PNH clone arising from the mutated hematopoietic stem cell expands and maintains a substantial proportion of the patient's hematopoiesis...
  50. ncbi New insights into molecular pathogenesis of bone marrow failure in paroxysmal nocturnal hemoglobinuria
    Tatsuya Kawaguchi
    Department of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
    Int J Hematol 86:27-32. 2007
    ..Here, we overview the current understanding of the molecular pathogenesis of bone marrow failure in PNH...
  51. ncbi The role of cholesterol and glycosylphosphatidylinositol-anchored proteins of erythrocyte rafts in regulating raft protein content and malarial infection
    B U Samuel
    Department of Pathology, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 276:29319-29. 2001
    ..However, infection is blocked following raft-cholesterol disruption, suggesting that erythrocyte rafts can be functionally exploited and providing the first evidence for the involvement of host rafts in an apicomplexan infection...
  52. ncbi Relative increase of granulocytes with a paroxysmal nocturnal haemoglobinuria phenotype in aplastic anaemia patients: the high prevalence at diagnosis
    H Wang
    Third Department of Medicine, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan 920-8641
    Eur J Haematol 66:200-5. 2001
    ....
  53. ncbi Shared and individual specificities of immunodominant cytotoxic T-cell clones in paroxysmal nocturnal hemoglobinuria as determined by molecular analysis
    Magdalena Plasilova
    Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Exp Hematol 32:261-9. 2004
    ..We previously described expansions of selective cytotoxic T-lymphocyte (CTL) clones in AA patients...
  54. ncbi Activation of human monocytes and granulocytes by monoclonal antibodies to glycosylphosphatidylinositol-anchored antigens
    F Lund-Johansen
    Department of Pathology, Gade Institute, University of Bergen, Haukeland Hospital
    Eur J Immunol 23:2782-91. 1993
    ..The results indicate that most, if not all, GPI-linked surface glycoproteins on myeloid cells are capable of mediating cell activation and suggest that the GPI anchor is a structure facilitating signal transduction...
  55. ncbi Haptoglobin therapy during pregnancy for paroxysmal nocturnal hemoglobinuria with renal failure
    T Shibasaki
    Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan
    Int J Gynaecol Obstet 98:267-8. 2007
  56. ncbi Allogeneic hematopoietic cell transplantation for paroxysmal nocturnal hemoglobinuria
    Jae Lyun Lee
    Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    Eur J Haematol 71:114-8. 2003
    ..Although allogeneic hematopoietic cell transplantation (HCT) has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), appropriate indication and conditioning regimen for HCT have not been established...
  57. ncbi Paroxysmal nocturnal hemoglobinuria in children
    Marry M van den Heuvel-Eibrink
    Department of Pediatric Oncology Hematology, Erasmus Medical Center Sophia Children s Hospital, Rotterdam, The Netherlands
    Paediatr Drugs 9:11-6. 2007
    ..This article reviews the reported cases of PNH in children using the recently published guidelines for classification, diagnostics, and treatment...
  58. ncbi Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria
    D J Araten
    Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, USA
    Br J Haematol 115:360-8. 2001
    ..However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia...
  59. ncbi Molecular genetics of paroxysmal nocturnal hemoglobinuria
    Norimitsu Inoue
    Department of Molecular Genetics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka University, Suita, Osaka, Japan
    Int J Hematol 77:107-12. 2003
    ..The next 10 years should witness the discovery of the molecular mechanisms of immunologic selection and the identification of abnormalities involved in the further clonal expansion of PNH cells...
  60. doi Bone marrow failure syndromes: paroxysmal nocturnal hemoglobinuria
    Charles J Parker
    Division of Hematology and Bone Marrow Transplantation, Department of Medicine, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA
    Hematol Oncol Clin North Am 23:333-46. 2009
    ..Management of PNH is discussed also...
  61. ncbi [Case of paroxysmal nocturnal hemoglobinuria complicated with IgA nephropathy who developed acute renal failure induced by hemolytic crisis]
    Kenichi Kato
    Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
    Nihon Jinzo Gakkai Shi 47:540-6. 2005
    ..After the transfusion of six units of washed red blood cells and two sessions of hemodialysis, the renal function returned to the levels before admission...
  62. ncbi Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells
    Xingmin Feng
    Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
    Blood 104:2425-31. 2004
    ..These findings indicate that DRS-1 may serve as an autoantigen eliciting immune attack against hematopoietic stem cells in a subset of AA patients characterized by increased PNH-type cells...
  63. ncbi Flow cytometric analysis of glycosylphosphatidyl-inositol-anchored proteins to assess paroxysmal nocturnal hemoglobinuria clone size
    J Piedras
    Department of Hematology and Oncology, Laboratory of Cell Biology, Instituto Nacional de la Nutricion Salvador Zubiran, Tlalpan, Mexico
    Cytometry 42:234-8. 2000
    ..80), and CD14 (r(2) = 0.75) antigens. These results are interpreted as indicating that the size of PNH clone is better assessed by immunophenotypic analysis of monocytes and granulocytes rather than of lymphocytes and erythrocytes...
  64. ncbi [Application of double immunomagnetic positive sorting to ex vivo expansion of marrow CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria]
    Juan Xiao
    Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    Zhongguo Shi Yan Xue Ye Xue Za Zhi 11:179-83. 2003
    ....
  65. ncbi Flowcytometric detection of PNH defect and response to therapy in aplastic anemia patients
    Neelam Varma
    Departments of Hematology, Internal Medicine and Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh
    Methods Cell Sci 24:77-8. 2002
  66. ncbi Off-pump coronary artery bypass grafting in a patient with paroxysmal nocturnal hemoglobinuria
    Yutaka Makino
    Department of Cardiovascular Surgery, Oji General Hospital, Tomakomai, Hokkaido, Japan
    Jpn J Thorac Cardiovasc Surg 52:469-72. 2004
    ..His postoperative course was uneventful. Combination of appropriate perioperative management and off-pump cardiac surgery yielded an effective result in treating this patient without major complications...
  67. ncbi Successful application of nonmyeloablative stem cell transplantation for paroxysmal nocturnal hemoglobinuria
    Wei Xu
    Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
    Chin Med J (Engl) 120:2056-8. 2007
  68. ncbi The distribution of PIG-A gene abnormalities in paroxysmal nocturnal hemoglobinuria granulocytes and cultured erythroblasts
    H Noji
    First Department of Internal Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima 960-1295, Japan
    Exp Hematol 29:391-400. 2001
    ....
  69. ncbi Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria following aplastic anaemia
    K M Hassan
    Department of Medicine, AFMC, Pune
    J Assoc Physicians India 49:753-5. 2001
    ..The role of immunosuppressive therapy for aplastic anaemia in causation of paroxysmal nocturnal haemoglobinuria is reviewed...
  70. ncbi [Study on the stroma of patients with paroxysmal nocturnal hematoglobinuria]
    B Han
    Department of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Peking Union Medical College Hospital, Beijing 100730, China
    Zhonghua Yi Xue Za Zhi 81:1430-3. 2001
    ..The stromata in patients with PNH had normal hematopoietic maintainence to the normal CD34+ cells. The mRNA expression of IL-6 and TNF-alpha in PNH stromata was almost normal...
  71. ncbi Efficient retrovirus-mediated PIG-A gene transfer and stable restoration of GPI-anchored protein expression in cells with the PNH phenotype
    - Nishimura Ji
    Division of Hematology and Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
    Blood 97:3004-10. 2001
    ..These findings set the stage for determining whether MPIN can restore PIG-A function in multipotential stem cells, thereby providing a potential new therapeutic option in PNH...
  72. ncbi Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: review and recommendations for management of the pregnant and nonpregnant patient
    J G Ray
    Department of Medicine, and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
    Haemostasis 30:103-17. 2000
    ....
  73. ncbi [The effects of sera from patients with paroxysmal nocturnal hematoglobinuria on the growth of CD34(+) cells]
    Bing Han
    Department of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Peking Union Medical College Hospital, Beijing 100730, China
    Zhongguo Shi Yan Xue Ye Xue Za Zhi 10:47-51. 2002
    ..patients had no significant influence on single hematopoietic stem/progenitor cells derived from normal subjects and from PNH patients, but the PNH sera might promote the colony formation of the CD34(+) CD59(+) cells in semi-solid culture..
  74. ncbi Evaluation of the haemopoietic reservoir in de novo haemolytic paroxysmal nocturnal haemoglobinuria
    Modupe O Elebute
    Department of Haematology, St George s Hospital Medical School, London, UK
    Br J Haematol 123:552-60. 2003
    ....
  75. doi Spectrum of renal involvement in paroxysmal nocturnal hemoglobinuria: report of three cases and a brief review of the literature
    R K Nair
    Department of Nephrology, All India Institute of Medical Sciences, Ansari Nagar 110029, New Delhi, India
    Int Urol Nephrol 40:471-5. 2008
    ..The renal involvement was documented on both histology and on imaging studies. Finally, we briefly review the main literature data on renal involvement in PNH...
  76. doi Fatal nephrotic syndrome complicating allogeneic stem cell transplantation: a case report
    Iddo Z Ben-Dov
    Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Nephrol Dial Transplant 24:2946-9. 2009
    ..Physicians should be aware of the possibility that infections and inflammation accompanying the post-transplantation period may rarely promote the development of systemic amyloidosis or exacerbate silent pre-existing disease...
  77. ncbi Hematopoietic cell transplantation from related and unrelated donors after minimal conditioning as a curative treatment modality for severe paroxysmal nocturnal hemoglobinuria
    U Hegenbart
    Division of Hematology and Oncology, University of Leipzig, Germany
    Biol Blood Marrow Transplant 9:689-97. 2003
    ..Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH...
  78. pmc Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab
    Dominique Helley
    Service d Hematologie Biologique, Hopital Europeen Georges Pompidou, 20 40 rue Leblanc, 75908 Paris Cedex 15, France
    Haematologica 95:574-81. 2010
    ..Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis through unknown mechanisms...
  79. ncbi Production of interferon-gamma by lymphocytes from paroxysmal nocturnal haemoglobinuria patients: relationship with clinical status
    Serelina Coluzzi
    Blood Bank, Department of Biotecnologie Cellulari ed Ematologia, University La Sapienza, via Chieti 7, 00161 Rome, Italy
    Br J Haematol 124:685-90. 2004
    ..This study supports the hypothesis that immune alteration are present in PNH and that the immunogenetic background could influence the development of the disease...
  80. ncbi Characterization of alternatively spliced PIG-A transcripts in normal and paroxysmal nocturnal hemoglobinuria cells
    J Yu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106
    Braz J Med Biol Res 27:195-201. 1994
    ..The other expressed a 1600-bp transcript with multiple nucleotide changes but normal 1200- and 950-bp "spliced" transcripts...
  81. ncbi Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP
    Nobuyoshi Hanaoka
    Department of Hematology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
    Blood 107:1184-91. 2006
    ..Granulocytes of the patients partly underwent killing by autologous cytotoxic cells, implying ULBP-associated blood cell injury. In this setting, the lack of ULBPs may allow immunoselection of PNH clones...
  82. ncbi Sustained long-term hematologic recovery despite a marked quantitative defect in the stem cell compartment of patients with aplastic anemia after immunosuppressive therapy
    J P Maciejewski
    Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA
    Am J Hematol 65:123-31. 2000
    ..Despite a limited expansion potential of a severely reduced stem cell pool, their numbers are sufficient to provide a long-term supply of mature blood cells. Am. J. Hematol. 65:123-131, 2000. Published 2000 Wiley-Liss, Inc...
  83. pmc How I treat paroxysmal nocturnal hemoglobinuria
    Robert A Brodsky
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 2196, USA
    Blood 113:6522-7. 2009
    ..Insights into the relevance of detecting PNH cells in PNH and other bone marrow failure disorders are highlighted, and indications for treating PNH patients with bone marrow transplantation and eculizumab are explored...
  84. ncbi Killer immunoglobulin-like receptor genotype in immune-mediated bone marrow failure syndromes
    Evan C Howe
    Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland, OH 44195, USA
    Exp Hematol 33:1357-62. 2005
    ....
  85. ncbi Cardiopulmonary bypass surgery in a patient with paroxysmal nocturnal haemoglobinuria
    D Dinesh
    New Zealand Blood Service, Wellington, New Zealand
    Transfus Med 16:206-8. 2006
    ..We describe a case of uncomplicated cardiopulmonary bypass surgery for aortic valve replacement and aortoplasty in a patient with PNH and discuss some recommendations to reduce the risk of peri-operative complications...
  86. doi Desmoplakin and KIF20B as target antigens in patients with paroxysmal nocturnal haemoglobinuria
    Adnan Alahmad
    Jose Carrerase Center for Immuno and Genetherapy, Department of Internal Medicine Ι, Saarland University Medical School, Homburg, Germany
    Br J Haematol 151:273-80. 2010
    ..The analysis of the mechanisms underlying the autoimmune response might contribute to our understanding of the clonal expansion in PNH...
  87. ncbi G-CSF induced progenitor mobilization in mice with PIGA- blood cells
    Bing Han
    Division of Hematology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Hematol J 5:347-52. 2004
    ..This suggested that GPI-linked proteins contribute to the regulation of progenitor trafficking from bone marrow to peripheral blood...
  88. ncbi Biological and molecular characterization of PNH-like lymphocytes emerging after Campath-1H therapy
    N S Fracchiolla
    Dipartimento di Ematologia, Ospedale Maggiore Policlinico IRCCS, Vis F. Sforza 35, 20122-Milan, Italy
    Br J Haematol 112:969-71. 2001
    ..Given the inhibitory activity of TGF-beta, its elevated levels may contribute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes...
  89. ncbi Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria
    Russell P Rother
    Alexion Pharmaceuticals, Inc, 352 Knotter Drive, Cheshire, Connecticut 06410, USA
    Nat Biotechnol 25:1256-64. 2007
    ....
  90. ncbi Expression of CD59 on lymphocyte and the subsets and its potential clinical application for paroxysmal nocturnal hemoglobinuria diagnosis
    W Cui
    Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
    Clin Lab Haematol 26:95-100. 2004
    ..CD59 expression on B-cells could thus be used as a new marker for the diagnosis of PNH...
  91. ncbi Thrombosis in paroxysmal nocturnal hemoglobinuria: sites, risks, outcome. An overview
    P D Ziakas
    J Thromb Haemost 5:642-5. 2007
  92. ncbi Clinical problem-solving. More than meets the eye
    John S Nguyen
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA
    N Engl J Med 355:1048-52. 2006
  93. ncbi Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria
    Anita Hill
    Haematology, Leeds Teaching Hospitals NHS Trust, UK
    Haematologica 90:ECR40. 2005
    ..Complement inhibition has been sustained for over 2 years and results in resolution of intravascular hemolysis and amelioration of symptoms associated with smooth muscle contractions...
  94. pmc Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization
    Anita Hill
    1Department of Haematology, St James University Hospital, Leeds, UK
    Haematologica 95:567-73. 2010
    ..This may be due to C3-mediated clearance of paroxysmal nocturnal hemoglobinuria red blood cells through the reticuloendothelial system...
  95. ncbi Rapid diagnosis of paroxysmal nocturnal haemoglobinuria by gel card test
    Seema Tyagi
    Indian J Pathol Microbiol 46:147-8. 2003
  96. ncbi Management issues in paroxysmal nocturnal hemoglobinuria
    Gabrielle Meyers
    Division of Hematology, University of Utah School of Medicine and VA Medical Center, Salt Lake City, Utah 84148, USA
    Int J Hematol 77:125-32. 2003
    ....
  97. doi Severe pancytopenia associated with a minor paroxysmal nocturnal haemoglobinuria clone and response to ciclosporin A in a heavily pretreated multiple myeloma patient
    Alexander Kulagin
    Br J Haematol 141:122-3. 2008
  98. ncbi [Ex vivo expansion of CD34(+) CD59(+) cells from bone marrow of paroxysmal nocturnal hemoglobinuria patients]
    Juan Xiao
    Department of Hematology, Pekin Union Medical College Hospital, CAMS and PUMC, Beijing 100730, China
    Zhonghua Xue Ye Xue Za Zhi 23:568-70. 2002
    ..To study the separation, purification and ex vivo expansion of CD(34)(+) CD(59)(+) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH), and explore the new treatment for the PNH patients...
  99. ncbi Stem cells in paroxysmal nocturnal haemoglobinuria and aplastic anaemia: increasing evidence for overlap of haemopoietic defect
    J C W Marsh
    Department of Haematology, St George s Hospital Medical School, London, UK
    Transfus Med 13:377-86. 2003
    ..This results in the selection of the PIG-deficient clone, in contrast to the PIG-normal stem cells which possess the PIG anchor and hence are targeted and depleted by the autoreactive T cells...
  100. ncbi High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome
    M Okamoto
    First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan
    Leukemia 20:627-34. 2006
    ..This partly explains the transformation of AA or MDS to PNH at intervals...
  101. ncbi [Recent progress in paroxysmal nocturnal hemoglobinuria]
    Jun ichi Nishimura
    Rinsho Ketsueki 48:1312-9. 2007

Research Grants11

  1. REGULATION OF THE ERYTHROPOIETIN GENE
    H Bunn; Fiscal Year: 2003
    ..These studies should provide unique and highly relevant information about common mechanisms of oxygen sensing, signal transduction and gene regulation that enable organisms to adapt to hypoxia. ..
  2. Measurement & modulation of the mutation rate in humans
    David Araten; Fiscal Year: 2007
    ..These studies will begin to elucidate the relationship between f and cancer risk and provide a highly relevant in vitro parameter with which to evaluate chemoprevention. ..
  3. Minimal Residual Disease in Pediatric ALL in Relation to Other Prognostic Factors
    Michael J Borowitz; Fiscal Year: 2010
    ..These studies will give us a better understanding of how to use prognostic information in treating children with ALL, and bring us closer to our goal of curing the maximum number of children with ALL with the least toxic therapy. ..
  4. Minimal Residual Disease in Childhood ALL in Relapse
    Michael Borowitz; Fiscal Year: 2006
    ..We will also be able to extend these studies to other situations where we can use MRD as a rapid means to compare therapies. ..
  5. Evolution of Autoimmunity in Rheumatoid Arthritis
    V Holers; Fiscal Year: 2005
    ..abstract_text> ..
  6. CELLULAR BASIS OF HYPERSENSITIVITY DISEASES IN HUMANS
    FRANK AUSTEN; Fiscal Year: 2007
    ..abstract_text> ..
  7. DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
    V Holers; Fiscal Year: 2007
    ..This latter project involves a newly established collaboration with a separate institution and group of clinicians skilled in the clinical investigation of RA. ..
  8. OXYGEN SENSING AND SIGNAL TRANSDUCTION
    H Bunn; Fiscal Year: 2003
    ..abstract_text> ..
  9. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 2008
    ..Specific Aim #3: Determine the functional activities and biologic relevance of novel SCR-containing candidate C3/C4 binding and regulatory proteins. ..
  10. C3D/EBV RECEPTOR LIGAND BINDING SITES
    V Holers; Fiscal Year: 2006
    ....