肝, 胆道疾患における血清ロイシンアミノペプチダーゼとそのアイソザイムに関する臨床的研究

L-ロイシルベーターナフチルアミドを基質とする血清ロイシンアミノペプチダーゼに関する研究

抄録

Recent attentions in clinical enzymology have been paid toward on evaluation ofdiagnostic significance for alteration of blood enzymes activities as well as apathophysiologic analysis of their isozyme patterns. This report deals with a study of leucine aminopeptidase which acting on L-leucyl-β-naphthylamide (LN-LAP). Determination of its activity in serum, bile and tissue samples was carried out with referencesto its isozyme patterns and activating or inhibitory effect of D-leucine upon the enzyme. Discussions were made on clinical usefullness of the serum LN-LAP activity in thehepatobiliary diseases, mechanism of increase in total LN-LAP levels and certain isozyme patterns of serum and tissue samples, relationship between the serum and tissue LNLAP levels.
A total of 347 sera from 40 normal subjects and 237 patients, majority of whom with various hepatobiliary disorders, were determinated for serum LN-LAP by the method of Goldbarg et al. Alteration of hydrolysis rate of LN-LAP by addition of D-leucine was investigated in 136 sera. Mobility of LN-LAP isozmes was measured by paper or starch block electrophoresis in 20 samples of serum, bile or hepatic tissue. LN-LAP activity was also determinated in 21 tissue specimens of the liver or stomach and 2 bile samples. The results are summarized as follows.
1) Patients with cancer of the liver demonstrated the highest level of serum LNLAP activity. Patients with malignant obstructive jaundice, cholangioltic hepatitis, cholelithiasis, viral hepatitis and cholecystitis showed the second place of higher values. Patients with malignant tumors other than liver, bile duct and head of pancreas usualy gave normal LN-LAP results.
2) Ninety eight percents of patients with cirrhosis of the liver showed below 300 units, while 91 percents of patients with primary cancer of the liver showed more than 300 units and 82 percents of patients with metastatic cancer of the liver showed over 300 units. Measurement of serum LN-LAP activity is usefulll in detection of occult cancer in the liver.
3) It was supposed that increased serum LN-LAP activity in patients with cancer of the liver is attributed to release of LN-LAP from injured hepatic cells, transference of LN-LAP from congested bile to circulating blood, increase of production of LN-LAP in the vicinity of tumor and increase of LN-LAP in residual normal hepatic tissue in the tumor bearing conditions.
4) It was difficult to differenciate the causes of biliary obstruction by the level of serum LN-LAP activity.
5) Serum LN-LAP activity was, unlike alkalin phosphatase, scarcely elevated in patients with bone or parathyroid diseases.
6) Five out of 60 patients with malignant tumor showed inhibition of serum LNLAP by addition of D-leucine, while 5 out of 43 normal subjects or patients with benign diseases other than hepatitis showed activation by D-leucine.
7) Electrophoretic mobility of serum LN-IAP isozymes showed one peak coincided with al-globulin in normal subjects and most of patients with hepatitis. The second peak coincided with α₁-globulin or the third peak coincided withβ-globulin was demonstrated in patients with obstructive jaundice or liver cancer. LN-LAP in hepatic tissue demonstrated 3 peaks with a major one being coincided with al-globulin and LN-LAP in bile showed a major peak coincided with, β-globulin.
8) LN-LAP activity in hepatic tissue was diminished in patients with hepatitis and cirrhosis of the liver, while it was elevated in patients with cancer. LN-LAP activity in cancerous tissue per se showed an increase in cancer of the stomach and a decrease in cancer of the liver.