Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of hepatitis C virus (HCV) in the general population has improved over the last decade. Patients treated with peginterferon alfa (PegIFN) and ribavirin (RBV) combination therapy demonstrate overall 50-55% sustained viral response (SVR) with rates as high as 80% in patients with genotypes 2 and 3. Because RBV induces hemolysis and subsequently increases blood transfusion requirements, combination therapy has been considered contraindicated for hemoglobinopathies. This report reviews the response to interferon alfa and RBV (IFN/RBV) and PegIFN/RBV combination therapies in patients treated in the Northern California Comprehensive Thalassemia Center. A total of six thalassemia major patients were treated with IFN/RBV (n = 5; age: 4-38 years) or with PegIFN/RBV (n = 1; age: 26 years). Quantitative HCV RNA polymerase chain reaction and liver iron level assessment were completed. Transfusion volumes were obtained from patients' medical records. On IFN/RBV combination, four of five patients demonstrated SVR. The one patient on PegIFN/RBV showed end-treatment viral response after 6 months of therapy (genotype 3), but subsequently relapsed. Liver iron pretreatment level ranged from 0.2 to 22 mg/g dry weight, with a mean +/- SD of 7.9 +/- 7.7. Transfusion requirement increased by a median of 43.5% (range: 32-137%). Five of the six patients had liver iron measurements within 1 year following completion of treatment, with quantitative liver iron increasing in two patients by 2.5 mg/g dry weight, decreasing in two patients by 3 and 14 mg/g dry weight, and remaining unchanged in one patient. All patients were able to complete combination therapy, although dose reductions were required. Patients with thalassemia and high iron overload can obtain SVR after combination therapy with rates similar to those in the general population and without significant complications. Although transfusion requirements increased in most patients, iron burden was not necessarily increased.
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PMID:Treatment of hepatitis C virus infection in thalassemia. 1633 77

Vibrio vulnificus can use the standard iron chelator deferoxamine (Desferal) for efficient iron-uptake via the specific receptor DesA, which is encoded by desA. We investigated the ubiquity of the deferoxamine-mediated iron-uptake system in V. vulnificus strains and the potential risk of the system. By polymerase chain reaction (PCR), desA was found in 10 of 10 clinical strains and in 9 of 10 environmental strains, and their growth was stimulated by deferoxamine. By reverse-transcriptase PCR, desA was expressed only under iron-limited conditions containing deferoxamine. V. vulnificus growth in the presence of deferoxamine was suppressed by desA mutation, and the suppressed growth was recovered by desA complementation. Deferoxamine stimulated V. vulnificus growth in iron-limited in vitro and ex vivo backgrounds containing transferrin-bound iron. Overall, V. vulnificus can use transferrin-bound iron via the widespread deferoxamine-mediated iron-uptake system; this cautions that deferoxamine therapy in patients with iron overload may increase the risk of fatal infections caused by V. vulnificus.
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PMID:A widespread deferoxamine-mediated iron-uptake system in Vibrio vulnificus. 1800 34

Regular blood transfusion puts beta-thalassemia major patients at a higher risk of developing hepatic iron overload and hepatitis C virus (HCV) infection. The association between several transfusion-related factors and an increased risk of developing HCV viremia has been reported. The effect of HCV infection on liver damage in transfusion-dependent thalassemia patients has been poorly described. A sample of 100 Egyptian transfusion-dependent beta-thalassemia major children were studied. Individual patients underwent full history taking, clinical examination and a panel of laboratory tests including HCV ribonucleic acid polymerase chain reaction (HCV-PCR) in blood samples. Liver biopsy was performed for 24 patients. HCV-PCR was positive in 64% of patients. A statistically significant correlation was found between HCV-PCR positivity (HCV viremia) and shorter inter-transfusion interval. There was a significant positive correlation between mean serum ferritin level and mean levels of alanine aminotransferase and aspartase aminotransferase. Histopathologic features of both chronic hepatitis and siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in 41.67%. A higher risk of HCV viremia is noted with a shorter inter-transfusion interval. The reduced role of HCV infection in chronic liver injury in this group of patients may be surpassed by the associated effects of iron overload because of the chronic transfusion. However, the latter finding should be verified in larger studies.
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PMID:Clinicovirologic analysis of hepatitis C infection in transfusion-dependent beta-thalassemia major children. 1938 13

Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA splicing machinery are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe(2+) in mutant and WT. Reactive oxygen species and DNA damage were not increased in SF3B1-mutant patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.
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PMID:Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron. 2485 90