Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human genome contains many simple tandem repeats that are widely dispersed and highly polymorphic. At least one group of simple tandem repeats, the DNA trinucleotide repeats, can dramaticallyexpand in size during transmission from one generation to the next to cause disease by a process known as dynamic mutation. We investigated the ability of trinucleotide repeats AAT and CAG to expand in size during DNA replication using a minimal in vitro system composed of the repeat tract, with and without unique flanking sequences, and DNA polymerase. Varying Mg2+concentration and temperature gave dramatic expansions of repeat size during DNA replication in vitro. Expansions of up to 1000-fold were observed. Mismatches partially stabilized the repeat tracts against expansion. Expansions were only detected when the primer was complementary to the repeat tract rather than the flanking sequence. The results imply that cellular environment and whether the growing strand contains a nick or gap are important factors for the expansion process in vivo.
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PMID:Effects of temperature, Mg2+ concentration and mismatches on triplet-repeat expansion during DNA replication in vitro. 1032 9

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drugs need dose modification. However, if the hepatic parenchymal abnormalities are caused by an underlying neoplasm and the neoplasm is sensitive to the drugs, it may not be necessary to reduce the dose. Clearly, this is an area where clinical judgment must be used to assess the risk/benefit ratio. Treatment of chronic hepatitis B virus (HBV) involves either the nucleoside analogue lamivudine or interferon alpha. The advantage of lamivudine includes limited adverse effects and the fact that histological improvement has been documented in the majority of patients. Primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HbsAg carriers. HbsAg screening is necessary before beginning chemotherapy for non Hodgkin's lymphoma patients. However, the main problem with long-term lamivudine therapy is the emergence of genotypic resistance because of base pair substitution at specific sites within the YMDD locus of the DNA polymerase gene. Significant hepatic dysfunction is uncommon among hepatitis C virus (HCV) infected patients treated with chemotherapy for hematological malignancies. However, infection with elevated AST levels is a significant risk factor for veno-occlusive disease after hematopoietic stem cell transplantation. Clinical judgment and a high index of suspicion remain critical tools in preventing and treating hepatic manifestations of cancer chemotherapy.
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PMID:[Hepatotoxicity of chemotherapy]. 1285 43

Adefovir is classified as a nucleotide reverse transcriptase inhibitor because it acts by inhibiting hepatitis B virus DNA polymerase (reverse transcriptase) and causing DNA chain termination after its incorporation into the viral DNA. Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine [ALT] or aspartate [AST]) or histologically active disease. It is useful in the treatment of patients with either hepatitis B e antigen-positive or -negative chronic hepatitis B. The recommended adefovir dipivoxil dose in the treatment of chronic hepatitis B in patients with adequate renal function is 10 mg once daily. Adefovir dipivoxil therapy can reduce viral load, improve ALT, and produce histologic improvement in patients with chronic hepatitis B. Improvements are generally seen within the first few weeks of therapy and have shown persistence up to at least 3 years with continued therapy. Therapy with adefovir dipivoxil is generally well tolerated. However, nephrotoxicity is a risk with adefovir therapy, especially in patients receiving higher doses (30-120 mg/d). Patients should have their renal function monitored closely throughout therapy and may require an adjustment in dose relative to changes in the creatinine clearance. Lactic acidosis and severe hepatomegaly with steatosis may also occur during therapy.
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PMID:Adefovir dipivoxil: focus on its use in the treatment of chronic hepatitis B. 1597 40


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