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Biomedical subjects

K Tanikawa

Publications and source records attributed to K Tanikawa.

At least 91 records · Page 5Linked to original sources
PubMed1997

Influence of extravariceal collateral channel pattern on recurrence of esophageal varices after sclerotherapy.

We investigated the influence of extravariceal collateral channel pattern on the recurrence of esophageal varices after sclerotherapy. One hundred and fifteen patients with cirrhosis and esophageal varices were studied. They were divided into four groups according to extravariceal collateral pattern on portal venography. Group 1 patients had neither paraesophageal veins nor gastrorenal veins (n = 49); group 2 patients had paraesophageal veins only (n = 30); group 3 patients had gastrorenal veins only (n = 25); and group 4 patients had paraesophageal veins plus gastrorenal veins (n = 11). Sclerotherapy was repeated to eradicate esophageal varices and follow-up endoscopic examination were performed. The overall recurrence-free rate at 36 months was 68%. The log-rank test showed the recurrence-free rate to be significantly higher in group 3 (76%) and group 4 patients (89%) than in group 1 patients (51%; P < 0.05 and P < 0.05, respectively). Although the recurrence-free rate was higher in group 4 than in group 2 patients (59%), this did not reach the level of significance (P = 0.10). No significant differences were found between other pairs of groups. These results suggest that gastrorenal veins play an important role in the protection against recurrent esophageal varices after sclerotherapy, while the protective role of paraesophageal veins appears to be small.

Aged↗
PubMed1997

Hepatic stellate cells and intralobular innervation in human liver cirrhosis.

In normal and cirrhotic human liver tissues, we examined immunolocalization of alpha-smooth muscle actin (alpha-SMA), endothelin-1 receptor (ET-1R), and S-100 protein, with special emphasis on the intralobular spaces, using immunohistochemical methods. The ratio of the number of hepatic stellate cells (HSCs) with closely apposing nerve endings to the total number of HSCs in normal livers was compared with that in cirrhotic livers by electron microscopy. Immunolocalization of alpha-SMA and ET-1R was obviously recognized along the sinusoidal walls in cirrhotic liver and was significantly increased in cirrhotic liver compared with that in normal liver. Immunoreactive products for these substances were mainly localized in HSCs. However, immunolocalization of S-100 protein in intralobular spaces was markedly decreased in cirrhotic liver compared with that in normal liver. Nerve fibers were ultrastructurally hardly visible in intralobular spaces of cirrhotic livers. The ratio of the number of HSCs with closely apposing nerve endings to the total number of HSCs was significantly reduced in cirrhotic liver compared with that in normal liver. These results indicate that in liver cirrhosis, alpha-SMA-positive HSCs may play an important role in hepatic sinusoidal microcirculation through vasoactive agents such as ET-1 rather than through intralobular innervation.

Actins↗
PubMed1997

Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.

The interaction between tumor cells and laminin mediated by laminin-binding integrins is critical for tumor invasion and metastasis. The aim of this study was to clarify the altered expression of laminin-binding integrins with the change of laminin deposition in hepatocellular carcinoma (HCC) in comparison with cirrhotic or normal liver by immunohistochemistry. In HCC, hepatoma cells and sinusoidal endothelial cells expressed integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. Integrins alpha1beta1 and alpha6beta1 were detected in a continuous pattern along the sinusoids in accordance with laminin assembly. Integrins alpha2beta1 and alpha3beta1 were detected in a discontinuous pattern at these sites. Integrin alpha6beta4 was not detected. In cirrhotic liver, although integrins alpha1beta1 and alpha6beta1 as well as laminin were detected in a continuous pattern along the sinusoids, integrins alpha2beta1, alpha3beta1, and alpha6beta4 were not detected. In normal liver, although integrin alpha1beta1 was detected in a continuous pattern along the sinusoids, neither integrins alpha2beta1, alpha3beta1, alpha6beta1, alpha6beta4, nor laminin were detected. We have clarified that, of laminin-binding integrins, the localization of integrin alpha6beta1 shows the best correspondence with the localization of laminin. These results suggest that of laminin-binding integrins, integrin alpha6beta1 is very important for cell-laminin interactions in HCC.

Adult↗
PubMed1997

GB virus C (GBV-C)/hepatitis G virus (HGV) infection among intravenous drug users in Japan.

A sero-epidemiologic survey of 74 IVDUs and 86 age-matched controls was performed to investigate the prevalence, clinical significance, and genetic distribution of GB virus C (GBV-C)/hepatitis G virus (HGV) infection among intravenous drug users (IVDUs) in Japan. GBV-C/HGV RNA was detected by reverse transcriptase-hemi-nested polymerase chain reaction (RT-hemi-nested PCR) for the 5'-untranslated region (5'-UTR) in 43.2% (32/79) of the IVDUs compared with 1.2% (1/86) of the controls (P < 0.001). The duration of drug use did not correlate with the prevalence of GBV-C/HGV. Thirteen subjects positive for GBV-C/HGV RNA without HCV RNA had normal serum aminotransferase concentrations. Phylogenetic tree showed that the 32 GBV-C/HGV-positive isolates from IVDUs were classified within a new GBV-C/HGV group, which has been identified mainly in Asian subjects (type 3). The present study illustrated, (1) the high incidence of GBV-C/HGV infection among Japanese IVDUs, (2) GBV-C/HGV alone may not be an important pathogenic factor for hepatic injury, and (3) type 3 GBV-C/HGV was the most prevalent among IVDUs in Japan.

Adolescent↗
PubMed1997

Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.

BACKGROUND/AIMS: Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. METHODS: The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. RESULTS: Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. CONCLUSIONS: Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.

Adult↗
PubMed1997

Therapeutic effects of restricted diet and exercise in obese patients with fatty liver.

BACKGROUND/AIMS: The incidence of obese patients with fatty liver has recently increased in Japan as well as in the United States and Europe. Fatty liver may occasionally progress to liver cirrhosis. In this study, we have compared the effects of restricted diet and exercise versus no treatment in obese patients with fatty liver. METHODS: Twenty-five obese patients with fatty liver were divided into treated and control groups. Fifteen obese patients followed a program of restricted diet (ideal weight x 25 Cal x kg(-1)) and exercise (walking or jogging) for a trial period of 3 months. No changes in diet or lifestyle were made by the other 10 patients during the same trial period. Blood biochemical tests and liver histology were compared in all patients before and after the trial. RESULTS: In the treated group, weight, blood biochemical data such as aminotransferase, albumin, cholinesterase, total cholesterol and fasting blood glucose values, and steatosis were significantly decreased after the trial. In the control group, there were no significant differences in the clinical and histological findings before and after the trial. CONCLUSIONS: These results indicate that restricted diet and exercise therapy, such as walking and jogging, are useful means of improving blood biochemical data and histological findings in liver tissues related to fatty liver.

Adolescent↗
PubMed1997

Splanchnic and extrasplanchnic arterial hemodynamics in patients with cirrhosis.

BACKGROUND/AIMS: This study was designed to assess the contribution of splanchnic and extrasplanchnic vascular hemodynamics to the hyperdynamic circulation in patients with cirrhosis. METHODS: Cardiac index and flow volume index and pulsatility index (PI) of superior mesenteric artery (SMA) and femoral artery (FA) were measured with Doppler ultrasonography in 40 controls and 86 patients with cirrhosis (Child-Pugh grade A=41, grade B=30, and grade C=15). Mean arterial pressure was also recorded to calculate systemic vascular resistance index. RESULTS: Systemic vascular resistance index was significantly lower in each Child-Pugh group than in controls. SMA blood flow index was significantly higher in each Child-Pugh group than in controls and the increase in SMA blood flow index paralleled the degree of liver dysfunction. SMA-PI was significantly lower in each Child-Pugh group than in controls and the decrease in SMA-PI paralleled the degree of liver dysfunction. FA blood flow index was slightly higher in Child-Pugh grade A patients and significantly higher in grade B patients than in controls, whereas grade C patients had normal FA blood flow index. FA-PI was significantly lower in grade A and grade B patients than in controls, whereas grade C patients had normal FA-PI. When all patients were examined together, SMA-PI significantly correlated with systemic vascular resistance index (r=0.69, p<0.01). In contrast, FA-PI did not significantly correlate with systemic vascular resistance index (r=0.15, p=0.18). CONCLUSIONS: Splanchnic arterial vasodilatation plays an important role in the pathogenesis of decreased systemic vascular resistance seen in patients with cirrhosis.

Analysis of Variance↗
PubMed1997

Effect of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis.

BACKGROUND/AIMS: This study aimed to investigate the effects of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis. METHODS: The mean arterial pressure, cardiac index, peripheral vascular resistance index, and flow volume index of the superior mesenteric artery (SMA) and femoral artery (FA) were measured in 10 patients with cirrhosis and portal hypertension and 10 controls after they had been standing for 2 h. Plasma atrial natriuretic peptide, plasma renin activity, and plasma glucagon levels were also determined. These measurements were repeated after 30 min and 60 min when the patients were recumbent. RESULTS: In the upright posture, systemic hemodynamics, FA blood flow index, plasma atrial natriuretic peptide level, and plasma renin activity level were similar in patients and controls. However, SMA blood flow index and plasma glucagon level were significantly higher in patients than in controls. On the assumption of the supine position, cardiac index and plasma atrial natriuretic peptide level significantly increased in the two groups, but the changes were greater in patients than in controls. Mean arterial pressure remained unchanged. The reduction in peripheral vascular resistance index was therefore greater in patients in controls. SMA and FA blood flow index increased significantly in the two groups, but the changes were greater in patients than in controls. Furthermore, SMA blood flow fraction (SMA blood flow index/cardiac index) was steady in controls, whereas it increased significantly in patients. In contrast, FA blood flow fraction (FA blood flow index/cardiac index) remained unchanged in the two groups. In patients, the change in peripheral vascular resistance index was correlated inversely with that of SMA blood flow index, but not with that of FA blood flow index. Plasma renin activity level dropped significantly, but the decline was similar in the two groups. Plasma glucagon level was not modified in either group. CONCLUSIONS: In patients with cirrhosis, splanchnic vasodilation appears to be present, even in the upright position, and further abnormal vasodilation occurs on recumbency-induced blood volume expansion. This abnormal shear-stress phenomenon observed in the splanchnic circulation seems to be mediated by a local vasodilator rather than a general vasodilator.

Blood Volume↗
PubMed1997

Portal-hypertensive gastropathy develops less in patients with cirrhosis and fundal varices.

BACKGROUND/AIMS: The aim of this prospective study was to examine the association of portal-hypertensive gastropathy and fundal varices in patients with cirrhosis. METHODS: We carried out an endoscopic observation in 476 patients with cirrhosis (study 1), including 62 patients undergoing endoscopic obliteration of esophageal varices (study 2). In study 1, patients were classified into five subgroups: no esophagofundal varices (n=119), small esophagofundal varices (n=127), dominant esophageal varices (n=177), dominant fundal varices (n=27), and large esophagofundal varices (n=26). The severity of liver dysfunction was assessed by Pugh-Child classification: class A (n=222), class B (n=200), and class C (n=54). In study 2, two groups, poorly developed fundal varices (n=50) and well developed fundal (n=12), were distinguished and the follow-up endoscopic examinations were performed on the basis of 3-month intervals for 2 years. In each study, the severity of portal-hypertensive gastropathy was scored: 0 (absent), 1 (mild), 2 (severe), and 3 (bleeding). RESULTS: Study 1: One-way ANOVA showed that both variceal pattern and Pugh-Child class significantly influenced portal-hypertensive gastropathy score. However, two-way ANOVA indicated that variceal pattern was the only significant variable. Portal-hypertensive gastropathy score was significantly higher in patients with dominant esophageal varices than in either patients with no esophagofundal varices or patients with small esophagofundal varices. In contrast, portal-hypertensive gastropathy score in patients with dominant fundal varices was similar to that in patients with no esophagofundal varices and was significantly lower compared with that in patients with dominant esophageal varices. Furthermore, portal-hypertensive gastropathy score was significantly lower in patients with large esophagofundal varices than in patients with dominant esophageal varices. Study 2: After the obliteration of esophageal varices, portal-hypertensive gastropathy score in patients with poorly developed fundal varices became significantly higher at 3-, 6-, 9-months while it was not modified in patients with well developed fundal varices during the follow-up period. Furthermore, the integrated incremental change in portal-hypertensive gastropathy score during the first 1-year follow-up period was significantly lower in patients with well developed fundal varices than in patients with poorly developed fundal varices. CONCLUSIONS: These results indicate that both spontaneous and obliteration-induced portal-hypertensive gastropathy lesions develop less in patients with cirrhosis and fundal varices.

Endoscopy, Digestive System↗
PubMed1997

Intralobular innervation and lipocyte contractility in the liver.

In the liver of humans, guinea pigs, cats, and tupaia, nerve endings are distributed all over the hepatic lobules from the portal spaces to the centralobular spaces. Nerve endings in the intralobular spaces are located mainly in the space of Disse, and are closely related to lipocytes. In the human liver, various neurotransmitters such as substance P (SP) exist in the nerve endings. Lipocytes are believed to contract through these substances. In fact, the contraction of lipocytes is induced by SP. Moreover, lipocytes possess endothelin (ET) receptors (ETA, ETB), and the cells are contracted by ET-1 by way of ET receptors in the autocrine or paracrine mechanism. Contraction of lipocytes seems to be related to the enhancement of the intracellular Ca2+ and inositol phosphates. In addition, alpha-smooth muscle actin, which is a contractile protein, exists in the cytoplasm of lipocytes. Lipocyte contractility may be similar to that of vascular smooth muscle cells. On the other hand, prostaglandin E2, Iloprost, and adrenomedullin cause the elevation of c-AMP levels in lipocytes and relax the cells. In addition, lipocytes produce nitric oxide (NO) and inhibit contractility by an autocrine mechanism related to NO. In this way, lipocytes appear to be associated with the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the cirrhotic liver, intralobular innervation is decreased or absent, but ET-1 and NO are overexpressed. These phenomena indicate that lipocytes may play an important role in the sinusoidal microcirculation through these agents rather than through intralobular innervation in liver cirrhosis.

Animals↗
PubMed1997

Formation of black pigment gallstone in a hamster model of experimental cirrhosis.

The relationship between liver cirrhosis and the pathogenesis of black pigment stones has not been clarified. We attempted to induce black pigment stone formation in the gallbladders of hamsters. Male golden hamsters were divided into a cirrhosis group and a control group. Liver cirrhosis was induced by administering drinking water containing thioacetamide. The control group was given tap water. Gallstones at 48 weeks after treatment were examined by stereoscopic microscopy and scanning electron microscopy. The copper content of the black pigment stones was analysed by atomic absorption spectrophotometry. Black pigment stones in the gallbladder were detected in 25% of the cirrhosis group. Their surface and cross-section appeared amorphous. Black pigment stones contained copper. We confirmed the formation of gallstones in an animal model of cirrhosis by thioacetamide. Our findings may contribute to the clarification of the relationship between the pathogenesis of black pigment stones and the pathophysiology of liver cirrhosis.

Animals↗
PubMed1997

Transmission routes and clinical courses in sporadic acute hepatitis C.

Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1-2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Acute Disease↗
PubMed1997

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.

Administration, Oral↗
PubMed1997

Early therapy with interferon for acute hepatitis C acquired through a needlestick.

Because there is no effective neutralizing antibody or vaccine for preventing hepatitis C virus (HCV) transmission, HCV can be transmitted to health care workers through accidental needlesticks. Recently, two of our health care workers acquired HCV infection through needlestick accidents and developed acute hepatitis C. The route of transmission was confirmed by molecular evolutionary analysis with use of the E2 region of the HCV genome. After the clinical onset of acute hepatitis, the health care workers were treated with interferon (IFN) (total dose, approximately 300 megaunits). Neither individual developed chronic hepatitis. This finding raises the possibility that treatment with low-dose IFN following an accidental needlestick may be beneficial, even when it is started after the clinical onset of hepatitis.

Acute Disease↗
PubMed1997

Detection of MAGE-4 protein in the sera of patients with hepatitis-C virus-associated hepatocellular carcinoma and liver cirrhosis.

The aim of this study was to determine whether MAGE-4 protein is detectable in sera of patients with hepatocellular carcinoma and other liver diseases. An enzyme-linked immunosorbent assay was employed for detection of MAGE-4 protein in sera of liver disease patients, healthy men and women (control I) and those undergoing prostatic cancer screening (control II). MAGE-4 protein levels in sera of patients with hepatitis C virus-associated HCC (HCC-C) (n = 45, mean = 2.160 ng/ml) and HCV-associated cirrhosis (LC-C) (n = 55, 1.072 ng/ml) were significantly higher (P < 0.0001) than those of control I (0.327 ng/ml) or control II (0.394 ng/ml). MAGE-4 protein was positive in 21/45 (46.7%) HCC-C patients and 18/55 (32.7%) LC-C patients (cut-off, mean plus 2 SD in healthy controls) but in 0/12 (0%) hepatitis B virus-associated HCC (HCC-B) patients, 3/49 (6.1%) hepatitis B virus-associated LC (LC-B) patients, 4/47 (8.5%) alcoholic liver disease patients, and 1/49 (2.0%) controls. Serum MAGE-4 protein level may be useful as a marker for identification of LC-C patients suffering from HCC that is undetectable by presently available methods.

Adult↗
PubMed1997

Bafilomycin A1, a specific inhibitor of V-type H+-ATPases, inhibits the acidification of endocytic structures and inhibits horseradish peroxidase uptake in isolated rat sinusoidal endothelial cells.

The role of vacuolar type H+-ATPases (v-ATPases) and pH gradient between the endocytic compartments and cytoplasm in the endocytosis of horseradish peroxidase, a mannose-terminated glycoprotein, was investigated morphologically in isolated rat sinusoidal endothelial cells. Toward this purpose, a specific inhibitor of v-ATPases, bafilomycin A1, was used to inhibit v-ATPases in the vacuolar system. Uptake of horseradish peroxidase was examined by electron microscopy. Fluorescent staining by acridine orange showed that bafilomycin A1 inhibited the acidification of the endocytic compartments. Horseradish peroxidase was taken up via mannose receptors and was distributed in the endocytic structures in the isolated sinusoidal endothelial cells. Uptake of horseradish peroxidase was significantly inhibited by bafilomycin A1, and this finding was confirmed by morphometrical analysis. These results suggest that: a) v-ATPases are necessary for acidification of the endocytic compartments in the sinusoidal endothelial cells and b) the pH gradient between the endocytic compartments and the cytoplasm that is generated by v-ATPases is necessary for the receptor-mediated endocytosis of a mannose-terminated glycoprotein, horseradish peroxidase.

Acridine Orange↗