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S Kawata

Publications and source records attributed to S Kawata.

At least 109 records · Page 6Linked to original sources
PubMed1994

Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes.

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.

Animals↗
PubMed1994

Enhanced expression of group II phospholipase A2 in human hepatocellular carcinoma.

Enzyme activity, protein contents, and mRNA contents of group II phospholipase A2 (PLA2) in hepatocellular carcinoma (HCC) surgically obtained from 8 patients were compared with those in either its neighboring liver tissues or control liver tissues. The PLA2 specific activity towards the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was significantly greater in the tumor tissues (6.62 +/- 1.46 nmol/min/mg) than those in the surrounding liver tissues (1.33 +/- 0.22 nmol/min/mg) and controls (0.43 +/- 0.04 nmol/min/mg). The results of immunoblot analysis using a specific anti-human group II PLA2 antibody and of Northern blot analysis using a human group II PLA2 cDNA as a probe demonstrated that group II PLA2 was responsible for the increased enzyme activity. The contents of immunoreactive group II PLA2 in the tumor tissues (8.81 +/- 1.24 ng/mg) were significantly higher than those in the surrounding liver tissues (1.74 +/- 0.27 ng/mg); those in the control tissues were below the analytical range of the method used. The group II PLA2 mRNA was also significantly increased in the tumor tissues, compared with that in the surrounding liver tissues, whereas it was not detectable in the controls. This indicates that group II PLA2 in HCC is induced at the pretranslational level.

Carcinoma, Hepatocellular↗
PubMed1994

Plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases.

BACKGROUND: Many kinds of human malignant tissue, including hepatocellular carcinoma (HCC), were reported to overexpress transforming growth factor-beta 1 (TGF-beta 1) gene. However, little work has been done on the circulating TGF-beta 1 in patients with malignant tumors. METHODS: Plasma TGF-beta 1 levels in patients with HCC (n = 26) were compared with those in patients with chronic hepatitis (CH) (n = 12) and cirrhosis (n = 11) and in normal subjects (n = 20) using an enzyme-linked immunosorbent assay system after acid/ethanol extraction. RESULTS: The patients with HCC had significantly higher plasma TGF-beta 1 levels (19.3 +/- 19.5 ng/ml; mean +/- standard deviation [SD]) than those in normal subjects (1.4 +/- 0.8 ng/ml) and in patients with CH (3.0 +/- 3.1 ng/ml) and cirrhosis (3.7 +/- 2.1 ng/ml) (P < 0.01). Plasma TGF-beta 1 concentrations in the patients with cirrhosis were also significantly higher than those in the normal subjects (P < 0.05). The extracted plasma TGF-beta 1 from the patients with HCC had biologic activity according to a growth inhibitory assay using mink lung epithelial cells. No significant correlation was found between the plasma TGF-beta 1 levels in the patients with HCC and serum alpha-fetoprotein levels. After successful treatment for HCC, the amount of plasma TGF-beta 1 significantly decreased from 22.6 plus or minus 16.7 ng/ml (mean +/- SD) to 10.2 plus or minus 6.5 ng/ml (P < 0.05). CONCLUSIONS: We demonstrated higher levels of plasma TGF-beta 1 in the patients with HCC than those in patients with chronic hepatitis and cirrhosis. Plasma TGF-beta 1 might be a candidate for a novel tumor marker for hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1994

Heparin-binding EGF-like growth factor is a potent mitogen for rat hepatocytes.

We examined the hepatotrophic activity of heparin-binding EGF-like growth factor (HB-EGF), a recently identified potent mitogen for vascular smooth muscle cells and fibroblasts. HB-EGF stimulated DNA synthesis of rat hepatocytes in primary culture in a dose-dependent manner up to 30 ng/ml. The maximal stimulation by HB-EGF represented more than 80% of that induced by HGF. In normal rat liver, the transcript of HB-EGF gene was detected in the non-parenchymal cells and very low level in the hepatocytes. In the regenerating liver on the 3rd day after 70% hepatectomy, the HB-EGF mRNA increased in the non-parenchymal cells, suggesting that HB-EGF may contribute to liver regeneration through a paracrine mechanism.

Animals↗
PubMed1994

Interleukin-6 in transcatheter arterial embolization for patients with hepatocellular carcinoma. Effects of serine protease inhibitor.

BACKGROUND: Modulation of serum levels of circulating cytokines and inflammatory responses with a serine protease inhibitor was studied in 34 patients with hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS: The 34 patients were randomly divided into two groups: 17 patients received 500 mg gabexate mesilate, a serine protease inhibitor, intravenously twice a day for 5 days after TAE, and the remaining 17 patients did not receive the drug. RESULTS: In the patients not given the drug, circulating interleukin-6 (IL-6) markedly increased 1 day after TAE, reached a peak (approximately 8 times the pretreatment value) after 4 days, and remained elevated 7 days after TAE. In comparison, in the patients given the drug, circulating IL-6 was at a significantly lower level at 4 and 7 days after TAE (P < 0.05, respectively). Both groups did not show significant change in circulating interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) during the week after TAE. The drug also showed a tendency to keep patient temperature below 38 degrees C, and the elevation of serum C-reactive protein (CRP) concentration to less than 1 mg/dl after TAE (P < 0.05, respectively). CONCLUSIONS: The serum level of circulating IL-6 can be modulated by serine protease inhibitor, and this may contribute to suppressing inflammatory responses, such as fever and acute-phase protein synthesis, in the liver after TAE.

Aged↗
PubMed1994

Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate synthetase deficiency.

Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency.

Adult↗
PubMed1994

Impaired ketogenesis in patients with adult-type citrullinemia.

BACKGROUND/AIMS: To clarify the mechanism causing fatty liver in adult-type citrullinemia, the effect of fasting on blood levels of free fatty acids, triglycerides, and ketone bodies was investigated in two cases. METHODS: Blood and urine samples were collected from two patients and healthy volunteers 12, 15, 17, 21.5, and 24 hours after their last meal. RESULTS: During 24-hour fasting free fatty acid concentrations increased in both cases to the concentrations found in the healthy volunteers. The levels of blood ketone bodies (beta-hydroxybutyrate and acetoacetate) were markedly suppressed throughout the fasting test without any increase in urinary excretion of ketone bodies or organic acids in both cases when plasma citrulline concentrations were more than 10-fold higher than in controls. Serum triglyceride concentrations in case 1 paradoxically increased from 185 mg/dL to 294 mg/dL during 24-hour fasting when the citrulline concentration was extremely high. When hemodialysis was performed and plasma citrulline consequently decreased to near the normal level in case 1, levels of both serum triglycerides and blood ketone bodies responded normally to 24-hour fasting. CONCLUSIONS: These data suggest that ketogenesis was impaired in adult-type citrullinemia.

Adult↗
PubMed1994

Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma.

BACKGROUND/AIMS: Growth factors are involved in the development and progression of cancer. The purpose of this study was to evaluate the possible role of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is a member of the EGF family, in the neoplastic transformation of hepatocytes. METHODS: Gene expression and protein production of HB-EGF were investigated in samples of human hepatocellular carcinoma (HCC) from 17 patients using Northern hybridization and immunohistochemical methods. RESULTS: The amount of HB-EGF messenger RNA was increased in the patients' HCC specimens compared with the surrounding liver tissues. In noncancerous hepatic tissues, HB-EGF was faintly positive in hepatocytes. Immunoreactive HB-EGF-producing cells were identified in HCC cells of all 17 patients with HCC, indicating that HB-EGF was produced in HCC cells themselves. However, none of the specimens from 10 patients with metastatic adenocarcinoma in the liver was positive for HB-EGF. The EGF receptor, which binds to HB-EGF, was also expressed on HCC cells. CONCLUSIONS: It is hypothesized that the enhanced expression of immunoreactive HB-EGF on the cell suggests a possible role of HB-EGF in the development or progression of human HCC in an autocrine and/or a juxtacrine manners.

Adult↗
PubMed1994

Occurrence of IDDM during interferon therapy for chronic viral hepatitis.

We report a case of IDDM which occurred during interferon therapy for chronic hepatitis. A 31-year-old man intermittently received 2.5 x 10(8) units of alpha-IFN and 1 x 10(8) units of beta-IFN for treatment of chronic viral hepatitis type B. Four years after the beginning of IFN therapy, he acutely developed moderate hyperglycemia and severe ketonuria with positive islet cell antibody, and then 28 units/day of insulin injection was started. After the start of insulin therapy, there was a remission period for about 3 years but insulin-dependency recurred thereafter. The clinical course of this case indicates that IFN therapy precedes IDDM. During and after IFN therapy we should consider the possibility of occurrence of IDDM as well as other autoimmune diseases and observe the clinical course carefully.

Adult↗
PubMed1994

Modulation of the mevalonate pathway and cell growth by pravastatin and d-limonene in a human hepatoma cell line (Hep G2).

Modulation of cell growth by a combination of pravastatin [a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor] and d-limonene (an inhibitor of protein isoprenylation) was studied using Hep G2, a human hepatoma-derived cell line. Pravastatin, at 0.1 mM, produced 85% inhibition of cholesterol biosynthesis in Hep G2 cells. The combination of 0.1 mM pravastatin and 1.0 mM d-limonene had no further effect on the reduction seen with pravastatin alone. Addition of 0.1 mM pravastatin or 1.0 mM d-limonene did not significantly suppress DNA synthesis by the cells, whereas the combination suppressed it to 50% of the control level. Production of m-p21ras was markedly decreased to 35% of the control level by the combination of these two inhibitors. Both the reduction by pravastatin of farnesylpyrophosphate as substrate for protein:farnesyl transferase and inhibition of protein farnesylation by d-limonene seem to be responsible for the profound suppression of m-p21ras formation in the cells. However, dolichol synthesis was not suppressed by the combination of these inhibitors. In human fibroblasts, the combination suppressed m-p21ras production but not DNA synthesis. These findings suggest that the combination of pravastatin and d-limonene acts on cancer cell growth through inhibition of the post-translational processing of cellular proteins including p21ras, rather than through the suppression of cholesterol and dolichol biosynthesis. Thus, the combination of an HMG-CoA reductase inhibitor and an inhibitor of protein isoprenylation offers potential as a new approach for cancer therapy.

Antineoplastic Agents↗
PubMed1994

Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: poor response to transforming growth factor-beta 1 and interferons.

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin-binding epidermal growth factor-like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor-beta 1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor-beta type II receptor gene was about 50% of that in normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Extralysosomal degradation of high-density lipoproteins in a human hepatoma cell line, Mahlavu.

Lipoprotein metabolism has been investigated in a novel human hepatoma cell line, Mahlavu, which has been reported to possess the characteristics of hepatocytes. Low-density lipoprotein (LDL) was degraded by Mahlavu cells. LDL taken up by the cells suppressed intracellular cholesterol biosynthesis and promoted cholesterol esterification in a manner similar to that of HepG2 cells. High-density lipoprotein (HDL) was also degraded by Mahlavu cells, whereas it was not degraded by fibroblasts. We compared the mode of intracellular metabolism of HDL to that of LDL. In contrast to the LDL receptor pathway, the degradation of HDL was not inhibited by 100 microM chloroquine added to the medium, indicating that the degradation may not occur in lysosomes. Cholesterol taken up as HDL-cholesterol by the Mahlavu cells had no effect on the intracellular biosynthesis of cholesterol nor on cholesterol esterification. The conditioned media in which Mahlavu cells had been cultured did not promote the degradation of HDL, suggesting that HDL is degraded intracellularly. These data suggest that HDL is taken up and degraded by the liver cells in contrast to extrahepatic peripheral cells such as fibroblasts and macrophages in which the degradation of HDL does not occur. The results indicate that HDL-associated cholesterol may be processed via a pathway different from that of LDL metabolism and that the degradation of HDL occurs extralysosomally.

Carcinoma, Hepatocellular↗
PubMed1993

Aromatase activity in human hepatocellular carcinoma. Relationship with the degree of histologic differentiation.

Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease. This relationship was not found in the five with Grade 3 disease. On the whole, aromatase activity was significantly higher in specimens from patients with Edmondson's Grade 2 tumors than in the less differentiated Grade 3 type (P < 0.05). These observations suggested that aromatase activity was present in human HCC and was related to the degree of histologic differentiation.

Aged↗
PubMed1993

A combined anterolateral thigh flap, anteromedial thigh flap, and vascularized iliac bone graft for a full-thickness defect of the mental region.

A triple combined anterolateral thigh flap, anteromedial thigh flap, and vascularized iliac bone graft was used for reconstruction of a full-thickness defect of the mental region after wide resection of advanced tongue cancer. The distal end of the pedicle vessels of these double skin flaps, i.e., the lateral circumflex femoral system, was directly anastomosed in tandem to the pedicle of the iliac bone graft, which was enveloped by these flaps. The advantages of this iliac osteocutaneous flap are as follows: It can be transferred within a shorter surgical time because the flaps can be obtained in the supine position simultaneously with tumor resectioning; and its skin components can be separated from the bone because each component has its own pedicle vessels, has a longer vascular pedicle (> 10 cm), and has a thicker crest of the bone graft. This flap is believed to be suitable for reconstruction of large full-thickness defects in various sizes of the mandibular and maxillary regions of the face.

Aged↗
PubMed1993

Metastasis of hepatocellular carcinoma to the colon demonstrated by Tc-99m PMT scintigraphy.

A 57-year-old man was found to have a tumor in the ascending colon after hepatic segmentectomy for ruptured hepatocellular carcinoma. Colonoscopy was performed, and metastasis of the hepatocellular carcinoma to the ascending colon was suspected based on the biopsy specimens obtained from the tumor. On hepatobiliary scintigraphy using Tc-99m PMT performed to confirm this diagnosis, Tc-99m PMT was clearly observed to accumulate in the tumor. Thus, the tumor was diagnosed as metastasis of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1993

The gluteal perforator-based flap for repair of sacral pressure sores.

A gluteal perforator-based flap employing the gluteus maximus muscle perforators located around the sacrum is described. A cadaveric study disclosed the existence of several significant perforators all around the gluteal region. Among these, the parasacral perforators originating from the internal pudendal artery and lateral sacral artery have proven useful for the repair of sacral pressure sores. A total of eight decubitus in seven patients were treated with gluteal perforator-based flaps. There were no postoperative complications, such as flap necrosis and wound infection, with the exception of fistula formation in one case. This flap requires no transection or sacrifice of the gluteus maximus muscle, and elevation time for the flap is short. However, the perforators are located at various sites and thus require some careful dissection.

Adult↗
PubMed1993

A HTLV-I carrier who showed various symptoms and antibodies of autoimmune diseases.

We report a 37-year-old female HTLV-I carrier with complicating primary biliary cirrhosis (PBC) and mixed connective tissue disease (MCTD). Serum anti-HTLV-I antibody titer was x256. Flower cells (4.5%) were found in the peripheral blood. Southern blot analysis showed no clonal integration in peripheral blood lymphocyte (PBL) DNA. Polymerase chain reaction showed the HTLV-I genome in PBL DNA. As cholestatic liver dysfunction and serum titer of anti-mitochondrial antibody were found, a clinical diagnosis of PBC was made. This patient later developed MCTD. These diseases responded well to prednisone. The pathogenetic relationship of HTLV-I infection with various autoimmune diseases is discussed.

Adult↗