Endoscopic ultrasonography for early gastric cancer.
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Gastroscopy↗
Biomedical subjects
M Tada
Publications and source records attributed to M Tada.
Adenosine blockade during reperfusion reverses the infarct limiting effect in preconditioned canine hearts.
OBJECTIVES: The aim was to investigate whether adenosine release after reperfusion contributes to infarct limitation by ischaemic preconditioning. METHODS: Dogs underwent preconditioning with four 5 min cycles of left anterior descending coronary artery (LAD) occlusion and reperfusion, followed by 90 min LAD occlusion and 5 h reperfusion with or without the non-specific adenosine receptor blocker, 8-phenyltheophylline (8-PT). Infarct size was assessed by a dual staining method with triphenyltetrazolium chloride and Evans blue. Blood flow measurements in the subendocardial region were made by infusion of coloured microspheres before occlusion and midway through the sustained occlusion. Transcardiac alteration of neutrophillic function was assessed by luminol-enhanced whole blood chemiluminescence induced by zymosan. RESULTS: Infarct size was significantly reduced in the preconditioned dogs [12.5(SEM 4.0)%, n = 10, p < 0.01] compared with the control dogs [40.5(6.1)%, n = 10], an effect significantly reduced by the 8-PT treatment [23.4(4.9)%, n = 8]. Treatment with 8-PT without ischaemic preconditioning had no effect on infarct size [42.8(6.3)%, n = 7]. There was no difference in myocardial blood flow in the ischaemic or non-ischaemic subendocardial tissue between any pair of the four groups. The ratio of whole blood chemiluminescence in the cardiac vein to that in the carotid artery was considerably reduced in preconditioned dogs compared with that in control dogs after reperfusion. Myeloperoxidase activity in the ischaemic myocardium and the peripheral neutrophil count at the end of the experiment were both also decreased compared with control dogs. In preconditioned dogs treated with 8-PT, neutrophillic function in the coronary circulation after reperfusion was increased compared with that in both controls and preconditioned dogs with no 8-PT treatment. There was no difference in neutrophillic function between the 8-PT-treated dogs with or without ischaemic preconditioning. Treatment with 8-PT increased myeloperoxidase activity in the ischaemic myocardium of the preconditioned dogs, and no difference was seen in activity between dogs treated with 8-PT with or without ischaemic preconditioning. CONCLUSIONS: An adenosine receptor blocker caused a moderate but significant reversal of infarct limitation by ischaemic preconditioning associated with a significant increase of neutrophillic function in the coronary circulation during early reperfusion.
Animals↗
High-molecular-weight hyaluronic acids inhibit chemotaxis and phagocytosis but not lysosomal enzyme release induced by receptor-mediated stimulations in guinea pig phagocytes.
The effects of high-molecular-weight (HMW) hyaluronic acids (HAs) of 1.9 x 10(6) Da, 8 x 10(5) Da and 3 x 10(5) Da on the receptor-mediated functions of guinea pig peritoneal phagocytes were studied. HMW-HAs of 1.9 x 10(6) Da (HA190) and 8 x 10(5) Da (HA80) effectively inhibited the chemotactic activity of polymorphonuclear leukocytes (PMNs) for formyl-Met-Leu-Phe (fMLP). The degree of inhibition was dose-dependent and the concentrations of HA190 and HA80 required for 50% inhibition were 0.5-1.5 mg/ml and 1.5-2.5 mg/ml, respectively. HMW-HA of 3 x 10(5) Da (HA30) hardly affected the chemotaxis within a concentration range of 0.5-5.0 mg/ml. The phagocytic activities of PMNs and macrophages (Mphis) for serum-opsonized zymosan (SOZ) and polystyrene latex particles were also inhibited by these HAs in a dose- and molecular-weight-dependent manner and HA190 was again the most inhibitory. By contrast, the release of lysosomal enzyme from Mphis stimulated with SOZ was not significantly affected by HMW-HAs at any concentration used. Furthermore, the binding of [3H]fMLP with PMNs and the rosette formation of Mphis with SOZ were not influenced by the presence of HMW-HAs. These findings suggested that the binding of HMW-HAs to the HA receptors on PMNs and M phi s might produce certain intracellular signals which would be responsible for the suppression of the chemotaxis and the phagocytosis but not for the release of lysosomal enzyme. For the generation of such signals, higher-molecular-weight HMW-HAs would be more effective than lower one.
Animals↗
Calcium overload and cardiac myocyte cell damage induced by arachidonate lipoxygenation.
The accumulation of arachidonic acid and lipoxygenase metabolites of arachidonate occurs in ischemic-reperfused myocardium. Although lipoxygenase inhibitors have been shown to attenuate myocardial infarct size after ischemia-reperfusion, the relationship between arachidonate lipoxygenation and myocardial injury remains unclear. To investigate the direct effect of arachidonate lipoxygenation on cardiac myocytes, isolated rat cardiac myocytes loaded with indo 1 were superfused with Tyrode solution containing arachidonic acid mixed with soybean lipoxygenase. Although neither arachidonic acid nor lipoxygenase alone had any effects, arachidonic acid plus lipoxygenase induced an increase in the twitch amplitude associated with an increased intracellular Ca2+ concentration ([Ca2+]i) and irreversible hypercontracture. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked these effects. Linolenic acid, which is also a lipoxygenase substrate, caused the same effects as arachidonic acid in the presence of lipoxygenase, whereas oleic and stearic acid, which do not function as lipoxygenase substrates, did not. Both ascorbic acid and alpha-tocopherol attenuated an increase in [Ca2+]i and the cellular damage, whereas nicardipine and superoxide dismutase had no effects. These results suggest that lipoxygenase metabolites of arachidonic acid cause intracellular Ca2+ overload and cellular damage to cardiomyocytes, probably through augmentation of lipid peroxidation of the cell membranes by free radicals.
Animals↗
Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction.
We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.
Animals↗
Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning.
Manganese superoxide dismutase (Mn-SOD) is induced in ischemic hearts 24 h after ischemic preconditioning, when tolerance to ischemia is acquired. We examined the relationship between Mn-SOD induction and the protective effect of preconditioning using cultured rat cardiac myocytes. Exposure of cardiac myocytes to brief hypoxia (1 h) decreased creatine kinase release induced by sustained hypoxia (3 h) that follows when the sustained hypoxia was applied 24 h after hypoxic preconditioning (57% of that in cells without preconditioning). The activity and content of Mn-SOD in cardiac myocytes were increased 24 h after hypoxic preconditioning (activity, 170%; content, 139% compared with cells without preconditioning) coincidentally with the acquisition of tolerance to hypoxia. Mn-SOD mRNA was also increased 20-40 min after preconditioning. Antisense oligodeoxyribonucleotides corresponding to the initiation site of Mn-SOD translation inhibited the increases in the Mn-SOD content and activity and abolished the expected decrease in creatine kinase release induced by sustained hypoxia after 24 h of hypoxic preconditioning. Sense oligodeoxyribonucleotides did not abolish either Mn-SOD induction or tolerance to hypoxia. These results suggest that the induction of Mn-SOD in myocytes by preconditioning plays a pivotal role in the acquisition of tolerance to ischemia at a later phase (24 h) of ischemic preconditioning.
Adaptation, Physiological↗
DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats.
3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable decrease in staining intensity was evident in most organs by 168 hr after administration of DMAB. Specific DNA lesions which could be responsible for carcinogenesis were not detected by the 32P-postlabeling method. The tumorigenic response of the ventral prostate in five strains of rats was roughly paralleled by DMAB-DNA adduct levels generated in the tissue. Strong enhancement of bladder tumor development by combined administration of the antioxidants, butylated hydroxyanisole, or butylated hydroxytoluene, with DMAB, was well correlated with an increase in DNA adducts. Our findings so far suggest that DNA adduct formation itself does not determine the carcinogenic organotropism of DMAB. Other factors (including cell proliferation and promotion by exogenous agents) may play important additional roles. For individual target organs or tissues, however, there seems to be a correlation between adduct levels and carcinogenic potential.
Aminobiphenyl Compounds↗
The carcinogenicity of methoxyl derivatives of 4-aminoazobenzene: correlation between DNA adducts and genotoxicity.
To elucidate the cause of the difference in genotoxic activity between carcinogenic 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and noncarcinogenic 2-methoxy-4-aminoazobenzene (2-MeO-AAB), we analyzed DNA adducts in the livers of rats exposed to either of these chemicals and studied the resulting biologic potential with the aid of in vitro modified M13 phage DNA. 32P-Postalbeling analysis revealed that the carcinogen 3-MeO-AAB produced 20-fold higher amounts of adducts than did 2-MeO-AAB. Five adducts were formed in the 3-MeO-AAB case whereas only one adduct was apparent in 2-MeO-AAB-treated rat. Studies of in vitro DNA replication using N-hydroxy (N-OH)-aminoazo dye-modified M13 phage DNA as a template demonstrated inhibition by 3-MeO-AAB adducts to be substantially greater than in the 2-MeO-AAB-adducts. The specificity of mutagenesis induced in M13mp9 phage DNA by these chemicals also was analyzed after transfection into SOS-induced Escherichia coli JM103, mutation frequencies being higher with N-OH-3-MeO-AAB- than N-OH-2-MeO-AAB-modified DNA. The mutation spectra differed in each case. Our data suggest that the difference in hepatocarcinogenic activity between the two chemicals depends not only on qualitative and quantitative variation in adduct formation but also on conformation changes in modified DNA.
Animals↗
Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells linked with cell cycle arrest in G1 phase.
The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle alterations in human malignant glioma cell lines, SF-188 and LN-382, were investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN-382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase increased, while the percentage of cells in the S phase decreased. LN-382 cells did not show any marked change in cell kinetics. TNF arrests certain human glioma cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid synthesis in the subsequent S phase, suppressing the proliferation pathway.
Brain Neoplasms↗
Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction.
To elucidate which cytokine receptors may be expressed by human glioblastoma and normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a number of cytokine receptors was examined in 16 glioblastoma cell lines and adult and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was synthesized and amplified with specific primers using the polymerase chain reaction method. The receptors studied were interleukin (IL)-1 receptor type I (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN-alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R), and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM-CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight, 14, three, and one cell lines, respectively. Normal astrocytes were positive for IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR, showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10, p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM-CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These expressions were consistent with those in the cell lines, except for IL-8R. It is concluded that glioblastoma cells and normal astrocytes express a similar set of cytokine receptor genes in vitro and in vivo. Possible autocrine loops are suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M-CSF/M-CSFR, and SCF/SCFR in glioblastomas.
Adult↗
Upper gastrointestinal tract.
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Duodenal Diseases↗
[A case of hepatocellular carcinoma with lumbar bone metastasis with high uptake of 18F-fluorodeoxygalactose in PET].
18F-fluorodeoxygalactose (18FDGal) is a tracer for the evaluation of galactose metabolism in the tissue. PET with 18FDGal was performed in a hepatoma (HCC) patient with lumbar bone metastasis. The image at 45 min after i.v. injection of 18FDGal demonstrated very high uptake by the bone metastasis with tumor-to-surrounding normal tissue ratio of 36. The tumor uptake expressed by differential absorption ratio was much higher than that in the cirrhotic liver and kidney. The result indicated that the HCC maintained high activity of galactose metabolism and rises the potential of this tracer for detecting extrahepatic metastases of HCC using PET.
Carcinoma, Hepatocellular↗
KN-62, a specific Ca++/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes.
Effects of KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine), a specific Ca++/calmodulin (CaM)-dependent protein kinase inhibitor, were examined on the rate of spontaneous beating and the intracellular Ca++ transient of cultured myocytes from fetal mouse ventricle. KN-62 depressed the rate of beating in a dose-dependent fashion. Spontaneous beating ceased 10 min after the administration of 1 microM KN-62 and recovered gradually after washing with cultured medium. Addition of KN-04 [N-(1-1[P-(5-isoquinolinsulfonyl)benzyl]-2-(4- phenylpiperazinyl)ethyl)-5-isoquinolinsulfonamide; 1 microM], an analog of KN-62, did not change the rate of beating. In the experiment using an intracellular Ca++ fluorescence indicator, fluo-3, KN-62 depressed the fluo-3 intensity at a systolic phase. The kinase activity to syntide-2 of Ca++/CaM kinase II purified from the rabbit heart was inhibited by KN-62, but not by KN-04. Addition of KN-62 inhibited the phosphorylation of phospholamban by Ca++/CaM kinase II in a dose-dependent manner. KN-62 depressed the Ca(++)-pumping ATPase activity in the presence of Ca++ and CaM by 32%. These findings indicate that Ca++/CaM kinase II changes an intracellular Ca++ transient and modulates the rate of beating at least in part.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Assessment of production of endothelium-derived relaxing factor (EDRF) by cultured human vascular endothelial cells based on its anti-aggregatory effect on human platelets.
In order to establish an experimental system to assess the production of endothelium-derived relaxing factor (EDRF) by cultured human umbilical vascular endothelial cells (HUVECs), the effect of endothelial cells on thrombin-induced platelet aggregation was examined. Cultured HUVECs were harvested from umbilical veins by collagenase treatment. The platelet aggregation experiments were performed using cuvettes lined with HUVECs. The cuvettes were prepared by seeding HUVECs in gelatin-coated cuvettes at a cell density of 2 x 10(5) cells/ml and culturing for 48 hours. Thrombin-induced platelet aggregation was inhibited in the presence of HUVECs. This HUVEC-dependent anti-platelet aggregatory effect was enhanced by the addition of bradykinin, which stimulates the production of EDRF, and thrombin-induced platelet aggregation was completely inhibited. Indomethacin reduced the HUVEC-dependent anti-platelet aggregatory effect. These findings suggest that this simple, new experimental system is useful in assessing the production of EDRF by HUVECs and in examining the effects of various chemicals (or agents) on EDRF production.
Biological Assay↗
[A case of mucous producing pancreatic tumor diagnosed by detecting RAS gene mutation in pancreatic juice].
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Adenocarcinoma, Papillary↗
Active and passive mechanisms of [fluorine-18] fluorodeoxyglucose uptake by proliferating and prenecrotic cancer cells in vivo: a microautoradiographic study.
UNLABELLED: In this study, [18F]FDG uptake mechanisms were investigated in neoplastic cells during cell proliferation and cell death. METHODS: Detailed analysis was performed on mouse tumor models of different growth rates using [18F]FDG, [6-13H]thymidine [3H]Thd (a precursor of DNA synthesis) and [125I]bovine serum albumin ([125I]BSA) (a marker of diffusion) with autoradiographic and histopathologic techniques and electron microscopy. RESULTS: The three compounds, [18F]FDG, [3H]Thd and [125I]BSA, showed different heterogeneous patterns of distribution within tumor tissue sections in neoplastic and non-neoplastic cellular elements. The uptake of [18F]FDG by prenecrotic (or necrobiotic) tumor cells surrounding focal necrotic cell debris was 1.5 to 2.3 times higher than that of viable tumor cells. Prenecrotic cells did not retain trapped [18F]FDG; therefore, the uptake was considered to be nonmetabolic. Inconspicuous cell membrane, vesicular cytoplasmic organelles and condensed nuclear chromatin were remarkable findings in the prenecrotic cells. A comparison of viable tumor cells in tumors undergoing different growth rates showed that the ratio of [18F]FDG uptake was similar to that of [3H]Thd uptake in each S-phase cell. Fluorine-18-FDG showed a cell cycle dependency, with a higher uptake observed in cells in G0/G1 and G2 phases of the cell cycle compared with the S and M phases. CONCLUSION: A passive mechanism of [18F]FDG uptake may exist in the necrobiotic/prenecrotic or hypoxic/anoxic cells in tumors. However, the discordance of [18F]FDG and [3H]Thd uptake may be the result of the different cell cycle dependency of tracer uptake in the same tumor.
Animals↗
Microautoradiographic study for the differentiation of intratumoral macrophages, granulation tissues and cancer cells by the dynamics of fluorine-18-fluorodeoxyglucose uptake.
UNLABELLED: A substantial amount of macrophage infiltration occurs in both human and animal tumors. We previously showed that 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake was higher in tumor-associated macrophages and young granulation tissues than in tumor cells. Differentiation of intratumoral non-neoplastic cells from neoplastic cells is important not only for the reduction of false-positives in FDG-PET tumor studies but also for patient management. METHODS: A time-course study was performed using micro- and macro-autoradiography and tissue distribution in C3H/He mice bearing transplanted syngeneic FM3A mammary carcinoma and MH134 hepatoma was evaluated to analyze the intratumoral cellular dynamics of [18F]FDG and 2-deoxy-D-[3H]glucose in vivo. RESULTS: The volume-doubling time in vivo was 1.3 days for MH134 and 4.9 days for FM3A, and the survival time of the host was 32.1 and 40.3 days, respectively. The peak uptake of both tracers in the tumor was 60 min after intravenous injection. The uptake by MH134 was 1.7-2.1 times higher than that by FM3A. The intracellular concentration as determined by counting the silver grains on micro-autoradiographic sections showed that the uptake by macrophages and focal small necrotic areas in both tumors was faster than the blood clearance until 15 min after tracer injection. CONCLUSION: Thus, non-neoplastic cellular elements can be differentiated from viable neoplastic cells by means of the dynamic analysis of [18F]FDG uptake.
Animals↗
Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma.
Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Differential diagnosis of pancreatic cancer and chronic pancreatitis sometimes presents a clinical dilemma. We recently developed a highly sensitive and specific polymerase chain reaction capable of detecting 3-30 copies of mutant K-ras genes harboring codon 12 single base changes in the presence of 300,000 normal copies. Mutant ras genes were detected in DNA purified from pancreatic juice from all 6 cases of pancreatic adenocarcinoma and 1 case of intraductal papillary neoplasms of the pancreas. In 2 of 6 other cases with pancreatic adenocarcinoma, circulating metastatic cells were detected in DNA purified from peripheral blood. Activated ras genes were not found in pancreatic juice of three control cases (chronic pancreatitis and choledocholithiasis) or in the peripheral blood of two patients with insulinomas. Notable conclusions of this study are that there can be significant levels of shed tumor cells in peripheral blood and an even higher number in pancreatic juice. In addition, two different K-ras mutations were found in some patients.
Adenocarcinoma↗