Biomedical subjects

T Torimura

Publications and source records attributed to T Torimura.

At least 37 records · Page 2Linked to original sources

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

Reduced contractility and histological changes in the gallbladder due to portal hypertension in a hamster cirrhosis model.

BACKGROUND/AIMS: Little is known about the relationship of portal venous pressure to contractility and histological changes in the gallbladder. In this study, we investigated the relationship between portal hypertension and contractility and histological changes in the gallbladder in a hamster cirrhosis model. METHODS: Liver cirrhosis was induced in the hamsters (n = 20) by thioacetamide (TAA). Portal venous pressure was directly measured using a pressure-measuring instrument. The contractility of the gallbladder was appraised by the diameter before and after caerulein treatment. Gallbladder wall thickness and vessel areas in tissues were evaluated in relation to the portal venous pressure. RESULTS: The portal venous pressure, gallbladder wall thickness with submucosal edema and area of vessels in the gallbladder wall in the cirrhosis group were significantly increased compared with those in the control group (n = 20, receiving saline instead of TAA). The gallbladder contraction rate in the cirrhosis group was significantly decreased compared with that in the control group. In the cirrhosis group, there were positive correlations between the portal venous pressure and the gallbladder contraction rate, gallbladder wall thickness, and area of vessels. CONCLUSIONS: In the gallbladders of experimental cirrhotic hamsters, portal hypertension caused dilatation of the vessels as well as submucosal edema, and was an important factor in the increased thickness and reduced contractility of the gallbladder wall.

Animals↗

PubMed1997

The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.

Adult↗

PubMed1996

Evaluation of hyaluronic acid binding ability of hepatic sinusoidal endothelial cells in rats with liver cirrhosis.

BACKGROUND & AIMS: In liver cirrhosis, the binding and degradation of hyaluronic acid in the hepatic sinusoidal endothelial cells are considered to be reduced by development of hepatic sinusoidal capillarization, resulting in high serum hyaluronic acid concentration. The aim of this study is to clarify the cause of high blood hyaluronic acid concentration in liver cirrhosis. METHODS: Liver cirrhosis was induced in rats by thioacetamide administration. In vivo observation of sinusoidal capillarization, in vitro immunolocalization of factor VIII-related antigen and CD44, and [14C]hyaluronic acid binding in cultured sinusoidal endothelial cells were determined. RESULTS: Basement membranes were observed on the basal side of sinusoidal endothelial cells. The fenestrae and fluorescent intensity of anti-CD44 bound to the cells decreased with progression of hepatic fibrosis. Immunofluorescent reactive products of factor VIII-related antigen were more abundant in the cirrhotic rats compared with the controls. Amount of [14C]hyaluronic acid binding was significantly decreased in the cirrhotic group compared with the controls. CONCLUSIONS: One reason that the blood hyaluronic acid concentration increases markedly in liver cirrhosis is considered to be the reduction in hyaluronic acid receptors of hepatic sinusoidal endothelial cells and in the amount of hyaluronic acid binding to the cells.

Animals↗

PubMed1996

Significance of serum tissue inhibitor of metalloproteinases-1 in various liver diseases.

BACKGROUND/AIMS: This study was performed to assess the significance of elevated serum tissue inhibitor of metalloproteinases-1 concentration in various liver diseases. METHODS: Tissue inhibitor of metalloproteinases-1 levels were measured in patients with various liver diseases, and were compared with serum type III procollagen-N-peptide (P III P), type IV collagen and laminin P1 levels, as well as with the histology of liver biopsy specimens. RESULTS: Mean tissue inhibitor of metalloproteinases-1 levels were significantly higher in subjects with acute viral hepatitis, cirrhosis, alcoholic hepatitis, and alcoholic cirrhosis than in the control group (p < 0.05). Serum tissue inhibitor of metalloproteinases-1 levels in the various liver diseases showed positive correlation with serum type IV collagen, P III P, and laminin P1 levels. Regarding the relationship between tissue inhibitor of metalloproteinases-1 and liver histology, serum tissue inhibitor of metalloproteinases-1 levels correlated with the degree of hepatic fibrosis and inflammation, such as focal necrosis and cell infiltration. Furthermore, elevated serum tissue inhibitor of metalloproteinases-1 levels were especially related to the cell infiltration, focal necrosis, portal fibrosis, and serum type IV collagen level. CONCLUSIONS: These findings suggest that the measurement of the serum tissue inhibitor of metalloproteinases-1 level in various liver diseases may be useful to estimate the active hepatic fibrogenesis associated with the active inflammatory stage of the liver injury.

Adult↗

PubMed1995

Transforming growth factor beta 1, extracellular matrix, and inflammatory cells in wound repair using a closed duodenal loop pancreatitis model rat. Immunohistochemical study.

BACKGROUND: Serial changes in the localization of various components of extracellular matrix in acute pancreatitis have been reported, but there have been no reports on serial changes in the localization of transforming growth factor beta and the determination of cells producing extracellular matrix. METHODS: In this study serial relationships between the localization of transforming growth factor beta 1, fibronectin and type-III collagen, inflammatory cells, and serum amylase levels in the process of tissue repair in acute pancreatitis were studied using a closed duodenal loop model rat. Furthermore, the cells producing transforming growth factor beta 1, fibronectin, and type-III collagen were investigated by immunoelectron microscopy. RESULTS: Three to 6 h after duodenal ligation slight localization of transforming growth factor beta 1 and fibronectin and inflammatory cell infiltration were observed in the interlobular space. Twelve to 24 h after duodenal ligation the infiltration of polymorphonuclear leukocytes and the deposition of transforming growth factor beta 1 and fibronectin were observed extensively in the interlobular and intralobular spaces. After release of the loop, infiltration of fibroblasts and marked deposition of fibronectin and type-III collagen were observed around the tubular complexes, but the deposition of transforming growth factor beta 1 was slight. Also, fibronectin and type-III collagen were shown to be produced by fibroblasts and acinar cells. CONCLUSIONS: These findings suggest that transforming growth factor beta 1 appears at the injured sites from the early stage of acute pancreatitis. Moreover, it is extensively related to the production of extracellular matrix such as fibronectin and type-III collagen. Furthermore, these substances are closely involved in the healing process of acute pancreatitis.

Acute Disease↗

PubMed1995

Leukocyte adhesion molecules in the liver and plasma cytokine levels in endotoxin-induced rat liver injury.

BACKGROUND: The interactions between polymorphonuclear neutrophils (PMNs) and sinusoidal endothelial cells (SECs) have been known to be involved in the pathogenesis of acute liver injury. It has been also reported that tumor necrosis factor-alpha (TNF-alpha) up-regulates ICAM-1 expression on SECs and that interleukin-8 (IL-8) provokes rapid activation of CD11/CD18 on PMNs. These findings expand into the relationship between the expression of leukocyte adhesion molecules (ICAM-1, CD11a/CD18 and CD11b/CD18) in liver tissues and plasma TNF and IL-8 levels after lipopolysaccharide (LPS)-induced liver injury in rats. METHODS: Male Wistar rats weighing 200-250 g were treated with 2 mg LPS/kg intravenously in a 0.2- to 0.25-ml volume. Liver and blood samples were obtained at 1, 3, 8, and 12 h after LPS exposure. Plasma TNF and IL-8 levels were measured using bioassay and specific enzyme-linked immunosorbent assay, respectively. Liver samples were fixed and studied by immunohistochemistry using specific monoclonal antibodies against ICAM-1, CD11a, and CD11b. RESULTS: The TNF level showed a peak at 1 h (23.3 +/- 11.4 IU/ml), and the IL-8 level showed a peak at 3 h (343.1 +/- 110.5 ng/ml) after LPS exposure. An increase in the number of PMNs in the liver was observed as early as 1 h and continued until 12 h after LPS exposure. PMNs adhered to degenerated SECs and hepatocytes. ICAM-1 on SECs was diffusely and strongly expressed at 8 h, and PMNs adhered to SECs expressed both CD11a and CD11b. ICAM-1 was also observed on hepatocytes. CONCLUSION: These data suggest that PMN-SEC and PMN-hepatocyte interactions via leukocyte adhesion molecules, related to inflammatory cytokines such as TNF and IL-8, exist and play an important role in the pathogenesis of acute liver injury.

Animals↗

PubMed1994

Cultured rat hepatic sinusoidal endothelial cells express intercellular adhesion molecule-1 (ICAM-1) by tumor necrosis factor-alpha or interleukin-1 alpha stimulation.

This study investigated the expression of intercellular adhesion molecule-1, a leukocyte adhesion molecule, on cultured rat hepatic sinusoidal endothelial cells during stimulation with tumor necrosis factor-alpha or interleukin-1 alpha. Using immunoelectron microscopy and the immunogold technique against intercellular adhesion molecule-1, gold particles were shown to increase significantly on the surface of sinusoidal epithelial cells treated with tumor necrosis factor-alpha (100 U/ml) or interleukin-1 alpha (10 U/ml) for 8 h compared with unstimulated cells. In addition, semi-quantitative analysis of intercellular adhesion molecule-1 on the sinusoidal endothelial cells was performed by cytofluorometer. Even without stimulation, intercellular adhesion molecule-1 was weakly expressed. However, 8 h after tumor necrosis factor-alpha or interleukin-1 alpha treatment, the expression of intercellular adhesion molecule-1 on cells was increased in a dose-dependent manner. Kinetic analysis showed that the expression of intercellular adhesion molecule-1 on sinusoidal endothelial cells treated with these cytokines increased gradually from the beginning of stimulation to 24 h. These findings suggest that hepatic sinusoidal endothelial cells may mediate the direct interaction between leukocytes and sinusoidal endothelial cells by expressing leukocyte adhesion molecules such as intercellular adhesion molecule-1.

Animals↗

PubMed1994

The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis.

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.

Adult↗

PubMed1994

A patient with hepatic granuloma formation and angiotensin-converting enzyme production by granuloma cells during clinical relapse of hepatitis A.

Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis.

Adult↗

PubMed1994

Morphological observation on extrahepatic bile duct of golden hamsters fed a lithogenic diet: histochemical, ultrastructural and cell kinetic studies.

Cholelithiasis is often accompanied with disorders of the extrahepatic bile duct and pancreas. However, studies on changes of the extrahepatic bile duct in cholecystolithiasis have not shown this clearly. We therefore investigated sequential histologic changes, mucous secretion and DNA synthetic activity of the extrahepatic bile duct epithelium in cholecystolithiasis. Serial changes in the mucosal epithelial cells of the extrahepatic bile duct in golden hamsters treated with a lithogenic diet were examined by light and electron microscopy and an ultrastructural quantitative technique. In addition, epithelial cell kinetics were studied using bromodeoxyuridine (BrdU). After the 2nd week of diet, the extrahepatic bile duct showed an increase in goblet cells of the mucosal epithelium, a large number of secretory granules in the upper nuclear area of the epithelial cells and an increase in the BrdU-labeling index compared with the controls. These findings indicate that mucous secretion and cell turnover were enhanced in the mucosal epithelial cells of the extrahepatic bile duct in cholelithiasis, suggesting that the epithelial cells of the bile duct were protected and regenerating.

Animals↗

PubMed1993

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↗

PubMed1993

Serum hyaluronate reflects hepatic sinusoidal capillarization.

BACKGROUND: Most of circulating hyaluronate has been commonly degraded by hepatic sinusoidal endothelial cells (SECs). In hepatic sinusoidal capillarization, SECs morphologically change and also seem to decrease hyaluronate degradation. This work expands on the relationship between serum hyaluronate levels and changes in hepatic SECs accompanying hepatic sinusoidal capillarization. METHODS: Serum hyaluronate levels were determined using an enzyme binding assay system. Liver biopsy specimens were collected to examine basement-membrane formation, the localization of Weibel-Palade bodies, and the localization of factor VIII-related antigen (FVIIIRAg) in SECs. RESULTS: Serum hyaluronate levels increased with the progression of liver disorder, being high in all patients with liver cirrhosis. Patients showing markedly high serum hyaluronate levels, 200 ng/mL or more, had liver cirrhosis involving the SECs, which showed basement-membrane formation, Weibel-Palade bodies, and FVIIIRAg and closely resembled vascular endothelial cells. CONCLUSIONS: Measurement of the serum hyaluronate concentration allows the evaluation of morphological and functional changes that occur in SEC accompanying hepatic sinusoidal capillarization in various liver disorders. The findings also suggest that patients with high serum hyaluronate levels, 200 ng/mL or more, have liver cirrhosis with typical hepatic sinusoidal capillarization formed by SECs containing FVIIIRAg.

Adolescent↗

PubMed1992

Vitronectin in liver disorders: biochemical and immunohistochemical studies.

The concentration of plasma vitronectin was determined and compared with various parameters of liver function including the blood coagulation system in patients with liver diseases. The severity of cirrhosis was graded according to Child's criteria and compared with the plasma vitronectin level. Furthermore, the distribution of vitronectin in the liver of patients with liver diseases was studied by light and electron microscopy using the indirect immunoperoxidase method. The plasma vitronectin level was low in all liver disease groups as compared with the healthy controls. The difference from the controls was significant in patients with hepatocellular carcinoma and decompensated cirrhosis. Moreover, the plasma vitronectin level was positively correlated with the levels of serum cholinesterase, albumin, plasma alpha 2 plasmin inhibitor-plasmin complex and the prothrombin time and results of the hepatoplastin test. Plasma vitronectin decreased with increasing severity of cirrhosis according to Child's criteria. These results suggest that the plasma vitronectin level is a useful parameter of hepatic synthetic function in patients with liver diseases; it may also reflect the severity of cirrhosis. Light microscopy revealed vitronectin in the area of focal necrosis and the portal tracts in the liver of patients with acute viral hepatitis, in the area of piecemeal necrosis in the liver of patients with chronic hepatitis and along the area of fiber deposition in the liver of patients with cirrhosis. Immunoelectron microscopy showed vitronectin in the rough endoplasmic reticulum of hepatocytes. Moreover, vitronectin was seen around inflammatory cells, endothelial cells, Ito cells and hepatocytes in the perisinusoidal area near focal necrosis and piecemeal necrosis and on collagen fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Sclerosing hepatocellular carcinoma with hypercalcemia--a case report.

A case of sclerosing hepatocellular carcinoma (SHCC) with hypercalcemia was reported. Clinical studies revealed a tumor at the liver hilum with invasion into the bile duct. Light microscopy of the tumor disclosed a moderately differentiated hepatocellular carcinoma (HCC) of the trabecular type with diffuse fibrous stroma. Abundant dense granules were observed in the cytoplasm of the tumor cells with electron microscopy. The elevated serum calcium (13.9 mg/dl) returned to the normal range after resection of the tumor.

Carcinoma, Hepatocellular↗

PubMed1992

Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen.

Serum type-IV collagen levels determined with a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen were compared with histologic changes in liver biopsy specimens from 107 patients with various liver diseases. Serum type-IV collagen levels were increased in the groups with liver diseases compared with controls. The serum type-IV collagen levels in the group with alcoholic cirrhosis showed significantly higher values than the other groups (P less than 0.05). A significant positive correlation was found between the serum type-IV collagen level and the degree of fibrosis or cell infiltration in 107 patients. Immunolocalization of type-IV collagen was observed around blood vessels and bile ducts increased in number in the portal tracts, with cell infiltration and fibrosis, increased around vessels in fibrous septa, and sinusoidal walls of areas with cell infiltration or necrosis in hepatic lobules, and along the boundary between fibrous septa and hepatocytes. The present data indicate that serum type-IV collagen may be a sensitive marker for active fibrosis and that the elevation of serum type-IV collagen level primarily reflects the enhancement of type-IV collagen synthesis and deposition in the liver tissue at the stage of active fibrosis in liver disease.

Adolescent↗

PubMed1991

Radiographic evidence of cholecystokinin octapeptide receptors in the hamster gallbladder.

The distribution of cholecystokinin receptors in the hamster gallbladder was investigated by 125I-labeled Bolton-Hunter-cholecystokinin octapeptide autoradiography. Light microscopic examination showed a marked accumulation of radiolabeled cholecystokinin within the domain of the muscle layer of the gallbladder. The electron microscopic study further disclosed the presence of radiolabeling mostly in those areas corresponding to cell-to-cell junctions of smooth-muscle cells. Our results suggest that contraction of the gallbladder may primarily be induced by cholecystokinin interacting with its specific receptor in smooth-muscle cells. That cholecystokinin receptors were more abundant in the junctional complexes of smooth-muscle cells suggests that cholecystokinin may have a major role in muscle contraction of the gallbladder, which eventually produces an effective bile emptying.

Animals↗

PubMed1991

Mechanism of fibrous capsule formation surrounding hepatocellular carcinoma. Immunohistochemical study.

In 14 cases of hepatocellular carcinoma with capsule, we studied the mechanism of capsule formation by the immunoperoxidase technique using antibodies to types I, III, and IV collagen, antilaminin antibody, and anti-prolyl hydroxylase antibody. Marked round cell infiltration was observed in the noncancerous side of the capsule and around compressed hepatocytes near the capsule. Thin capsules were composed primarily of type III collagen produced by an increased number of fibroblasts, transitional Ito cells, and hepatocytes near the capsule. In thickened capsules, the noncancerous side consisted primarily of type III collagen and the cancerous side of types I and III collagen. Type I as well as type III collagen was produced by fibroblasts, transitional Ito cells, and hepatocytes. The capsule thus formed is suggested to be part of the defense mechanisms against the growth of hepatocellular carcinoma.

Adult↗