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

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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)

Patients with chronic hepatitis B with active viral replication had a significantly greater fall in DNA polymerase and hepatitis-Be antigen when treated with interferon and acyclovir together than when treated with either interferon or acyclovir alone. Apart from fatigue and thrombophlebitis, tolerance of the combination therapy was excellent. The combination therapy appears the most promising for conversion of a state of active viral replication into virus latency.
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PMID:Acyclovir enhances the antiviral effect of interferon in chronic hepatitis B. 286 16

Recombinant human interleukin 2 was administered to 10 patients with chronic type B hepatitis as a part of a pilot study to evaluate its antiviral activity. Patients received 1 to 3 x 10(5) units per day of interleukin 2 for 21 to 28 days, and all completed the treatment schedule. During therapy, serum values of DNA polymerase decreased in 6 and became negative in four patients. However, when therapy was discontinued, DNA polymerase levels increased to pretreatment levels in most cases. Serum HBeAg levels did not change during treatment. Serum aminotransferase levels transiently increased in 6 of the 10 patients during therapy; but once therapy was stopped, levels fell markedly. Side effects of interleukin 2 therapy included fever, chills, anorexia and fatigue. After 1 year of follow-up, three treated patients had lost HBeAg and had marked improvement in aminotransferase levels. These serologic and biochemical improvements occurred 1.5 to 11 months after therapy was stopped. Whether a 3- to 4-week course of interleukin 2 therapy leads to an increased rate of seroconversion from HBeAg to antibody in chronic type B hepatitis deserves further evaluation in prospectively randomized, controlled trials.
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PMID:Pilot study of recombinant human interleukin 2 for chronic type B hepatitis. 313 Dec 27

Ten patients were entered into an open study of interferon (IFN) 'induction' and oral acyclovir (ACV) 'maintenance' therapy. They received 5 Mega units (Mu)/m2 IFN by intramuscular injection daily for 3 days, followed by 7.5 Mu/m2 IFN daily for 7 days. IFN therapy was then discontinued and a 6-week course of oral ACV at a dose of 800 mg 4 times daily commenced. At 6 months, 2 patients had become HBeAg-negative and 1 had developed anti-HBe. Elimination of HBeAg in these patients was accompanied by return of serum liver function tests to normal. There was a statistically significant inhibition of DNA polymerase levels after the 1st week of IFN therapy, which then slowly increased to pretreatment values over 8 weeks. There were no significant adverse effects of ACV therapy, while fever, 'flu-like illness', fatigue, anorexia, and leucopenia were the main side-effects observed during the course of IFN which necessitated dose reduction in 7 patients. Combination therapy appears to effectively inhibit viral replication, although the 'maintenance' effect of oral ACV is minimal. A more effective drug to combine with IFN is needed.
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PMID:An open study of human lymphoblastoid interferon and oral acyclovir in chronic hepatitis B virus infection. 359 55

We conducted a clinical trial to study the effects of a 10-week course of prednisone therapy and its withdrawal on serum aminotransferase levels and on hepatitis B virus (HBV) markers in patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis (CAH-B). Eighteen patients with CAH-B were treated with prednisone, while another 18 patients matched for age, sex, race and sexual preference were followed simultaneously without treatment for the same duration. Nine of 18 prednisone-treated patients became transiently DNA polymerase positive. All nine patients developed a transient rise in serum alanine aminotransferase (ALT) levels of greater than 300 U/L above baseline values, which was associated with a drop in HBsAg levels from a mean of 186 micrograms/ml prior to therapy to 92 micrograms/ml at 6 months following treatment. Six of these patients developed fatigue, anorexia and dark urine, and four also developed either ascites or hemorrhage from esophageal varices, which was accompanied by hepatic encephalopathy. All six of these patients had histologic evidence of CAH with cirrhosis. In comparison, none of the control, untreated patients with CAH-B had any change in either HBV markers or serum ALT levels. Therefore, even a short course of prednisone in patients with CAH-B with cirrhosis is detrimental and its use should be discouraged.
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PMID:Effects of short-term, high-dose prednisone treatment of patients with HBsAg-positive chronic active hepatitis. 388 51

Nine patients with chronic type B hepatitis were entered into a preliminary study of recombinant, human alpha-interferon therapy. Patients received one to four courses of interferon, each consisting of a fixed dose of 18, 36, 50, 68, or 100 million units given three times a week for 2 wk. Side effects including fever, chills, fatigue, myalgias, headache, and neutropenia were common and especially severe with higher doses. Serum hepatitis B virus DNA polymerase activity fell during therapy to 15%-30% of the pretreatment levels irrespective of interferon dose, but rose to the initial level by 10 days after the course ended. During follow-up, 2 patients had a sustained clinical remission in which hepatitis B virus DNA, DNA polymerase, and hepatitis B e antigen disappeared from serum and amino-transferase activities fell to normal. One patient became hepatitis B surface antigen negative. We conclude that higher doses (50 and 68 million units) of interferon have greater side effects than lower doses (18 and 36 million units), without having any greater antiviral efficacy. Further studies should be directed at therapy with lower doses given over longer periods.
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PMID:Pilot study of recombinant human alpha-interferon for chronic type B hepatitis. 394 Feb 41

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
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PMID:Peripheral neuropathy and antiretroviral drugs. 1129 2

Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy, lipodystrophy, and myopathy. Because not all patients experience these side effects, genetic factors could be involved. It is believed that the main toxicity of nucleoside analog drugs is due to a decrease in mitochondrial function, possibly by inhibition of mitochondrial DNA (mtDNA) replication. mtDNA is replicated by a multienzyme complex, the main component of which is the nuclear-encoded DNA polymerase gamma. Presently, the only known variation in the DNA polymerase gamma gene is variation in the number of CAG repeats in the second exon. To investigate whether CAG repeat expansion or mutations in the DNA polymerase gamma (POLG) gene could predispose to peripheral neuropathy or lactic acidosis, we have sequenced part of the second exon of the DNA polymerase gamma gene, containing the CAG repeat, of 59 drug-treated HIV-infected patients, 11 of whom experienced drug-induced neuropathy, and 3 of whom died from lactic acidosis. No correlation was found between numbers of CAG repeats and any of the symptoms. The coding regions of the POLG gene from the three lactic acidosis patients were then completely sequenced, but no mutations were found. In addition, no variation was detected in exons 3, 8, and 19 of seven neuropathy patients and three control subjects without symptoms. These exons were the only sites of amino acid changes between human and chimpanzee POLG genes, and were chosen as targets of tolerated variation.
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PMID:Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment. 1203 82

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.
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PMID:Acute human immunodeficiency virus syndrome in an adolescent. 1452 19

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

Combination of the splenic marginal zone B-cell lymphoma (SMZL) and classical Hodgkin lymphoma (cHL) is extremely rare. We report a unique case with concurrent SMZL and cHL. The patient was a 63-year-old man who presented with fatigue and anemia, showing a splenomegaly and retroperitoneal lymphadenopathy. A splenectomy revealed monotonous marginal zone lymphocytic infiltrates and numerous large Reed-Sternberg-like cells. Flow cytometry revealed a kappa light-chain-restricted CD5 (-), CD23 (-) B-cell population. DNA polymerase chain reaction analysis confirmed the presence of clonal rearrangement of the immunoglobulin heavy-chain gene. Immunohistochemical studies revealed that the large atypical cells were CD30 (+), CD15 (weakly +), CD20 (-), CD45 (-), Pax5 (weakly +), BOB.1 (-), and Oct2 (-), indicating the coexistence of SMZL with cHL. After the chemotherapy, the patient achieved a clinical/radiologic remission, whereas cHL was detected in liver and bone marrow subsequently. The case indicates that both components of lymphoma can present concurrently as a composite form of lymphoma and both need to be treated adequately.
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PMID:Classical Hodgkin lymphoma concurrently evolving in a patient with marginal zone B-cell lymphoma of the spleen. 1848 99


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