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)

The Sysmex R-3000 (TOA Medical Electronics, Kobe, Japan) evaluates maturation of reticulocytes by quantitating the fraction of reticulocytes within low-, middle-, and high-fluorescence intensity regions. We defined the immature reticulocyte fraction (IRF) as the sum of the fraction of high-fluorescence intensity regions plus the fraction of middle-fluorescence intensity regions. Then, we studied the clinical significance of IRF in the evaluation of anemia by comparing the IRF with the absolute reticulocyte count (ARC) and with the reticulocyte production index (RPI) and by reviewing pertinent clinical information about the patients. In the study, 132 specimens from 102 patients undergoing evaluation of anemia were analyzed. By using simple regression analysis, our results showed that the IRF has a weak but significantly positive correlation with ARC and with RPI, indicating that IRF is an additional useful parameter to evaluate the erythropoietic activity in anemia. Interpretation by integrating IRF and reticulocyte enumeration (ARC and RPI) provided useful information for further subclassification of anemia. Increased IRF (IRF > or = 0.23) and increased ARC generally indicated an adequate erythroid response to anemia. All but three specimens with an IRF less than 0.23 showed an RPI of 2 or less. These specimens were from patients with underlying diseases known to lead to decreased erythropoietic activity, predominantly chronic renal insufficiency. Specimens with a subnormal or normal ARC (with a corresponding RPI < or = 2) but with an IRF of more than 0.23 were from patients with various underlying conditions, including acute infection, iron deficiency anemia, human immunodeficiency virus infection, sickle disease with crisis, pregnancy, and myelodysplastic syndrome. Our results indicate that an IRF of 0.23 or less in patients with anemia reflects bone marrow that is nonresponsive or underresponsive to the anemia. Patients with an increased IRF (IRF > or = 0.23) may require further examination to clarify the cause of the anemia.
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PMID:Clinical significance of immature reticulocyte fraction determined by automated reticulocyte counting. 920 80

The Mpl ligands are a family of closely related hematopoietic growth factors that bind to the thrombopoietin receptor, c-Mpl. In addition to the endogenous Mpl ligand, thrombopoietin, two recombinant Mpl ligands, recombinant thrombopoietin and pegylated megakaryocyte growth and development factor (PEG-MGDF) are under investigation. Endogenous thrombopoietin regulates most of the normal production of platelets but also is essential for the normal development of other lineages. When recombinant thrombopoietin or PEG-MGDF is administered to normal animals or humans, there is a dose-dependent increase in the platelet count but no effect on leukocytes or erythrocytes. When administered following chemotherapy in animal models or humans, Mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The Mpl ligands also may be effective in reducing the thrombocytopenia of patients with HIV infection, liver disease, myelodysplasia, or after plateletpheresis.
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PMID:In vivo effects of Mpl ligand administration and emerging clinical applications for the Mpl ligands. 920 31

Recombinant human erythropoietin has been available for clinical use since 1985. It was an immediate success in treating the anemia of chronic renal failure and has also enjoyed some objective success in the treatment of other anemias in either a therapeutic or prophylactic setting, but the issues of appropriate patient selection and cost-benefit ratios are still unresolved. This review discusses the most recent literature concerning the use of recombinant human erythropoietin for the anemia associated with cancer, HIV infection, myelodysplasia, prematurity, autologous blood transfusion, bone marrow transplantation, and chronic renal failure.
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PMID:Clinical use of erythropoietin. 937 81

The purpose of this review is to give an update of the recent progress in research on erythropoietin (Epo), the hormone that regulates red blood cell production. Epo is a glycoprotein with a molecular mass of approx 30 kDa, which circulates in plasma of the human with 165 amino acids with three N-linked and one O-linked acidic oligosaccharide side chains in the molecule. Both the alpha (39% CHO) and beta (24% CHO) forms are available for clinical use, and there does not appear to be any difference in the pharmacokinetics of these two forms of Epo. Radioimmunoassays and enzyme-linked immunoabsorbant (ELISA) assays are available in a kit form. Serum levels of Epo in normal human subjects range between 1 and 27 mmu/ml or approx 5 pmol/l. It seems clear that the cells in the adult mammalian kidney which produce Epo are the interstitial cells in the peritubular capillary bed and the perivenous hepatocytes in the liver. Expression of the human Epo gene sequences that direct expression in the kidney are located 6-14 kilobases 5' to the gene; whereas the sequences that control hepatocyte-specific expression are located within 0.7 KS to the 3'-flanking region and 0.5 KS to the 5'-flanking region. The signal transduction pathways postulated to be involved in the expression of Epo are: kinases A, G and C; both a constitutive factor and a second hypoxia-inducible factor-1 (HIF-1) located in the 5' end of an hypoxia inducible enhancer region of the Epo gene; and reactive oxygen species. The primary target cell in the bone marrow acted on by Epo is the colony-forming unit erythroid (CFU-E) which has the highest number of Epo receptors. It has been postulated that Epo decreases the rate which Epo-dependent progenitor cells undergo programed cell death (apoptosis). There are two major signal transduction pathways activated by the Epo receptor: the JAK2-STAT5 pathway and the ras pathway. Both pathways involve tyrosine phosphorylation. The approved clinical uses of Epo are the anemias associated with end-stage renal disease, cancer chemotherapeutic agents, and patients with HIV infection receiving AZT. Other anemias reported to respond to Epo therapy are anemia of prematurity, rheumatoid arthritis, and myelodysplasia. Other uses of Epo under investigation are in perioperative surgery and preoperative autologous blood donation.
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PMID:Erythropoietin: physiologic and pharmacologic aspects. 940 40

Experiments were done to test cell lines for their capacity to express human immunodeficiency virus type 1 (HIV-1) proteins in a stable manner. Marked differences were seen in the ability to stably express and export viral Gag and Pol proteins. Two cell lines, one suspension (MDS) and one monolayer (SW480), were established which exported these proteins at high level. Two other cell lines, HeLa and THP-1, showed poorer expression and very limited particle release. Single cell cloning was used to select the optimal producing clones from the lines. These produced large quantities of viral core particles pelletable from the supernatants. Cell lines were constructed from these clones which stably expressed in addition either the HIV-1 Envelope or a packageable HIV-based vector. The vector was shown to be packaged within the viral core particles. Transient transfection of envelope expressing constructs into a gag-pol plus vector cell line, or the vector into a gag-pol plus envelope expressing cell line resulted in gene transfer to CD4+ target cells. These cell lines provide useful tools with which to study the assembly and export of viral proteins and RNA, for assay of alternative envelope proteins to pseudotype HIV cores, for assessment of antiviral drugs and as a source of correctly processed proteins for immunological studies.
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PMID:Development of cell lines stably expressing human immunodeficiency virus type 1 proteins for studies in encapsidation and gene transfer. 947 7

This review attempts to put together the changes in the blood and bone marrow observed in those who are infected with human immunodeficiency virus (HIV). These are contribution of many published and unpublished data and experience on; blood counts, blood film and bone marrow films prepared and stained by MayGrunwald-Giemsa or Leishman stain. Some changes in haemostasis are also included. The salient changes are cytopaenias; leucopaenia, anaemia, thrombocytopaenia, and bone marrow hypoplasia, although the latter occurs, it is found in a minority of cases. Other changes include myelodysplasia, functionally defective cells, and enhanced bleeding tendency particularly in those with bleeding defects. There are also malignancies associated with HIV infection such as Kaposi's Sarcoma and malignant lymphomas. The pathogenesis of these events are multi-factorial, varied and involve; killing of cells by the virus, syncytial formation by the cells, destruction of the stem cells, immune and drugs effects. These mechanisms are modified by factors of viral, host environment and their interactions. Changes are commonly found in patients with acquired immunodeficiency syndrome (AIDS) but can be seen in some cases anytime during the course of the disease. Once developed the changes are progressive. The management of these complications remain individualised and symptomatic. Treatment trials with the haematopoesis growth factors, particularly colony stimulating factors are producing some encouraging results. However other cytokines, for example, interleukin-6 may be having untoward effect such as association with the causation of Kaposi's sarcoma and the malignant non-Hodgkin's lymphomas. While standard approaches to the management of the malignancies tend to be the practice, adjustments are usually necessary in most patients.
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PMID:Haematological changes in human immunodeficiency virus infection. Part I: Review article. 955 49

This second part of the review looks at change seen in the bone marrow haemostasis and malignancies found in HIV infection. Examination of bone marrow is requested in the presence of cytopaenias, splenomegaly, lymphomas and myelodysplasia. The findings include marrow hypocellularity, myelodysplasia and poor marrow recovery. Dysmegakaryocytpoiesis is found in 88% while dyserythropoeisis in 83% of cases. Mechanisms leading to these pertubations include direct HIV effect on marrow progenitor cells, effect of drugs and other infective diseases. Altered levels and functions of growth modifies IL6 and G-CSF are also to contribute. Haemostatic disorder frequently noted is bleeding due to thrombocytopaenia. Non-Hodgkin's lymphomas with aggressive characteristics and Kaposi's sarcoma are the commonly associated malignancies. Currently IL6 is being linked with the causation of KS and NHL. While standard approaches to the management of these malignancies tend to be the practices, adjustments are usually necessary in most patients.
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PMID:Haematological changes in human immunodeficiency virus infection. Part II. 955 50

C-mpl ligand acts primarily as a lineage-specific hematopoietic growth factor by promoting proliferation of megakaryocyte precursors and their differentiation into megakaryocytes and platelets. In addition to the ability of c-mpl ligand to support megakaryocytic development from CD34+ precursor cells, several lines of evidence also point to a stimulatory effect on hematopoietic stem cells. When recombinant thrombopoietin or pegylated megakaryocyte growth and development factor is administered to normal animals or humans, there is a dose-dependent increase in the platelet count. When administered following chemotherapy in animal models or humans, c-mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The issue of whether clinically relevant thrombocytopenia can be ameliorated has so far been more difficult to resolve. Because severe thrombocytopenia is not commonly seen with standard chemotherapy regimens, clinical studies examining c-mpl ligands for their ability to ameliorate chemotherapy-induced thrombocytopenia will focus on treatment of acute leukemias and bone marrow transplantation. The potential utility of c-mpl ligands for treatment of myelodysplastic syndromes, aplastic anemias, or in HIV infection, will have to be evaluated in the future. Possibly the greatest potential of thrombopoietic growth factors in the near future may be in transfusion medicine, to collect and to store platelets from healthy donors or in autologous settings.
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PMID:Megakaryocytic growth factors: is there a new approach for management of thrombocytopenia in patients with malignancies? 1004 50

C-mpl ligand acts primarily as a lineage-specific hematopoietic growth factor by promoting proliferation of megakaryocyte precursors and their differentiation into megakaryocytes and platelets. In addition to the ability of c-mpl ligand to support megakaryocytic development from CD34+ precursor cells, several lines of evidence also point to a stimulatory effect on hematopoietic stem cells. When recombinant thrombopoietin or pegylated megakaryocyte growth and development factor is administered to normal animals or humans, there is a dose-dependent increase in the platelet count. When administered following chemotherapy in animal models or humans, c-mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The issue of whether clinically relevant thrombocytopenia can be ameliorated has so far been more difficult to resolve. Because severe thrombocytopenia is not commonly seen with standard chemotherapy regimens, clinical studies examining c-mpl ligands for their ability to ameliorate chemotherapy-induced thrombocytopenia will focus on treatment of acute leukemias and bone marrow transplantation. The potential utility of c-mpl ligands for treatment of myelodysplastic syndromes, aplastic anemias, or in HIV infection, will have to be evaluated in the future. Possibly the greatest potential of thrombopoietic growth factors in the near future may be in transfusion medicine, to collect and to store platelets from healthy donors or in autologous settings.
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PMID:Memorial lecture. Megakaryocytic growth factors: is there a new approach for management of thrombocytopenia in patients with malignancies? 1023 62

Three pediatric patients with refractory anemia with ringed sideroblasts (RARS) are presented. Bone marrow aspirates were examined using Romanowsky and Prussian blue iron stains in all three patients, and electron microscopic analysis was performed in one patient. All three patients had cytogenetic analysis of the bone marrow. Other studies included analysis of serum iron, total iron-binding capacity, ferritin, copper, vitamins B6 and B12, and folate levels. Antibody titers to Parvovirus, HIV, and other viruses were measured. The patients had contrasting clinical courses. Patients 1 and 2 had dysplastic hematopoietic features and cytogenetic findings (with either partial or one allele loss of chromosome 7), suggestive of myelodysplastic syndrome. Patient 1 experienced acute myeloid leukemia (AML) and had a good response to AML-directed therapy. Patient 2 had prolonged cytopenias and underwent bone marrow transplantation (BMT). Patient 3 had features suggestive of refractory anemia associated with mitochondrial cytopathy, including normal cytogenetics with pronounced vacuolization of marrow precursors. His anemia regressed spontaneously a few months after diagnosis. These patients represent two subgroups of pediatric RARS. Patients with the myelodysplastic syndrome (MDS) type may progress to cytopenias or leukemia and may require aggressive therapy; the type is characterized by clonal cytogenetic findings. The non-MDS type, which may relate to mitochondrial cytopathy, often shows spontaneous regression and requires only supportive treatment; it has normal cytogenetic findings.
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PMID:Refractory anemia with ringed sideroblasts in children: two diseases with a similar phenotype? 1052 57


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