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Biomedical subjects

T Monna

Publications and source records attributed to T Monna.

At least 55 records · Page 3Linked to original sources
PubMed1992

Calcium-dependent prostaglandin biosynthesis by lipopolysaccharide-stimulated rat Kupffer cells.

Isolated rat Kupffer cells produced and released prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) in response to lipopolysaccharide (LPS) stimulation. This elevation of PGE2, 6-keto-PGF1 alpha and TXB2 in the medium was not observed when cells were cultured in the absence of extracellular calcium or in the presence of an extracellular calcium chelator, EGTA. An intracellular calcium antagonist, TMB-8, also suppressed the production of PGE2, 6-keto-PGF1 alpha and TXB2 in a concentration-dependent manner. The intra-cellular calcium concentration of Kupffer cells elevated early after the addition of LPS determined by the use of fura-2 and a fluorescence microscopy. Moreover, calmodulin inhibitors, W-7 and W-13, apparently inhibited the production of PGF2, 6-keto-PGF1 alpha and TXB2. All these results suggest that LPS-induced PG production by stimulated rat Kupffer cells may be regulated by a calcium-calmodulin pathway.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

[Randomized trial-comparing UFT and FT in the treatment of advanced hepatocellular carcinoma (second report: well controlled study on patients with transcatheter arterial embolization) Osaka Research Society for Liver, Gallbladder and Pancreas].

In a randomized trial Tegafur (FT) or Tegafur.Uracil (UFT) was administrated to 90 patients with advanced hepatocellular carcinoma for whom transcatheter arterial embolization was applied. Efficacy in the reduction of tumor size, subjective symptoms and clinical laboratory findings was comparable in both groups. However, survival rate in the UFT group was significantly higher than in the FT group in only 2 limited subgroups of patients without prior chemotherapy and with tumors found in both lobes of the liver. With respect to adverse effects, complaints about gastrointestinal tract were often noted in the UFT group, but no significant difference was found between the two groups.

Adult↗
PubMed1992

Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde.

The authors studied histochemically the morphologic features of proliferating hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to analyze the process of liver regeneration in embedded tissues fixed with formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens from patients with acute viral hepatitis (AVH) and confluent necrosis, many small basophilic hepatocytes surrounding large clear hepatocytes were positively stained in the areas next to the confluent necrosis. Therefore these small hepatocytes may be daughter cells derived from large clear hepatocytes that probably enter the mitotic cell cycle repeatedly to repair a large necrotic area. In the case of AVH with spotty necrosis, the positively stained hepatocytes were scattered around the necrotic foci. In the liver specimens from patients with chronic active hepatitis, most of the positively stained hepatocytes were located next to the necrotic area. As for cirrhosis of the liver, the number of hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules, and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive for PCNA/cyclin were detected throughout the cancer nests.

Antibodies, Monoclonal↗
PubMed1992

Immunocytochemical identification of proliferative hepatocytes using monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with immunocytochemical staining for DNA polymerase-alpha.

The authors investigated whether immunocytochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to identify proliferative hepatocytes in frozen sections fixed in a mixture of periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used, which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained from 27 patients with various hepatic diseases. Hepatocytes that were positive for PCNA/cyclin were observed in both types of substrate specimens. In acute hepatitis and chronic active hepatitis, most hepatocytes that were labeled for PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were detected most often near fibrotic septa; the number of immunoreactive cells varied greatly in different areas of tissue sections in such cases. In hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha showed a similar distribution pattern in serial sections of study cases.

Adult↗
PubMed1992

[Effect of acute ethanol administration on lipid composition of rat liver plasma membrane and serum--with two different doses of ethanol].

This investigation was performed to determine whether acute ethanol administration (5 g and 3 g/kg body wt.) alters the lipid composition both of liver plasma membrane (LPM) and serum in rat or not. The changes of lipid composition of LPM and serum were observed during peak values which blood ethanol concentration was achieved, after both 5 g and 3 g/kg body wt. ethanol administration; LPM cholesterol (CH) content was significantly decreased, but LPM phospholipids (PL) content was not changed statistically. Serum CH and PL contents were significantly increased. However, CH/PL molar ratio showed significant decreases in both LPM and serum. SPM/PC in LPM was also decreased significantly. These changes of lipid composition in LPM were associated with the increase of the fluidity as demonstrated in our previous reports. These lipid values in ethanol treated animals expressed as a ratio of those from corresponding control animals, taken as 1, consisted with 0.7-0.8, that is very interesting from viewpoint of "homeoviscous adaptation", and in addition, suggesting the possibility that serum CH/PL molar ratio may be useful for the estimation of the changes of lipid composition concerned with LPM fluidity.

Animals↗
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 single ethanol administration on hepatic ornithine decarboxylase induction and polyamine metabolism.

The effects of a single ethanol administration on ornithine decarboxylase induction, polyamine metabolism and DNA synthesis in rat liver after partial hepatectomy were studied. Ethanol given 1 hr before partial hepatectomy at the dose of 2, 3 or 5 gm/kg body wt inhibited the increase in ornithine decarboxylase activity and that in the putrescine level in the liver 4 hr after partial hepatectomy. The hepatectomy increased the amount of ornithine decarboxylase messenger RNA expressed, and this amount was unaffected by ethanol administration. Further, ethanol did not accelerate the degradation of ornithine decarboxylase 4 hr after partial hepatectomy, indicating that the inhibition of ornithine decarboxylase activity caused by ethanol was not caused by a decrease in the ornithine decarboxylase messenger RNA level or by the acceleration of ODC degradation. The single dose of ethanol inhibited [3H]thymidine incorporation into the hepatic DNA 24 hr after partial hepatectomy. The suppression of [3H]thymidine incorporation was partially reversed by the administration of putrescine. These results suggested that ethanol inhibits the increase in ornithine decarboxylase activity after transcription, suppressing the accumulation of putrescine, which prevents DNA synthesis in response to hepatectomy.

Animals↗
PubMed1991

Measurement of hepatic blood flow by use of per-rectal portal scintigraphy with 133Xe.

A relatively noninvasive method is needed to evaluate the hepatic blood flow of patients with liver disease. We used per-rectal portal scintigraphy with 133Xe, and analysed the time-activity curves of the liver and portal vein. To do this, wash-out curves of the liver were plotted, and the hepatic blood flow and the ratio of the blood flow to the right lobe of the liver to that to the left lobe (R/L ratio) were calculated. The mean hepatic blood flow was 137 +/- 23 ml/100 g/min for four patients with fatty liver, 139 +/- 16 ml/100 g/min for seven patients with chronic persistent hepatitis, 120 +/- 15 ml/100 g/min for ten patients with chronic aggressive hepatitis, and 75 +/- 21 ml/100 g/min for 14 patients with cirrhosis. All seven patients with hepatic blood flow that was less than 100 ml/100 g/min and an R/L ratio less than 1.0 had cirrhosis. Only two of the 22 patients with hepatic blood flow that was greater than 100 ml/100 g/min and an R/L ratio greater than 1.0 had cirrhosis. Per-rectal portal scintigraphy can be used to measure the hepatic blood flow, but it was not useful for the diagnosis of fatty liver.

Administration, Rectal↗
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

Detection of hepatitis C virus antibodies and hepatitis C virus RNA in patients with alcoholic liver disease.

The relationship between alcoholic liver disease and hepatitis C virus was studied in 80 patients by searching for hepatitis C virus RNA with the polymerase chain reaction and by measuring hepatitis C virus antibodies. By C-100 enzyme-linked immunosorbent assay, hepatitis C virus antibodies were found in 2 of 10 patients with fibrosteatosis, 8 of 20 patients with alcoholic hepatitis, 14 of 19 patients with chronic hepatitis and 19 of 31 patients with cirrhosis. Percentages of patients with antibodies found by C-100 radioimmunoassay and by enzyme-linked immunosorbent assay based on sequence peptide 42 were lower; of the 16 patients with a low titer by C-100 enzyme-linked immunosorbent assay, 10 were negative by radioimmunoassay and 6 were negative by sequence peptide 42. By a second-generation recombinant immunoblot assay, hepatitis C virus antibodies were found in 1 of 10 patients with fibrosteatosis, 2 of 20 patients with alcoholic hepatitis, 15 of 19 patients with chronic hepatitis and 18 of 31 patients with cirrhosis. Hepatitis C virus RNA was found in 1 of 10 patients with fibrosteatosis, 3 of 20 patients with alcoholic hepatitis, 13 of 19 patients with chronic hepatitis and 20 of 31 patients with cirrhosis. Of the 37 patients with hepatitis C virus RNA, 31 had antibodies by C-100 enzyme-linked immunosorbent assay (25 patients at a high titer [cut-off index greater than 6]), and 31 had antibodies by second-generation recombinant immunoblot assay. Patients with cirrhosis and hepatitis C virus RNA had higher ALT activity than such patients without hepatitis C virus RNA (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Effects of single ethanol administration on liver regeneration in rats].

The effects of a single ethanol administration on liver weight gain, RNA synthesis, DNA synthesis, and polyamine metabolism as parameters of liver regeneration in rat liver after partial hepatectomy were studied. Ethanol, given 1 hr before partial hepatectomy at the dose of 3 g/kg, inhibited RNA synthesis 4 hr after partial hepatectomy and DNA synthesis 24 hr after partial hepatectomy in the liver, but did not affect liver weight gain. Further, we studied the effects of a single ethanol administration on polyamine metabolism in order to elucidate the mechanism of the inhibition of liver regeneration by ethanol. Ethanol inhibited the increase in the putrescine level in the liver 4 and 8 hr after surgery, which was a metabolic product of ornithine decarboxylase. But spermidine and spermidine levels in the liver were not affected by ethanol administration. Hepatic spermidine N1-acetyl transferase activity increased by ethanol administration 6 hr after partial hepatectomy in compensation for the suppression of putrescine. Judging from these results, a single dose of ethanol inhibited liver regeneration polyamine metabolism after partial hepatectomy in rats.

Acetyltransferases↗
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

[Relationship between the condition of the liver in patients and carriers with hepatitis B virus (HBV) and whether there is intrafamilial clustering of HBV].

We analyzed the relationship between the presence of intrafamilial clustering of infection with hepatitis B virus (HBV) and the condition of the liver. Parents and siblings of subjects infected with HBV, some patients and some carriers, were tested for the presence of HBsAg, HBeAg, HBeAb, and liver damage. Then the original subjects with HBV were classified by the results into one of three groups. The subjects in the group without clustering had a higher rate of being seronegative for HBeAg than the groups with clustering, at all ages (P less than 0.01; test). Of the original subjects who were seronegative for HBeAg, the group without clustering had less damage of the liver than the groups with clustering. Of the subjects infected by horizontal transmission, the group without clustering had a higher rate of being seronegative for HBeAg and less damage of the liver than the groups with clustering. Subjects with HBV in a family with members who had normal liver function and who were seronegative for HBeAg were less likely to develop chronic hepatitis B than such subjects in a family with members having chronic liver damage. Thus the presence of intrafamilial clustering might affect the chance of subjects with HBV developing liver damage. The mode of infection and some genetic factors in the infected subjects seem to contribute to the condition of subjects with HBV infection.

Adolescent↗
PubMed1990

Diagnosis of hepatocellular carcinoma by factor analysis.

We examined the usefulness of factor analysis for the diagnosis of hepatocellular carcinoma by analysis of the data obtained by radionuclide angiography. The data could be separated into two factors, a hepatic phase (hepatic artery and portal vein) and an arterial phase (aorta and kidney). In patients with hepatocellular carcinoma, the factor of the tumor is included in the arterial phase, so that the cancerous region could be differentiated from the noncancerous region. The ratio of the radioactivity of the cancerous region to the noncancerous region was used to estimate the blood flow of the tumor region.

Carcinoma, Hepatocellular↗
PubMed1990

Interferon gamma stimulates prostaglandin E2 production by mouse Kupffer cells.

When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release arachidonic acid metabolites, prostaglandins (PGs) and leukotrienes (LTs). In this study, we examined the effect of in vitro Kupffer cell activation with recombinant murine IFN gamma on PGE2 and LTB4 secretion. IFN gamma enhanced PGE2 secretion, and this effect of IFN gamma was stronger than that of IL-1 or TNF. Moreover, IFN gamma promoted LTB4 release especially in the absence of PGs. On the other hand, dexamethasone and indomethacin inhibited and, EGTA and TMB-8, which reduce intracellular Ca++ Levels, blocked IFN gamma induced PGE2 production, which suggested that the activation of phospholipase A2 and cyclooxygenase in Kupffer cells requires the elevation of intracellular Ca++ levels.

Animals↗