Kazuaki Kamisaka

The binding of indocyanine green and other organic anions to serum proteins in liver diseases

Abstract Using Sephadex G-200 column chromatography, the binding patterns of organic anions with serum proteins were studied in normal subjects and in patients with liver diseases. BSP, [131I]BSP and [131I] Rose Bengal were bound mainly to albumin while small amounts were bound to globulin fractions. In normal sera, indocyanine green (ICG) in lower concentrations was bound mainly to β-lipoprotein while in higher concentrations it was bound to all fractions of proteins. In the various liver diseases, the binding patterns of ICG showed characteristic changes in comparison to those other organic anions. In acute hepatitis, obstructive jaundice and the Dubin-Johnson syndrome, the characteristic ICG peak II was decreased. In chronic liver diseases, such as chronic hepatitis and liver cirrhosis, the ICG peak II was increased remarkably and was bound to heavier proteins. Using single radial immunodiffusion and autoradiography, the binding of [131I]BSP with normal sera were studied. [131I] BSP was mainly to albumin, prealbumin and β-lipoprotein while small amounts were bound to the globulin fractions.

Organic anion transport study in mutant rats with autosomal recessive conjugated hyperbilirubinemia

The EHBR is a mutant rat strain with congenital conjugated hyperbilirubinemia bred from a Sprague-Dawley rat. Transport of conjugated bilirubin, indocyanine green, and tetrabromosulfophtalein from liver to bile is severely impaired in these rats. Serum bilirubin amounts to 6.0 +/- 0.05 mg/dl (n = 4) in adult rats, with 97% conjugates. The bile flow is reduced to about 65% of the control group, whereas total bile acid in 10-min bile samples is similar. Liver histology of 10 week-old rats revealed neither intracellular pigmentation nor architectural abnormalities.

Regulation of Hepatic Thrombopoietin Production by Portal Hemodynamics in Liver Cirrhosis

Objective:This study was designed to clarify how thrombopoietin (TPO) functions in and, to some extent, causes thrombocytopenia complicating liver cirrhosis and portal hypertension.Methods:Our study population consisted of 19 cirrhotic and six noncirrhotic patients who underwent percutaneous transhepatic portography (PTP) and hepatic venography.Results:The platelet counts of the cirrhotic patients were significantly lower than those of the noncirrhotic patients (8.7 ± 4.1 vs 17.4 ± 7 × 104/μl; p < 0.01). The flow direction in the splenic vein was confirmed by PTP. Ten hepatofugal and nine hepatopetal flow directions in the splenic vein were noted among the cirrhotics. The hepatofugal group showed lower portal venous pressure (20 ± 10 vs 32 ± 4 cm H2O; p < 0.01) than the hepatopetal group and had a higher incidence of hepatic encephalopathy (six of 10 vs zero of nine; p < 0.01). The hepatic vein-portal difference in TPO did not differ substantially between the cirrhotics and noncirrhotics (0.12 ± 0.04 vs 0.24 ± 0.07 fmol/ml). Comparisons of this value among the three groups showed the TPO difference to be lowest in the hepatofugal group (hepatofugal: 0.04 ± 0.03, hepatopetal: 0.21 ± 0.07, noncirrhotic: 0.24 ± 0.07; p < 0.05).Conclusions:Our findings suggest that TPO production in the cirrhotic liver is regulated by the portal blood supply to the liver. Thus, portal hemodynamics may play a critical role in the development of thrombocytopenia.

Ligandin reverses bilirubin inhibition of liver mitochondrial respiration in vitro.

Extract: Ligandin, an abundant cytoplasmic binding protein of bilirubin and other ligands in liver cells, completely prevented the inhibitory effect of bilirubin on respiration and oxidative phosphorylation by isolated rat liver mitochondria. At equimolar concentrations of bilirubin and ligandin or human serum albumin, mitochondrial respiration was fully restored to control values. At greater ratios of bilirubin and ligandin or human serum albumin, the latter had a stronger protective effect. These studies suggest that ligandin may have a physiologic role in protecting mitochondrial systems against bilirubin toxicity.Speculation: Some organs, such as liver, kidney, and intestine, transport various organic anions such as bilirubin and possess a soluble binding protein (ligandin) for protection of intracellular organelles. Other organs, such as the brain, lack this protective mechanism and, therefore, are more susceptible to toxicity as, for example, from bilirubin (kernicterus).

Effects on Gastric Circulation of Treatment for Portal Hypertension in Cirrhosis

We evaluated the gastric circulatory effects ofthe type of treatment administered for portalhypertension. Of 14 patients with cirrhosis, sevenreceived a transjugular intrahepatic portosystemic shunt (TIPS; group T) and seven received percutaneoustranshepatic portographic embolization (PTPE; group P).Patients were evaluated over the course of one year.After treatment, portal venous pressure wassignificantly reduced from 39 ± 6 cmH2O to 32 ± 5 (P < 0.001) in groupT and was significantly elevated from 29 ± 10 to33 ± 8 (P < 0.05) in group P. The portal flowvelocity (Vmean) was significantly higher in group T vs group P (P < 0.0001).The congestion index was significantly lower in group Tthan in group P (P < 0.0001). The gastric mucosalblood flow was increased in group T but was unchanged in group P. Esophageal varices showed someimprovement in both groups, but the portal hypertensivegastropathy was improved only in group T. These findingshelp to explain the differing effects on the gastric circulation related to the type of treatmentused for portal hypertension.

Purification of acidic Z protein from human liver.

Preparation of Z protein from human liver is described. Z protein consists of 2 forms which have different isoelectric points, pI 5.8 and pI 8.7, respectively. The acidic Z protein has a molecular weight of about 11,000 and has binding affinity for BSP using gel filtration.

Percutaneous transhepatic lymphography (PTL) for visualizing metastasized lesions from hepatocellular carcinoma

Abstract We performed percutaneous transhepatic lymphography (PTL) in order to evaluate lymphatic flow, especially metastatic lymph nodes, in patients with hepatocellular carcinoma (HCC). Lymphatics could be visualized in eight out of ten patients (80%), and LPD R (iodized oil) spreading showed its accumulation in two different patterns. In one type, the oil was limited to the lymphatics around the hepatic hilum, and in the other, it spread to the periaortic lymphatics. lymph nodes were visualized in four of the eight patients. This entire procedure was performed within 30 min without any side effects. Accordingly, we recommend this method for evaluating lymphatic metastases from hepatocellular carcinoma.

Clinical features of paradiverticulitis

Colonic diverticula have been generally acceptedas a source of massive hemorrhaging. Little is known,however, about fecal occult blood loss from colonicdiverticula and diverticulosis. We retrospectively investigated the possibility of minor bleedingin 737 diverticula cases diagnosed from April 1989 toMay 1994. Thirty-seven cases (5%) of diverticula areexplained as the sources of positive occult blood testing ascertained clearly by colonoscopy.These divide into three types: (1) fromintradiverticular bleeding (intradiverticulitis), (2)from peridiverticular bleeding (peridiverticulitis), and(3) from interdiverticular colonic mucosal erosion(interdiverticulitis). These findings account for theoccult blood loss that we call paradiverticulitis. Thetwo-year prospective study found 67 cases (11.3%) of paradiverticulitis in 595 diverticula cases.We concluded that paradiverticulitis is one of thecauses of positive occult blood tests.

Incidence of hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with interferon (IFN).

C型慢性肝炎に対し, インターフェロン (IFN) 治療を施行し, 治療終了後2年以上, 平均44カ月間定期的に経過観察されている371例を対象に肝細胞癌の発生率を検討した. 著効群 (治療終了6カ月後の血中HCV-RNA陰性かつalanine aminotransferase (ALT) 正常) 98例及び有効群 (治療終了6カ月後の血中HCV-RNA陽性かつALT正常) 27例からの発癌は経過観察期間中認められなかった. 無効群 (著効, 有効以外) 246例中7例に0.79%/年/人の割合で肝細胞癌の発生を認め, Staging別では, 1, 2, 3, 4でそれぞれ0%/年/人, 0.73%/年/人, 1.95%/年/人, 4.76%/年/人に肝細胞癌の発生を認めたが1～3においてはコントロール群に比し有意に低率であった.

Clinical characteristics of liver cirrhosis with extrahepatic portal-systemic shunt and in portal vein pressure <20 cmH_2O

門脈圧亢進症とは一般に門脈圧が20cmH2O以上とされている.しかし実際臨床の場では肝外門脈シャントは存在するが門脈圧20cmH2O未満の肝硬変症例を経験する.今回我々は門脈圧が20cmH2O未満の肝硬変症例10例の臨床的特徴について検討した.経皮経肝門脈造影(PTP)による評価では肝硬変症例110例中10例(9.1%)がそれに該当し,Child重症度はAl, B6, C3例であり,各病期に分散していた.コイル塞栓療法を施行した5例の門脈圧は14±4より23±2に上昇した.主要肝外門脈シャントの主要起始静脈として左胃静脈の関与例はなかった.内視鏡的にはF2以上の食道静脈瘤例は認めなかったが,F2以上の胃静脈瘤は3例にみられた.臨床症状は50%に反復性肝性脳症が認められたが,出血歴はなかった.