Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil-associated IgG (NAIgG) and neutrophil-binding IgG in sara (NBIgG) of 77 patients with neutropenia suspected to be caused by autoimmune mechanisms (group A) and 31 patients with aplastic anemia or myelodysplastic syndrome (group B) were assayed by flow cytometry. Auto-NBIgG was elevated in 32% of the patients in group A, particularly in about 70% of those with collagen diseases or ITP, but the level was normal in group B. Elevated NAIgG with normal auto-NBIgG levels was found in 27% of the patients in group A and in 64% of the patients in group B. The assay of auto-NBIgG was useful for detection of anti-neutrophil autoantibodies and for the diagnosis of autoimmune neutropenia. In addition, the level of NAIgG may be non-specifically elevated in non-immune neutropenia.
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PMID:[Neutrophil-associated IgG and neutrophil-binding IgG in autoimmune neutropenia]. 258 44

Although immune mechanisms are known to be partially responsible for the thrombocytopenia of patients infected with HIV-1, an understanding of the mechanism underlying this disorder is incomplete. A casual observation that bone marrow biopsies of HIV-infected individuals seem to exhibit an unusually large number of denuded megakaryocyte nuclei (DN-MK) prompted a study comparing MK of 20 HIV-seropositive individuals with those of 10 patients with HIV-negative idiopathic thrombocytopenic purpura and 10 hematologically normal subjects. In normal marrows the number of DN-MK average 2.1 +/- 0.5 SE per 10 low power field. In patients with ITP the average number was 6.5 +/- 1.4 SEM, whereas HIV-ITP marrows had an average of 42.5 +/- 3.7 SEM. Electron microscopy of AIDS megakaryocytes exhibited ballooning of the peripheral zone to an extent not seen by us in any other myelodysplastic syndromes. These observations support the concept that the pathophysiology affecting MK/platelets in HIV-infection should not be equated with the destructive process underlying other immune thrombocytopenias.
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PMID:Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1). 275 19

3 patients with preleukaemia (idiopathic acquired myelodysplasia) presenting with isolated peripheral thrombocytopenia and an increased number of megakaryocytes are described. The diagnosis of preleukaemia, however, was strongly suspected on bone marrow morphology, revealing an abnormal megakaryocytic series. Megakaryoblasts with characteristic nuclei and basophilic pseudopodes, and immature megakaryocytes were frequent. These last cells had 1 or 2 nuclei and a basophilic poorly granulated cytoplasm, often containing large vacuoles, corresponding to dilated interconnecting demarcation membranes in electron microscopy. Megakaryocytes were not considered able to produce a normal amount of platelets, explaining the peripheral thrombocytopenia; platelet survival (51Cr) was indeed too long for ITP. Cytogenetic analysis confirmed the diagnosis of an abnormal haematopoietic clone. Ferrokinetics, in vitro agar cultures, bone marrow biopsy and platelet function tests were helpful additional examinations for establishing the correct diagnosis. It is important to differentiate preleukaemia from ITP. Prognosis is totally different and the treatment is not only ineffective in the great majority of the preleukaemic patients, but may be hazardous.
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PMID:Thrombocytopenia as presenting symptom of preleukaemia in 3 patients. 720 Nov 57

In order to distinguish various types of MDS, such as RA/AA, RA/ITP or RA/HA, from AA, ITP or HA, bone marrow (BM) cells were studied by using cytogenetic techniques including R-banding karyotypic analysis and sister chromatid differentiation (SCD) assay in 334 cases of hematological diseases (160 MDS, 54 RA/AA, RA/ITP or RA/HA; 60 AA, 3 other known anemias, 38 PNH and 19 ITP). The results showed: (1) karyotypes and SCD values were both normal in more than 90% of AA, PNH, ITP and other known anemias, but they were both abnormal in about 35.6% of MDS and only 13.0% of RA/AA, RA/ITP or RA/HA. These results indicated that cytogenetic techniques were useful in hematological clinic and that RA/AA, or RA/ITP or RA/HA might be pre-RA or atypic RA. This was supported by the results of following up on some RA/AA, RA/ITP or RA/HA cases, (2) clonal abnormal karyotypes were found in 64.4% of MDS. The recurrent chromosomal alterations were +8, 20q-, -5/5q-, -7/7q-, similar to those reported in literatures. (3) 16 MDS cases were followed up and 15 MDS with SCD negative, but one with SCD positive developed leukemia in our hospital. It is suggested that change from SCD positive to negative was indicative of malignant transformation of BM cells. This was supported by the results of cytogenetic analysis in RA/AA, RA/ITP, RA, RAEB, RAEBT and leukemias. (4) Because more structural chromosome alterations occur in SCD negative than SCD positive MDS, the numerous chromosome alterations (monosomy) might occur in earliest development of MDS into leukemias.
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PMID:[Cytogenetic studies on 334 myelodysplastic syndrome (MDS), aplastic anemia (AA) and other hematological diseases]. 760 Aug 65

To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand) measurements, and clarify the regulatory mechanisms of TPO in normal and in thrombocytopenic conditions, the plasma TPO concentration was determined in normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3), chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome (MDS; n = 11), and sequentially during peripheral blood progenitor cell transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples were used for the analysis. The plasma TPO concentration in the normals and umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The corresponding values in patients with SAA and chemotherapy-induced bone marrow hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the TPO concentration, measured sequentially after myeloablative chemotherapy and peripheral blood progenitor cell transplantation, was inversely related to the platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/- 20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels. In conclusion, TPO levels were significantly elevated in patients in which bone marrow megakaryocytes and platelets in circulation were markedly reduced, whereas TPO levels were normal in ITP patients, and only slightly increased in the MDS patients. These latter patients displayed a preserved number of megakaryocytes in bone marrow biopsies. Our data support the suggestion that megakaryocyte mass affects the plasma TPO concentration. In thrombocytopenic patients a substantially increased plasma TPO implies deficient megakaryocyte numbers. However, TPO measurements do not distinguish between ITP and thrombocytopenia due to dysmegakaryopoiesis, as seen in MDS patients.
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PMID:Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes. 963 81

The expansion of myeloma cells is regulated by cytokines, among which IL-6 is a major growth factor. It has been recently suggested that serum transforming growth factor beta 1 (TGF beta 1), a cytokine found in large amounts in alpha-granules of platelets, might play a role in multiple myeloma (MM). It was the purpose of this study to determine serum TGF beta 1 levels in MM patients and to seek a correlation with disease parameters. Measurements were done by ELISA. We studied 35 MM patients (19 stage II, 16 stage III, 20 IgG, 8 IgA and 6 BJ, 1 IgD) in different phases of the disease, 27 healthy individuals and 17 thrombocytopenic patients with other haematological diseases (three MDS, three congenital thrombocytopenia, 11 ITP). Overall samples from MM patients were included: 10 at diagnosis, 18 in remission and 32 in relapse. In normal controls TGF beta 1 serum levels ranged from 1 to 33 ng/ml (median 16.5 ng/ml). In both thrombocytopenic controls with other diseases and thrombocytopenic MM patients (seven samples), TGF beta 1 serum levels were very low (median 3.2 and 4.5 ng/ml respectively). In MM patients with PLT > 100 x 10(9)/L (53 samples), TGF beta 1 serum levels were in the normal range in patients without immunoparesis (1 to 27 ng/ml, median 16.6 ng/ml), whereas they were higher in patients with immunoparesis (polyclonal immunoglobulins (Igs) below lower normal reference values) ranging from 10.2 to 45 ng/ml (median 26.8 ng/ml) (P < 0.01). Serum TGF beta 1 levels fluctuated in the same patient at different times but not according to relapse or remission. Correlation was found only between serum TGF beta 1 levels and immunoparesis and not between serum TGF beta 1 levels and disease stage or Ig subtype nor with prognostic factors for MM (serum CRP, beta 2M or IL-6). This finding suggests that the remaining normal plasma cells are sensitive to the inhibitory action of TGF beta 1 on Ig production. In conclusion TGF beta 1 serum levels are very low in thrombocytopenic patients confirming that platelets are the major source of this cytokine. Furthermore, a strong correlation was found between TGF beta 1 serum levels and immunoparesis in MM patients.
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PMID:Serum transforming growth factor-beta 1 is related to the degree of immunoparesis in patients with multiple myeloma. 978 21

By using R-banding karyotypic analysis technique, the bone marrow (BM) cells were performed in 223 hematopoietic malignacies and 105 diopathic throbocytopenic purpura (ITP), which served as control. The following results were obtained: (1) Nonrandom chromosome loss (NCL), such as, -11, -14, -21, etc, which were found in the affected members of leukemia families, were found in about 30% sporadic ANLL, MDS and about 50% ALL, espedislly in 100% (5/5) CLL, but not found in ITP (P < 0.001). These results indicated that the familial nonrandom chromosome loss were associated with leukomogenesis. (2) Because most of BM cells are hypodiploed and have the same kinds of NCL in each cases of CLL, which can develop into ALL, ANLL and also cancers, ALL BM hypo- and hyper-diploid and/or polyploid cells might be origin of hypodiploid cells. (3) 28% (6/21) of pediatric patients with AL, MDS, or FA (Fanconi Anemia) have one parent, who have up to 30% BM hypodiploid cells and similar kinds of NCL and also have the rearrangement of C-erbB and abnormal proliferation of BM. The NCL were found in the three consecutive generations of a family with 5 ALL among 10 members of third generation. It indicated that the familial NCL might be inherited and be coded by a unknown gene alteration, which might be related to leukomo and carcinogenesis, because there are genes or their candidates for leukemia in the chromosomes 11, 14 and 21. (4) Based on the works of my colleages and I, the model of leukomo and carcinogenesis was proposed and the relationship between chromosome monosomy, deletion, translocations and leukomogenesis were showed elswhere. The significance of monosomy 11, 14 and 21 etc. were discussed briefly.
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PMID:[Relationship between the familial nonrandom chromosome loss (NCL) and leukomogenesis]. 1037 57

Impaired platelet production may result from four mechanisms: 1) marrow hypoplasia, 2) ineffective thrombopoiesis, 3) aberration of thrombopoietic regulation and 4) hereditary thrombocytopenia. Megakaryocytic hypoplasia(reduced numbers of megakaryocytes) is seen in a wide variety of disorders including aplastic anemia, radiation, drugs such as chemotherapeutic agents, infiltrative neoplasms of the marrow, acquired amegakaryocytic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria(PNH), and Fanconi's anemia. Ineffective thrombopoiesis(normal to increased numbers of megakaryocytes) is recognized in megaloblastic anemia and myelodysplastic syndrome. Disorders of thrombopoietic control are uncommon and seen in cyclic thrombocytopenia and thrombocytopenia with absent radii. Hereditary thrombocytopenia is overall a very rare disorder, and may be inherited as an X-linked recessive trait, an autosomal dominant trait, or autosomal recessive trait. It is important to recognize hereditary thrombocytopenia because clinically they resemble ITP, but the patients do not respond to steroid treatment or splenectomy.
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PMID:[Thrombocytopenia due to deficient platelet production]. 1271 78

The aim of this study was to find platelet specific autoantibodies against glycoproteins in myelodysplastic syndrome (MDS) and to explore its role in pathogenesis of MDS. The plasma autoantibodies against GP IIb/IIIa and GP Ib/IX were measured by using a modified monoclonal antibody specific immobolization platelet antigens assay (MAIPA). Absorbance greater than mean value plus tripled standard deviation recorded from the normal controls were regarded as positive. The results indicated that the total positive rate in patients with MDS was 16.67% (5/30), the total positive rate in patients with ITP was 46.67% (14/30), the difference between MDS group and ITP group was significant (P < 0.05). It is concluded that partial patients with MDS have plasma specific autoantibodies against platelet GP II b/III a and GP Ib/IX, indicating correlation of thrombocytopenia of patients with immune factors and the autoantibody-mediated platelet destruction may be involved in the pathogenesis of MDS. It provides a new basis for immunosuppression therapy for MDS.
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PMID:[Expression of specific antibodies against platelet glycoproteins in patients with mds and its significance]. 1749 May 30

Initially, immune (idiopathic) thrombocytopenic purpura (ITP) was considered to be a disease of increased platelet destruction. Consequently, treatments for ITP patients were focused on reducing the destruction of platelets. However, recent research on the pathogenesis of ITP points to a role of suboptimal platelet production, and this has led to the development of new treatment options which increase platelet production such as the novel thrombopoiesis-stimulating agent, romiplostim. In two, multicentre, randomized, placebo-controlled, double-blinded, phase III trials, romiplostim was able to increase and sustain platelet counts in both splenectomized and non-splenectomized patients. Eighty-three per cent (69/83) of the romiplostim-treated patients achieved an overall platelet response compared with 7% (3/42) of patients receiving placebo (P < 0.0001; Cochran-Mantel-Haenszel test controlled for splenectomy and baseline concurrent ITP therapy). Patients from the romiplostim studies, with platelet counts below 50 x 10(9)/L, were able to enter a long-term, open-label, extension study. The results of the long-term study showed that platelet counts above 50 x 10(9)/L were maintained for > or =10, > or =25 and > or =52 consecutive weeks by 78% (102/131), 54% (66/122) and 35% (29/84) of patients, respectively. Romiplostim appears to be generally well tolerated and several patients have now been treated for more than 3 yrs. Most adverse events tend to be mild to moderate in nature. Romiplostim provides a valid treatment option that may bring about a change in the way that patients with ITP are treated in the future. Further studies are now being undertaken in paediatric patients with ITP, patients with myelodysplastic syndrome and patients with chemotherapy-induced thrombocytopenia.
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PMID:Romiplostim: a breakthrough treatment for the management of immune thrombocytopenic purpura. 1920 Mar 4


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