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Biomedical subjects

Y Mizoguchi

Publications and source records attributed to Y Mizoguchi.

At least 91 records · Page 5Linked to original sources
PubMed1991

Detection of proliferating liver cells in various diseases by a monoclonal antibody against DNA polymerase-alpha: with special reference to the relationship between hepatocytes and sinusoidal cells.

Proliferating cells in liver specimens from patients with various diseases were detected by use of a monoclonal antibody against human DNA polymerase-alpha, which is present in the nuclei of cells in the G1, S, M and G2 phases of the mitotic cell cycle and absent in the G0 phase, to clarify the kinetics and morphological characteristics of these cells. This monoclonal antibody was supernatant derived from clone CL22-2-42B, and the peroxidase antiperoxidase method was used. Not only epithelial cells (hepatocytes, biliary epithelial cells and hepatocellular carcinoma cells) but also nonepithelial cells (Kupffer cells and other macrophages, endothelial cells, fat-storing cells, lymphocytes and fibroblasts) were stained for DNA polymerase-alpha. In acute viral hepatitis with confluent necrosis, small hepatocytes with basophilic cytoplasm next to the necrosis accounted for most of the proliferating cells. In these areas, Kupffer cells and other macrophages and lymphocytes had often proliferated. Hepatocellular carcinoma cells were frequently stained for DNA polymerase-alpha, in addition to endothelial cells, macrophages and lymphocytes. These nonepithelial cells were stained more frequently in specimens with many stained carcinoma cells than in those with only a few cells stained. In fibrotic areas, fibroblasts were often stained for this enzyme. In proliferating bile ducts, both small epithelial cells and large mature cells were stained. The differences between stained and nonstained cells that were not hepatocytes could not be defined by their ultrastructural characteristics. From these findings, it seemed possible that sinusoidal cells, especially Kupffer cells and other macrophages, might be much involved in hepatocytic proliferation during regeneration of the liver and also in the occurrence of malignant tumors.

Adult↗
PubMed1991

Effects of irsoglandine maleate in an experimentally-induced acute hepatic failure model using mice.

When heat-killed Propionibacterium acnes was intravenously injected into mice followed by an intravenous injection of a small amount of Gram-negative lipopolysaccharide seven days later, most of the mice died of massive hepatic cell necrosis within 24 hours. However, when irsoglandine maleate, an anti-ulcer agent, was administered to mice during the period of experimental induction of acute hepatic failure, the survival rate, serum transaminase levels and histological changes of the liver remarkably improved. These results suggested that irsoglandine maleate may have protective effects on the liver in our experimentally-induced acute hepatic failure model using mice. Therefore, in the absence of a definitive therapy for fulminant hepatitis, irsoglandine maleate may be a promising therapeutic agent.

Animals↗
PubMed1991

Effect of gomisin A in an immunologically-induced acute hepatic failure model.

Guinea pigs were sensitized with trinitrophenylated liver macromolecular protein fraction (TNP-LP1) prepared by using sodium trinitrobenzenesulfonate of strong immunogenicity as the hapten and LP1 as the carrier protein. The administration of trinitrophenylated hepatocytes and lipopolysaccharide to these TNP-LP1-sensitized guinea pigs through the mesenteric vein 2 weeks later resulted in the induction of acute hepatic failure accompanied by massive hepatic cell necrosis in almost all of the guinea pigs. Using this experimental model, the effect of Gomisin A on the induction of immunological acute hepatic failure was examined. As a result, the administration of gomisin A remarkably improved the survival rate and serum transaminase levels of the immunologically-induced acute hepatic failure guinea pigs. Gomisin A also improved the histological changes of the liver in these guinea pigs. These results suggested that gomisin A is effective for the improvement of immunologically-induced acute hepatic failure in our experimental model.

Animals↗
PubMed1991

Effect of gomisin A in the prevention of acute hepatic failure induction.

Nearly all rats develop massive hepatic cell necrosis and die upon intravenous administration of heat-killed Propionibacterium acnes followed by a small amount of Gram-negative lipopolysaccharide 7 days later. However, when such an experimental liver disorder is induced in rats raised for 4 or more weeks on food containing 0.06% of gomisin A extracted and purified from Schizandra chinensis, the survival rate rises, histological changes of the liver improve remarkably, and splenocyte reactivity to phytohemagglutinin and pokeweed mitogen as well as splenocyte interleukin 1 productivity are retained. These results suggested the possibility that the development of acute hepatic failure may be prevented with the oral administration of gomisin A.

Animals↗
PubMed1991

There is no correlation between function and lymphokine production of HBs-antigen-specific human CD4(+)-cloned T cells.

The question whether antigen-specific human CD4+ T cells can be classified on the basis of appropriate and fixed lymphokine production patterns and their corresponding functions still remains to be elucidated. We generated ten CD4+ T-cell clones specific for HBsAg from HBsAb-positive but HBsAg-negative individuals. Seven of these clones exhibited helper activity for HBsAb response, while the three other clones did not. Both helper- and non-helper-type T-cell clones produced interleukin 4 (IL-4) after antigenic stimulation. By stimulation with phytohaemagglutinin (PHA) plus phorbol myristate acetate (PMA), three of the seven helper-type clones produced interleukin 2 (IL-2) in addition to IL-4. However, the other four helper-type clones did not produce IL-2 by such stimulation, although they continued the production of IL-4. All non-helper-type T-cell clones produced a large amount of IL-2, and some of them completely became an IL-2 producer after certain stimulation. These results suggested that both helper- and non-helper-type CD4+ T-cell clones specific for HBsAg might have no strict pattern of lymphokine production as in the TH1/TH2 dichotomy of murine CD4+ T cells. The data also revealed that lymphokine-producing capacity of individual cloned T cells is changeable depending upon the sort of activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Interferon gamma modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells.

When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). In this study, we examined the effect of in vitro Kupffer cell activation by recombinant murine interferon gamma (IFN gamma) on IL-1 and TNF secretion. IFN gamma enhanced TNF production in the presence or absence of lipopolysaccharide (LPS), but suppressed IL-1 production by Kupffer cells. Because IFN gamma also stimulated prostaglandin E2 (PGE2) production, the effect of indomethacin, which is an inhibitor of cyclooxygenase and which inhibits PGE2 biosynthesis, on IL-1 and TNF production by Kupffer cells was examined. As a result, indomethacin enhanced TNF production by Kupffer cells, but had no effect on IL-1 synthesis. These results suggested that IFN gamma modulates the production of IL-1 and TNF by Kupffer cells through different mechanisms.

Animals↗
PubMed1991

Detection of proliferating hepatocytes in patients with acute hepatic failure by mitotic figures and a monoclonal antibody against DNA polymerase alpha.

Information on the ultrastructure and phenotypes of proliferative hepatocytes is scarce, so we set out to detect proliferating hepatocytes immunohistochemically by use of a monoclonal antibody against DNA polymerase alpha (DNA-PA). The findings from this method were compared with conventional features, such as mitotic figures, and hepatic regeneration after injury was considered in the light of these findings. The subjects of the basic study were 23 patients with acute hepatic failure. There were 6.8 +/- 5.5 (mean +/- SD) mitotic hepatocytes per 1,000 hepatocytic nuclei, and 209 +/- 158 hepatocytes stained for DNA-PA per 1,000 hepatocytic nuclei. By light and electron microscopy (n = 4), hepatocytes stained for DNA-PA showed various morphological features, including development of organelles, but some resembled hepatocytes in mitosis. Accordingly, this histochemical method may be useful in studies of hepatic regeneration. In acute confluent necrosis, when hepatocytic proliferation is urgently needed for survival, small hepatocytes next to necrotic areas (probably immature cells, to judge from the development of their organelles) were predominant in hepatic regeneration. These findings suggest that hepatocytes in different stages of development can easily enter the mitotic cell cycle repeatedly when rapid regeneration is needed.

Antibodies, Monoclonal↗
PubMed1991

Allergic hepatitis in guinea pigs induced by 2,4,6-trinitrophenyl liver protein conjugate.

Experimental drug-induced allergic hepatitis was induced in guinea pigs which had been immunized to the 2,4,6-trinitrophenyl (TNP)-conjugated liver protein first peak (TNP-LP1) emulsified in complete Freund's adjuvant (CFA). Delayed-type hypersensitivity (DTH) was elicited in the immunized animals by intradermal challenge with TNP-LP1. When TNP-LP1 was introduced into the liver via the mesenteric vein, allergic hepatitis was provoked. Histological examination of the liver revealed massive monocytic infiltration and focal hepatic necrosis in the periportal areas. Blood biochemical analysis showed increased levels of glutamate oxalacetate transaminase (GOT) and total bilirubin. TNP-modified hepatocytes were found to be effective as a challenge elicitor to the immunized animals to induce both DTH skin reaction and allergic hepatitis. In the latter case, the severity of the lesion was stronger than that observed by the challenge with TNP-LP1.

Alanine Transaminase↗
PubMed1991

Preparation of a drug-induced allergic hepatic disorder model with penicillin as hapten.

A drug-induced allergic hepatic disorder model was established using a hapten and carrier. Penicillin G was bound to glycine for the preparation of N-hydroxy succinic imidylglycinyl benzylpenicillate (PG-Gly-OSu). Using this as the hapten and liver protein as the carrier, guinea pigs were sensitized with liver protein bound to PG-Gly-OSu. After 2 weeks, the sensitized guinea pigs were directly challenged with hepatocytes bound to PG-Gly-OSu through a mesenteric vein and hepatocellular disorder was induced. When the sensitized guinea pigs were challenged with PG-Gly-OSu alone or with liver protein alone, hepatocellular disorder could not be induced. These results suggest that the combination of PG-Gly-OSu as the hapten and liver protein as the carrier elicits a hepatocellular disorder similar to drug-induced allergic hepatitis.

Animals↗
PubMed1991

The effect of lipo-prostaglandin E1 on the production of interleukin 1 and platelet-activating factor by hepatic sinusoidal endothelial cells in mice.

We first studied the production of interleukin 1 (IL1) and platelet-activating factor (PAF) by mouse hepatic sinusoidal endothelial cells and then the effect of Lipo-prostaglandin E1 (Lipo-PGE1) on IL1 and PAF production by these cells. The incubation of mouse hepatic sinusoidal endothelial cells with lipopolysaccharide (LPS) or calcium-ionophore (CaI) A23187 resulted in a concentration-dependent production of IL1 and PAF. However, Lipo-PGE1 dose-dependently decreased the LPS- or CaI A23187-induced production of IL1 and PAF. These results suggested that Lipo-PGE1 acts on hepatic sinusoidal endothelial cells to decrease the production of IL1 and PAF, thereby ameliorating inflammatory reactions in the liver.

Alprostadil↗
PubMed1991

Effect of sho-saiko-to (TJ-9, Japanese herbal medicine) on estradiol receptors in the cytosol of hepatic sinusoidal endothelial cells.

We first confirmed the presence of estradiol receptors in the cytosol of rat hepatic sinusoidal endothelial cells and then studied the effects of Sho-saiko-to (TJ-9) on the level of these cytosol estradiol receptors. As a result, we found that estradiol receptors are present in the cytosol of hepatic sinusoidal endothelial cells from rats. Moreover, when these cells were incubated with TJ-9, the level of cytosol estradiol receptors increased. These results suggested that TJ-9 acts on hepatic sinusoidal endothelial cells to increase the level of estradiol receptors, thereby affecting the immune reactions in the liver.

Animals↗
PubMed1991

[Serum concentration of hyaluronic acid in healthy populations and patients with rheumatoid arthritis--relationship to clinical disease activity of RA].

With the sandwich binding protein assay utilizing hyaluronic acid binding protein, we measured serum concentration of hyaluronic acid in 458 healthy persons, 71 patients with rheumatoid arthritis (RA) and 51 patients with various rheumatic diseases such as osteoarthritis (OA), progressive systemic sclerosis (PSS), systemic lupus erythematosus (SLE) and gout. The mean concentration +/- standard deviation (SD) of healthy persons whose age ranged 2 to 92 years old was 38.5 +/- 35.7ng/ml, and those with over 50 years old had apparently higher concentrations (51.9 +/- 40.5ng/ml) than those with below 50 of age (20.6 +/- 14.8ng/ml). When the upper limit of normal range was set up at 130 ng/ml, abnormal percentages were 62.0% (44/71) in RA, 0% (0/18) in OA, 6.3% (1/16) in PSS, 18.2% (2/11) in SLE and 0% (0/6) in gout. Patients who apparently had arthritis but not RA revealed normal or near to the upper limit in serum hyaluronic acid compared to RA patients having the mean +/- SD of 351.4 +/- 463.7ng/ml. When patients with RA were classified into stage I to IV with X ray of bone destruction, patients with more advanced X ray stage showed significantly higher serum concentrations of hyaluronic acid. Similarly, patients with lower activity of daily living revealed significantly higher serum concentrations of hyaluronic acid. In addition, serum hyaluronic acid level did correlate to concentration of serum CRP and sialic acid. Lansbury's index, strength of grip, joint score and erythrocyte sedimentation rate, but did not to duration of morning stiffness and titer of rheumatoid factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1991

[A case of retroperitoneal venous aneurysm].

Venous aneurysm is a rare entity and the disease occurring in the retroperitoneal space has been reported in only 4 cases. Therefore, the fifth case of retroperitoneal venous aneurysm on the literature was described. A 59-year-old male was referred to our clinic because of painless large mass in the left abdomen. Computed tomography, ultrasonography, and magnetic resonance imaging revealed a cystic mass at the perinephric space. The resected cyst contained yellow-grayish fluid. The cyst wall was microscopically formed of 4 layers; blood and cholesterin, hyaline, muscle and collagen from the inner to outer side. He is well without any trouble after the operation.

Aneurysm↗
PubMed1990

Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis.

We prospectively monitored 140 cirrhotic patients for the development of hepatocellular carcinoma for 6 yr, using periodical screening by high-resolution convex-array ultrasonography and alpha-fetoprotein. Twenty-eight patients were positive for HBs antigen, 26 patients had received blood transfusions and were negative for HBs antigen and 26 patients had a history of heavy drinking. We detected hepatocellular carcinoma in 40 patients during this period. The overall cumulative incidence of hepatocellular carcinoma in the 6 yr was 39%; the cumulative incidence was 59% in patients with HBsAg, 53% in patients who had had blood transfusions and were negative for HBsAg and 22% in patients who had a history of heavy drinking and who were without HBsAg. Detection of the carcinoma in 85% of these 40 patients was based on results of ultrasonography. Twenty-six of the patients (65%) had a small hepatocellular carcinoma of 2 cm or less. alpha-Fetoprotein levels were lower than 100 ng/ml in 56% of these 40 patients. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma, especially patients with HBsAg or with a history of blood transfusion who are negative for HBsAg. Periodic monitoring by use of ultrasonography in particular is recommended for early detection of hepatocellular carcinoma.

Adult↗
PubMed1990

Arachidonic acid metabolites in carbon tetrachloride-induced liver injury.

The changes in the levels of leukotrienes (LTs) and prostaglandins (PGs) in the liver tissue of rats with carbon tetrachloride (CCl4)-induced liver injury were studied. As a result, after the administration of CCl4, the levels of LTs increased at an early stage while the levels of PGs increased at a later stage. This suggests that LTs may have an adverse effect on liver injury induced by CCl4, and that PGs may not have a direct effect on liver injury. In addition, serum GOT and GPT levels improved with the administration of AA-861, a 5-lipoxygenase inhibitor, while these levels did not change with the administration of indomethacin, a cyclooxygenase inhibitor. These results suggest that arachidonic acid metabolites may play an important role in the induction of liver cell injury.

Alanine Transaminase↗
PubMed1990

Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha.

To analyze the process of liver regeneration and the initiation of hepatocellular carcinoma (HCC), we studied histochemically the morphologic features of proliferating parenchymal cells stained for DNA polymerase alpha (DPA), in 31 patients with various diseases, by use of a monoclonal antibody against DPA. In specimens from patients with acute viral hepatitis with confluent necrosis, most stained hepatocytes were small, with basophilic cytoplasm, and were located next to the necrotic areas. Under electron microscopy, stained granules were seen in the nucleus. Most stained hepatocytes had immature organelles. In specimens from patients with cirrhosis of the liver, the number of stained hepatocytes greatly differed in different pseudolobules. In specimens from patients with adenomatous hyperplasia, stained hepatocytes, mostly small and basophilic, were found diffusely; electron microscopy showed slightly indented nuclei with a few organelles and less condensed chromatin than normal. In specimens from patients with HCC, most stained cancer cells were small and basophilic; electron microscopy showed indented nuclei with a few organelles and less than normal condensed chromatin. Staining showed that during regeneration, immature hepatocytes reentered the cell cycle and repaired a large necrotic area. It was conceivable that in the initiation of HCC, some small hepatocytes with indented nuclei and less condensed chromatin might become HCC cells.

Antibodies, Monoclonal↗