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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

At least 127 records · Page 7Linked to original sources
PubMed1994

Immunohistochemical study of expression and cellular localization of the multidrug resistance gene product P-glycoprotein in primary liver carcinoma.

BACKGROUND: Expression and cellular localization of the multidrug resistance gene product P-glycoprotein, which plays an important role in multidrug resistance to cancer chemotherapy, were immunohistochemically studied in paraffin sections from 55 patients with primary liver carcinoma. METHODS: Tumor samples from 43 patients with hepatocellular carcinoma (HCC) and from 12 with cholangiocellular carcinoma (CCC) were obtained at autopsy or at surgical resection. Immunohistochemical study was performed by the avidin-biotin-peroxidase technique using monoclonal antibody JSB-1 directed against P-glycoprotein. RESULTS: Anti-P-glycoprotein immunostaining was observed in 67.4% of cases with HCC and in 66.7% of cases with CCC. When P-glycoprotein was detected in HCC, it was localized on the contact surface among tumor cells regardless of histologic type and on the cellular surface facing the blood space in the trabecular type and on the luminal surface in the pseudoglandular type. In CCC, relatively weak immunoreactivity for P-glycoprotein was localized in the cytoplasm of tumor cell both in glandular and nonglandular types, and stronger immunoreactivity was sometimes seen on the luminal surface of glandular type. The incidence of expression of P-glycoprotein was not influenced by previous cancer chemotherapy both in HCC and CCC. In the trabecular type of HCC, however, all cases with P-glycoprotein expression on the cellular surface facing the blood space were from the patients treated with antitumor agents. CONCLUSIONS: Resistance to cancer chemotherapy in primary liver carcinoma results from P-glycoprotein protein expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Serum levels of integrins in chronic liver diseases.

The serum levels of beta 1 integrin (microgram/ml) were significantly higher in the patients with chronic persistent hepatitis (2.59 +/- 0.04), chronic active hepatitis (3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Serum levels of beta 3 integrin (microgram/ml) were significantly higher in the patients with chronic active hepatitis (10.48 +/- 1.22), liver cirrhosis (13.55 +/- 1.54) and hepatocellular carcinoma (14.1 +/- 1.77) when compared with normal subjects (5.51 +/- 0.52). A positive correlation was found between serum levels of beta 1 and beta 3 integrins (p < 0.001). A strong positive correlation was observed between serum levels of beta 1 integrin and histologic features, particularly in the degree of hepatic fibrosis, while no correlation was found between serum levels of beta 3 integrin and hepatic fibrosis. Immunohistochemical studies revealed that the beta 1 integrin was present on the plasma membranes of hepatocytes and sinusoidal lining cells in the normal liver, and was increased in fibrotic areas, and on the plasma membranes of hepatocytes and sinusoidal lining cells of the chronic liver disease. However, no positive staining for beta 3 integrin was observed in fibrotic area. The serum level of beta 1 integrin in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.

Chronic Disease↗
PubMed1994

Serum tenascin levels in chronic liver disease.

To evaluate the diagnostic significance of tenascin, the extracellular matrix glycoprotein in chronic liver disease, serum tenascin levels were measured by a newly developed ELISA in 21 patients with chronic persistent hepatitis, in 55 with chronic active hepatitis, in 59 with liver cirrhosis, in 31 with hepatocellular carcinoma, in 26 with acute hepatitis and in 66 healthy subjects. The serum tenascin level was significantly elevated in the patients with chronic active hepatitis, liver cirrhosis, hepatocellular carcinoma, and acute hepatitis when compared with the healthy subjects (p < 0.001). The serum tenascin level also increased with increasing severity of chronic liver diseases. A significant correlation was observed between the serum tenascin levels and serum levels of various extracellular matrix proteins such as type III procollagen N-aminoterminal peptide (PIIIP), laminin and the 7S domain of type IV collagen (p < 0.001). A strong positive correlation was observed between the serum tenascin levels and histologic findings, particularly in the degree of hepatic fibrosis. This is the first report documenting serum tenascin level increases in patients with various chronic liver diseases. The measurement of the serum tenascin levels may provide additional information relevant to the study of connective tissue.

Adult↗
PubMed1994

HCV-marker-positive autoimmune-type chronic active hepatitis: a possible relation between HCV infection and liver autoreaction.

This study focused on 32 patients who were diagnosed as having autoimmune hepatitis based upon clinical and histological factors. Fifteen of these patients were positive for HCV-RNA and for one of the HCV-related markers tested, including anti-C100, ELISA II, and RIBA 2 (Group 2). The remaining 17 patients were negative for all HCV-related markers (Group 1). Clinical factors in the two groups, including the frequency of autoantibodies, serum levels of aminotransferase and gammaglobulin, HLA phenotypes, and the response to corticosteroid treatments, were compared. The titer of serum anti-nuclear antibodies and the level of serum aminotransferase at initial diagnosis were significantly higher in Group 1 than in Group 2. Furthermore, the genetic background of the two groups, as indicated by HLA phenotypes, differed. All cases in Group 1 were HLA-DR4-positive, whereas only 60% of those in Group 2 cases had HLA-DR4. Also, all cases in Group 1 but only 66.7% of the cases in Group 2 showed good clinical responses to corticosteroid treatment. Finally, no cases of HCV-related-marker-positive autoimmune hepatitis (Group 2) had antibodies for LKM, suggesting that these cases were clinically different from type II autoimmune hepatitis. These data indicated that immunosuppressive treatment might be the preferred initial treatment in patients who either satisfy the criteria for AIH or who are sero-positive for an HCV-marker.

Autoantibodies↗
PubMed1994

Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to alcoholic liver cirrhosis.

OBJECTIVES: Cytochrome P450IIE1 (P450IIE1) is involved in ethanol metabolism and in the metabolic activation of carcinogenic nitrosoamines. The purpose of our investigation was to determine whether P450IIE1 restriction fragment length polymorphisms (RFLP) were associated with the development of alcoholic cirrhosis in Japanese alcoholics. METHODS: We determined the human P450IIE1 RFLP with the restriction endonucleases, RsaI and PstI, using the polymerase chain reaction (PCR) on lymphocytes from 82 male Japanese alcoholics. Twenty patients had alcoholic fatty liver or nonspecific reaction (nonfibrotic group), and 62 had severe hepatic fibrosis or liver cirrhosis (fibrotic group). RESULTS: PCR-RFLP revealed three P450IIE1 genotypes, namely, heterozygotes [type B (c1/c2)] and two homozygotes [types A (c1/c1) and C (c2/c2)]. Homozygotes (c1/c1) were significantly more prevalent in the fibrotic group than in the nonfibrotic group (p < 0.05). CONCLUSIONS: This result suggests that susceptibility to alcoholic liver cirrhosis may be associated with the RsaI and PstI polymorphism of the P450IIE1 gene.

Cytochrome P-450 CYP2E1↗
PubMed1994

[Primary biliary cirrhosis (PBC): concept, pathogenesis and classification].

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of median size intrahepatic bile ducts. The characteristic histological process is described as chronic nonsuppurative destractive cholangitis (CNSDC). Our knowledge for the pathogenesis of PBC remains incomplete. However, immunological mechanisms seems to play one of the most important role. The immunohistochemical examination represents accumulation of stimmulated T lymphocytes in the portal area. Attachment of CD8 positive T cells to bile duct epithelial cells is observed. The animal model of PBC indicates autoreactive CD4 positive T cells seems to be important at the early stage of PBC and CD8 positive cytotoxic T cells are essential for the progression of the disease. PBC is histologically classified into four overlapping stages by Scheuer. Clinically, PBC is classified into asymptomatic PBC (aPBC), PBC with itching alone (s1PBC) and with jaundice (s2PBC).

Animals↗
PubMed1994

[Defects of defence mechanisms against bacterial infections in patients with liver cirrhosis].

Patients with decompensated liver cirrhosis have a high risk of bacterial infection and a worse prognosis. They have defects of the humoral defence mechanism; impaired antibody production and depressed serum complement levels. The cellular defence mechanism is also defective. The function of neutrophil and reticuloendothelial system is depressed. The clearance of enteric organisms from the portal circulation is impaired by portosystemic shunt and impaired Kupffer cell function. Patients with massive ascites are prone to spontaneous bacterial peritonitis due to gram negative enteric organisms.

Gram-Negative Bacterial Infections↗
PubMed1994

Humoral inhibitor of rat hepatocyte DNA synthesis from patients with fulminant liver failure.

Sera and ultrafiltrates (relative molecular mass < 10,000 Da) from patients with fulminant liver failure inhibit hepatocyte DNA synthesis in vivo. In this study the effects of ultrafiltrates from pooled sera from fulminant liver failure patients in the United Kingdom and plasma ultrafiltrates from fulminant liver failure patients in Japan have been investigated in primary cultured rat hepatocytes, with incubation for up to 72 hr. Both types of ultrafiltrate inhibited the incorporation of [3H]thymidine into acid-precipitable material and reduced the cell labeling index as determined on autoradiography in hepatocytes stimulated by epidermal growth factor and insulin compared with normal sera/plasma ultrafiltrates. The inhibitory effects observed were dose dependent, reversible when the fulminant liver failure ultrafiltrate was removed and were not associated with increased release of lactate dehydrogenase or suppression of protein synthesis as assessed on the basis of the incorporation of [3H]leucine. The effects appeared to be specific for hepatocytes; in preliminary experiments DNA synthesis was not inhibited in cultured fibroblasts (NIH 3T3 cells). These experiments are further evidence of the presence of an inhibitory factor of relative molecular mass less than 10,000 Da in the blood of patients with fulminant liver failure.

Adolescent↗
PubMed1993

Immunogenetic background of hepatitis B virus infection and autoimmune hepatitis in Japan.

Human leucocyte antigen (HLA)-typing was studied in 82 hepatitis B carriers and 15 cases of autoimmune hepatitis (AIH) to elucidate the genetic factors which may associated with the etio-pathogenesis of chronic hepatitis in Japan. There were two types of HLA phenotypes: HLA A2 was associated with the progression of the disease induced by HBV infection, and HLA A26 and DR5 were related to the retardation of the disease. A family study confirmed the strong association of these HLA phenotypes with the disease induced by HBV infection. In the analysis of AIH, HLA DR4 is a risk factor related to susceptibility of Japanese AIH which shows different clinical manifestations compared to HLA-DR3-positive AIH, dominantly observed in Western countries. These results suggest that genetic background as expressed by HLA, is an important factor in restricting the development of type B hepatitis and AIH, and can explain racial differences of disease susceptibility.

Autoimmune Diseases↗
PubMed1993

Serum vitronectin receptor in alcoholic liver disease: correlation with fibronectin receptor and morphological features.

In order to clarify the significance of serum level of vitronectin receptor (VNR) in alcoholic liver disease (ALD), we have investigated the relationship with fibronectin receptor (FNR) and histological liver features in 21 ALD patients. Serum level of VNR and FNR was measured by enzyme immunoassay. Liver disease activity was scored based on levels of fibrosis and focal intralobular necrosis and degeneration. The serum level of VNR (micrograms/ml) was significantly higher in the patients with hepatic fibrosis (9.87 +/- 2.51) and liver cirrhosis (10.80 +/- 1.52) than in normal subjects (5.51 +/- 0.52, P < 0.01) and fatty liver subjects (6.58 +/- 0.58, P < 0.05). A positive correlation was found between serum levels of VNR and fibronectin receptor (FNR) (P < 0.05). A positive correlation was observed between the serum level of FNR and the degree of hepatic fibrosis or focal intralobular necrosis and degeneration, while no correlation was found between the serum level of VNR and the degree of histological features. A positive correlation was also noted between the serum level of FNR and N-terminal type III procollagen aminopeptide (PIIIP) (P < 0.001), while no correlation was observed between the serum level of VNR and PIIIP. We conclude that the serum level of VNR is increased in patients with advanced alcoholic liver disease. However, the mechanism by which serum levels of beta subunit of VNR and FNR are increased may be different.

Adult↗
PubMed1993

Serum level of carbohydrate-deficient transferrin as a marker of alcoholic liver disease.

Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease.

Adult↗
PubMed1993

Serum levels of intercellular adhesion molecule-1 in patients with alcoholic liver disease.

Serum levels of intercellular adhesion molecule-1 (ICAM-1) were measured in 37 patients with alcoholic liver disease, six alcoholics without liver disease and ten healthy subjects. The serum level of ICAM-1 was significantly higher in the patients with alcoholic cirrhosis than in the noncirrhotic alcoholic liver disease patients (P < 0.005) and the healthy subjects (P < 0.001). Furthermore, the serum level of ICAM-1 was significantly higher in the patients with alcoholic hepatitis than in those with alcoholic cirrhosis (P < 0.001). No significant difference in serum ICAM-1 levels was found between normal subjects and alcoholics without liver diseases. In the patients with alcoholic hepatitis, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) derived from macrophages were increased in the presence of endotoxemia. The increase in serum ICAM-1 may therefore be related to the strong expression of ICAM-1 of hepatocytes and endothelial cells accompanied by the increase in serum TNF-alpha.

Adult↗
PubMed1993

Urinary level of L-fucose as a marker of alcoholic liver disease.

The urinary levels of L-fucose were measured in 93 alcoholics; 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L-fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 +/- 97 vs. 240 +/- 95 mumol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 +/- 29 vs. 155 +/- 60 mumol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 +/- 97 mumol/g of creatinine) than with viral cirrhosis (265 +/- 42 mumol/g of creatinine) (p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.

Adult↗