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)

The Fanconi anemia (FA) complementation group C gene product (FANCC) functions to protect hematopoietic cells from cytotoxicity induced by interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and double-stranded RNA (dsRNA). Because apoptotic responses of mutant FA-C cells involve activation of interferon-inducible, dsRNA-dependent protein kinase PKR, we sought to identify FANCC-binding cofactors that may modulate PKR activation. We identified the molecular chaperone Hsp70 as an interacting partner of FANCC in lymphoblasts and HeLa cells using 'pull-down' and co-immunoprecipitation experiments. In vitro binding assays showed that the association of FANCC and Hsp70 involves the ATPase domain of Hsp70 and the central 320 residues of FANCC, and that both Hsp40 and ATP/ADP are required. In whole cells, Hsp70-FANCC binding and protection from IFN-gamma/TNF-alpha-induced cytotoxicity were blocked by alanine mutations located in a conserved motif within the Hsp70-interacting domain of FANCC. We therefore conclude that FANCC acts in concert with Hsp70 to prevent apoptosis in hematopoietic cells exposed to IFN-gamma and TNF-alpha.
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PMID:FANCC interacts with Hsp70 to protect hematopoietic cells from IFN-gamma/TNF-alpha-mediated cytotoxicity. 1150 Mar 75

The Fanconi anemia (FA) group C gene product (FANCC) functions to protect cells from cytotoxic and genotoxic effects of cross-linking agents. FANCC is also required for optimal activation of STAT1 in response to cytokine and growth factors and for suppressing cytokine-induced apoptosis by modulating the activity of double-stranded RNA-dependent protein kinase. Because not all FANCC mutations affect STAT1 activation, the hypothesis was considered that cross-linker resistance function of FANCC depends on structural elements that differ from those required for the cytokine signaling functions of FANCC. Structure-function studies were designed to test this notion. Six separate alanine-substituted mutations were generated in 3 highly conserved motifs of FANCC. All mutants complemented mitomycin C (MMC) hypersensitive phenotype of FA-C cells and corrected aberrant posttranslational activation of FANCD2 in FA-C mutant cells. However, 2 of the mutants, S249A and E251A, failed to correct defective STAT1 activation. FA-C lymphoblasts carrying these 2 mutants demonstrated a defect in recruitment of STAT1 to the interferon gamma (IFN-gamma) receptor and GST-fusion proteins bearing S249A and E251A mutations were less efficient binding partners for STAT1 in stimulated lymphoblasts. These same mutations failed to complement the characteristic hypersensitive apoptotic responses of FA-C cells to tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Cells bearing a naturally occurring FANCC mutation (322delG) that preserves this conserved region showed normal STAT1 activation but remained hypersensitive to MMC. The conclusion is that a central highly conserved domain of FANCC is required for functional interaction with STAT1 and that structural elements required for STAT1-related functions differ from those required for genotoxic responses to cross-linking agents. Preservation of signaling capacity of cells bearing the del322G mutation may account for the reduced severity and later onset of bone marrow failure associated with this mutation.
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PMID:The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality. 1152 Jul 87

Phosphorylation of the Fanconi anemia complementation group A (FANCA) protein is thought to be important for the function of the FA pathway. However, the kinase for FANCA (so-called FANCA-PK) remains to be identified. FANCA has a consensus sequence for Akt kinase near serine 1149 (Ser1149), suggesting that Akt can phosphorylate FANCA. We performed in vitro kinase assays using as substrate either a GST-fusion wild-type (WT) FANCA fragment or a GST-fusion FANCA fragment containing a mutation from serine to alanine at 1149 (FANCA-S1149A). These experiments confirmed that FANCA is phosphorylated at Ser 1149, in vitro. However, (32)P-orthophosphate labeling experiments revealed that FANCA-S1149A was more efficiently phosphorylated than WT-FANCA. Furthermore, phosphorylation of wild-type FANCA was blocked by coexpression of a constitutively active (CA)-Akt and enhanced by a dominant-negative (DN) Akt. Our results suggest that Akt is a negative regulator of FANCA phosphorylation.
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PMID:Phosphorylation of Fanconi anemia protein, FANCA, is regulated by Akt kinase. 1185 36

Hemoglobin Lyon-Bron was found in two members of a family of German ascent presenting with a moderate normocytic anemia. In this alpha 2 globin variant, the N-terminal valine of the chain was replaced by an alanine. Electrospray mass spectrometry of the alpha chain showed that, as normally, the initiator methionine was cleaved during globin processing but that the N alpha-terminal group was totally acetylated. This resulted in structural modifications of a region crucial for oxygen binding. As a consequence, hemoglobin Lyon-Bron displayed both a reduced chloride effect and a decreased oxygen affinity, this last point explaining the apparent anemia.
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PMID:New alpha 2 globin chain variant with low oxygen affinity affecting the N-terminal residue and leading to N-acetylation [Hb Lyon-Bron alpha 1(NA1)Val --> Ac-Ala]. 1189 10

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for > 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm3. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.
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PMID:Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001. 1275 19

We investigated the interrelationships between behavior and serum amino acid concentrations in iron-deficient anemic rats. Concentrations of proline, alanine, glycine, and phenylalanine in serum samples were significantly higher than those in rats fed a normal diet, while serum threonine, glutamic acid, and valine levels were significantly lower. Activities of locomotion, rearing, hole-poking, and grooming, determined by using a hole board apparatus, were significantly reduced in anemic rats. The supplementation of inorganic iron and amino acids proline, arginine, or glutamic acid to the normal diet lead to the recovery of normal behavior. Proline enhanced a significant increase in the number of red blood cells and hemoglobin by the supplementation of iron alone. We propose that the combination of amino acid (especially proline) and inorganic iron might lead to an improvement in behavioral disorders caused by iron-deficient anemia.
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PMID:Co-administration of proline and inorganic iron enhance the improvement of behavioral and hematological function of iron-deficient anemic rats. 1288 90

Kwashiorkor remains a significant cause of childhood morbidity and mortality in tropical regions. However, there are relatively few reproducible animal models to elucidate the aetiopathogenesis, biochemical derangements, and morphological changes of this condition. In the present study, 64 weanling male Wistar albino rats were divided into high protein chow, high protein maize starch, and low protein maize starch groups. After 4 weeks on these respective diets, animals on the low protein diet were commenced on the high protein maize starch diet, while those in the other groups were continued on their original diets for a further period of 5 weeks each The low protein group of animals initially showed growth failure, hair loss, oedoma, fatty liver, metabolic acidosis, hypoalbuminaemia, and anaemia, which are characteristic features of human kwashiorkor. These changes were all reversed by dietary rehabilitation with the high protein diet. The reduced plasma retinol, increased plasma alanine and aspartate aminotransferases and fatty liver observed in the low protein group of animals probably suggest an important role for free radicals in the aetiopathogenesis of kwashiorkor.
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PMID:Biochemical changes and liver tissue pathology in weanling Wistar albino rats with protein-energy malnutrition (PEM). 1295 86

We report the case of a 3-year-old Japanese boy with phosphoglycerate kinase 1 (PGK1) deficiency (Online Mendelian Inheritance in Man entry 311800). The patient had anaemia and jaundice at birth, necessitating exchange transfusions for 2 d. After one red blood cell transfusion at age 2 months, his Hb level was 8-9 g/dl, his reticulocyte counts were 300-500 x 109/l, and his total bilirubin level was 25.65-42.75 micro mol/l. The patient suffered two episodes of respiratory infection-associated haemolytic crisis and rhabdomyolysis during early infancy. At age 3.0 years, his developmental milestones (developmental quotients measured using the Tsumori-Inage methods) score was 49% (normal 74-131%), and his height was below average by -2.0 standard deviations. The diagnosis of PGK1 deficiency was made based on his remarkably low (< 10% of normal) erythrocyte PGK enzyme activity level and the identification of a novel missense (1060G-->C) PGK1 gene mutation. This mutation results in the Ala-353Pro amino acid substitution, which has been designated PGK Kyoto. The patient developed the full clinical symptoms of PGK1 deficiency including haemolytic anaemia, myopathy, central nervous system disorder and growth retardation, which is unusual.
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PMID:A novel missense mutation (1060G --> C) in the phosphoglycerate kinase gene in a Japanese boy with chronic haemolytic anaemia, developmental delay and rhabdomyolysis. 1295 73

The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion of TSG101 (TSG-3') potently disrupts both HIV-1 and MLV budding. In addition, it has been reported that, while the release of a number of retroviruses is disrupted by proteasome inhibitors, equine infectious anemia virus (EIAV) budding is not affected by these agents. In this study, we tested the ability of TSG-5', TSG-3', and full-length TSG101 (TSG-F) overexpression, a dominant negative form of the AAA ATPase Vps4, and proteasome inhibitors to disrupt the budding of EIAV particles bearing each of the three types of L domain. The results indicate that (i) inhibition by TSG-5' correlates with dependence on PTAP; (ii) the release of wild-type EIAV (EIAV/WT) is insensitive to TSG-3', whereas this C-terminal TSG101 fragment potently impairs the budding of EIAV when it is rendered PTAP or PPPY dependent; (iii) budding of all EIAV clones is blocked by dominant negative Vps4; and (iv) EIAV/WT release is not impaired by proteasome inhibitors, while EIAV/PTAP and EIAV/PPPY release is strongly disrupted by these compounds. These findings highlight intriguing similarities and differences in host factor utilization by retroviral L domains and suggest that the insensitivity of EIAV to proteasome inhibitors is conferred by the L domain itself and not by determinants in Gag outside the L domain.
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PMID:Late domain-dependent inhibition of equine infectious anemia virus budding. 1469 4

Hb Iowa is a rare hemoglobin (Hb) variant with a Gly --> Ala substitution at position 119 of beta-globin. It was previously reported only in an African American infant who was also heterozygous for Hb S [beta6(A3)Glu --> Val] and her mother (Hb A/Iowa). Here we describe the second report of Hb Iowa, the first in conjunction with Hb C [beta6(A3)Glu --> Lys]. The patient was an African American girl, originally diagnosed as homozygous Hb C during neonatal screening. When seen in our clinic, hematological data for both the child and her mother (Hb C trait) indicated mild anemia with slightly low mean corpuscular volume (MCV) but normal red blood cell (RBC) count. Analysis of blood from the child by capillary isoelectric focusing (cIEF) identified Hb C and an unknown Hb variant with an isoelectric point (pI) intermediate to that of Hbs F and A. The unknown variant was identified as Hb Iowa by DNA sequence analysis of the beta-globin gene (GGC --> GCC). Both reported cases of Hb Iowa indicated that there are no abnormal hematological manifestations associated with this rare Hb variant. In both cases, however, Hb Iowa was mistaken for Hb F during routine neonatal screening by high performance liquid chromatography (HPLC) and/or gel IEF. Neonatal misidentification of Hb Iowa led to misdiagnosis of sickle cell disease and Hb C disease, respectively. In our patient, Hb Iowa was also misidentified as Hb A at 2 years of age by a commercial reference laboratory using cellulose acetate and citrate agar gel electrophoresis. This led to an incorrect diagnosis of Hb C trait. These results show that commonly used analytical methods can easily misidentify Hb Iowa as Hbs F or A in neonates, or older individuals, resulting in incorrect identification of the Hb phenotype. We conclude that the presence of Hb Iowa, or other variants with similar pIs, should be considered in cases where the results of follow-up testing conflict with neonatal diagnosis of sickle cell or Hb C disease, or where clinical presentation does not agree with diagnosis of either homozygous or heterozygous Hb S or Hb C.
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PMID:Diagnosis and characterization of Hb C/Hb Iowa: a rare but easily misidentified compound heterozygous condition. 1500 60


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