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Biomedical subjects

A Yoshimura

Publications and source records attributed to A Yoshimura.

At least 163 records · Page 9Linked to original sources
PubMed1996

Different immunosuppressive effects of liposomal FK506 in liver and kidney transplantation.

The efficacy of liposomal FK506 was compared between a canine liver transplantation model and a canine kidney transplantation model. The present study revealed that liposomal FK506 increased immunosuppressive efficacy of FK506 in liver transplantation but decreased in kidney transplantation. Because liposomal FK506 increased FK506 levels in the liver and spleen, and decreased FK506 levels in the kidney, it was suggested that enhanced immunosuppressive efficacy in liver transplantation should be attributed to the local immunosuppressive effects in the hepatic allograft rather than effective suppression of splenocyte activity.

Animals↗
PubMed1996

Liver transplantation for hepatocellular carcinoma: consideration from the findings on autopsy.

Extrahepatic spread of hepatocellular carcinoma was investigated in twenty autopsy cases with unresected hepatocellular carcinoma to define the appropriate patient selection criteria for liver transplantation. Diagnosis of extrahepatic spread of cancer by diagnostic imaging was not easy, and unsatisfactory prognosis after liver transplantation in patients with hepatocellular carcinoma might have been attributed to the high incidence of extrahepatic occult foci of cancer. All patients with multiple nodular, massive and diffuse tumor had extrahepatic spread of cancer. Only patients with a single nodular type tumor, no larger than 30 mm in diameter, had no extrahepatic metastasis, and these patients are the preferred candidates for liver transplantation.

Aged↗
PubMed1996

[Role of apoptosis in the progression of secondary hyperparathyroidism].

In many tissues, cell proliferation is counterbalanced by apoptosis. Hyperparathyroidism is one of the most important complications in long term dialysis patients and is characterized by remarkable cell proliferation of parathyroid cells. Therefore, alteration in the regulation and clearance of excess cells by apoptosis may occur in hyperparathyroidism. In the present study, we evaluated the expression of Ki-67 (proliferative cell associated protein) and Bcl-2(apoptosis-preventing molecules), and the number of apoptotic cells in the nodular lesion of parathyroid glands with secondary hyperparathyroidism(2 degrees HPT), as compared with primary hyperparathyroidism(1 degree HPT) for clarification of the role of apoptosis in the development of 2 degrees HPT. The number of Ki-67+ cells was remarkably increased in 2 degrees HPT(12.02 +/- 10.87, mean +/- SD) compared to in 1 degree HPT(0.81 +/- 0.53) (p < 0.01). However, the number of apoptotic cells was significantly decreased in 2 degrees HPT(0.10 +/- 0.06) compared to in 1 degree HPT(0.31 +/- 0.19) (p < 0.05). To the contrary, Bcl-2+ cells were increased in 2 degrees HPT(0.35 +/- 0.23) compared to in 1 degree HPT(0.10 +/- 0.13) (p < 0.05). These results suggest that the mechanisms of parathyroid cell proliferation are different in each nodular lesion of 1 degree HPT and 2 degrees HPT. Furthermore, the remarkable proliferation of parathyroid glands may have been due to the reduction of the apoptotic process via Bcl-2 expression in 2 degrees HPT.

Adult↗
PubMed1995

Molecular cloning and functional characterization of a novel member of the C-C chemokine family.

Chemokines play an important role in immune and inflammatory responses by inducing migration and adhesion of leukocytes. We have isolated a novel chemokine cDNA, designated CCF18, from a cDNA library of an IL-3-dependent murine pro-B cell line, Ba/F3. The cDNA encodes a protein structurally related to the C-C chemokine members. Among this family, C10 shows the highest homology to CCF18, and MIP-1 alpha also has a significant homology but to a lesser extent. CCF18 produced from COS cells induced chemotaxis and Ca2+ flux in CD4+ T cell clones. Moreover, prior administration of MIP-1 alpha desensitized the cells to CCF18. The CCF18 gene (Scya10) was mapped to a middle region of murine chromosome 11, where other genes for several C-C chemokine members are localized. These results clearly indicate that CCF18 is a new member of the C-C chemokine family. Since a high level of CCF18 mRNA is constitutively expressed in macrophage and myeloid cell lines, CCF18 may play a role in inflammatory processes.

Amino Acid Sequence↗
PubMed1995

A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.

Cytokines manifest their function through alteration of gene expression. However, target genes for signals from cytokine receptors are largely unknown. We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle. To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter. The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation. Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction.

Amino Acid Sequence↗
PubMed1995

The enhanced immunosuppressive efficacy of newly developed liposomal FK506 in canine liver transplantation.

Local delivery of immunosuppressants to the graft and lymphatic tissue is a potential appraoch to enhance the immunosuppressive efficacy and to alleviate systemic adverse effects simultaneously. By taking advantage of this method, we developed liposomal FK506. Previous pharmacokinetic study of liposomal FK506 indicated increased FK506 levels in the liver and spleen. Because the liver is the site of the allograft in liver transplantation and the spleen is a major lymphoid tissue, we hypothesized that liposomal FK506 would increase immunosuppressive efficacy in liver transplantation. We evaluated this hypothesis in a canine model. Orthotopic liver transplantation was performed using beagle dogs, and the recipients were divided into the following groups: group I, no immunosuppression (n = 5); group II, 0.05 mg/kg/day of FK506 i.v. in a commercially available i.v. formulation for 14 days (n = 5); and group III, 0.05 mg/kg/day of FK506 i.v. in a liposomal formulation for 14 days (n = 5). All recipients in group I died within 2 weeks. Recipients in group II died within 33 days. In contrast, three recipients in group III survived for more than 200 days (P < 0.05 versus group I or group II). In DNA analysis, splenocyte proliferation activity in group III was significantly suppressed in comparison with group II. These results suggest that liposomal FK506 markedly increase the immunosuppressive efficacy of FK506 in liver transplantation. A local immunosuppressive effect in the grafted liver and significant suppression of splenocyte proliferation might contribute to enhancement of the immunosuppressive efficacy of liposomal FK506.

Animals↗
PubMed1995

Successful management of portal hypertension following artificial arterioportal shunting: report of a case.

A 63-year-old woman diagnosed as having hepatic hilar cancer underwent an extended left lobectomy of the liver with excision of the right hepatic artery which was involved by the tumor. Because the hepatic artery could not be reconstructed by direct anastomosis, an artificial arterioportal (A-P) shunt was constructed between the common hepatic artery and the portal vein. However, 4 weeks after the operation, portal hypertension with severe esophageal varices developed. Under the diagnosis of portal hypertension caused by excessive blood flow from the A-P shunt, coil embolization of the common hepatic artery was performed using an angiographic technique, following which the esophageal varices completely disappeared. This case demonstrates that portal hypertension after A-P shunting can be effectively treated with coil embolization.

Angiography↗
PubMed1995

Ki-ras mutations and p53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology.

BACKGROUND & AIMS: We previously reported that intrahepatic cholangiocarcinomas (ICCs) can be divided into three categories according to their gross appearance with possible links to biological behavior. Ki-ras and p53 gene alterations are thought to be involved in early and late phases of carcinogenesis, respectively. This study was performed to investigate the relationship between the gross appearance and genetic alterations of ICC. METHODS: We examined 21 patients with ICC. Ki-ras point mutations were assessed by polymerase chain reaction/single-strand conformation polymorphism methods followed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. RESULTS: Ki-ras point mutations were found in 10 patients (48%), and expressions of p53 protein were detected in 4 (19%). Applying the gross classification that we previously proposed, Ki-ras mutations were prominent in the periductal extension type (4 of 6; 67%) and the spicula-forming type (6 of 10; 60%). On the other hand, none of the five mass-forming-type tumors harbored Ki-ras mutations. Expressions of p53 protein did not show any clear association with gross appearance. CONCLUSIONS: Ki-ras gene alterations may be involved in the cholangiocarcinogenesis of periductal extension and spicula-forming but not mass-forming types, suggesting that the underlying processes of development are different.

Adult↗
PubMed1995

Endothelin-1 and endothelin B type receptor are induced in mesangial proliferative nephritis in the rat.

We studied whether endothelin-1 (ET-1) and its receptor subtypes (ETAR, endothelin A type receptor; and ETBR, B type receptor) were up-regulated in the glomerulus of a rat model of mesangial proliferative glomerulonephritis induced by anti-thymocyte serum (anti-Thy-1 GN). A marked increase in preproET-1 mRNA could be demonstrated in glomerular RNA 3 and six days after disease induction (4.1- and 4.9-fold vs. day 0, respectively), corresponding to the time of mesangial cell proliferation, to the time of macrophage infiltration into glomeruli, and also to the time of increase in glomerular PDGF B-chain mRNA expression. The localization of ET-1 protein in the mesangial area and along the inner aspect of the glomerular capillary wall was also demonstrated by immunohistochemistry from day 3 and maximal at day 6. The major source of the cells expressing ET-1 in glomeruli appeared to be mesangial cells, glomerular endothelial cells and monocyte/macrophages. Furthermore, both gene and protein expression of ET-1 were associated with increased urinary excretion of ET-1. There was no increase in the plasma ET-1 immunoreactivity. Glomerular expression of ETBR mRNA increased in anti-Thy-1 GN (1.5-fold vs. day 0 at day 3 after disease induction, 3.6-fold at day 6 and 2.7-fold at day 10), but there was minimal change in ETAR mRNA expression. These results suggest that preproET-1 mRNA, which is induced in anti-Thy-1 GN, is linked primarily with ETBR mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Augmented lung adenocarcinoma cytotoxicity by the combination of a genetically modified anti-Lewis Y antibody and antibodies to complement regulatory proteins.

Complement-dependent cytotoxicity (CDC) mediated by a chimeric anti-Lewis Y monoclonal antibody (cH18A; human IgG1) was investigated in this study. Human lung adenocarcinoma cell lines (PC7, PC9, and PC14) were used as the target cells. PC7 and PC9 cells, expressed Lewis Y antigen and were lysed by cH18A as effectively as by the parent mouse anti-Lewis Y antibodies (mH18A) in a concentration-dependent manner. PC14 cells did not express Lewis Y antigen and were not lysed by either cH18A or mH18A. cH18A mediated CDC activity against PC7 and PC9 cells was enhanced by the combined use of monoclonal antibodies directed against CD46(MCP), CD55(DAF), and CD59. These molecules are complement-regulatory proteins which protect host cells from CDC. PC7 and PC9 cells, showed high levels of surface expression of these proteins, PC7 cells were more susceptible to cH18A-mediated CDC than PC9 cells. Use of multiple blocking antibodies to the complement-regulatory proteins produced more enhancement of cH18A-mediated CDC than a single antibody. Moreover, expression of CD55 and CD59 by PC7 and PC9 cells was decreased after treatment with PI-PLC, resulting in increased susceptibility to cH18A-mediated CDC. Although the reason is unknown, PC7 cells became more susceptible to CDC than PC9 cells after PI-PLC treatment even in the absence of cH18A. These data suggest that chimeric monoclonal antibodies can be used to induce CDC against lung adenocarcinoma, and that such CDC is potentiated by a variety of antibodies blocking compliment-regulatory proteins on the tumour cell surface.

Adenocarcinoma↗
PubMed1995

Pulmonary hypertension in rats. 1. Role of bromodeoxyuridine-positive mononuclear cells and alveolar macrophages.

The role of activated cells determined by staining with bromodeoxyuridine (BrdU) and the role of alveolar macrophages as a source of cytokines were investigated in monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. BrdU was mainly incorporated by mononuclear cells; their number increased strikingly prior to the development of PH. Cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor were produced during the development of PH. The amount of IL-6 showed significant correlation (p < 0.05) with the number of BrdU-positive cells, which, in turn, correlated with the extent of PH. These results indicate that BrdU-positive cells and cytokines produced by alveolar macrophages may play an important role in the pathogenesis of MCT-induced PH in rats.

Animals↗
PubMed1995

Pulmonary hypertension in rats. 2. Role of interleukin-6.

We administered human interleukin (IL)-6 to rats to examine whether it is implicated in the development of pulmonary hypertension (PH). The rats injected with IL-6 developed PH as determined by the weight ratio of the right ventricle to the left ventricle+septum. This ratio decreased with the appearance of IgG anti-human IL-6 antibody. Histologically we observed in the lungs, luminal occlusion of small muscular arteries, capillaries filled with fibrin thrombi, and localized hemorrhage. IL-6 increased the number of platelets, and the number of platelets correlated with the extent of PH. Thus, it seems likely that (IL-6) is involved in the formation of PH in this model.

Animals↗
PubMed1995

Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit artery.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25 U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7, p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at the injured site was confirmed by microscopy. The activated partial thromboplastin time and fibrinogen level did not change significantly. PDGF-B chain was prominent at the neointimal layer in all the controls, whereas it was less in the locally treated arteries. Thus local delivery of heparin can inhibit neointimal hyperplasia after balloon injury by reducing thrombus-related growth stimulation.

Angioscopy↗
PubMed1995

[Serum lipid states in elderly patients with acute myocardial infarction: comparison between patients aged 60 to 79 and 80 years and over].

Recently, the prevalence of acute myocardial infarction (AMI) in the elderly patients has increased. The clinical features have not been extensively studied, so this study attempted to clarify the clinical course and prognosis of elderly patients with AMI. The patients were divided into two groups, those over 80 years old and those between 60 and 79 years old. The clinical symptoms, electrocardiographic findings, complications, and short-term prognosis were compared. The serum lipid levels were compared between the AMI groups and age-matched control groups consisting of subjects without sclerotic heart disease. There was no significant difference in clinical symptoms between the two groups, electrocardiographic findings, incidence of complications, and mortality. The total cholesterol and LDL cholesterol levels, and atherogenic index were significantly higher in the 60-79 years old AMI group, but no significant difference was observed in the 80 years and over AMI group compared to the control group. The HDL cholesterol level of the 60-79 years old AMI group was significantly lower, but no significant difference was observed in the 80 years and over group. There was no significant difference in triglyceride level in either AMI group. Therefore, in patients aged 60-79 years hyperlipidemia is a risk factor for ischemic heart disease, but the relationship between serum lipid and AMI is not positively established in patients older than 80 years. These results suggest that the significance of hyperlipidemia in patients over 80 years old should be reconsidered.

Age Factors↗