Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suramin has recently been shown to inhibit the activity of the duck hepatitis B virus DNA polymerase (DHBV DNAp) in vitro. However, we found no demonstrable in vivo suppression of human hepatitis B virus DNA polymerase (HBV DNAp) activity in three male patients with severe chronic active hepatitis. Suramin treatment resulted in prolongation of the prothrombin time in all cases and a rise in bilirubin in two and it may have led to haemorrhage from oesophageal varices in one patient and to hepatic encephalopathy in another. Its use in chronic hepatitis is not recommended.
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PMID:Suramin treatment for chronic active hepatitis B--toxic and ineffective. 349 74

Poly(A)-RNA enriched for prothrombin was isolated by specific immunoprecipitation of bovine liver polysomes. Prothrombin consisted of about 8% of the cell-free translation products of this RNA. A double-stranded cDNA was synthesized by using reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) and made blunt-ended with nuclease S1. After tailing with dCTP and terminal transferase, the double-stranded cDNA was annealed to pBR322 DNA that had been cleaved previously at the single Pst I site and similarly tailed with dGTP. The resulting plasmids were used to transform Escherichia coli strain RR1 under P3-EK1 conditions. Sixty-three tetracycline-resistant clones were obtained that hybridized to 32P-labeled cDNA synthesized from prothrombin-enriched mRNA. Recombinants containing cDNA to prothrombin mRNA sequences were screened by a solution hybridization assay with a [3H]cDNA synthesized from mRNA. This enriched mRNA was 50% prothrombin mRNA, as determined by a reticulocyte lysate translation assay. Three positive clones were identified by this assay; they contained bovine DNA inserts of 700, 500, and 400 base pairs. The DNA sequence of the 700-base-pair insert was then determined. This recombinant plasmid contained DNA coding for the carboxyl-terminal 160 residues of bovine prothrombin followed by a noncoding region of 119 base pairs and a poly(A) tail of 60 base pairs.
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PMID:Cloning and analysis of a cDNA coding for bovine prothrombin. 625 59

Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.
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PMID:Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine. 1468 51

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
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PMID:Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant. 1516 53

We report a case of simultaneous acute cytomegalovirus infection and venous thrombosis in a renal transplant recipient. On posttransplant month 3, the patient started complaining of left leg pain and swelling. Tibiopopliteal and femoral deep venous thrombosis were confirmed by Doppler ultrasonography. A serological test for CMV ELISA was strongly positive for IgM antibodies. Acute CMV infection was diagnosed by serum quantitative DNA polymerase chain reaction. Genetic predisposing risk factors for thrombosis (eg, protein C and S deficiency, factor V Leiden and prothrombin G20210A mutations, and antithrombin III deficiency) were not present. Results of tests for anticardiolipin antibodies, lupus anticoagulant, and antinuclear antibodies were also negative. No other clinical or biologic risk factors for thrombosis were detected in the patient. The patient responded well to intravenous gancyclovir and low-molecular weight heparin therapy. He was discharged in good condition. Our observation suggests that acute CMV infection may be the cause of a thrombotic event in renal transplant recipients.
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PMID:Acute cytomegalovirus infection complicated by venous thrombosis in a renal transplant recipient. 1711 13