Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-10-18
1998-12-01
Scheiner, Toni R.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 72, 435 721, 435 79, 5303871, 53038822, 53038885, 5303891, 5303911, 5303913, G01N 3353, C07K 1628
Patent
active
058436774
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a method for measuring concentration of asialoglycoprotein receptors (hereinafter collectively referred to as "AGPR"), which is useful in the diagnosis of the functions of hepatocytes with improved sensitivity and accuracy. The invention also relates to a reagent used in the method and to a method for screening therapeutic drugs employing the method.
BACKGROUND ART
The liver is the largest parenchymatous organ in the human body and plays a central role in metabolism. Its main functions are diversified and include: (1) intermediary metabolism in relation to nutrients; i.e., oxidation of substances such as saccharides, fatty acids, and amino acids that are absorbed intestinally or mobilized from the peripheral tissue, as well as gluconeogenesis, synthesis and storage of lipids and proteins, and supply of lipids and proteins to other organs and peripheral tissues; (2) metabolism of various proteins other than nutrients and of precursors of such proteins; e.g., synthesis of constituent proteins of body tissue, serum proteins, and a variety of enzymes related to metabolism in the liver; (3) detoxication, conjugation, destruction, and deactivation of exogenous drugs, intrinsic hormones, ammonia, etc.; (4) intake and excretion as reticuloendothelial functions; (5) excretion and digestive functions associated with the production of bile; and (6) maintaining the internal environment by metabolism of water, electrolytes, and vitamins. Accordingly, lesions in the liver cause systemically abnormal metabolism, which induces secondary disorders in other organs to affect the body generally. Therefore, it is very important to know liver functions in morbid livers.
In the meantime, with recent advancement in medical equipment, progress of hepatectomy, and development of liver preserving fluids and immunosuppressants, hepatectomy in cases of liver carcinoma and liver transplantation in cases of hepatic cirrhosis have come to be performed actively. Therefore, grasping of liver functions is critical after surgery.
Hitherto, "standards for the selection and combination of liver function tests"--which were suggested by the liver function study group of the Japan Digestive System Disease Society as biochemical clinical test items for investigating liver functions (Nisshokai-shi, Vol. 85, pp. 1210-1214, 1988) have been widely used by internists and surgeons.
In the field of surgery, Ozawa et al. demonstrated that evaluation of the function of liver mitochondria in a non-invasive and more direct manner; i.e., using the ketone body ratio in arterial blood (AKBR), is an excellent liver function test (Gastroenterology, Vol. 76, pp. 691-696, 1979).
However, conventional biochemical test items tend to have low liver specificity and are frequently influenced by factors external to the liver. Moreover, in the method employing AKBR, care must be taken in collection of blood, handling of specimens, measurement, and in interpretation of data; thus this method cannot be said to be a suitable method. In spite that estimation of the post operational prognosis is important in consideration of high frequency of onset of post-operational liver disorders, a suitable test method has not yet been discovered.
In the field of internal medicine, Niitsu et al. reported that assay of asialoglycoprotein receptors (AGPR), which are highly specific to the liver, is suitable for use in the diagnosis of liver diseases (Japanese Patent Application Laid-Open (kokai) No. 4-356198).
AGPR is a lectin that recognize galactose and N-acetylgalactosamine residue (Morell et al., J. Biol. Chem., vol. 246, pp. 1461-1467, 1971). It is a liver-specific transmembrane glycoprotein which is present on the surface of the cell membrane of the liver parenchyma (Matsuura et al., J. cell Biol., Vol 95, pp. 864-875, 1982). Moreover, as a result of research using .sup.125 I-labeled asialoorosomucoid, which is a ligand of AGPR, the amount of AGPR on the surface of the cell membrane of the liver parenchyma has been found to decrease
REFERENCES:
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Kohgo Y. et al. 1993. Hybridoma 12(5): 591-598.
Whittaker, R.G. et al. 1983. J. Sci. Food Agric. 34(10):1143-48.
Morohoshi, N et al. 1989. Bull Sep For Tokyo Univ. Agric. Technol 6(26): 69-78.
Anonymous, Oct. 10, 1990-RD 318067.
Hanada Hisashi
Kato Junji
Kohgo Yutaka
Niitsu Yoshiro
Ushizawa Koji
Daiichi Pure Chemicals Co. Ltd.
Johnson Nancy A.
Scheiner Toni R.
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