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Biomedical subjects

Y Shiratori

Publications and source records attributed to Y Shiratori.

At least 199 records · Page 11Linked to original sources
PubMed1993

Quantification of sinusoidal cell function in vivo.

Although the clearance and distribution of ligand molecules in circulation represent the function of hepatic sinusoidal cells, these mechanisms revealed a network that is more intricate than would at first seem, since several receptors are common to not only one type of cell, but also to two or three types of cells in the liver. In the case of latex particles in which their uptake by a particular cell type seems to be determined by their size, sinusoidal endothelial cells are able to internalize particles up to 0.23 microns under physiologic conditions, in vivo, and larger particles are taken up by Kupffer cells. However, when the phagocytic function of Kupffer cells is impaired by frog virus 3 or alcohol, endothelial cells have been found to take up particles larger than 1 micron in diameter after the injection of an excess amount of latex particles. Endothelial cells would thus constitute a second line of defense in the liver in that they remove foreign materials from the blood when Kupffer cell phagocytic function is totally disturbed. This potential role may not, however, be fully expressed under physiologic conditions when Kupffer cells are active in clearing foreign substance from the circulation. The functions of liver sinusoidal cells are varied and complex and these cells can be regarded as "a sinusoidal cell unit." This cellular interaction must be taken into account for any quantitative analysis.

Animals↗
PubMed1993

Changes in plasma levels of prothrombin fragment F 1 + 2 in cases of disseminated intravascular coagulation.

Plasma levels of prothrombin fragment F 1 + 2 (PTF) and thrombin-antithrombin III complex (TAT) were assayed in 86 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, which suggested that the in vivo generation of thrombin is highly accelerated by the cleavage of the prothrombin molecule by factor Xa. On the contrary, no significant elevation of plasma levels of PTF was observed in cases of DIC with severe hepatic failure or fulminant hepatitis in spite of significant elevation of TAT. Plasma levels of PTF were directly proportional to those of TAT in 86 cases of DIC as a whole (r = 0.682, p < 0.001). The measurement of both parameters was considered to be useful to estimate the hemostatic activation in DIC.

Antithrombin III↗
PubMed1993

Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients.

OBJECTIVE: Sonographically guided percutaneous ethanol injection therapy has been used widely in the treatment of hepatocellular carcinoma. However, few reports have been published on the results of this treatment in large numbers of patients. Accordingly, we describe our experience with 146 patients who had this treatment. The study is an update of our previous reports on this subject. SUBJECTS AND METHODS: We used ethanol injection, with or without transcatheter arterial embolization, 1048 times in 146 patients who had 242 lesions of hepatocellular carcinoma. In 98 patients, ethanol injection was used to attempt a cure of the disease. In the remaining 48 patients, ethanol injection was used palliatively only to reduce the tumor burden. In most cases, 2-8 ml of absolute ethanol was injected in one treatment session. Patients were given the injections two or three times each week until ethanol was injected throughout the lesion. When tumors were greater than 2 cm in diameter, ethanol was injected into the edges of the lesion. RESULTS: Histopathologic examination after treatment in 21 cases showed that the lesion was completely necrotic in 15 cases, 90% necrotic in five cases, and 70% necrotic in the remaining case. Follow-up angiography performed in 69 cases showed no contrast stains in the treated tumors in 60 cases. Elevated serum levels of alpha-fetoprotein decreased in 39 of 43 cases. The 1-, 2-, 3-, 4-, and 5-year survival rates of all 146 patients were 79%, 64%, 46%, 38%, and 38%, respectively. Among 98 patients in whom ethanol injection was used as a potentially curative therapy, these rates were 85%, 70%, 62%, 52%, and 52%, respectively. After ethanol injection, the cancer recurred frequently; the 1-, 2-, 3-, 4-, and 5-year recurrence rates in the potentially curative group were 26%, 38%, 51%, 60%, and 60%, respectively. However, 84% of recurrences were new lesions in different portions of the liver; recurrence of lesions treated by ethanol injection was rare. Major complications of the treatment were peritoneal bleeding in two cases and pleural effusion in one case. CONCLUSION: Histopathologic examination, angiography, and serum levels of alpha-fetoprotein showed that percutaneous ethanol injection is a valuable treatment of hepatocellular carcinoma. The therapy increased the long-term survival of patients who have this disease.

Carcinoma, Hepatocellular↗
PubMed1993

Production of chemotactic factor, interleukin-8, from hepatocytes exposed to ethanol.

In a previous paper, we demonstrated proteinous chemotactic factors released from hepatocytes exposed to ethanol. In this study, we further characterized the chemotactic factors released from ethanol-treated hepatocytes. After fractionating the conditioned medium with gel chromatography, we demonstrated chemotactic activity at molecular weights of around 20 and 40 kD. When the conditioned medium was mixed with antiserum against interleukin-8, chemotactic activity was almost completely abolished. In addition, antiserum against interleukin-8 completely reduced chemotactic activity of the 20-kD chemotactic factor but did not influence the chemotactic activity of the 40-kD chemotactic factor. After gel electrophoresis of the conditioned medium, the protein reacted with antibody against interleukin-8 was demonstrated at a molecular weight of 20 kD but was not found at a molecular weight of 40 kD. These results suggest that a major part of the proteinous chemotactic factors released from hepatocytes exposed to ethanol could be a dimer form of interleukin-8, one of the proinflammatory cytokines, possibly contributing to the pathogenesis of alcoholic hepatitis.

Animals↗
PubMed1992

Inhibition of hepatic metastasis of colon carcinoma by asialo GM1--positive cells in the liver.

This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM1-positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver.

Animals↗
PubMed1992

Generation of chemotactic factor by hepatocytes isolated from chronically ethanol-fed rats.

In an attempt to clarify a mechanism of polymorphonuclear cell and/or macrophage infiltration in alcoholic liver disease, we investigated a novel chemotactic and activating factor generated by rat hepatocytes isolated from the chronically ethanol-fed rats. Hepatocytes and hepatic macrophages were isolated from rat liver by perfusion and digestion with collagenase and subsequently by differential centrifugation on a metrizamide gradient. Rat polymorphonuclear cells were prepared from blood by the dextran sedimentation and Hypaque-Ficoll technique. Chemotactic activity was measured as migration of polymorphonuclear cells or hepatic macrophages using a chemotactic chamber. When hepatocytes isolated from the ethanol-fed rats were cultured in vitro, chemotactic activity for rat polymorphonuclear cells and hepatic macrophages was demonstrated in the culture supernatant. Inhibitors of transcription and protein synthesis reduced generation of chemotactic factor from these hepatocytes. Chemotactic activity of the conditioned medium was reduced after trypsin (0.25%, 37 degrees C, 30 min) or heat (56 degrees C, 30 min) treatment. The chemotactic activity was eluted at molecular weights of 20-25 kDa and 40-45 kDa following Sephadex G-150 chromatography. Superoxide anion production by polymorphonuclear cells and hepatic macrophages under the stimulation of phorbolmyristate acetate was enhanced in the presence of this chemotactic factor. This chemotactic factor may contribute to the pathogenesis of alcoholic liver disease.

Animals↗
PubMed1992

Mechanism of accumulation of macrophages in galactosamine-induced liver injury: effect of lipoxygenase inhibitors on chemotaxis of spleen cells.

In an attempt to clarify a mechanism of macrophage infiltration in galactosamine-induced hepatic injury, we investigated chemotactic factor(s) generated by murine hepatocytes exposed to galactosamine. Hepatocytes, isolated from murine liver by perfusion and digestion with collagenase, were incubated with galactosamine. Conditioned medium was collected 24 h later and chemotaxis of murine spleen cells was measured by stimulation of the conditioned medium using a modified Boyden chamber. Chemotactic activity was demonstrated in the conditioned medium of hepatocytes exposed to more than 3 mM galactosamine. Chemotactic activity of the conditioned medium was not reduced after freeze-thawing, and found to be dialyzable (molecular weight < 12,000). Trypsin (0.25%, 37 degrees C, 30 min) or heat (56 degrees C, 30 min) treatment reduced chemotactic activity of the conditioned medium. Furthermore, chemotaxis of spleen cells was decreased in the presence of lipoxygenase inhibitors (azelastine, ketotifen). These results suggest that accumulation of macrophages in the liver could be mediated by chemotactic factor produced by the galactosamine-treated hepatocytes, and that this mechanism may contribute to the pathogenesis of hepatic injury induced by galactosamine.

Animals↗
PubMed1991

Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study.

Histopathologic examination was done on 18 cases after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma. In eight cases, the lesion was treated by PEIT alone; in the other ten cases, PEIT was combined with transcatheter arterial embolization. The lesion was completely necrotic in 13 cases, 90% necrotic in four cases, and 70% necrotic in the rest. In addition, PEIT seemed to be effective against intercapsular, extracapsular, and vascular invasions. In the four cases of incomplete necrosis, the viable cancer tissue remained in small tumor nodules around the main tumor, in portions isolated by septa, or along the edge of the lesion. Therefore, ethanol should be injected not only into the center of the lesion, but also into sites close to its edge. Ethanol did not damage noncancerous liver parenchyma distant from injected sites. Local dissemination of the cancer cells was not found in any case. Therefore, PEIT seems to be a valuable therapy and may be an alternative to surgery in some cases.

Adult↗
PubMed1991

[Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed.

Adenoma, Bile Duct↗
PubMed1991

[Seven cases of eye involvement in adult with acute leukemia].

Seven acute leukemia cases with oculomotor paralysis and/or optic nerve paralysis were reported. Five cases were lymphoblastic and two were myelogenous leukemia. The average age was 30.7 years old and male to female ratio was 5:2. The eye involvement developed during hematological complete remission stage in 4 cases, and during relapsing stage in 2 cases. For the remaining case, eye symptom was an initial symptom of the disease. The computed tomography of ocular region showed tumorous involvement in 3 cases and no abnormality in other 4 cases. The white blood cell count on admission was over 30,000/microliters and leukemic cells occupied over 59% of bone marrow nucleated cells in 5 cases. Intrathecal administration, a whole brain irradiation and intra-arterial injection of Nimustin as well as standard systemic chemotherapy were performed against oculomotor and optic nerve involvement. Leucoencephalopathy occurred in 2 of 7 cases after intrathecal administration and irradiation. Since 1980, continuous treatment for prophylaxis of central nervous system leukemia have been done and this protocol was effective for meningeal involvement but not for ocular involvement.

Acute Disease↗
PubMed1990

Synthesis of a new helical protein: the effect of secondary structure rearrangement on structure formation.

A new helical protein was designed and synthesized to alter the sequential connectivity of the 4 helices in human growth hormone and to delete the long surface loop structures. The protein accumulated as an insoluble form in E. coli was solubilized and purified to apparent homogeneity in the presence of 7M urea, and refolded by the aid of 1% n-octyl-beta-D-glucopyranoside. The circular dichroism spectrum was typical of a highly helical protein. The molecular weight estimated by gel permeation chromatography and the red-shift of the fluorescence maximum by urea-induced denaturation suggest that the protein folds into a compact globular form. The new protein obtained, however, was destabilized relative to the original human growth hormone.

Amino Acid Sequence↗
PubMed1990

Role of endotoxin-responsive macrophages in hepatic injury.

Although administration of 100 mg galactosamine caused severe hepatic injury in C3H/HeN mice, splenectomy reduced the grade of this hepatotoxicity. However, this hepatic injury was scarcely detected in the endotoxin-resistant C3H/HeJ mice. In addition, in contrast to high lethality in C3H/HeN mice with a combined administration of galactosamine and endotoxin, splenectomy rendered C3H/HeN mice slightly resistant to this treatment. Further resistance was demonstrated in C3H/HeJ mice. In an attempt to clarify the role of endotoxin-responsive spleen cells in the pathogenesis of hepatic injury, we investigated galactosamine-induced hepatic injury by transfer of lipopolysaccharide-treated C3H/HeN or C3H/HeJ spleen cells. Both oxygen-derived free radical production and the proportion of macrophages in spleen cells were markedly enhanced in C3H/HeN mice after an intraperitoneal injection of lipopolysaccharide. Further increase in oxidative free radical production was found in the dish-adherent cells (macrophages). These enhancements were not demonstrated in lipopolysaccharide-treated C3H/HeJ spleen cells. Although hepatic injury was not demonstrated in both C3H/HeN and C3H/HeJ mice treated with 35 mg galactosamine alone, severe hepatotoxicity was found in these galactosamine-treated mice when they received lipopolysaccharide-activated C3H/HeN spleen cells, especially macrophages. Simultaneous administration of superoxide dismutase with the activated spleen cells reduced the grade of hepatic injury. On the other hand, hepatic injury was not demonstrated in the galactosamine-treated C3H/HeN or C3H/HeJ mice when they received lipopolysaccharide-treated C3H/HeJ spleen cells, although 3H-galactosamine incorporation into hepatocytes was nearly identical in both C3H/HeN and C3H/HeJ mice. These results suggest that oxidative free radicals of lipopolysaccharide-responsive macrophages could contribute to the pathogenesis of galactosamine-induced hepatic injury.

Alanine Transaminase↗
PubMed1990

Leukotriene inhibitors modulate hepatic injury induced by lipopolysaccharide-activated macrophages.

In an attempt to elucidate the effect of lipoxygenase inhibitors on hepatic injury, we investigated D-galactosamine (GalN)-treated C57BL/6 mice receiving an intravenous (i.v.) injection of lipopolysaccharide (LPS)-activated autologous spleen cells. As compared with control spleen cells, the number of monocytes in the spleen cells isolated from LPS-treated mice and their oxidative free radical production increased markedly. Oxygen radical production by the dish-adherent cells (macrophage-rich population) was enhanced a further 4-fold. Although hepatotoxicity was not demonstrated in mice treated with 20 mg GalN alone, marked hepatic injury was found in the GalN-treated mice with a supplementation of LPS-activated spleen cells. The dish-adherent cells aggravated this hepatic injury, in contrast to minor hepatotoxicity by the nonadherent cells. Oxygen radical production by LPS-activated spleen cells was markedly reduced by the lipoxygenase inhibitors (azelastine, ketotifen and AA861). Hepatotoxicity was scarcely detected in the GalN-treated mice with a supplementation of the LPS-activated spleen cells which had been previously treated with lipoxygenase inhibitors. From these results, LPS-activated spleen macrophages contributed to hepatic injury induced by GalN, and lipoxygenase inhibitors which reduced oxygen radical production by the activated cells, protected against macrophage-induced hepatic injury in mice.

Alanine Transaminase↗