Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using monoclonal antibodies against proliferating cell nuclear antigen or PCNA (PC10) and the Ki-67 antigen (MIB1), an immunohistochemical and morphometric study was performed on routinely processed splenic tissue from ten patients with primary (idiopathic) osteomyelofibrosis (OMF). To determine the proliferation capacity of erythroid precursors and the endoreduplicative activity of megakaryocytes, corresponding antibodies (Ret40f and CD61) were applied in combination with the cell-cycle markers (sequential double-immunostaining). Morphometric analysis revealed no significant differences in PCNA or Ki-67 reactivity in either cell lineages. In comparison with previous studies on normal bone marrow, in splenic tissue showing myeloid metaplasia, the numbers of PCNA-labelled proerythroblasts, erythroblasts and megakaryocytes were conspicuously increased. Considering the ineffective erythropoiesis in OMF, there seemed to be a disproportional enhancement in PCNA and Ki-67 immunostaining of the red cell lineage. Similarly, the small size of megakaryocytes in advanced, OMF-associated myeloid metaplasia was in keeping with an impairment of endoreduplicative activity. In addition to various other contributory factors, anaemia in OMF may be partially caused by secondary folate (haematinic) deficiency. From experimental studies this defect is known to cause an abnormal arrest in the S-phase of the cell-cycle, comparable to that characterising pernicious anaemia. As a sequel of this pathomechanism, an undue overexpression of PCNA and Ki-67 has to be assumed, that is not necessarily associated with DNA synthesis or cell cycling.
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PMID:Splenic haematopoiesis in primary (idiopathic) osteomyelofibrosis: immunohistochemical and morphometric evaluation of proliferative activity of erytro- and endoreduplicative capacity of megakaryopoiesis (PCNA- and Ki-67 staining). 790 16

A 20-year-old woman from a consanguineous family in the Hunan Province of the People's Republic of China was diagnosed as having Glanzmann's thrombasthenia based on (1) nearly a lifelong history of epistaxis, gum bleeding, petechiae, and purpura; (2) severe menorrhagia resulting in anemia and need for whole-blood transfusion; (3) normal coagulation assays; (4) prolonged bleeding time; (5) absent clot retraction; (6) decreased glass bead retention; (7) absent platelet aggregation in response to adenine diphosphate, epinephrine, and collagen; and (8) normal initial slope of platelet aggregation in response to ristocetin, but with a diminished maximal extent. The patient's platelets had a decreased level of platelet fibrinogen, but the deficiency was not as severe as in other Glanzmann's thrombasthenia patients. As judged by monoclonal antibody binding studies, surface glycoprotein (GP) IIb/IIIa (alpha IIb beta 3) expression was less than 15% of normal and alpha v beta 3 vitronectin receptor expression was 15% to 19% of normal, suggesting that the defect was in GPIIIa (beta 3). Immunoblotting of platelet lysates demonstrated decreased levels of GPIIb (approximately 30% to 35% of normal) and GPIIIa (approximately 10% of normal), and the GPIIb had undergone normal maturational processing into GPIIb heavy and light chains. Sequence analysis of the patient's GPIIIa RNA identified a G to A mutation at nucleotide 1219, predicting a Cys to Tyr substitution at residue 374. The patient's parents, who are first cousins, are asymptomatic and have only minor reductions in platelet aggregation. Direct sequencing of polymerase chain reaction-amplified cDNA and GPIIIa exon VIII indicated that the patient is homozygous and her parents are heterozygous for the mutation. Transient transfection studies in Chinese hamster ovary cells indicated that the mutation results in an 85% to 90% reduction in GPIIb/IIIa surface expression, but these cells retain the ability to mediate adhesion to immobilized fibrinogen. The relative preservation of platelet fibrinogen despite the very low level of platelet surface GPIIb/IIIa expression in this patient raises some interesting questions regarding the mechanism of fibrinogen uptake and the pathophysiology of Glanzmann's thrombasthenia.
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PMID:A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia. 878 22

In this report an attempt has been made to discuss some of the issues pertinent to myelofibrosis complicating chronic myeloproliferative disorders (CMPDs) that are significantly associated with megakaryocyte function. In this context, biochemical, clinical and particularly morphological features were reviewed. Morphological findings based on elaborate techniques were in keeping with the assumption that in chronic myeloid leukemia (1) the number of CD61-positive megakaryocytes, and in particular their precursors were the parameters most closely associated with myelofibrosis (2) an increased content of reticulin fibers in follow-up biopsies significantly correlated with laboratory data indicative of a high tumor burden (anemia, peripheral blasts, hepatosplenomegaly) and thus a more advanced stage of the disease process (3) even a slight increase in reticulin, i.e. doubling of the normal fiber density was associated with a worse prognosis independent of therapeutic regimens given (4) Dynamics of myelofibrosis was significantly influenced by treatment. In this context, calculation of the myelofibrosis progression index (MPI) revealed a higher score following interferon therapy compared with busulfan. In addition, in idiopathic myelofibrosis (5) the evolution of myelofibrosis was unpredictable and according to the MPI, progression occurred at a relatively low rate (6) proliferation and dilatation of sinusoids accompanying intravascular hematopoiesis and collagen type IV deposits were predominant features in later (fibro-osteosclerotic) stages in the course of disease (7) transmural migration of megakaryocytes demonstrated by three dimensional reconstruction revealed a mole-like tunneling through the thickened sinusoidal wall. A very careful assessment of the numerous correlations between bone marrow features and laboratory data will allow clinicians and pathologists to gain a better insight into the mutual relationships between hematological and morphological findings in CMPDs.
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PMID:Clinicopathological impact of the interaction between megakaryocytes and myeloid stroma in chronic myeloproliferative disorders: a concise update. 908 37

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.
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PMID:Bone marrow features and clinical findings in chronic myeloid leukemia--a comparative, multicenter, immunohistological and morphometric study on 614 patients. 1067 1

Cytologic, immunologic, and cytogenetic studies were performed on the blast cells of a newborn with Down syndrome and transient myeloproliferative disease. This hematologic disorder is uncommon, and occurs primarily in infants with Down syndrome. This boy presented with a high white blood cell count and a high percentage of blast cells, without anemia or thrombocytopenia. Chromosome analysis showed a constitutional trisomy 21 without any other clonal abnormality. A three-color flow cytometric analysis was performed and revealed two different CD45 dim, CD34(+), CD117(+), CD56(+) immature subpopulations: the normal immature myeloid precursor and an immature blast cell population that expressed CD41, CD42, CD61, CD36, CD13, CD1a, and CD2. We postulate that this population could be the leukemic precursor involved in the acute megakaryoblastic leukemia frequently observed in children with Down syndrome.
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PMID:Immunophenotype of a transient myeloproliferative disorder in a newborn with trisomy 21. 1079 50

A new mutation is described in the X-linked gene GATA1, resulting in macrothrombocytopenia and mild dyserythropoietic features but no marked anemia in a 4-generation family. The molecular basis for the observed phenotype is a substitution of glycine for aspartate in the strictly conserved codon 218 (D218G) of the amino-terminal zinc finger loop of the transcription factor GATA1. Zinc finger interaction studies demonstrated that this mutation results in a weak loss of affinity of GATA1 for its essential cofactor FOG1, whereas direct D218G-GATA1 binding to DNA was normal. The phenotypic effects of this mutation in the patients' platelets have been studied. Semiquantitative RNA analysis, normalized for beta-actin messenger RNA, showed extremely low transcription of the GATA1 target genes GPIbbeta and GPIX but also a significantly lower expression of the nondirectly GATA1-regulated Gsalpha gene, suggestive of incomplete megakaryocyte maturation. In contrast, GPIIIa expression was close to normal in agreement with its early appearance during megakaryocyte differentiation. Flow cytometric analysis of patient platelets confirmed the existence of a platelet population with abnormal size distribution and reduced GPIb complex levels but with normal GPIIIa expression. It also showed the presence of very immature platelets lacking almost all membrane glycoproteins studied (GPIbalpha, GPIbbeta, GPIIIa, GPIX, and GPV). Patients' platelets showed weak ristocetin-induced agglutination, compatible with the disturbed GPIb complex. Accordingly, electron microscopy of the patients' platelets revealed giant platelets with cytoplasmic clusters consisting of smooth endoplasmic reticulum and abnormal membrane complexes. In conclusion, GATA1 mutations can lead to isolated X-linked macrothrombocytopenia without anemia.
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PMID:Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. 1141 66

The aim of this study was to investigate the clinical, pathological and biological features of acute megakaryoblastic leukemia in childhood. The morphology of cells was observed by means of bone marrow smear; the immunophenotype was detected by flow cytometry and immunohistochemistry assay. The results indicated that the fever, hemorrhage, hepatosplenomegaly and lymphadenopathy in this case were the primary presentations accompanying by leukocytosis, anemia and thrombocytopenia. An adequate marrow aspirate could not be obtained. At the time of diagnosis, the bone marrow had more than 30% megakaryoblasts in nucleated cells. Flow cytometric analysis revealed the dual expression of CD41 and CD61 by tumor cells in bone marrow. The histopathological examination of bone marrow demonstrated infiltration of large-sized CD42b(+) cells. According to all above mentioned results, this case was diagnosed as acute megakaryoblastic leukemia. In conclusion, childhood acute megakaryoblastic leukemia is a rare and easily misdiagnosed disease with poor prognosis. Flow cytometry analysis and immunohistochemistry assay of bone marrow can help in detecting this leukemia subtype and evaluating its prognosis.
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PMID:[Childhood acute megakaryoblastic leukemia]. 1760 59

As opposed to erythropoiesis, which is regularly assessed in the peripheral blood of animals by reticulocyte count, thrombopoiesis is rarely assessed in assays that detect immature platelets in the peripheral blood. An assessment of recent thrombopoiesis is feasible with the analysis of reticulated platelets in the peripheral blood via flow cytometry, but rarely performed. The aim of this study was to establish an assay for the detection of reticulated platelets in whole blood of rats via flow cytometry, using a two-color staining method with a platelet-specific antibody (CD61-PE) and thiazole orange to detect RNA-containing platelets. Platelets were detected in K3EDTA-anticoagulated, paraformaldehyde-fixed samples, using a CD61-PE antibody as well as a gate specific for the light scatter properties of platelets. The intra-assay coefficient of variation varied between 3.6% and 8.3% (n=6 animals). The stability of the assay was determined by storing blood prior to staining, storing stained samples for up to 2h at room temperature, and by diluting the blood prior to analysis with autologous plasma to create samples with artificial anemia and thrombocytopenia. Only samples stored at room temperature prior to analysis showed a significantly lower percentage of reticulated platelets. Percentage of reticulated platelets in the reference population (n=41 rats) was 10.0+/-1.3% reticulated platelets (mean+/-SD; min=6.2%; max=12.5%). These data show that the detection of reticulated platelets in whole blood of rats using a platelet-specific antibody is feasible. This test presents a minimal-invasive method to assess thrombopoiesis in rats that can be used for example in preclinical toxicological studies.
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PMID:Detection of reticulated platelets in whole blood of rats using flow cytometry. 1860 17

A 5-year-old male cynomolgus monkey (Macaca fascicularis) with a clinical history of bleeding tendency, severe anaemia, thrombocytopenia and elevated serum concentration of liver-related enzymes was examined post mortem. Ecchymotic haemorrhages were present on the left eyelid and forehead. The liver, kidney and spleen were markedly enlarged and the kidneys had capsular petechiae. Microscopically, numerous atypical cells resembling myeloid cells were observed in the bone marrow, and myelofibrosis was present. Atypical cells were also present in the blood vessels of the liver, kidney, spleen, lymph nodes, lung, heart, bladder, adrenal gland and brain. Some neoplastic cells had oval or pleomorphic macronuclei and others were multinucleated. Immunohistochemically, the majority of the neoplastic cells had granular cytoplasmic expression of the megakaryocyte-associated antigens Von Willebrand Factor and CD61-IIIa, but were negative for myeloperoxidase. A diagnosis of acute megakaryocytic leukaemia (AMKL)-like disease was made. This would appear to be the first report of AMKL-like disease in non-human primates. This monkey was infected with simian retrovirus type D and it is possible that this viral infection was associated with the development of neoplasia.
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PMID:Acute megakaryocytic leukaemia (AMKL)-like disease in a cynomolgus monkey (Macaca fascicularis). 1915 98

Natural killer (NK) cell neoplasms are a group of rare but highly malignant tumors. We report here one case of NK cell leukemia. A 54-yr-old woman presented with a 2-month history of progressive left neck mass. Based on the positive result of tissue PCR for Mycobacterium tuberculosis, she was at first diagnosed with tuberculous lymphadenopathy. After two weeks, she developed generalized lymphadenopathy, hepatosplenomegaly, fever and anemia. Subsequent evaluation was performed including bone marrow aspiration and biopsy. Peripheral blood smear showed leukoerythroblastic features with 31% blasts. Bone marrow was packed with agranular blastoid cells, which were periodic acid-Schiff (PAS) positive and myeloperoxidase (MPO) negative. Immunophenotyping showed that these cells were positive for CD45 and HLA-DR, whereas negative for CD3, CD5, CD7, CD10, CD13, CD14, CD19, CD20, CD22, CD33, CD34, and CD61. Because of the absence of the markers of T-cell, B-cell, and myeloid lineage-specific antigens, we added CD16/56 for the immunophenotyping and the blasts were positive (94%). The tumor cells of biopsied lymph node were only positive for CD56, consistent with NK cell lymphoma. Epstein-Barr virus (EBV) was not detected by RNA in situ hybridization. Culture for M. tuberculosis was negative. Thus this patient was diagnosed with blastic NK cell lymphoma/leukemia involving bone marrow and lymph node.
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PMID:A case of natural killer cell leukemia misdiagnosed as tuberculous lymphadenopathy. 1957 15


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