Levels of two types of lectin-reactive alpha-fetoprotein (AFP), designated AFP-L3 and AFP-P4+P5, were analyzed with Lens culinaris agglutinin A and AFP-P4+P5 with erythroagglutinating phytohemagglutinin, respectively, in an attempt to determine the utility and significance of these macromolecules as early indicators of hepatocellular carcinoma during the periodic follow-up of cirrhotic patients. The subjects were 51 of 190 consecutive cirrhotic patients in whom hepatocellular carcinoma developed during a 6-year follow-up period and 21 cirrhotic patients without hepatocellular carcinoma. Serum AFP levels were of limited value to diagnose and predict hepatocellular carcinoma. The relative levels of AFP-L3 and AFP-P4+P5 in patients with hepatocellular carcinoma at the time of tumor detection were significantly higher than those in patients with cirrhosis. The sensitivity was 61%, and the specificity was 90%. Fourteen patients (48%) of 29 patients with small hepatocellular carcinomas less than 2 cm in diameter showed elevated percentage of lectin-reactive AFP. Retrospective examination of 21 patients who were positive for lectin-reactive AFP at diagnosis of hepatocellular carcinoma showed that 41% of them had already expressed lectin-reactive AFP 12 months before the direct detection of hepatocellular carcinoma by diagnostic imaging. These results lead us to conclude that the level of lectin-reactive AFP is a suitable predictive marker for the early recognition of hepatocellular carcinoma in the follow-up of patients with cirrhosis, and that measurements of the level of lectin-reactive AFP should be added to the screening methods that are now in use.
We found functionally active thrombomodulin in human platelets (60 +/- 18 molecules per platelet). Protein C appeared not to be activated by thrombin with gel-filtered platelets. However, the activation of protein C by thrombin was accelerated by thrombin-stimulated and washed platelets. This cofactor activity of the platelets was neutralized by the anti-lung thrombomodulin-F(ab')2. From the Triton X-extract of platelets, thrombomodulin was partially purified by diisopropylphosphoryl-thrombin-agarose affinity chromatography. The Mr of the predominant platelet thrombomodulin was 78,000 before and 109,000 after reduction on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, values identical to those of placental thrombomodulin. The specific activity of the cofactor activity, apparent Kd (0.4 nM) for thrombin and Km (0.67 microM) for protein C of platelet thrombomodulin were also identical to those of placenta thrombomodulin. Thrombomodulin may play a role in activation of protein C on the surface of platelets.
hepatitis C virus, making many patients uneasy. Under such ''Sho-saiko-to'' (TJ-9) consists of 7 herbal components.circumstances, interferon (IFN) was reported to be effective In Japan, it is widely prescribed to patients with chronic in chronic hepatitis C. 1-4 IFN became acceptable therapy for viral liver disease. TJ-9 is known to suppress liver canhepatitis C under the national insurance coverage in 1992; cer development and possess macrobiotic effects, but its the resulting expenses of this treatment have been substanmode of action is not fully understood. This study investial. In some patients, the hepatitis C virus was completely tigated the following: 1) cytokine production levels, eliminated from the body and hepatitis apparently cured. mainly interleukin (IL)-10, in peripheral blood mononuHowever, unfortunately, IFN was effective in only 30% to clear cells of chronic active hepatitis B and C patients, 40% of treated patients. IFN was ineffective in patients who and healthy volunteers; 2) effects of TJ-9 on these prohad high virus levels or advanced histological grades. In addiductions; and 3) effects of each of its herb components tion, some patients were withdrawn from treatment due to on cytokine production in cell fractions. Results showed side effects. For these ineffective cases in IFN therapies, and that without stimulants, IL-10 production in mononufor those who had poor tolerability to IFN, the most widely clear cells of hepatitis B and C patients was significantly prescribed oral medicines in Japan are the following: herbal lower than that of healthy subjects (P õ .01). IL-10 production induced by either phytohemagglutinin (PHA) or medicine ''Sho-saiko-to'' (TJ-9; Xiao-Chai-Hu-Tang in Chipokeweed mitogen (PWM) in mononuclear cells of hepa-nese) and ursodesoxycholic acid, and by intravenous injectitis C patients were significantly lower than in patients tion, strong neominophagen C. with hepatitis B (P õ .01) and healthy subjects (P õ .05).In Japan, many herbal medicines, which originated and IL-10 production induced by anti-CD3 or lipopolysaccha-have been used for several thousand years in China, are manride (LPS) was significantly lower than in healthy sub-ufactured with uniform quality and quantity of components jects (P õ .05). The addition of TJ-9 to the cultures as drugs for hospital uses. These medicines have received strongly induced IL-10, and this induction was mainly official approval, have been used by Japan's Western mediattributable to the effects of 2 components (scutellaria cine practitioners for 20 years, and their clinical efficacy has root and glycyrrhiza root) on the monocyte/macrophage been well recognized. Among them, TJ-9, which has been fraction. The production of IL-4 and IL-5 in cultures with used in treatment for pyretic diseases in China, is well known concanavalin A (conA) was significantly higher in pa-for gradually improving subjective symptoms and abnormal tients with hepatitis C than in the healthy subjects (P õ liver functions of patients with chronic viral live...
To determine the risk of death at an early stage of fulminant viral hepatitis, we created severity indexes drawn from clinical data on the day of development of encephalopathy in 128 patients with fulminant hepatitis B and 103 with fulminant hepatitis non-A, non-B. In fulminant hepatitis B, the risk score was 2.75 x BL + 2.75 x BR + 2.7 x AG + 2.3 x WB + 1.67 x CD + 1.56 x AL - 0.098 x PR - 0.88, where BL is 1 if total bilirubin is higher than 20 mg/dl, BR is 1 if the ratio of total to direct bilirubin exceeds 2.2, AG is 1 if age is above 40 yr, WB is 1 if white blood cell count is less than 4,000 cells/mm3 or more than 18,000 cells/mm3, CD is 1 if a hazardous disease coexists and AL is 1 if ALT is less than 100 times the upper limit of normal (otherwise all are 0), and PR is prothrombin time (percentage of normal value). Using a cutoff score of 0, we found the positive predictive value, negative predictive value and predictive accuracy to be 0.90, 0.86 and 0.89, respectively. Sensitivity and specificity were 0.94 and 0.77, respectively. In fulminant non-A, non-B hepatitis, the risk score was 2.66 x BR + 2.25 x BL + 2.24 x DI + 2.05 x AL +/- 1.38 x AG + 0.00021 x WB - 6.33.(ABSTRACT TRUNCATED AT 250 WORDS)
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