Agmatinase, which hydrolyzes agmatine to putrescine and urea, not only represents a potentially important mechanism for regulating the biological effects of agmatine in mammalian cells but also represents an alternative to ornithine decarboxylase for polyamine biosynthesis. We have isolated a full-length cDNA encoding human agmatinase whose function was confirmed by complementation in yeast. The single-copy human agmatinase gene located on chromosome 1 encodes a 352-residue protein with a putative mitochondrial targeting sequence at the NH(3)-terminus. Human agmatinase has about 30% identity to bacterial agmatinases and <20% identity to mammalian arginases. Residues required for binding of Mn(2+) at the active site in bacterial agmatinase and other members of the arginase superfamily are fully conserved in human agmatinase. Agmatinase mRNA is most abundant in human liver and kidney but also is expressed in several other tissues, including skeletal muscle and brain. Its expression in human liver is induced during hepatitis B virus infection, suggesting that agmatinase may play a role in the pathophysiology of this disease.
A pproximately 200 000 to 300 000 acute infections with hepatitis B virus (HBV) occur each year in the United States. More than 1 million persons have chronic HBV infection and ϳ5000 persons die each year from HBV-induced hepatocellular carcinoma and chronic liver disease in the United States.1,2 HBV is usually transmitted through sexual contact, exposure to blood or blood products, from mothers to neonates at birth, and inapparent percutaneous and permucosal exposures.Previous attempts at controlling HBV infection in the United States consisted of vaccinating high-risk populations and serologic screening of all pregnant women for hepatitis B surface antigen (HBsAg). However, these measures had little impact on the control of HBV infections; therefore, in 1992, the American Academy of Pediatrics recommended universal hepatitis B vaccination for newborns and routine vaccination of adolescents when feasible. Since then, immunization rates for newborns and adolescents with hepatitis B vaccine have steadily risen. The 2 currently available recombinant hepatitis B vaccines are Recombivax HB and Engerix B. Both contain purified recombinant HBsAg obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of HBV. CASE REPORTAs part of a class function, a 17-year and 8-month-old male donated blood at a local blood collection center. One week later he received a letter indicating he tested positive for HBsAg and recommending review with his personal physician. He was also notified that his name was added to the confidential Deferred Donor Directory stating, "You are now permanently deferred from donating blood, plasma, tissues or organs for others." He was brought to the pediatric clinic for additional evaluation of HBV infection. On further review of the laboratory studies from the blood collection center, he was noted to have a reactive HBsAg by enzyme immunoassay (EIA), a positive HBsAg confirmatory test by neutralization, alanine aminotransferase (Ͻ100 IU/L), nonreactive antibody to hepatitis B core antigen, and nonreactive antibody to hepatitis C virus. Evaluation in the pediatric clinic revealed no risk factors for HBV infection. In further discussion with him, it was determined that he received his third Engerix B vaccination (20-g dose) 18 days before his blood donation. Physical examination did not reveal any abnormalities. Laboratory studies were obtained 48 days after his third hepatitis B vaccination and revealed a nonreactive HBsAg by EIA, asparate aminotransferase (25 IU/L; normal: 8 -42), alanine aminotransferase (14 IU/L; normal: 0 -55), total bilirubin (.4 mg/dL; normal: .2-1.2), and direct bilirubin (.2 mg/dL; normal: .0 -.4). Repeat laboratory studies were performed 117 days after his third hepatitis B vaccination and revealed a negative HBsAg by EIA, negative immunoglobulin G and immunoglobulin M antibodies to hepatitis B core antigen by EIA, and a positive antibody to HBsAg. This is consistent with successful hepatitis B immunization.HBsAg is the ...
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