Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty anaemic (iron deficiency anaemia-27, thalassemia major-8, and aplastic anaemia-5) and 10 non-anaemic children (serving as controls) aged from 8 months to 10 years were selected for the study. The salivary iron was significantly higher in iron deficient and iron overload conditions compared to controls. The mean salivary:serum iron ratio was same in control and iron overload cases, while it was twice as high in iron deficient anaemic children. The correlation between salivary iron and serum iron was significant (r = 0.7392, P less than 0.001) in these cases. The iron deficient anaemic children with hypoalbuminaemia had significantly reduced serum and salivary protein (P less than 0.001), but iron concentrations in serum and saliva remained unaltered. The salivary protein level had significant correlations with serum albumin and serum protein (P less than 0.001). Thus, the iron in saliva is maintained at a higher level and more so in iron deficiency anaemia; it correlates well with serum iron (r = 0.6853, P less than 0.001) in iron deficient anaemic children also and is not affected by co-existing hypoproteinaemic situation.
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PMID:Salivary iron status in children with iron deficiency and iron overload. 156 37

Serum albumin, cholinesterase, and cholesterol were measured in ten patients with aplastic anemia and eight with myelodysplastic syndrome who received the administration of recombinant human GM-CSF. Serum albumin, cholinesterase, and cholesterol were significantly lowered by the administration of GM-CSF and recovered after the cessation of GM-CSF. These data suggest that GM-CSF impairs the biosynthesis of liver cells and that cholesterol-lowering activity of GM-CSF, which is previously reported, is due to the impairment of liver biosynthesis by GM-CSF.
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PMID:GM-CSF-mediated impairment of liver to synthesize albumin, cholinesterase, and cholesterol. 199 59

Suspensions of enriched human megakaryocytes (MK) devoid of MK progenitors (CFU-MK) undergo complete cytoplasmic maturation in vitro. MK were cultured in the presence of normal human AB serum (NABS) to mimic "normal" development. The rate of maturation was not statistically altered by higher concentrations (10%-20%-30%) of NABS, or by the addition of bovine serum albumin (1.5%-3.0%), but was accelerated in the presence of aplastic anemia serum (AAS). Sera from eight different patients with severe aplastic anemia were effective in accelerating terminal differentiation. MK-CSF, a glycoprotein isolated from AAS, specifically augments MK colony formation by two- to sixfold. Similar doses of MK-CSF were ineffective in altering terminal cytoplasmic maturation. Anti-MK-CSF, a polyclonal antibody prepared against purified MK-CSF, neutralizes the ability of both purified MK-CSF and AAS to promote MK colony formation. However, AAS adsorbed with anti-MK-CSF still retained its ability to accelerate terminal differentiation. Apparently, AAS contains at least two separate humoral factors, which can regulate in vitro human megakaryocytopoiesis: MK-CSF, which stimulates proliferation of the progenitors (CFU-MK), and a maturation factor, which accelerates cytoplasmic maturation of morphologically recognizable megakaryocytes.
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PMID:Effects of megakaryocyte colony-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes. 359 64

When human marrow cells were cultured in a medium containing alpha-medium, methylcellulose, fetal calf serum, bovine serum albumin, erythropoietin, and leucocyte-conditioned medium, mixed colonies composed of erythrocytic cells and granulocytes were formed. The clonal nature of the mixed colonies was confirmed by the linear relationship between the numbers of cells plated and the number of colonies, and the absence or presence of Y-chromatin in the mixed colonies in a co-culture experiment with male and female cells. Using the methylcellulose cell culture techniques, the pluripotent hemopoietic precursors (CFUMIX) in marrow cells from 15 patients with aplastic anemia were assayed. In the control subjects of patients with iron-deficiency anemia, lymphoadenitis, reactive leucocytosis or Hodgkin's disease, 8 X 10(5) marrow cells in 4 dishes produced 12.7 +/- 6.9 (mean +/- SD) mixed colonies. On the other hand, 8 X 10(5) marrow cells from patients with aplastic anemia formed only 2.1 +/- 5.5 (mean +/- SD) mixed colonies. Furthermore, the marrow cells from 5 patients who were repeatedly receiving transfusions contained no CFUMIX which give rise to mixed colonies. The present results provided the first direct evidence that pancytopenia in most patients with aplastic anemia results from a reduced influx into the compartment of maturing hemopoietic cells from the compartment of pluripotent hemopoietic precursors.
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PMID:Pluripotent hemopoietic precursors in vitro (CFUMIX) in aplastic anemia. 722 71

Felbamate is an anti-epileptic drug associated with hepatotoxicity and aplastic anemia. These toxicities are believed to be mediated by the formation of the reactive species 2-phenylpropenal. 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one is a metabolic precursor for 2-phenylpropenal. 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one exists in equilibrium with 3-oxo-2-phenylpropyl carbamate, which can undergo beta-elimination to form 2-phenylpropenal. The work presented here investigates the interaction between 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one and human serum albumin (HSA). HSA (40 mg/mL) was found to decrease the half-life of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one from 4.57 +/- 0.44 h to 1.07 +/- 0.10 h at pH 7.4. This decrease in the half-life of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one was due to increased beta-elimination of 3-oxo-2-phenylpropyl carbamate, presumably through HSA-mediated general base catalysis. The k(cat) for HSA-catalyzed decomposition of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one was determined to be 12.04 min(-)(1) M(-)(1). Competitive binding assays using warfarin and ibuprofen showed that HSA-catalyzed decomposition of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one is dependent on the subdomain IIA binding site of HSA. LC/MS/MS analyses of trypsin digests of HSA incubations with either 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one or 2-phenylpropenal identified HSA-2-phenylpropenal adducts formed specifically at residues His-242 and His-247. These HSA-2-phenylpropenal adducts were found to be slowly reversible, with a decrease in alkylation of 74.0 +/- 0.6% after extensive dialysis. Interestingly, only the bis-adduct (His-242 and His-247) could be identified after dialysis. These results demonstrate the first direct example of 2-phenylpropenal conjugation to a human protein in vitro and suggest the possibility that HSA may be involved in the development of felbamate toxicity either by antigen formation or as a route of detoxification of 2-phenylpropenal.
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PMID:Interaction between human serum albumin and the felbamate metabolites 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one and 2-phenylpropenal. 1206 49