PubMed Health⌕ Search

Biomedical subjects

S Inuzuka

Publications and source records attributed to S Inuzuka.

At least 37 records · Page 2Linked to original sources
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

[An investigation of drug abuse and the utility of toxicology screening for use in emergency centers].

The results of toxicology screening of samples from 725 patients admitted to the Critical Care Medical Center (CCMC) of Nippon Medical School during a 10-month period from 1992-1993 (Group A) and a 4-month period from 1995-1996 (Group B) were discussed. We investigated the drug use of emergency patients using immunoassay. EMIT and Triage. The results were confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Blood samples were analyzed for ethanol (EtOH) by head space gas chromatography. Overall, 18% of the 725 cases tested positive for drugs, 13% for EtOH. Recently the positive rates of drugs and EtOH have been increasing. The positive rates for drugs in Group A and Group B were 15% and 23%, and EtOH were 11% and 17%, respectively. False positive cases caused by the cross-reactivity to analog were found in both EMIT and Triage. But the reliability of both methods was sufficient for clinical use. Rapid in easy toxicology screening can provide useful clinical information for patients admitted to a CCMC, especially for patients who have been injured, have sustained unknown-etiology consciousness disturbances, have CPAOA (Cardio Pulmonary Arrest on Arrival) or have committed drug abuse. We conclude that toxicology screening using immunoassay methods is suitable for use in an emergency center.

Adolescent↗
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

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

Construction and characterization of adenoviral vector expressing biologically active brain-derived neurotrophic factor.

To deliver brain-derived neurotrophic factor (BDNF) to the central nervous system, we sought to attain adenovirus-mediated transfer and expression of the gene in both in vitro and in vivo experiments. For this purpose, we constructed AxCA-BDNF, a recombinant adenoviral vector containing the BDNF cDNA expression cassette. Reverse transcription polymerase chain reaction analyses of the infected HeLa cells and the transduced mouse brain revealed successful expression of the BDNF gene both in vitro and in vivo. The results of a survival assay of chick dorsal root ganglion cells showed that the produced BDNF was biologically active. We consider, therefore, this newly constructed recombinant adenovirus to be a useful tool to deliver BDNF to degenerating neurons and to be applicable to gene therapy of neurodegenerative diseases and nerve trauma.

Adenoviridae↗
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

Patent vitelline duct in an adult deceptively appeared to be acquired umbilical urachal sinus: a case report.

Here is presented a surprisingly rare case in a 40-year-old male who had patent vitelline duct by nature. However, his congenital disease appeared deceptively to be an acquired umbilical urachal sinus on the diagnostic evaluations including fistulography before surgery. The diagnosis was definitely confirmed after the successful surgical procedure. The principal reason why these diseases were indistinguishable was reviewed. The incidence of each disease and incidence of association with umbilical fistula in each disease were discussed. With regard to these incidences, we compared urachal anomalies with vitelline duct anomalies through reference of several literatures. This is the most unique event we have ever clinically experienced.

Adult↗
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

Fibrogenesis in acute liver injuries.

We describe changes in the hepatic extracellular matrix (ECM) and its producing cells in acute liver injuries, primarily referring to transforming growth factor-beta 1 (TGF-beta), which is the most important cytokine involved in fibrogenesis. In addition, we describe the relationship between vitronectin (VN) and plasminogen activator inhibitor 1(PAI-1) in the self regulating mechanism of TGF-beta action for fibrogenesis in acute viral hepatitis. In the very early stage of acute liver injury, following aggregation of platelets, immunolocalization of TGF-beta is observed in injured areas. And at the cell migration stage, the infiltration pattern of inflammatory cells was characterized by an ordered progression of inflammatory cells, beginning with platelets and followed by polymorphonuclear leukocytes and macrophages. Following recruitment of inflammatory cells to the necrotic area, it appears that TGF-beta could be produced and activated by these inflammatory cells, resulting in the intensification of active TGF-beta distributions in the injured area. At the fibrosis stage, TGF-beta could also be produced by Ito cells, endothelial cells and hepatocytes at the periphery of the necrotic area, and may play important roles in the promotion of production and accumulation of ECM components in injured regions. In addition, the consistent localization of PAI-1 with VN in ECM near the necroinflammatory areas suggests that PAI-1 and VN could be involved in the modulation of fibrogenesis in acute liver injuries. In many kinds of acute liver injuries, fibrogenesis is usually considered to be transient, and injured liver tissues able to nearly recover in order.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
PubMed1993

The effects of prostacyclin analog OP-41483 on normothermic liver ischemia and reperfusion injury in rats.

To estimate the effects of the prostacyclin analog (OP-41483) on normothermic liver ischemia and reperfusion injury, saline (Group 1, N = 8), heparin (group 2, N = 8, 100 u/kg) or OP-41483 (group 3, N = 8, 400 ng/kg/min) was infused intravenously for 30 min before and after liver ischemia in rats. There were no significant differences in survival, or transaminase at 30 min after reperfusion among the three groups. Hepatic vessel flow and tissue flow were measured for the first 30 min after reperfusion. Hepatic tissue flow increased for the first 30 min after reperfusion in the group 3 rats, but not in the groups 2 and 3 rats. There were significant differences in hepatic tissue flow between the groups 1 and 3 rats at 20 min (p < 0.05), as well as significant differences between the groups 1 and 3 rats (p < 0.01) and the groups 1 and 2 rats (p < 0.05) at 30 min after reperfusion. There were no significant differences in total hepatic inflow among the three groups. Our data suggest that OP-41483 exerts beneficial effects by improving the microcirculation and increasing the effective hepatic blood flow in the ischemically injured liver after reperfusion.

Animals↗