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The role of rat liver and kidneys in the catabolism of uracil and 5-fluorouracil in vivo
EXPRESSION OF HEPATITIS B VIRUS MARKERS IN ASYMPTOMATIC HBsAg CARRIERS WITH SPECIAL EMPHASIS TO PRE-S EXPRESSION
G. Hess, G. Gerken, W. Gerlich*, C. Weber, M. Manns, K.H. Meyer zum B(}schenfelde. I. Med. Klinik und Poliklinik, University of Mainz, FRG and *Abt. fiir Med. Mikrobiologie, University of G6ttingen, FRG In order to assess as to whether asymptomatic HBsAG carriers may vary in respect of expression of pre-S encoded proteins, their sere were evaluated. Thirtyfour sere of 1974 recognized and 1984 reevaluated HBsAg carriers were taken for this study, all were HBeAg negative, four had histologically a chronic hepatitis, all others a normal or largely normal liver by histology. HBsAg, HBeAg and anti-HBe were tested by commercial tests, HBV-DNA was examined as described by Scotto et el (Hepatology 1 9 8 3 : 2 7 9 - 284). Pre-S 1 encoded protein was tested by ELISA using a monoclonal antibody (J. Virol 1 9 8 4 : 3 9 6 - 402) and poly-HSA binding sites were analysed according to Hansson and Purcell (Infect Immun 1979: 125 - 13o). All individuals with chronic hepatitis had detectable poly-HSA and pre-S 1 encoded protein. In individuals with histologically normal or largely normal livers, l o were pre-S 1 and poly-HSA positive, 13 were poly-HSA positive and pre-S 1 negative and 7 lacked poly-HSA and pre-S 1 encoded proteins. The highest HBsAg concentrations were detected in poly HSA and pre-S 1 positive sera followed by poly-HSA positive and pre-S 1 negative sera. The lowest HBsAg concentrations were found in poly-HSA and pre-S 1 negative sera, there was however a significant overlapping between these groups. The study indicates that expression of pre-s encoded proteins is heterogenous in asymptomatic HBsAg carriers and is frequently related to the amount of HBsAg in the serum, may however, in some cases also be due to differences in pre-S gen expression.
THE ROLE OF RAT LIVER AND KIDNEYS IN THE CATABOLISM OF URACIL AND 5-FLUOROURACIL IN VIVO A. Holstege, J. Pausch, W. Gerok Department of Internal Medicine, University of Freiburg, D-7800 Freiburg, West-Germany Measurements of the a c t i v i t y of the entire enzymatic pathway of uracil catabolism in the cytosolic supernatant of d i f f e r e n t rat organs as well as the determination of the t o t a l amount of 5-fluorouracil catabolites, accumulated in these tissues, served to c l a r i f y the role of l i v e r and kidneys in the complete systemic breakdown of uracil (Ura) or 5-fluoroura-
weight).Total r a d i o a c t i v i t y in a l l other organs ranged from lO to 18~Ci/kg wet weight and was comparable to the amount of label in blood plasma. The sum of t o t a l acid-soluble catabol i t e s including dihydrofluorouracil,W-fluoro-A-ureidopropionicacid, and ~-fluoro-#I-alanine • ade up more than ~% of the label in both organs.lnjection of 5-diazouracil 2 h before a tracer dose of [6-1qC]FUra suppressed the rise in total acid-soluble r a d i o a c t i v i t y of l i v e r and kidneys by 75% and 66%, respectively. This was caused by a lowering of the sum of t o t a l FUra catabolites in both tissues. In blood plasma and a l l other organs, however, pretreatment with 5-diazouracil was followed by a 2-fold enhancement of the r a d i o a c t i v i t y contents due to the appearance of unchanged FUra amounting to more than 80% of the t o t a l label in each organ.Within 2 h, 12.7% of the administered r a d i o a c t i v i t y from FUra was excreted into bile. 5-Diazouracil lowered the b i l i a r y excretion of r a d i o a c t i v i t y to 2% of the injected dose.- Complete degradation of circulating pyrimidine bases was restricted to rat l i v e r and kidneys, with the major part occuring in liver. Inhibition of the catabolic pathway by 5diazouracil considerably increased the b i o a v a i l a b i l i t y of FUra.
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G. Hess, G. Gerken, W. Gerlich*, C. Weber, M. Manns, K.H. Meyer zum B(}schenfelde. I. Med. Klinik und Poliklinik, University of Mainz, FRG and *Abt. fiir Med. Mikrobiologie, University of G6ttingen, FRG In order to assess as to whether asymptomatic HBsAG carriers may vary in respect of expression of pre-S encoded proteins, their sere were evaluated. Thirtyfour sere of 1974 recognized and 1984 reevaluated HBsAg carriers were taken for this study, all were HBeAg negative, four had histologically a chronic hepatitis, all others a normal or largely normal liver by histology. HBsAg, HBeAg and anti-HBe were tested by commercial tests, HBV-DNA was examined as described by Scotto et el (Hepatology 1 9 8 3 : 2 7 9 - 284). Pre-S 1 encoded protein was tested by ELISA using a monoclonal antibody (J. Virol 1 9 8 4 : 3 9 6 - 402) and poly-HSA binding sites were analysed according to Hansson and Purcell (Infect Immun 1979: 125 - 13o). All individuals with chronic hepatitis had detectable poly-HSA and pre-S 1 encoded protein. In individuals with histologically normal or largely normal livers, l o were pre-S 1 and poly-HSA positive, 13 were poly-HSA positive and pre-S 1 negative and 7 lacked poly-HSA and pre-S 1 encoded proteins. The highest HBsAg concentrations were detected in poly HSA and pre-S 1 positive sera followed by poly-HSA positive and pre-S 1 negative sera. The lowest HBsAg concentrations were found in poly-HSA and pre-S 1 negative sera, there was however a significant overlapping between these groups. The study indicates that expression of pre-s encoded proteins is heterogenous in asymptomatic HBsAg carriers and is frequently related to the amount of HBsAg in the serum, may however, in some cases also be due to differences in pre-S gen expression.
THE ROLE OF RAT LIVER AND KIDNEYS IN THE CATABOLISM OF URACIL AND 5-FLUOROURACIL IN VIVO A. Holstege, J. Pausch, W. Gerok Department of Internal Medicine, University of Freiburg, D-7800 Freiburg, West-Germany Measurements of the a c t i v i t y of the entire enzymatic pathway of uracil catabolism in the cytosolic supernatant of d i f f e r e n t rat organs as well as the determination of the t o t a l amount of 5-fluorouracil catabolites, accumulated in these tissues, served to c l a r i f y the role of l i v e r and kidneys in the complete systemic breakdown of uracil (Ura) or 5-fluoroura-
weight).Total r a d i o a c t i v i t y in a l l other organs ranged from lO to 18~Ci/kg wet weight and was comparable to the amount of label in blood plasma. The sum of t o t a l acid-soluble catabol i t e s including dihydrofluorouracil,W-fluoro-A-ureidopropionicacid, and ~-fluoro-#I-alanine • ade up more than ~% of the label in both organs.lnjection of 5-diazouracil 2 h before a tracer dose of [6-1qC]FUra suppressed the rise in total acid-soluble r a d i o a c t i v i t y of l i v e r and kidneys by 75% and 66%, respectively. This was caused by a lowering of the sum of t o t a l FUra catabolites in both tissues. In blood plasma and a l l other organs, however, pretreatment with 5-diazouracil was followed by a 2-fold enhancement of the r a d i o a c t i v i t y contents due to the appearance of unchanged FUra amounting to more than 80% of the t o t a l label in each organ.Within 2 h, 12.7% of the administered r a d i o a c t i v i t y from FUra was excreted into bile. 5-Diazouracil lowered the b i l i a r y excretion of r a d i o a c t i v i t y to 2% of the injected dose.- Complete degradation of circulating pyrimidine bases was restricted to rat l i v e r and kidneys, with the major part occuring in liver. Inhibition of the catabolic pathway by 5diazouracil considerably increased the b i o a v a i l a b i l i t y of FUra.
$130