Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both ganciclovir, a nucleoside analogue, and foscarnet, a pyrophosphate analogue, specifically bind cytomegalovirus (CMV) DNA polymerase and inhibit CMV replication at plasma concentrations achievable with intravenous administration. The agents have similar plasma half-lives, and both are cleared solely by the kidneys. Foscarnet has a low solubility and a high degree of ionization at physiologic pH, requiring it to be administered in higher doses and larger volumes. Both drugs are administered as an initial induction regimen followed by a long-term maintenance regimen. Among patients with the acquired immune deficiency syndrome (AIDS) who have CMV retinitis, the efficacy of long-term maintenance therapy, as measured by median time to retinitis progression, appears to be similar for the two drugs. The major toxicity of ganciclovir is myelosuppression, with dose-limiting neutropenia occurring in approximately 16% and thrombocytopenia in 5% of AIDS patients. The major toxicity of foscarnet is nephrotoxicity, with dose-limiting toxicity occurring in approximately 10-23% of patients; other effects of foscarnet include hypocalcemia, which may be associated with seizure and arrhythmia. Studies in vitro indicate an additive or synergistic inhibitory effect on CMV when these two drugs are combined, suggesting that lower-dose combination regimens or higher-dose alternating regimens may result in greater efficacy with less toxicity than with either drug alone.
...
PMID:Approaches to the treatment of cytomegalovirus retinitis: ganciclovir and foscarnet. 184 16

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by positivity for hepatitis B e antigen and hepatitis B virus DNA, with increased DNA polymerase levels for more than 6 months, were entered into a prospective trial of low-dose recombinant human alpha-interferon therapy. All patients were treated with 5 million units of recombinant interferon alfa-2b given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNA polymerase levels (p less than or equal to 0.001), which reached normal values in ten (48%). After 10 months' mean follow up, seven patients (33%) were hepatitis B e antigen negative and five (24%) subsequently became positive for antibodies to e antigen. By 27 months, nine patients (43%) were both hepatitis B e antigen negative and e antibody positive. Only one patient became permanently negative for hepatitis B surface antigen. One patient relapsed during the second year of follow up. Side effects necessitated withdrawal of therapy in two patients: one due to worsening thrombocytopenia after two doses of interferon (data omitted from the study results) and one due to a local reaction at the injection sites. Our data indicate that small doses of recombinant interferon alfa-2b given during a 12-week period induce a significant reduction in viral replication and approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
...
PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a long-term follow-up study. 207 69

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
...
PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study. 268 91

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.
...
PMID:Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP). 617 19

Antibodies to the proliferating cell nuclear antigen (PCNA) detected in patients with systemic lupus erythematosus (SLE) were allowed to react with a nuclear antigen expressed predominantly in proliferating cells such as cultured cells and mitogen-transformed cells. The characterization of both structure and function of PCNA has been studied. PCNA has been identified as a protein with a molecular weight of about 33 kD and isoelectric point of 4.8. The expression of PCNA increased in the cell from the late G1 and S phases of the cell cycle immediately preceding DNA synthesis. Recent studies have revealed that the auxiliary protein of DNA polymerase-d is identical to PCNA. Anti-PCNA antibodies can be detected by the methods of immunofluorescence (IF), double immunodiffusion (DID), counterimmunoelectrophoresis (CIE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB). Anti-PCNA antibodies were specifically detected in 2-5% of the patients with SLE by DID. In spite of their low frequency, anti-PCNA antibodies are useful as a clinical marker for SLE. Several reports indicated that patients with PCNA positive SLE showed a high frequency of renal and central nerve system (CNS) involvements and thrombocytopenia. In these patients, the anti-PCNA antibody titer was elevated before the development by proteinuria and the titer of anti-PCNA antibodies was decreased by treatment with corticosteroids. In addition, anti-PCNA antibodies have been known as a useful tool to detect activated lymphocytes and malignant proliferating cell.
...
PMID:[Anti-PCNA antibody]. 810 8

Acute human immunodeficiency virus (HIV) seroconversion illness is a difficult diagnosis to make because of its nonspecific and protean manifestations. We present such a case in an adolescent. A 15-year-old boy presented with a 5-day history of fever, sore throat, vomiting, and diarrhea. The patient also reported a nonproductive cough, coryza, and fatigue. The patient's only risk factor for HIV infection was a history of unprotected intercourse with 5 girls. Physical examination was significant for fever, exudative tonsillopharyngitis, shotty cervical lymphadenopathy, and palpable purpura on both feet. Laboratory studies demonstrated lymphopenia and mild thrombocytopenia. Hemoglobin, serum creatinine, and urinalysis were normal. The following day, the patient remained febrile. Physical examination revealed oral ulcerations, conjunctivitis, and erythematous papules on the thorax; the purpura was unchanged. Serologies for hepatitis B, syphilis, HIV, and Epstein-Barr virus were negative. Bacterial cultures of blood and stool and viral cultures of throat and conjunctiva showed no pathogens. Coagulation profile and liver enzymes were normal. Within 1 week, all symptoms had resolved. The platelet count normalized. Repeat HIV serology was positive, as was HIV DNA polymerase chain reaction. Subsequent HIV viral load was 350 000, and the CD4 lymphocyte count was 351/mm3. HIV is the seventh leading cause of death among people aged 15 to 24 in the United States, and up to half of all new infections occur in adolescents. Our patient presented with many of the typical signs and symptoms of acute HIV infection: fever, fatigue, rash, pharyngitis, lymphadenopathy, oral ulcers, emesis, and diarrhea. Other symptoms commonly reported include headache, myalgias, arthralgias, aseptic meningitis, peripheral neuropathy, thrush, weight loss, night sweats, and genital ulcers. Common seroconversion laboratory findings include leukopenia, thrombocytopenia, and elevated transaminases. The suspicion of acute HIV illness should prompt virologic and serologic analysis. Initial serology is usually negative. Diagnosis therefore depends on direct detection of the virus, by assay of viral load (HIV RNA), DNA polymerase chain reaction, or p24 antigen. Both false-positive and false-negative results for these tests have been reported, further complicating early diagnosis. Pediatricians should play an active role in identifying HIV-infected patients. Our case, the first report of acute HIV illness in an adolescent, emphasizes that clinicians should consider acute HIV seroconversion in the appropriate setting. Recognition of acute HIV syndrome is especially important for improving prognosis and limiting transmission. It is imperative that we maintain a high index of suspicion as primary care physicians for adolescents who present with a viral syndrome and appropriate risk factors.
...
PMID:Acute human immunodeficiency virus syndrome in an adolescent. 1452 19

Clofarabine is a purine nucleoside analog that inhibits DNA synthesis and repair. Its effects are mediated via the inhibition of ribonucleotide reductase and DNA polymerase. Clofarabine also disrupts the integrity of mitochondrial membranes, resulting in programmed cell death. In 61 pediatric patients with relapsed or refractory acute lymphoblastic leukemia treated with clofarabine 52 mg/m2 infused intravenously over 2 hours once daily for 5 days every 2-6 weeks, rates of complete remission, complete remission without platelet recovery, and partial remission were 12%, 8%, and 10%, respectively. Data are from two non-comparative, multicenter, phase II studies. The most common adverse events associated with clofarabine 52 mg/m2 once daily for 5 days every 2-6 weeks in 96 patients with acute myelogenous or lymphoblastic leukemia (combined analysis of phase I/II trials) were hematologic events (including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutro-penia), gastrointestinal events (including vomiting, nausea, and diarrhea), infections, and transient elevations in liver enzymes. Capillary leak syndrome or systemic inflammatory response syndrome was reported in four patients.
...
PMID:Clofarabine: in pediatric patients with acute lymphoblastic leukemia. 1611 62

Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS < or = 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m(2)) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0-7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested.
...
PMID:Phase II study of troxacitabine (BCH-4556) in patients with advanced non-small-cell lung cancer. 1621 62

Acyclovir is used for its potent antiviral properties for the mucocutaneous herpes, herpes zoster, herpes encephalitis, and genital herpes simplex. The drug has a very wide distribution involving almost every organ of the body, with excretion into the urine. Urine analysis, kidney function, liver function, and complete blood counts are some of the monitoring parameters. The active triphosphate form of the drug inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA. Because the drug is only absorbed by the cells that are virus infected, acyclovir has minimal side effects at therapeutic doses. However, at high intravenous infusions, severe central nervous system (malaise), gastrointestinal (nausea/vomiting), renal (elevated blood urea nitrogen/creatinine), hepatic (elevated liver enzymes), and skin dyscrasias have been found to occur. There have been few case reports of bone marrow suppression and only one case report so far of acyclovir-related isolated thrombocytopenia. Whether there is any further association between acyclovir and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome is the next dilemma if such an association is established. Here, the authors present a case report of a 58-year-old man with acquired immune deficiency syndrome on highly active antiretroviral therapy who went into severe thrombocytopenia on starting acyclovir.
...
PMID:A rare case of acyclovir-induced thrombocytopenia. 2334 9

In order to facilitate the detection of newly emerging or rare viral infectious diseases, a negative-strand RNA virus-severe fever with thrombocytopenia syndrome bunyavirus, and a positive-strand RNA virus-dengue virus, were used to investigate RNA viral genome unspecific amplification by multiple displacement amplification technique from clinical samples. Series of 10-fold diluted purified viral RNA were utilized as analog samples with different pathogen loads, after a series of reactions were sequentially processed, single-strand cDNA, double-strand cDNA, double-strand cDNA treated with ligation without or with supplemental RNA were generated, then a Phi29 DNA polymerase depended isothermal amplification was employed, and finally the target gene copies were detected by real time PCR assays to evaluate the amplification efficiencies of various methods. The results showed that multiple displacement amplification effects of single-strand or double-strand cDNA templates were limited, while the fold increases of double-strand cDNA templates treated with ligation could be up to 6 X 10(3), even 2 X 10(5) when supplemental RNA existed, and better results were obtained when viral RNA loads were lower. A RNA viral genome amplification system using multiple displacement amplification technique was established in this study and effective amplification of RNA viral genome with low load was achieved, which could provide a tool to synthesize adequate viral genome for multiplex pathogens detection.
...
PMID:[Investigation of RNA viral genome amplification by multiple displacement amplification technique]. 2389 10


1 2 Next >>

---