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Biomedical subjects

K Tanikawa

Publications and source records attributed to K Tanikawa.

At least 235 records · Page 13Linked to original sources

Ito cell contraction in response to endothelin-1 and substance P.

The contractile response of cultured Ito cells to endothelin-1 and substance P was examined. Ito cells were obtained from rat liver by perfusion with collagenase, followed by separation through centrifugal elutriation, and were cultured for 24 hr. The area of the Ito cells was measured after treatment with endothelin-1 or substance P at various concentrations in the culture medium. The area of the cells decreased dose dependently after treatment with endothelin-1 or substance P. The area of Ito cells before addition of interleukin-1 or substance P was defined as 100%. The area of the cells after treatment with endothelin-1 or substance P medium was expressed as the percentage against the area before treatment with endothelin-1 or substance P. The percentage in area after treatment with 200 nmol/L endothelin-1 was as follows: 81% +/- 13% at 30 min, 77% +/- 15% at 60 min, 87% +/- 15% at 120 min and 99% +/- 18% at 180 min. The maximal decrease in area occurred at 60 min after treatment. The percentage values for 200 nmol/L substance P were as follows: 88% +/- 15% at 10 min, 95% +/- 17% at 30 min and 101% +/- 17% at 60 min. The maximal decrease in area was noted at 10 min. Thus Ito cells contracted in response to treatment with endothelin-1 or substance P. The mode of the extent and onset of the contraction was different for the two peptides. These findings suggest that Ito cells are involved in the regulation of the hepatic sinusoidal microcirculation.

Animals↗

The relationship between LeY antigen and the therapeutic efficacy of interferon in chronic hepatitis C.

The expression of LeY antigen (Fuc alpha 1-->2Gal beta 1-->4 [Fuc alpha-->3] GlcNAc beta 1-->R), recognized by the monoclonal antibody BM-1, was studied in peripheral blood T-lymphocyte subpopulations in patients with viral hepatitis, and in liver tissue of patients with acute viral hepatitis. The relationship between the expression of LeY antigen on peripheral blood T-lymphocytes and the effects of interferon (IFN) therapy for chronic hepatitis type C were also evaluated. LeY antigen is not markedly expressed in B or T-lymphocytes of healthy individuals. However, it was strongly expressed in CD8 and CD4 T-lymphocytes in patients with viral hepatitis. In the acute phase of acute viral hepatitis, the expression of LeY antigen was more markedly expressed on peripheral CD8 T-lymphocytes than on CD4 T-lymphocytes. In chronic hepatitis type B and type C, it was significantly expressed more often on CD4 T-lymphocytes. In the liver tissues of patients with acute viral hepatitis, LeY antigen was expressed on hepatocytes and infiltrating lymphocytes. IFN therapy for chronic active hepatitis type C proved most effective when LeY antigen was more markedly expressed on the patient's CD4 and CD8 peripheral blood T-lymphocytes before treatment. Further studies are needed to clarify the relationship between the mechanisms of hepatic cell injury and LeY antigen.

Adult↗

Mechanism of thrombocytopenia in liver cirrhosis: kinetics of indium-111 tropolone labelled platelets.

Using indium-111 tropolone-labelled platelets, a study of platelet kinetics was performed on the basis of the relationship between platelet count, platelet survival time, platelet dynamics, platelet-associated immunoglobulin G (PA-IgG) and splenic volume in 31 patients with liver cirrhosis and a platelet count of less than 100 x 10(9)/l. The mean platelet count was 46.6 +/- 25.3 x 10(9)/l, and the mean platelet survival time was 6.50 +/- 1.33 days. The mean uptake into the spleen was 43.2% +/- 14.8% on the 1st day, and 53.7% +/- 14.3% on the 7th day. The mean PA-IgG level was 107.6 +/- 66.0 ng/10(7) platelets in five patients with chronic active hepatitis who were studied as controls, the mean platelet count was 197 +/- 30 x 10(9)/l, the mean platelet survival time 9.33 +/- 0.78 days, and the mean PA-IgG 21.2 +/- 2.9 ng/10(7) platelets. The former two parameters were significantly higher (P < 0.05), and the latter significantly lower (P < 0.05). In liver cirrhosis, the platelet count showed a positive correlation with the platelet survival time and a negative correlation with PA-IgG and the splenic volume. These results suggest that the increases in both the splenic platelet pool and platelet destruction in the spleen through immunological mechanisms may influence thrombocytopenia in liver cirrhosis.

Blood Platelets↗

Reduced portosystemic hemodynamic responsiveness after orthostasis in patients with cirrhosis.

We studied portosystemic hemodynamic responsiveness after 1 min orthostasis in nine patients with cirrhosis and nine age-matched normal subjects. Orthostasis increased diastolic arterial pressure, which is a close indicator of arterial tone, in normal subjects (+17%, P < 0.01). In contrast, no significant change in diastolic arterial pressure was observed in patients with cirrhosis (-3%, NS). The increase in heart rate was less in patients with cirrhosis than in normal subjects (+15% vs +28%, P < 0.05). Orthostasis also decreased portal blood flow, which was assessed by an echo-Doppler flowmetry, in normal subjects (-27%, P < 0.01), but in patients with cirrhosis it was not modified (-3%, NS). Plasma noradrenaline concentration showed similar increase in both groups (normal vs cirrhosis; +61% vs +55%, NS). Although the change in plasma noradrenaline concentration was related with that in diastolic arterial pressure (r = 0.71, P < 0.05) and inversely with that in portal blood flow (r = -0.69, P < 0.05) in normal subjects, no such significant correlation was found in patients with cirrhosis. We conclude that (1) a reduced hemodynamic responsiveness to sympathetic stimulation exists on both systemic and portohepatic vascular beds and (2) such a blunted baroreflex function is probably located at the receptor or effector level in patients with cirrhosis.

Adult↗

The endothelin-1 binding site in rat liver tissue: light- and electron-microscopic autoradiographic studies.

BACKGROUND: Endothelin (ET) is known as a vasoconstrictive substance. The receptors for ET have been shown in various organs. However, little is known about the endothelin-1 (ET-1) binding sites in the liver. The aim of this study was to examine ET-1 binding sites in the liver. METHODS: ET-1 binding sites in rat liver were studied in vivo by light- and electron-microscopic autoradiography using 125I-ET-1. RESULTS: Light-microscopic autoradiographic observation revealed strong localization of grains in the sinusoidal lining cells of the hepatic lobule and a small number of grains in the luminal space of the portal vein and central vein. In the hepatic lobule, more grains were located in the periportal region, and the quantity tended to decrease from the midzonal to the pericentral region. Electron-microscopic autoradiographic observation revealed grains in Ito cells and in the endothelial cells of the portal vein, central vein, and hepatic sinusoids. CONCLUSIONS: These results suggest that ET-1 acts on Ito cells and on endothelial cells of the hepatic sinusoids, portal vein, and central vein and that its action is related to hemodynamics of the liver, particularly regulation of the microcirculation of the hepatic sinusoids.

Animals↗

Effects of vasopressin and nicardipine on hemodynamics and liver function in patients with cirrhosis: comparison with vasopressin alone.

The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.

Aged↗

Observer agreement and variability in measuring gastric mucosal blood flow by laser Doppler flowmetry in humans.

We evaluated the reliability (i.e. reproducibility and variability) in measuring regional gastric mucosal blood flow by laser Doppler flowmetry in a total of 32 subjects (12 normal subjects and 20 patients with cirrhosis). The measurements were performed in quadruplicate within 10 min by observer A (A1, A2) and B (B1, B2) using blind techniques. The intraclass correlation coefficient (Ri) was used to assess observer agreement. Overall, the level of intra- (Ri, 0.87 for A1 vs. A2 and 0.87 for B1 vs. B2) and interobserver agreement (0.86 for A vs. B) was excellent. In contrast, there was a higher observer variability assessed by coefficient of variation. Overall, the mean value of coefficient of variation was 12% (max. 35%) for A1 vs. A2, 12% (max. 35%) for B1 vs. B2, and 13% (max. 33%) for A vs. B. These results suggest that laser Doppler flowmetry, although the reproducibility may be clinically acceptable, seems to still be a subjective method for quantitation of gastric mucosal blood flow in humans. Therefore, studies using this method can only be acceptable when the changes that investigators intend to measure are significantly higher than the variability.

Adult↗

Chronic hepatitis C in alcoholic patients: studies with various HCV assay procedures.

Chronic hepatitis (CH) is one of the features of alcoholic liver disease (ALD). The role of hepatitis C virus (HCV) infection was investigated in 50 alcoholic patients with CH, employing various types of HCV antibody. All patients had a drinking history of more than 80 g/day of ethanol and the diagnosis of CH was made by liver histology within 2 weeks of abstinence. We assayed serum HCV using C100-3 antibody (Ortho EIA and RIA), the second generation (HCV-2nd) (DAINABOT EIA and PHA), and we also examined HCV-RNA by PCR. The positive rate of C100-3 antibody was 56% by EIA and 66% by RIA. The HCV-2nd was much higher; 80% and 82% by EIA and PHA, respectively. The HCV-RNA was positive in 82% of patients. The positive rate for either of the HCV markers was 92% (46/50). In patients positive for C100-3, serum aminotransferase levels were still elevated even after abstinence and most of them showed chronic active hepatitis by liver histology. Follow-up liver biopsies showed histological progression even after abstinence. On the other hand, in some patients positive only for HCV-2nd and/or HCV-RNA, serum aminotransferase levels were normalized and histological improvement was observed soon after abstinence. These results suggest that histological determined CH in alcoholics is attributed mainly to the infection of HCV, HCV plays an important role in the histological deterioration after abstinence, and that the presence of C100-3 antibody reflects the activity of liver disease caused by HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Roles of the splenic cytokines and arachidonic acid metabolites in severe hepatic injury after lipopolysaccharide injection in chronically alcohol-fed rats.

We examined the early changes after lipopolysaccharide (LPS) injection in chronically alcohol-fed rats with or without splenectomy. Administration of 2 mg/kg body weight LPS caused severe hepatic injury. The plasma aspartate aminotransferase (ASAT) activity was significantly higher in sham-operated rats 8 hr after LPS injection than in splenectomized rats. The plasma tumor necrosis factor (TNF) activity was also significantly higher 1 hr after LPS injection in sham-operated rats than in splenectomized rats. The plasma thromboxane (TX) B2/6-keto-prostaglandin (PG) F1 alpha ratio increased in sham-operated rats after LPS injection. Therefore, the balance of arachidonic acid metabolites was in a hypercoagulated state in sham-operated rats after the LPS injection. Neutrophil infiltration into liver tissue increased in sham-operated rats after the LPS injection. The cytokines and arachidonic acid metabolites released from the spleen after LPS injection in alcohol-fed rats may play important roles in severe hepatic injury.

Animals↗

Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis.

Among the patients with alcoholic hepatitis, the patients with severe alcoholic hepatitis (SAH) were distinguished by clinical course, laboratory data and histological findings. The aim of this study was to clarify the clinicopathological features, pathological condition and pathogenesis of SAH. Twenty-four SAH patients were compared with 55 patients with acute type fulminant hepatitis (FH) and the other types of alcoholic liver disease. SAH showed a very poor prognosis with a survival rate of 25% and was complicated by multiple organ failure earlier than FH. IgA class lipid A antibody, endotoxin (Et) and tumor necrosis factor-alpha (TNF-alpha) levels in the blood well reflected the pathological condition and severity of SAH. The white blood cell count in the peripheral blood was thought to be the simplest indicator for the prediction of the prognosis of SAH. In conclusion, SAH involves hyper-endotoxemia due to dysfunction of the reticuloendothelial system in the liver, and cytokines including TNF-alpha and neutrophils play an important role in the severity of liver injury.

Adult↗

A hospital-based case-control study on hepatocellular carcinoma in Fukuoka and Saga Prefectures, northern Kyushu, Japan.

Three hundred and sixty-eight case-control sets (male 287 pairs; female 81 sets) were collected for a hospital-based case-control study of primary hepatocellular carcinoma (HCC) conducted in Northern Kyushu, Japan. All incident cases of HCC were collected weekly from the inpatients (aged 40-69) of the Second Department of Internal Medicine, Kurume University Hospital between April, 1986 and May, 1992. One control for a male case and 4 controls for a female case were sampled, being matched to a case on age (same 5-year age class), sex, residence (prefecture) and time of hospitalization (within 2 months after a case interview) from the inpatients of two general hospitals in Kurume. Information was collected by interview in person by a well-trained interviewer and from a review of hospital records by the authors. Multivariate analyses based on a conditional logistic regression model without an interaction term revealed that hepatitis B surface antigen (HBsAg) positive status (odds ratio (OR) = 8.67; 95% confidence interval (95%CI) = 2.54-29.57), history of blood transfusion over 10 years previously (2.40; 1.26-4.56), parental history of hepatic diseases (2.31; 1.11-4.80) and heavy alcohol drinking (60 < or = drink-years) by age 40 (3.23; 1.61-6.51) were statistically significant risk factors of male HCC. Univariate analysis for females also showed an elevated OR of HBsAg (7.58; 1.96-29.35). Although the sample size was limited, univariate analysis indicated that anti-hepatitis C virus antibody by c100-3 antigen positive status had a statistically significant OR for HCC in both sexes.

Adult↗

Serum alpha-fetoprotein and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein in patients with hepatocellular carcinoma.

A fraction of serum alpha-fetoprotein (AFP) reactive with lens culinaris agglutinin (LCA) was measured by affinity chromatography in serum samples from 102 patients with hepatocellular carcinoma (HCC) and 48 patients with chronic liver diseases without HCC. Its usefulness as a marker of HCC was evaluated. The mean +/- SD percentage of this fraction in total AFP was 3.10 +/- 3.17% in 48 patients with chronic liver diseases without HCC. When the cut-off level was set at 12.6% (mean + 3 SD), the sensitivity was 36.3%, the specificity was 100%, and the accuracy was 56.7% in the 102 patients with HCC. This lentil lectin-reactive AFP was positive in 7 of 25 patients (28%) who had single small liver cancer (phi < 20 mm), suggesting its clinical usefulness as a tumor marker. The lentil lectin-reactive AFP showed no correlation with the serum concentration of AFP or des-gamma-carboxy prothrombin (DCP). In patients with HCC showing an AFP level of 20 ng/ml or above, the lentil lectin-reactive fraction is a highly specific tumor marker. We consider it to be useful as an adjunct in the diagnosis of HCC.

Biomarkers↗

A study of erythrocyte C3b receptors (E-CR1) in patients with acute viral hepatitis.

Erythrocyte C3b receptors (E-CR1) were assayed by ELISA in 16 patients with acute viral hepatitis. In 13 patients with hepatitis type A, type B, or type non-A non-B, the E-CR1 level was significantly lower in the acute phase than in healthy controls, and recovered in the convalescent phase. The E-CR1 levels in 3 patients with non-A, non-B hepatitis remained below the mean level of the healthy controls. These findings suggest that the E-CR1 level fluctuates in acute viral hepatitis, and that it continues to be reduced in some patients with non-A non-B acute hepatitis.

Acute Disease↗

Sarcoidosis accompanied by pancreatic impairment.

A 64-year-old male complained of weight loss and slight fever. Bilateral hilar lymphadenopathy and hepato-splenomegaly were observed. Serum ACE level was high, and liver function was impaired. Laparoscopy demonstrated small white nodules on the liver surface. A definite diagnosis of sarcoidosis was made by histological study of the specimen by liver biopsy and noncaseating epithelioid cell granulomas composed of giant cells and epithelioid cells were revealed. Various pancreatic enzymes were increased on admission, suggesting pancreatic impairment due to sarcoidosis. Corticosteroid therapy improved liver and pancreatic functions and decreased splenomegaly. He has been followed up for 4 years and 5 months.

Humans↗

Prevalence of gastroesophageal varices supplied by intrahepatic portal branch.

The contribution of the intrahepatic portal branch to the gastroesophageal varices is rare. This anomalous pathway (a large left intrahepatic portal branch) was proved by portographic study and by imaging techniques in a 54-year-old man with cirrhosis. The overall prevalence of this type of collateral in the literature is only 1.9% in 908 patients with portal hypertension. In addition, all are via the left portal venous branch. It may be speculated that the mechanism of this variation is due to dilatation of the rest of the intrahepatic portal system via a small anastomosis due to portal hypertension.

Collateral Circulation↗

Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation.

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.

Acute Disease↗

Incidence of antibodies to hepatitis C virus in patients undergoing chronic dialysis and CAPD.

We measured antibodies to hepatitis C virus (anti-HCV) in patients who were receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Sixty seven patients (28%) were anti-HCV positive. The anti-HCV positive frequency increased with the time of treatment with dialysis, the frequency being 50% with a dialysis period > or = 10 years. The frequency of anti-HCV positivity was similar in patients with a history of blood transfusion (48/152, 32%) and in those without this history (19/89, 21%, p > 0.05). Therefore, in addition to blood transfusion, there may be other routes of HCV infection associated with long-term dialysis. Chronic liver disease was observed in 31% (21/67) of the patients positive for anti-HCV but in only 6% (11/174) of the negative patients (p < 0.01). HCV seems to be important as a cause of chronic liver disease in dialysis patients.

Adult↗