Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.
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PMID:Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice. 865 13

A 62-year-old man with a history of hereditary spherocytosis had an abnormal shadow on a chest X-ray film, but the shadow was not examined further. The patient was admitted to our hospital because of severe anemia, multiple gallstones, and splenomegaly. Acute cholecystitis developed due to gallstones. A smear of peripheral blood showed spherocytosis, and the osmotic fragility as measured by Parpart's method was abnormally high. These findings are consistent with hereditary spherocytosis. Splenectomy and cholecystectomy were done. The chest X-ray film, CT scan, and MRI revealed multiple well-demarcatd paravertebral masses. A biopsy of a mediastinal mass was done with an ultrasonically guided needle, and hyperplasic erythroid hemopoietic tissue was obtained. This finding led to the diagnosis of extramedullary hematopoeisis. We think extramedullary hematopoeisis should be included in the differential diagnosis of posterior mediastinal masses.
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PMID:[Intrathoracic extramedullary hematopoiesis in a case of hereditary spherocytosis]. 871 95

The case of an 11 year old girl with three line type of polycythaemia vera, with 4 cm splenomegaly and a plethoric complexion is presented. Peripheral blood values were as follows: RBC: 7.75 x 10(12)/l, Hb: 18.8 g/l, WBC: 15.2 x 10(9)/l, platelets: 920 x 10(9)/l. Serum erythropoietin level: < 1 mU/ml. In vitro, erythroid colonies developed from the bone marrow in the absence of added erythropoetin. For three years the haematocrit value has been controlled by regular venesections. Since extreme thrombocytosis developed, the treatment was continued with interferon alpha. Different treatment protocols are discussed.
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PMID:[Polycytemia vera in an 11-year old girl]. 872 60

A 20-year-old Japanese woman was admitted to our hospital with anemia and mild splenomegaly. Peripheral blood examination revealed Hb 9.4 g/dl, Ht 29.3%, RBC 4.74 x 10(6)/microliters, reticulocytes 2.4%, WBC 5,200/microliters, platelets 24.9 x 10(4)/microliters, MCV 61.7 fl, and MCH 19.9 pg. Poikilocytosis with target cells was recognized on the peripheral blood smear. A bone marrow aspirate revealed erythroid hyperplasia. Serum iron and ferritin were in the normal range. beta-thalassemia was suggested by the increase in HbA2 (6.5%) and HbF (7.5%). Analysis of beta globin DNA by single strand conformation polymorphism (SSCP) and amplification refractory mutation system (ARMS) confirmed a diagnosis of homozygous beta(+)-thalassemia due to -31 A to G mutation. A familial study revealed that her parents were heterozygous for this allele. This is the 8th case of homozygous beta(+)-thalassemia due to -31 A to G mutation in Japan.
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PMID:[Homozygous beta(+)-thalassemia due to -31 A to G mutation]. 875 83

The splenomegaly and the appearance of a significant number of CFU-E (erythroid colony-forming units) and BFU-E1 (erythroid burst-forming units) in the Belgrade laboratory rat (b/b) spleen prompted us to analyse further the molecular evidence for increased hematopoietic proliferation in the b/b spleen. Messenger RNAs (mRNAs) specific for globins, proteins for iron transport and deposition and the band 3 protein were used in rat erythropoietic tissues as markers for proliferation and erythroid differentiation. In the b/b spleen, all mRNAs analysed display an erythroid-specific pattern of expression. This analysis also revealed an enhanced level of mRNA for ferritin in the +/b spleen, whereas erythrocyte-specific mRNA production was normal.
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PMID:Molecular evidence for increased hematopoietic proliferation in the spleen of the b/b laboratory rat. 877 53

Recent progress in the molecular analysis of red cell enzymopathies showed over 160 mutations in the 10 distinct genes which were essential in red cell metabolisms. In addition, since three-dimensional structure of several enzymes including pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) have been elucidated from X-ray crystallographic studies, the effect of amino acid substitutions on enzyme activity became predictable in some extent. On the contrary, the mechanism of hemolysis remains still unclear. To clarify the pathophysiology of red cell enzymopathies, establishment of an animal model have been long awaited. Recently we discovered the novel mice model of PK deficiency. The mutant mice with splenomegaly and nonspherocytic hemolytic anemia in an inbred colony of the CBA strain were enzymatically diagnosed as PK deficiency. A homozygous missense mutation was identified in the red cell (R)-type PKcDNA sequence of the mutant, and it caused a single amino acid substitution near the substrate binding site of PK. The erythroid-progenitor cell number increased in spleen of the mutant mice to a level approximately 66 times higher than in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice might partly compensate the anemia. The mutant mice will be useful as an experimental model for understanding the pathophysiology of this disorder.
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PMID:[Molecular basis and pathophysiology of red cell enzymopathies]. 889 May 66

The paper presents new findings in favor of recognition of splenic lymphocytoma (SLC). This disease was characterized by A. I. Vorob'ev and M. D. Brilliant in 1982 in terms of detailed clinicomorphological features, prognosis and optimal treatment policy. The study included 52 patients (mean age 53 years) of which 36 were females and 16 males. They were followed up for 5.7 years, on the average. SLC manifested clinically by splenomegaly with minimally enlarged lymph nodes, morphologically by nodular lymphocytic proliferates in the spleen, bone marrow and liver, diffuse or diffuse-nodular proliferation in the lymph node. Peripheral blood contained middle-size lymphoid cells with round nuclei. SLC immunophenotype exhibits moderate or marked expression of CD22 and membrane immunoglobulins, the absence of CD5, CD23 and EM receptor, combination of CR1-/ CR2+. Paraprotein secretion was recorded in 49% of cases. There were frequent autoimmune reactions, especially against erythroid cells and platelets (42%). Optimal therapeutic policy is expectation and eventual splenectomy producing a persistent clinical effect in 94% of patients. In progressive disease long-term therapy with cyclophosphamide is recommended. Thus, SLC is a mature-cell lymphatic tumor growing as a rule in the spleen. Its prognosis in valid therapy is favourable.
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PMID:[Lymphocytoma of the spleen--a separate nosological form requiring a specific management procedure]. 892 72

The prognostic importance of pretreatment clinical and laboratory features was investigated in a group of 243 patients with Philadelphia chromosome positive chronic phase chronic myeloid leukemia from 1977-1995. Chemotherapy consisted of busulfan before 1993 or hydroxyurea after 1993. The overall median survival from diagnosis was 28 months. The mean age of the patients was 38 years, about 10 years below that of Western populations. Univariate analysis identified 4 poor prognostic features: thrombocytopenia, more than 5% peripheral blasts, more than 5% erythroid precursors and less than 7 g/dl of hemoglobin. The median survival times of patients with these 4 risk factors were 5, 11, 11 and 12 months respectively. Multivariate analysis only identified 2 significant prognostic features: thrombocytopenia and more than 5% peripheral blasts. Splenomegaly of more than 10 cm, basophilia and leukocytosis were associated with a shorter median survival but was not statistically significant. A risk scoring system was developed and used to classify patients into low, intermediate and high risk groups at 30.9%, 30.2% and 38.8% respectively. The median survival time according to the low, intermediate and high risk group was observed at 60, 27 and 14 months respectively. Prognostic factors for Thai patients with chronic myeloid leukemia have both similarities and differences with previously observed factors but the median patient survival time is shorter.
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PMID:Multivariate analysis of prognostic factors in Philadelphia chromosome positive chronic myeloid leukemia: an update of the first series in Thailand. 898 Jul 97

The purpose of the present work was to evaluate the proliferative character of polycythaemia vera (PV). Therefore, in 15 patients with different stages of PV we assessed the level of CD34 positive (CD34+) cells in peripheral blood and bone marrow, erythroid colony growth of bone marrow cells and plasma erythropoietin (EPO). The mean concentration of CD34+ cells in blood was significantly increased in PV patients (9.0 +/- 11.2 x 10(3)/mL) compared to healthy controls (2.0 +/- 1.7 x 10(3)/mL). In aspirated bone marrow no such difference between PV and control subjects was present. Six patients with splenomegaly and/or requirement for chemotherapy had significantly higher mean blood levels of CD34+ cells compared to the remaining PV patients. All PV patients presented EPO independent erythroid colonies. Three PV patients with anaemia and long disease duration had high EPO levels.
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PMID:Increase of CD34 positive cells in polycythaemia vera. 931 Jan 25

We describe a dominantly inherited beta-thalassemia intermedia phenotype observed in a five-generation Portuguese family. Carriers are characterized by moderate anemia, hypochromia, microcytosis, elevated hemoglobin (Hb)A2 and HbF levels, splenomegaly, hepatomegaly, and inclusion bodies in peripheral red blood cells after splenectomy. The molecular basis of this condition is a small deletion within the 5' consensus splicing sequence of the second intron of the beta-globin gene, IVS-II-4,5 (-AG). Reticulocyte RNA studies performed by reverse transcription-polymerase chain reaction (RT-PCR) and primer extension analysis showed three abnormally processed transcripts, which, upon sequencing, were shown to correspond to (1) skipping of exon 2, and (2) activation of two cryptic splice sites (between codons 59/60, and at IVS-II-47). In vitro translation studies of these patients' reticulocyte RNA have shown that at least one of these aberrant mRNA species is translated into an abnormally elongated peptide whose cytotoxic properties could, in part, be causing the atypical dominant mode of inheritance observed in this family. We suggest that this elongated beta chain is unable to combine with an alpha-globin chain to form a functional Hb molecule. Its degradation would, then, exhaust the proteolytic defense mechanism of the erythroid precursors, leading to inefficient proteolysis of the free alpha chains in excess.
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PMID:Dominantly transmitted beta-thalassemia arising from the production of several aberrant mRNA species and one abnormal peptide. 942 26


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