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)

Mechanisms involved in the erythroid failure characterizing Diamond-Blackfan anaemia (DBA) remain unidentified. The general consensus is that the defect is intrinsic to the marrow erythroid progenitor, but the target progenitor cell has not been precisely identified, and in vitro studies have revealed considerable heterogeneity between patients. In order to understand better the meaning of such a biological heterogeneity, we examined the in vitro response of erythroid progenitors CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) to erythropoietin (Epo), interleukin-3 (IL-3) and stem cell factor (SCF) in a large series of 24 patients from 1 month to over 20 years of age. Results of colony assays revealed a striking correlation between the age of the patient and the extent of the abnormalities detected in vitro. Therefore, despite profound anaemia, 80% (7/10) of the patients studied within 1 year of diagnosis had normal numbers of both CFU-E and BFU-E which exhibited a normal response to cytokines. In contrast, 12/14 patients followed up for more than 3 years had decreased numbers of erythroid progenitors, in seven cases associated with decreased colony-forming unit granulocyte-macrophage (CFU-GM). The number of CFU-E and BFU-E was not normalized even by the addition of high concentrations of combined Epo, IL-3 and SCF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age-related alterations in erythroid and granulopoietic progenitors in Diamond-Blackfan anaemia. 752 24

In this study we evaluated the in vivo effects of interleukin-11 (IL-11) and stem cell factor (SCF), in combination with erythropoietin (EPO) on murine erythropoiesis. Mice were treated for 7 d with IL-11. SCF and EPO, each at three dose levels. In total, 27 different dose combinations were tested. IL-11 as well as SCF could only marginally stimulate erythroid progenitor cell numbers, but IL-11 in combination with SCF was able to increase BFU-E and CFU-E numbers 4-fold, in the absence of exogenous EPO. This resulted in an increased reticulocyte count. In contrast with the stimulatory effect on immature erythroid cell stages, IL-11 treatment induced a mild anaemia, which probably resulted from a plasma volume expansion. The additional treatment with EPO resulted in strong synergistic effects on CFU-E numbers. The combination of high-dose IL-11 and high-dose SCF was able to increase the overall efficiency of EPO-induced erythroid amplification, which was reflected by a left-shift of the in vivo EPO dose-response curve. The stimulating effects of IL-11 and SCF were further demonstrated when the effects on the reticulocyte count of a single high-dose EPO injection were assessed in normal and SCF+IL-11 treated mice. Whereas a single EPO dose increased the reticulocyte count by a factor of 3, IL-11 + SCF pretreatment increased this to a factor of 7. This study shows that in vivo SCF and IL-11 are important modulators of red blood cell production. First, these factors probably increase the input from the stem cell compartment into the erythroid lineage, where subsequently EPO is required for further amplification. Additionally, however, IL-11 and SCF increase the overall efficiency of EPO-induced amplification, probably due to a stimulatory effect on late-stage erythroid cells and to a redistribution of cells from marrow to spleen.
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PMID:In vivo effects of interleukin-11 and stem cell factor in combination with erythropoietin in the regulation of erythropoiesis. 754 23

Highly purified human blood burst-forming units-erythroid (BFU-E) were used to study the effects of interferon gamma (IFN gamma). IFN gamma inhibited erythroid colony formation, cell proliferation, and differentiation of day 3 to day 6 mature BFU-E in a dose-dependent manner. The primitive BFU-E (day 1 and day 2 cells) and later day 7 cells were less affected. IFN gamma dose-response experiments demonstrated that the number and size of erythroid colonies were reduced at a concentration of 500 U/ml with more complete inhibition at 1,000 U/ml. Inhibition of day 4 to day 6 erythroid progenitors was first noted by 72 h of incubation with IFN gamma, and target cell growth and differentiation continued to decrease with further incubation. IFN gamma also induced erythroblast apoptosis which was demonstrated by both nuclear condensation and fragmentation plus flow cytometry with in situ end-labelling. Because day 3 to day 6 cells need stem cell factor (SCF) for development in serum-free culture, the relationship of IFN gamma inhibition to this growth factor was investigated. The reduction in the number of erythroid colonies by IFN gamma was reversed by SCF although the colony size was not completely re-established. In contrast, interleukin-3 did not have the capacity to overcome the inhibitory effects of IFN gamma. Since IFN gamma blood levels are elevated in some anemias of chronic disease, IFN gamma may have a role in promoting this anemia and its inhibitory effect might be better overcome by SCF plus EP. However, the mechanism by which these growth factors overcome the inhibition of IFN gamma, or vice versa, is unknown at the present time.
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PMID:Stem cell factor can overcome inhibition of highly purified human burst-forming units-erythroid by interferon gamma. 759 10

Chronic B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1) is one cause of reversible anemia in this patient group. This report describes a case of concurrent HIV-1 and B19 parvovirus infection with pure red cell aplasia in which the anemia resolved with gammaglobulin treatment. When cultured in vitro with recombinant human stem cell factor, the red blood cell precursors from this patient demonstrated increases in both number and size, suggesting that simultaneous infection with B19 parvovirus and HIV-1 does not preclude a response to erythroid-acting growth factors. Although rare, persistent B19 parvovirus infection has become an increasingly recognized treatable cause of anemia in HIV-infected patients. Further in vitro and in vivo studies are required to determine whether cytokines such as stem cell factor have a consistent effect in these anemic states.
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PMID:In vitro erythroid effects of human stem cell factor in a case of human immunodeficiency virus-related chronic parvovirus B19 induced anemia. 768 13

Recent attempts to reduce 3' azido-3' deoxythymidine (AZT)-induced anemia in AIDS patients have focused both on AZT dose reduction and on the use of recombinant cytokines. The newly cloned cytokine stem cell factor (SCF) is a potent regulator of hematopoietic progenitor cell proliferation. Therefore, we attempted to ameliorate AZT-induced anemia using stem cell factor (SCF) in the LP-BM5 murine leukemia virus-induced model of AIDS (MAIDS). SCF was administered with oral AZT for up to 1 month, and effects on erythropoiesis examined. SCF alone increased both splenic BFU-E and CFU-E. AZT alone also increased the number of splenic BFU-E and CFU-E. SCF, administered to AZT-treated MAIDS mice, did not further enhance these increases. SCF increased bone marrow cellularity in AZT-treated MAIDS mice. However, the total number of bone marrow BFU-E was unaffected. In contrast, AZT, SCF, and the combination significantly decreased bone marrow CFU-E. SCF alone increased the absolute numbers of peripheral blood reticulocytes in MAIDS mice, but did not increase reticulocyte numbers in AZT-treated mice. SCF did not significantly increase hematocrits in either control or AZT-treated mice. Further studies are needed to maximize the differentiating capacity of the enlarged erythroid progenitor cell pool induced by SCF.
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PMID:Failure of stem cell factor to ameliorate AZT-induced anemia in immunodeficient mice. 768 17

W/Wv and S1/S1d mice with macrocytic anemias are a potential model for human inherited pure red cell anemia, called Diamond-Blackfan anemia (DBA). The W mutation involves the gene for c-kit, and the S1 mutation the gene for the kit ligand, called mast cell growth factor, steel factor, or stem cell factor. Since many children with DBA respond to treatment with corticosteroids, we administered steroids to these genetically anemic mice, to determine whether they might provide a model for the human disease. There was no improvement in the murine anemia, consistent with other evidence suggesting that mutations in kit or steel may not be involved in Diamond-Blackfan anemia.
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PMID:Lack of effect of corticosteroids in W/Wv and S1/S1d mice: these strains are not a model for steroid-responsive Diamond-Blackfan anemia. 768 5

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C-reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.
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PMID:Prediction of response to erythropoietin treatment in chronic anemia of cancer. 788 86

Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.
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PMID:Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression. 797 17

Cases of rare congenital forms of aplastic anaemia are presented. Fanconi anaemia is most frequently diagnosed, while reticular dysgenesis, amegakaryocytic thrombocytopenia and dyskeratosis congenita occur exceptionally rarely. A presumably new entity of congenital aplastic anaemia called "RAC" syndrome (retinopathy--aplastic anaemia--central nervous system abnormalities) is presented too. A short summary of the pathomechanism of congenital aplastic anaemias and present therapeutic attempts, including the possible therapeutic use of the newly discovered stem cell factor are described.
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PMID:[Rare congenital forms of bone marrow deficiency]. 850 68

The anaemia of prematurity has been attributed to an insufficient erythropoietin (Epo) level. However, haemopoiesis is known to be regulated by a cohort of growth factors including interleukin-3 (IL-3), IL-6, stem cell factor (SCF), granulocyte monocyte-colony stimulating factor (GM-CSF) and insulin-like growth factors-I and -II (IGF-1, IGF-II). Circulating levels of these growth factors were measured in cord blood at the following gestational ages: 25-28 weeks, 29-32 weeks, 33-36 weeks and > 37 weeks. This study indicates that low concentrations of IGFs as well as a low Epo level in early gestational ages may play a role in anaemia of prematurity.
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PMID:The role of haemopoietic growth factors in the pathogenesis of the early anaemia of premature infants. 854 69


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