Measurement of Circulating Desialylated Glycoproteins and Correlation with Hepatocellular Damage

Marshall, James S.; Green, Allan M.; Pensky, Jack; Williams, Stanford; Zinn, Arthur B.; Carlson, Don M.

doi:10.1172/jci107792

Cited by 136 publications

(38 citation statements)

References 18 publications

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“…1. The normal control thrombin time ranged between 19 and 23 s with a mean of 22 s, whereas the thrombin times of the patient fibrinogens ranged from 31 s to 50 s. The prolongation of the thrombin time of the purified protein was similar to that of the respective patient's plasma. The 12 abnormal fibrinogens exhibited a progressive delay in the thrombin time with increasing sialic acid content.…”

Section: Resultsmentioning

confidence: 75%

“…Altered carbohydrate content of plasma glycoproteins has been described in patients with a variety of liver diseases. An R-type vitamin B12-binding protein and a thyroxine-binding globulin have been reported to have abnormal sialic acid content in certain patients with liver disease (18,19). Our studies taken together with these reports suggest that patients with a variety of liver diseases may exhibit a disturbance of the carbohydrate content of several of the plasma glycoproteins synthesized by this organ, and this alteration of the carbohydrate moiety may, in some cases, be responsible for a ftinctional defect of the protein.…”

Section: Discussionmentioning

confidence: 99%

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Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Martinez¹,

Palascak²,

Kwasniak³

1978

J. Clin. Invest.

111

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A B S T R A C T To evaluate the possibility that the carbohydrate composition of fibrinogen may be altered in the dysfibrinogenemia associated with liver disease, we studied the sialic acid content of purified fibrinogen from 12 patients with liver disease and its relationship to the prolongation of the thrombin time. Purified fibrinogen showed intact Aa-, Ba8-, and y-chains when reduced and analyzed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and exhibited prolongation of the thrombin time similar to that of the plasma from which it was derived. Sialic acid content of the purified fibrinogen ranged from 12.7 to 71.4% higher in patient fibrinogens when compared to normal controls. A progressive delay in thrombin time was associated with increasing sialic acid content of the patient fibrinogen. Enzymatic removal of sialic acid from four of the abnormal fibrinogens resulted in a shortening of their thrombin times to the range of the desialylated normal control. Periodic acid-Schiff reagent stained only the B,8-and y-chains of the reduced patient fibrinogens after sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the excess sialic acid is located on these two chains. These studies demonstrate a biochemical alteration of the functionally abnormal fibrinogen fouind in some patients with liver disease, and indicate that the excess sialic acid plays an important role in the ftunctional defect of this protein.

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Section: Resultsmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Martinez¹,

Palascak²,

Kwasniak³

1978

J. Clin. Invest.

111

View full text Add to dashboard Cite

show abstract

“…Asialoglycoproteins bind to asialoglycoprotein receptors and are subsequently taken up by receptor-mediated endocytosis and delivered to lysosomes for degradation. A significant decrease in asialoglycoprotein receptors together with accumulation of plasma asialoglycoproteins is seen in patients with chronic liver diseases (24,25). At first, 99m Tc-labeled galactosylneoglycoalbumin was developed as a synthetic asialoglycoprotein to visualize and quantify its hepatic binding to the asialoglycoprotein receptor (26).…”

Section: M Tc-gsa Scintigraphy Backgroundmentioning

confidence: 99%

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Graaf¹,

Bennink²,

Veteläinen³

et al. 2010

J Nucl Med

138

120

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This review describes the application of 2 nuclear imaging techniques for assessment of hepatic function in the setting of liver surgery and transplantation. The biochemical and technical background, as well as the clinical applications, of 99m Tc-labeled diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) scintigraphy and hepatobiliary scintigraphy (HBS) with 99m Tc-labeled iminodiacetic acid derivates is discussed. 99m Tc-mebrofenin is considered the most suitable iminodiacetic acid agent for 99m Tc-HBS. 99m Tc-GSA scintigraphy and 99m Tcmebrofenin HBS are based on 2 different principles. 99m Tc-GSA scintigraphy is a receptor-mediated technique whereas HBS represents hepatic uptake and excretion function. Both techniques are noninvasive and provide visual and quantitative information on both total and regional liver function. They can be used for preoperative assessment of future remnant liver function, follow-up after preoperative portal vein embolization, and evaluation of postoperative liver regeneration. In liver transplantation, these methods are used to assess graft function and biliary complications.

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“…99m Tc-GSA is a synthetic asialoglycoprotein that binds to the asialoglycoprotein receptor (ASGPR). ASGPR is abundantly expressed on the hepatocyte sinusoidal surface (12), and its expression is reduced with increased severity of chronic liver disease such as cirrhosis (3,13,14). Dynamic 99m Tc-GSA scintigraphy can be combined with SPECT, enabling the assessment of liver function and functional liver volume (FLV) within 1 test (1,3).…”

mentioning

confidence: 99%

Quantitative Assessment of Hepatic Function During Liver Regeneration in a Standardized Rat Model

et al. 2011

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Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. 99m Tcgalactosyl human serum albumin ( 99m Tc-GSA) scintigraphy, 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare 99m Tc-GSA scintigraphy, 99m Tc-mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. Methods: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. Results: During liver regeneration, functional liver volume measured by 99m Tc-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by 99m Tc-mebrofenin uptake and excretion rates, 99m Tc-GSA uptake rate, and ICG clearance. On days 5 and 7, 99m Tc-mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas 99m Tc-GSA uptake reflected a reduced liver function in relation to conventional liver volume and 99m Tc-mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. Conclusion: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, 99m Tc-GSA uptake underestimates hepatic regeneration in comparison to liver volume and 99m Tc-mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. 99m Tc-mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function.

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Measurement of Circulating Desialylated Glycoproteins and Correlation with Hepatocellular Damage

Cited by 136 publications

References 18 publications

Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Quantitative Assessment of Hepatic Function During Liver Regeneration in a Standardized Rat Model

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