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E Sato

Publications and source records attributed to E Sato.

At least 127 records · Page 7Linked to original sources

Bleomycin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity.

We determined whether human lung fibroblasts might release chemotactic activity for neutrophils (NCA) and monocytes (MCA) in response to bleomycin. The human lung fibroblasts supernatant fluids were evaluated for chemotactic activity by a blind well chamber technique. Human lung fibroblasts released NCA and MCA in a dose- and time-dependent manner in response to bleomycin. Checkerboard analysis of supernatant fluids revealed that both NCA and MCA were chemotactic. Partial characterization revealed that NCA was partly heat labile, trypsin sensitive, and predominantly ethyl acetate extractable. In contrast, MCA was partly trypsin sensitive and ethyl acetate extractable. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by leukotriene B4 receptor antagonist and anti-IL-8 and G-CSF Abs. MCA was attenuated by leukotriene B4 receptor antagonist, and monocyte chemoattractant protein-1, GM-CSF, and TGF-beta Abs. Leukotriene B4 receptor antagonist and these Abs inhibited the corresponding m.w. chemotactic activity separated by column chromatography. The concentrations of IL-8, G-CSF, monocyte chemoattractant protein-1, GM-CSF, and TGF-beta in the supernatant fluids significantly increased in response to bleomycin. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to bleomycin.

Bleomycin↗

Differing expression of MMPs-1 and -9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma.

Gastric cancer is classified into intestinal and diffuse types, which exhibit different biological behavior. Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMPs)-1 and -9 are considered to play important roles in cancer invasion and metastasis. We have already suggested a functional duality of these matrix-degrading enzymes/factors; they may also be involved in the matrix turnover (remodeling) or host immune/inflammatory reactions as far as they are expressed by host cells. We performed a retrospective study on the immuno-histochemical expression of these enzymes/factors in surgical specimens from patients with gastric cancer, including 26 with the diffuse and 78 with the intestinal type. We also evaluated macrophages since they are major sources of uPAR. The positivity rate for uPA in cancer cells was significantly lower in diffuse-type than in intestinal-type. Stromal expression was seen mainly along the invasive margin (tumor-host interface). The degree of stromal expression of uPAR and MMP-9 and the macrophage number were markedly decreased in diffuse-type compared with intestinal-type. Stromal expression of uPAR and macrophage number in intestinal-type were higher in patients without liver metastasis than in patients with liver metastasis, while uPA expression in cancer cells was more pronounced in patients with liver metastasis. Studies using frozen sections revealed that the expression of MMP-1, restricted to the stromal area, was more decreased in diffuse-type (18 patients) than in intestinal-type (21 patients). Our results show that the in situ expression of matrix-degrading enzymes/factors in gastric cancer is significantly more diminished in diffuse-type than in intestinal-type, suggesting a multifunctional aspect of the matrix-degradation process in cancer tissue.

Antigens, CD↗

Neuronal apoptosis inhibitory protein (NAIP) may enhance the survival of granulosa cells thus indirectly affecting oocyte survival.

In mammals, the postnatal loss of more than 99% of female germ cells is due mainly to the process of ovarian follicular atresia. Atresia is known to be mediated by apoptotic granulosa cell-death. Here we show the involvement of neuronal apoptosis inhibitory protein (NAIP) in ovarian folliculogenesis in which it prevents granulosa cell-death. NAIP has been isolated in association with a neurodegenerative disorder, spinal muscular atrophy (SMA), in which it has been shown to suppress mammalian cell-death induced by a variety of stimuli (Liston et al., 1996, Nature 379:349-353). In an in situ hybridization analysis with mouse ovaries, active expression of NAIP mRNA was localized in the granulosa cells of developing follicles from the primary stage to the Graafian stages, whereas the NAIP gene was not expressed or was weakly expressed in follicles that might be undergoing atresia. Gonadotropin, which is known to inhibit apoptosis in ovarian follicles, caused a 2.4-fold increase in NAIP gene expression in the ovary. To study the role of ovarian NAIP, antisense NAIP oligonucleotides were locally delivered into the ovarian bursa. Suppression of ovarian NAIP expression with antisense oligonucleotides evoked a decrease in the number of morphologically normal ovulated oocytes, implying an indirect involvement of NAIP in germ cell development by enhancing the survival of granulosa cells. These findings suggest that gonadotropin-inducible NAIP may indirectly affect oocyte survival as a result of the inhibition of apoptotic granulosa cell-death during folliculogenesis.

Animals↗

Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma.

Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC-IP) and mass forming type (ICC-M). The survival of patients with BDCC or ICC-IP is significantly better than that of patients with ICC-M. We examined these subtypes (ICC-IP and ICC-M) and BDCC for their expression of MUC1 mucins of different glycoforms. ICC-M showed significantly higher MUC1 expression rates (90%, 95%, and 85% positive rates as measured with the DF3, MY.1E12, and MUC1-Glycoprotein antibodies, respectively) than BDCC and ICC-IP (14% and 33%, 58% and 58%, and 0% and 50% positive respectively, as measured by the same antibodies). In contrast, BDCC (86% positive) and ICC-IP (67% positive) showed significantly higher MUC2 expression rates than ICC-M (25% positive) as measured with the anti-MRP antibody. Thus, the immunohistochemical staining pattern of ICC-IP resembled the pattern of BDCC more than they resembled ICC-M. In general, MUC1 expression is associated with poor patient outcome, irrespective of the glycosylation status. In particular, high expression of more sialylated forms of MUC1 mucins was correlated with poor survival. In contrast, expression of non-sialylated MUC2 mucin is a favorable prognostic indicator. These results suggest that ICC-IP is a different entity from ICC-M. This reclassification may have value in determining prognosis and treatment method.

Antigens, Neoplasm↗

Vitrification of two-cell rat embryos derived from immature hypothyroid rdw rats by in vitro fertilization in ethylene glycol-based solutions.

Two-cell embryos derived from immature rdw rats by in vitro fertilization (IVF) were vitrified in ethylene glycol-based solutions. Embryos exposed to EFS20 before being vitrified in EFS40 exhibited improved viability in vitro. All embryos exposed to EFS20 for 1-3 min before vitrification in EFS40 were morphologically normal. However, 2-3 min of exposure to EFS20 increased the number of embryos that developed beyond the four-cell stage. More embryos exposed to EFS20 for 2-3 min developed to morulae (63-64%) and blastocysts (34-38%) than those exposed for 1 min (35 and 10%, respectively). After transfer, 33% of embryos exposed to EFS20 for 3 min and vitrified in EFS40 developed to term compared to 29% of fresh embryos. Fifteen (47%) of live young were homozygous rdw and all of the others were heterozygous rats. The present study demonstrated that vitrification in EFS solution can be routinely used to cryopreserve rat two-cell IVF-embryos with no loss of viability.

Animals↗

Effects of reactive oxygen and nitrogen metabolites on RANTES- and IL-5-induced eosinophil chemotactic activity in vitro.

Eosinophils and increased production of nitric oxide (NO) and superoxide, components of peroxynitrite, have been implicated in the pathogenesis of a number of allergic disorders including asthma. Peroxynitrite induced protein nitration may compromise enzyme and protein function. We hypothesized that peroxynitrite may modulate eosinophil migration by modulating chemotactic cytokines. To test this hypothesis, the eosinophil chemotactic responses of regulated on activation, normal T cell expressed and secreted (RANTES) and interleukin (IL)-5 incubated with and without peroxynitrite were evaluated. Peroxynitrite-attenuated RANTES and IL-5 induced eosinophil chemotactic activity (ECA) in a dose-dependent manner (P < 0.05) but did not attenuate leukotriene B4 or complement-activated serum ECA. The reducing agents deferoxamine and dithiothreitol reversed the ECA inhibition by peroxynitrite, and exogenous L-tyrosine abrogated the inhibition by peroxynitrite. PAPA-NONOate, a NO donor, or superoxide generated by lumazine or xanthine and xanthine oxidase, did not show an inhibitory effect on ECA. The peroxynitrite generator, 3-morpholinosydnonimine, caused a concentration-dependent inhibition of ECA. Peroxynitrite reduced RANTES and IL-5 binding to eosinophils and resulted in nitrotyrosine formation. These findings are consistent with nitration of tyrosine by peroxynitrite with subsequent inhibition of RANTES and IL-5 binding to eosinophils and suggest that peroxynitrite may play a role in regulation of eosinophil chemotaxis.

Chemokine CCL5↗

Role of superoxide, NO and oxygen in the regulation of energy metabolism and suppression of senile diseases.

Although nitric oxide (NO) rapidly reacts with molecular oxygen under air atmospheric conditions, thereby losing its biological functions, the lifetime of this gaseous radical increases under physiologically low intracellular oxygen tensions. To understand the pathophysiological roles of NO and related molecules in aerobic life, we analyzed the effect of oxygen tensions on the NO-dependent processes in resistance arteries, isolated mitochondria, intact cells and enteric bacteria. Kinetic analysis revealed that NO enhanced the generation of cGMP and induced vasorelaxation of resistance arteries more potently under physiologically low oxygen tensions than under hyperbaric conditions. NO reversibly inhibited the respiration of isolated mitochondria, intact cells and Escherichia coli; the inhibitory effect was more marked under hypoxic conditions than under hyperbaric conditions. Kinetic analysis revealed that NO has pivotal action to increase arterial supply of molecular oxygen for the generation of ATP in peripheral tissues and to suppress energy production in mitochondria and cells in an oxygen-dependent manner. These functions of NO are enhanced by decreasing oxygen tension in situ and suppressed by locally generated superoxide radicals. Thus, cross-talk of NO, superoxide and molecular oxygen constitutes a supersystem by which the energy metabolism in cells and tissues is beautifully regulated in a site-specific manner depending on the relative concentrations of these three radical species.

Aged↗

Effect of hyaluronic acid on the development of porcine 1-cell embryos produced by a conventional or new in vitro maturation/fertilization system.

In pigs, it is difficult to produce normal fertilized embryos from immature oocytes in vitro. However, a new maturation/fertilization system in which the percentage of normal fertilized embryos is comparatively high has been developed recently. In the present study, porcine 1-cell embryos were produced both by a conventional and a new system and then cultured in NCSU-23 supplemented with hyaluronic acid at various concentrations. In the conventional system, the percentage of oocytes with monospermic penetration and 1 male pronucleus and 1 female pronucleus was only 6%. At 144 h after insemination, the percentage (5%) of embryos developing to the blastocyst stage in medium supplemented with 0.5 mg/mL hyaluronic acid was significantly (P<0.05) higher than that (2%) in medium without hyaluronic acid. When oocytes were matured and inseminated using the new system, monospermic penetration and the formation of 1 male and 1 female pronucleus were observed in 69% of the penetrated oocytes. However, blastocyst formation (8 to 14%) at 144 h after insemination was not affected by the concentration (0 to 1.0 mg/mL) of hyaluronic acid. These results indicate that the effect of hyaluronic acid on the development of in vitro-produced porcine embryos varies with the conditions of oocyte maturation and fertilization.

Animals↗

The impact of vasoactive peptides on nitric oxide production in cultured sympathetic neurons.

The concentration of nitric oxide was found to be decreased in a hypersympathetic condition. We carried out experiments on cultured sympathetic neurons from 12-14-days-old chick embryos to investigate the role of vasoactive peptides and amine on nitric oxide production. Stimulation of cultured neurons with endothelin-1, norepinephrine and angiotensin-II initially increases nitric oxide production and subsequently decreases it in a dose-dependent manner (P<0.05, n = 7). Stimulation of Fura-2 acetoxymethyl ester-loaded neurons with endothelin-1, norepinephrine and angiotensin-II increases the calcium influx (within 30-90 s) and it is then restored to the initial level (P<0.05, n = 7). An additional observation was that specific stimulator L-arginine significantly increases the nitric oxide release and calcium influx into the cells, whereas N(W)-nitro-L-arginine methyl ester blunts nitric oxide release dose dependently (P<0.05, n = 7) and does not change the calcium concentration in the cells. We propose that vasoactive peptides and amines inhibit nitric oxide production in the cultured sympathetic neuron by regulation of intracellular calcium concentration.

Angiotensin II↗

Phosphate exposure during the late 1-cell and early 2-cell stages induces a time-specific decrease in cyclin B and cdc25B mRNAs in AKR/N mouse embryos in vitro.

Phosphate induces 2-cell block in AKR/N mouse embryos in vitro. In an attempt to define the mechanism responsible for the inhibitory effect of phosphate, the critical period for this effect was determined. Then the amounts of the mRNAs for cyclin B and cdc25B, factors related to activation of M-phase promoting factor (MPF), were measured by quantitative reverse transcription-polymerase chain reaction. Exposure to phosphate during the late 1-cell (10-20 h after insemination) and early 2-cell stages (0-12 h after first cleavage) was found to induce 2-cell block in AKR/N mouse embryos. This period corresponds to the initiation of zygotic gene activation (ZGA). The presence of phosphate during second cleavage had no effect on 2-cell block of the embryos. The relative levels of cyclin B and cdc25B mRNAs did not change significantly during the 1-cell stage and decreased during the early 2-cell stage to almost half of the initial levels. When the amounts of mRNA in embryos cultured with and without phosphate were compared they were found to be almost identical even in the 2-cell block embryos, and a significant decrease in mRNA was observed only 33 h after insemination in embryos about to undergo phosphate block at the 2-cell stage. These results show that phosphate does not directly inhibit MPF activity and confirm the presence of cyclin B and cdc25B even in 2-cell block embryos. Furthermore, the fact that the decrease in mRNA levels corresponded to the critical period for the inhibitory effect of phosphate suggests that suppression of initial ZGA induction is involved in the 2-cell block of mouse embryos in vitro.

Animals↗

The potential of various lipopolysaccharides to release monocyte chemotactic activity from lung epithelial cells and fibroblasts.

Although the cytotoxicity of lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa, i.e. Limulus amoebocyte lysate activity, is less potent than that from Escherichia coli 0127:B8, P. aeruginosa induces prominent sustained lung inflammation, as in cystic fibrosis. The present study was designed to examine the potential for several LPSs obtained from E. coli and P. aeruginosa to release monocyte chemotactic activity (MCA) from lung cells. LPSs differentially stimulated A549 cells, BEAS-2B cells and lung fibroblasts to release MCA (P. aeruginosa >E. coli 0127:B8 from Difco >055:B5 from Sigma >026:B6 (Sigma)). E. coli 0127:B8 (Sigma) and 0111:B4 (Sigma) did not stimulate these cells. MCA was determined by means of checkerboard analysis. Molecular sieve column chromatography revealed four chemotactic peaks. The release of MCA was inhibited by cycloheximide and lipoxygenase inhibitors. Experiments with blocking antibodies suggested that much of the MCA was secondary to monocyte chemoattractant protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, the concentrations of these chemoattractants were examined and it was found that the potency of the various LPSs to stimulate MCA closely paralleled their potency in releasing MCP-1 and GM-GSF. Serum augmented the release of MCP-1 and GM-CSF. However, the differences among LPSs from E. coli and P. aeruginosa in stimulating A549 cells were observed. These data suggest that Pseudomonas aeruginosa lipopolysaccharide may stimulate lung cells to release more monocyte chemotactic activity than lipopolysaccharides derived from Escherichia coli, leading to sustained prominent lung inflammation.

Cells, Cultured↗

Respiratory distress due to tracheal compression by the dilated innominate artery.

The case reported is of an 88 yr old female with hypertension and respiratory distress. A chest radiograph revealed a widening of the upper mediastinum. Computed tomographic scanning revealed tracheal compression by the innominate artery, which was elongated and curved. After intubation, she was treated with antihypertensive drugs. This resulted in the remarkable recovery of the patient from respiratory distress. To the authors' knowledge, this is the first reported case of respiratory distress owing to tracheal compression by elongation and curvature of the innominate artery.

Aged↗

Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity.

Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.

Adrenergic beta-Agonists↗

Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor.

Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be

Adenocarcinoma, Mucinous↗

Sarcomatoid carcinoma of the pancreas: a case report with immunohistochemical study.

Sarcomatoid carcinoma of the pancreas is an uncommon neoplasm. The immunohistochemical characteristics of this unique type of pancreatic tumor were studied. Histologically, there was diffuse proliferation of atypical spindle cells that had hyperchromatic, short, spindle-shaped nuclei and pale cytoplasm. A few tiny foci of small tubular structures were seen in connection with the atypical spindle-shaped cells. Immunohistochemical examination showed that the spindle cells were positive for epithelial cell markers (cytokeratin AE3, cytokeratin AE1, epithelial membrane antigen) and DF3 (MUC1 apomucin-related antigen (ARA)), and were negative for markers such as vimentin, desmin, neuron-specific enolase, and myoglobin. DF3 antigen is known to be expressed in invasive ductal carcinoma of the pancreas and liver, as well as of the breast. Other MUC1-ARA (MY.1E12, MUC1 glycoprotein, HMFG-1, HMFG-2) and anti-CA19-9 were also detected in the present case. Thus, this tumor was diagnosed as anaplastic carcinoma (sarcomatoid carcinoma).

Aged↗