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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aplastic anemia (AA) is a most difficult disease to study in vitro. By the time the disease presents, the marrow is already hypocellular and the peripheral blood shows pancytopenia, leaving little material remaining for study. However, an understanding of its pathogenesis could provide insight into the control of normal hemopoiesis since AA is an in vivo manifestation of failure of normal hemopoiesis and may provide a way of examining stromal cell-stem cell relationships. Recent interest in the pathogenesis of AA has resulted from a) new laboratory techniques, such as stem cell purification used with modifications of the long-term bone marrow culture system and analysis of stem cells at the molecular level with X-linked DNA probes, and b) the availability of recombinant human hemopoietic growth factors (HGF) in large quantities. Consequently, analyses of the function of some of the individual components of stromal cell mediated hemopoiesis in AA patients have been performed. This has been paralleled, and in some instances preceded, by clinical trials of HGF in patients with AA.
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PMID:In vitro revelations of aplastic anemia. 145 12

The X-linked lymphoproliferative syndrome (XLP), also known as Duncan's disease, is an X-linked recessive disorder that is characterized by the inability of affected individuals to mount a sufficient immune response to Epstein-Barr virus (EBV). After EBV primary infection, male family members suffer from severe infectious mononucleosis (IM), aplastic anemia, hypogammaglobulinemia, and a spectrum of lymphoproliferative diseases. Autosomal mode of inheritance with similar symptoms as in XLP has been reported. We have studied two families with EBV-associated syndromes and an X-linked and an autosomal mode of inheritance, respectively. Affected family members presented with severe IM, hemophagocytosis, aplastic anemia, acquired hypogammaglobulinemia, and B-cell lymphoproliferative diseases.
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PMID:Epstein-Barr virus-associated lymphoproliferative syndromes: studies in two European families. 164 73

Patients with X-linked lymphoproliferative (XLP) disease are characterized by extreme vulnerability to Epstein-Barr virus (EBV). Following infection with EBV, affected males develop fatal infectious mononucleosis (IM), hypogammaglobulinemia (H), or non-Hodgkin's lymphoma (NHL). In addition, hyper IgM, red cell aplasia, necrotizing lymphoid vasculitis (NLV), and aplastic anemia occur rarely. The recent use of DNA restriction fragment length polymorphism (RFLP) probes in linkage with the XLP gene now permit detection of affected males prior to primary EBV infection. We have measured immunoglobulin class and subclass levels in sera from EBV-negative males who were either positive or negative for the XLP genotype by RFLP analysis. Elevated IgA or IgM and/or variable deficiency of IgG, IgG1, and IgG3 occurred in the sera of 13/13 RFLP-positive, EBV-negative males. No consistent abnormalities were noted in 14 RFLP-negative, EBV-negative males. We conclude that the immune defect in XLP is not solely EBV-specific, although EBV is responsible for most of the morbidity and all of the mortality. Further, serial measurement of Ig levels may provide information regarding status of EBV-negative males at risk where RFLP analysis is uninformative or in families where sporadic cases of fatal IM, acquired hypogammaglobulinemia or NHL have occurred, but wherein the genotype of XLP cannot be documented.
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PMID:Immunoglobulin class and subclass deficiencies prior to Epstein-Barr virus infection in males with X-linked lymphoproliferative disease. 168 54

Two brothers in a Chinese family were affected with dyskeratosis congenita (DC). The proband's stepbrother died of pancytopenia and rectal adenocarcinoma. The proband with progressive pancytopenia was studied in genetics and hematology. Family investigations suggest that the disorder was inherited as an X-linked recessive transmission. No specific chromosome aberrations were detected in both peripheral blood and bone marrow cells. Bone marrow biopsy revealed markedly hypocellular marrow without prominent reticulin fibers. Hematopoiesis was assessed by assay of granulomonocytic (CFU-GM) colonies and clusters in vitro. Numbers of CFU-GM were profoundly reduced in marrow cultures from our patient. Although a defect in the stromal microenvironment and lymphocyte mediated suppression could not be excluded. It is possible that the defect is intrinsic to the hematopoietic stem cells. The familial disease described by this paper favors that the dyskeratosis congenita is X-linked with constitutional aplastic anemia. It is believed that the pancytopenia with hypocellular marrow in DC is an inherited rather than an acquired condition.
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PMID:[X-linked dyskeratosis congenita with aplastic anemia--genetic and hematologic studies]. 247 34

Allogeneic bone marrow transplantation (BMT) was applied in 1968 to treat severe combined immunodeficiency disease (SCID). Almost simultaneously, marrow from an MHC-matched donor corrected the immunological deficiency of a patient with Wiscott-Aldrich Syndrome (WAS). In the first successful treatment of X-linked SCID the match was imperfect and, although SCID was cured, a graft vs. host reaction caused pancytopenia. A second BMT from the same donor successfully treated a complicating aplastic anemia. Subsequently, it has been possible to cure most patients with SCID who are in reasonably good condition at the time of BMT without other manipulation if a matched sibling donor is available. Successes are reported from Holland, France, Italy, England, Scandinavia, Japan, Germany, and from many centers in the United States. Similarly, BMT is used to correct SCID due to adenosine deaminase (ADA) deficiency or nucleoside phosphorylase (NP) deficiency, which underlie two forms of SCID. Bone marrow transplantation using HLA-matched sibling donors can now treat, successfully, at least eight genetically separable forms of SCID. Highly lethal defects of phagocytic function (including LFA-1, MO-1, CR-3 deficiencies, IL-2 and IL-1 receptor deficiencies), defects of killing after phagocytosis (as in chronic granulomatous disease, WAS, and Kostmann's Syndrome), and certain inborn errors of metabolism can be cured by BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for immunodeficiency diseases. 330 7

Two brothers with the X-linked disorder, dyskeratosis congenita, are described. They showed the dermatologic triad of reticular hyperpigmentation, dystrophic nails, and leukoplakia oris as well as the other major feature of this disorder, aplastic anemia. Less common features observed included prenatal and postnatal growth retardation, mental retardation, elevated immunoglobulin levels, and gastrointestinal hemorrhage from mucosal ulceration. Previously unreported findings were intracranial calcifications and nutmeg-like cirrhotic changes of the liver. These brothers demonstrated that skeletal changes and bony fragility may predate anemia or steroid therapy. Although a DNA repair defect is postulated as a possible primary defect, cytogenetic studies revealed no evidence of increased chromosomal breakage.
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PMID:Dyskeratosis congenita: two examples of this multisystem disorder. 660 Dec 57

X-linked lymphoproliferative disease (XLP) is a rare worldwide occurring inherited immunodeficiency which is triggered by Epstein-Barr virus infection. Clinical phenotypes in 21 affected males from 5 German families with XLP ranged from severe and fatal infectious mononucleosis (57%) to acquired hypogammaglobulinaemia (28%), malignant lymphoma (28%), aplastic anaemia (19%) and hypergammaglobulinaemia M (19%). Molecular genetic studies with various polymorphic X-chromosomal DNA markers in 14 XLP families mapped the XLP gene locus to Xq25-q26. Haplotype analysis enables detection of XLP-positive and XLP-negative males already before EBV-infection as well as diagnosis of healthy female carriers within XLP families.
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PMID:[X-chromosome recessive lymphoproliferative disease (XLP): molecular genetic studies]. 750 Jun 2

To evaluate quality of hematologic recovery in aplastic anemia (AA) patients treated with cyclosporine A (CyA), we examined polymorphonuclear leukocytes (PMNCL) from 25 AA patients for clonality and glycosyl-phosphatidylinositol (GPI)-anchored membrane protein expression. Using three different X-linked gene probes, we failed to detect clonal hematopoiesis in seven CyA-responsive female patients. Clonal hematopoiesis was detected in two of six female patients refractory to CyA therapy, although one of these two patients had shown monoclonality before therapy. Flow-cytometric analysis revealed a normal expression of GPI-linked membrane proteins, including CD55, CD59, and CD16 on PMN in all patients treated with CyA, irrespective of response, except for one patient who had a small proportion of GPI-anchored membrane protein-negative cells before therapy. The proportion remained unchanged 41 months after hematologic recovery following CyA therapy. These findings suggest that successful therapy of AA with CyA may not be associated with a significant risk of developing late clonal complications, such as paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplasia.
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PMID:Quality of hematologic recovery in patients with aplastic anemia following cyclosporine therapy. 753 14

We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.
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PMID:Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. 757 86

Clonality analysis, by means of polymorphisms of X-linked genes and their methylation patterns, was performed in 41 female patients with various types of refractory anemia. Bone marrow cells, peripheral blood cells, and granulocytic and lymphocytic fractions were analysed by Southern blotting with PGK, HPRT, and M27 beta probes. Clonal hematopoiesis was evidenced in 8 of 19 patients with aplastic anemia, 4 of 6 patients with RA or RARS, 3 of 7 patients with PNH, and 5 of 9 patients whose hematological characteristics did not meet the criteria of either of these entities. For aplastic anemia, clonal hematopoiesis was demonstrated in higher frequency in the patients who had longer history after diagnosis. In refractory anemia, as a whole, no clear correlation was observed between existence of clonal hematopoiesis and morphological characteristics of hematological cells.
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PMID:[Clonality in refractory anemia]. 809 42


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