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Biomedical subjects

Y Mizoguchi

Publications and source records attributed to Y Mizoguchi.

At least 145 records · Page 8Linked to original sources

Release of peptide leukotrienes from rat Kupffer cells.

Kupffer cells isolated from the normal rat liver were incubated with calcium ionophore A23187, and the levels of peptide leukotrienes (LTC4, LTD4, and LTE4) contained in the culture supernatant were determined by the combined technique of reverse-phase high-performance liquid chromatography and radioimmunoassay. In response to A23187, Kupffer cells released LTC4, LTD4, and LTE4. After 10 min-preincubation of Kupffer cells with AA861, a 5-lipoxygenase inhibitor, the generation of LTC4, LTD4, and LTE4 from A23187-stimulated Kupffer cells was significantly suppressed. Platelet activating factor (PAF), a phospholipid mediator, significantly enhanced the release of LTC4, LTD4, and LTE4 from Kupffer cells stimulated with A23187. These results suggested that Kupffer cells may participate in inflammatory and immunologic events in the liver tissue by the release of peptide leukotrienes.

Animals↗

Effects of the polysaccharide chain of lipopolysaccharide in an experimental massive hepatic cell necrosis model.

When small amounts (1 microgram) of lipopolysaccharide (LPS) purified from Salmonella minnesota (SM) wild, SM R60 and SM R345 were intravenously injected into mice 7 days after heat-killed Propionibacterium acnes was intravenously injected, massive hepatic cell necrosis was induced and most of the mice died within 24 hours. However, when LPS from SM R345 treated galactosidase, SM R5 and SM R7 and lipid A from SM R595 were administered, the survival rate was much higher and no histological changes of the liver such as necrosis could be seen in any of the mice. In each of the LPS used in this study, the structure of the polysaccharide chain was different and it was shorter in the following order: SM wild----SM R60----SM R345----SM R345 treated with galactosidase----SM R5----SM R7----SM R595. This suggests that the polysaccharide chain of LPS plays an important role in the induction of massive hepatic cell necrosis in this experimental model.

Animals↗

Effects of an anti-tumor polysaccharide, schizophyllan, on interferon-gamma and interleukin 2 production by peripheral blood mononuclear cells.

We examined the effect of schizophyllan, a neutral glucan isolated from the culture filtrate of Schizophyllum commune Fries, on the production of interferon-gamma (IFN-gamma) and interleukin 2 (IL 2) from the mitogen-stimulated human peripheral blood mononuclear cells (PBMC). When the levels of IFN-gamma and IL 2 in the culture medium of phytohemagglutin (PHA)- or concanavalin A (Con A)-stimulated PBMC were measured by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) respectively, a significant increase in the production of both cytokines by schizophyllan was demonstrated. These results suggest that the increased production of IFN-gamma and IL 2 may be responsible for the anti-tumor activity of this glucan.

Concanavalin A↗

Effects of the polysaccharide chain of lipopolysaccharide in an experimental massive hepatic cell necrosis model in the mice.

When a small amount (1 microgram) of lipopolysaccharide (LPS) purified from Salmonella minnesota wild, Salmonella minnesota R60, and Salmonella minnesota R345 was intravenously injected into mice 7 days after heat-killed Propionibacterium acnes was intravenously injected, massive hepatic cell necrosis was induced and most of the mice died within 24 hours. However, when LPS from Salmonella minnesota R5 and Salmonella minnesota R7 and lipid A from Salmonella minnesota R595 were administered, the survival rate was much higher and no histological changes in the liver such as necrosis could be seen in any of the mice. In each of the LPS used in this study, the structure of the polysaccharide chain was different, and it decreased in the following order: Salmonella minnesota wild----Salmonella minnesota R60----Salmonella minnesota R345----Salmonella minnesota R5----Salmonella minnesota R7----Salmonella minnesota R595. This suggested that the polysaccharide chain of LPS played an important role in the induction of massive hepatic cell necrosis in this experimental model.

Animals↗

Protective effects of a leukotriene inhibitor in an experimental massive hepatic cell necrosis model.

When heat-killed Propionibacterium acnes was intravenously injected into mice and seven days later, a small amount of gram-negative lipopolysaccharide was also intravenously injected, most of them died of massive hepatic cell necrosis. However, when azelastine hydrochloride, a leukotriene antagonist chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, or AA861, 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1, 4-benzoquinone, a specific inhibitor of 5-lipoxygenase, was administered during this experimental induction of massive hepatic cell necrosis, the survival rate of the mice increased and the histological changes of the liver improved remarkably. These results suggested that leukotriene may be important for the induction of massive hepatic cell necrosis in our experimental model.

Animals↗

Effect of interleukin 1 and interleukin 2 on antibody production in asymptomatic hepatitis B virus (HBV) carriers.

Peripheral blood mononuclear cells from asymptomatic hepatitis B virus (HBV) carriers and healthy controls were incubated with recombinant interleukin 1 (r-IL1) or recombinant interleukin 2 (r-IL2) at 37 degrees C for 24 hours and with pokeweed mitogen (PWM) and estradiol for 72 hours. The number of antibody-producing cells was counted by hemolytic plaque assay. When the mononuclear cells were not pretreated with r-IL1 or r-IL2, the number of antibody-producing cells was not increased by estradiol in asymptomatic HBV carriers. However, when the mononuclear cells were pretreated with r-IL1 or r-IL2, the number of antibody-producing cells was increased. As we have reported before, this may be have been due to the increase in the estradiol-binding capacity of the mononuclear cells by treatment with IL1 and IL2. In asymptomatic HBv carriers, IL1 and IL2 production of the mononuclear cells or the response of the mononuclear cells to IL1 and IL2 is reduced. Consequently, the estradiol binding capacity is decreased, and antibody production is not increased by estradiol.

Antibody Formation↗

Tryptophan metabolism in D-galactosamine-induced liver injury.

We have reported that in rats with D-galactosamine-induced liver injury, the serum level of indoleacetic acid (IAA), a metabolite of tryptophan (TRP), increases before the increase in serum transaminase activity. To determine whether this IAA is derived from hepatocytes, isolated hepatocytes were treated with D-galactosamine and loaded with TRP, and the changes in TRP and IAA levels in the culture supernatant of the isolated hepatocytes were measured at various time intervals. As a result, IAA level in the culture supernatant of hepatocytes treated with D-galactosamine and loaded with TRP significantly increased in a time-dependent manner. This indicates that in D-galactosamine-induced liver injury, a metabolic pathway which produces IAA from TRP through tryptamine is present in hepatocytes.

Animals↗

Determination of serum cholestatic factor level by ELISA in drug-induced allergic hepatitis.

We have shown that intrahepatic cholestasis often observed in drug-induced allergic hepatitis may be induced by a kind of lymphokine, the cholestatic factor (CF). In this study, we measured the CF level in the serum of patients with jaundice by ELISA using anti-CF monoclonal antibody. As a result, CF was detected in the serum of most of the patients at the peak of jaundice, but it was not detected when the patients were recovering from jaundice. When the changes in the serum CF level were followed during the clinical course of a patient, it reached its maximum level before that of the serum total bilirubin level and quickly decreased thereafter. These results also suggest that intrahepatic cholestasis in drug-induced allergic hepatitis may be induced by CF.

Adult↗

Effects of recombinant interleukin 2 on immunological effector cells of the peripheral blood in patients with HBe antigen-positive chronic hepatitis.

Changes in peripheral blood immunological effector cells after systemic administration of recombinant interleukin 2 (rIL2) were studied in 14 patients with HBe antigen-positive chronic hepatitis. The patients were intravenously injected with rIL2 for 4 weeks, and the experiments were performed using mononuclear cells isolated from the peripheral blood during and after rIL2 administration. No significant changes in OKT4-positive cell population, OKT8-positive cell population, OKT4/OKT8 ratio and Leu7-positive cell population were detected during and after intravenous injection of rIL2. However, the natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities significantly increased in the fourth week of rIL2 administration, while the K cell activity in the antibody-dependent cell-mediated cytotoxicity reaction, antibody response, lectin-induced lymphocyte transformation and IL1 production of LPS-stimulated monocytes were not affected. These results suggest that IL2 increases the NK cell and LAK cell activities in vivo.

Adult↗

Experimental immunological intrahepatic cholestasis model.

Heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into tuberculin-sensitized guinea pigs, and 7 days later, purified protein derivative (PPD) was also injected intravenously resulting in marked reductions in bile flow and bile acid excretion. Serum levels of bile acids and cholesterol were increased, and the activities of alkaline phosphatase (ALK-p) and leucine aminopeptidase (LAP) were also elevated. Histological examination revealed dilatation of bile canaliculi and diminution of microvilli. These results indicated that intrahepatic cholestasis was induced. These pathological changes were not detected in guinea pigs in which PPD was not injected. In this experimental model, the tuberculin-sensitized lymphocytes were infiltrated into the liver by P. acnes injection and the cholestatic factor was produced by PPD injection, resulting in the induction of intrahepatic cholestasis.

Animals↗

Immunohistochemical and immunoelectron microscopic study of an amylase-producing, CA19-9 positive ovarian mucinous cystadenocarcinoma.

A 75-year-old woman with a right ovarian tumor revealed high levels of serum amylase and CA19-9 which decreased to within normal limits after the operation. A histopathological study of surgically excised tumor tissue revealed a mucinous cystadenocarcinoma. The tumor was composed of three elements: adenoma, adenoma with low potential malignancy, and adenocarcinoma. Using the light microscopic indirect immunoperoxidase technique for amylase and CEA, and the Avidin-Biotin affinity technique for CA19-9 and CA12-5, the amylase and CA19-9 were stained in the cytoplasm of the adenoma and adenocarcinoma although CEA was stained only in the cytoplasm of the adenocarcinoma. An ultrastructural study using the immunoperoxidase method revealed that CA19-9 was positive in the apical portion of the tumor cells and amylase was positive in the entire secretory vesicles of the tumor cells. Furthermore, ciliated tumor cells derived from fallopian tube epithelium were not observed in the light and electron microscopic specimens.

Aged↗

Impairment in the response of peripheral blood mononuclear cells from asymptomatic hepatitis B virus carriers to estradiol.

Sex hormones are known to affect the immune system. Asymptomatic hepatitis B virus (HBV) carriers are thought to be immunologically tolerant to HBV, but in some HBV carriers, the immune response to HBV is induced, especially in females during their sexually-mature periods. This may be caused by the effects of estrogens on the immune system. In this study, we found that the level of estradiol receptors in the cytosol of peripheral blood mononuclear cells was significantly lower in asymptomatic HBV carriers compared to healthy controls. This suggests that in asymptomatic HBV carriers, antibody production of peripheral blood mononuclear cells was lower compared to that of healthy controls as a result of the low level of estradiol receptors.

Carrier State↗

[Evaluation of transcatheter arterial embolization in terms of serum alpha-fetoprotein doubling time in hepatocellular carcinoma].

We measured alpha-fetoprotein doubling time (T2AFP) in 51 patients with hepatocellular carcinoma treated by transcatheter arterial embolization (TAE). We also studied vascular invasion and the survival rate, and looked for correlations. For six patients with T2AFP less than or equal to 30 days after TAE, the time until the finding of vascular invasion by ultrasonography and angiography was 8.5 +/- 3.9 months; for seven patients with T2AFP greater than or equal to 31 days after TAE, it was 17.6 +/- 5.2 months (p less than 0.01). Of 45 patients for whom T2AFP was measured after TAE, 9 were in group A with T2AFP greater than or equal to 61 days, 18 were in group B with an intermediate value, and 18 were in group C with T2AFP less than or equal to 30 days. The two-year survival rate after the first TAE was 55.6% in group A, 42.5% in group B, and 6.0% in group C. The longest survival period was 51 months in group A, 30 months in group B, and 28 months (patient still alive) in group C. In the 18 patients for whom T2AFP was measured before and after TAE, the T2AFP was markedly decreased after TAE in 7 (39%). The pattern of change in T2AFP after TAE was not clearly correlated with the decrease in AFP or the T2AFP value before TAE.

Carcinoma, Hepatocellular↗

[A case of renal cell carcinoma suspected of multilocular cystic nephroma].

A 52-year-old, healthy looking woman was referred for further evaluation of left renal mass, She had had a history of hematuria for ten years. Admission laboratory studies were within normal limits except for slight elevation of white blood cell count, c-reactive protein, blood sedimentation rate and immunosuppressive acidic protein. Retrograde pyelography demonstrated a large mass with ringed calcification in the middle lobe of the left kidney. The multiloculated mass was also confirmed by computed tomography and ultrasonography. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. Under a presumptive diagnosis of multilocular cystic nephroma or renal cell carcinoma, left radical nephrectomy was performed. In surgical specimen, many lobules were filled with serous fluid and clotted blood. Microscopic examination revealed that the lining of the cyst wall consisted of renal cell carcinoma cell. At present, 5 months after the operation, she is well without any signs or symptoms of recurrence.

Carcinoma, Renal Cell↗