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N Sato

Publications and source records attributed to N Sato.

At least 487 records · Page 27Linked to original sources
PubMed1998

Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I expression on H-ras-transformed cells.

We examined the effect of IL-10 on sensitivity to NK-cell-mediated cytotoxicity of the H-ras-induced transformants, W14 and W31. Incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the expression of MHC class I antigens, but not in the ICAM-1 expression. However, prior incubation of W31 cells with rhIL-10 markedly decreased their susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the IL-10-mediated decrease in MHC class I expression might not dominate the regulation of the NK sensitivity. This was true when rat IL-10 cDNA-introduced W31 cells were used as an endogenous IL-10 producer. The NK sensitivity in vitro of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalent level of W31 cells pretreated with exogenous rhIL-10. The decreased NK-sensitivity of W31T-H cells was further confirmed by in vivo Winn assay, in which nude mice challenged with W31T-H cells and rat NK cells together developed tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone, and NK cells did not. Since neither exogenous nor endogenous IL-10 affected the proliferation of W31 cells, the data indicated that W31T-H cells could evade the NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel mechanism for an IL-10-mediated escape of tumor cells from host immune system by NK cells.

Animals↗
PubMed1998

Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha.

Recently, we developed a transgenic mouse with cardiac-specific Gsalpha overexpression (TG mouse), which exhibits enhanced postsynaptic beta-adrenergic receptor signaling, ultimately developing a cardiomyopathy. The goal of the present study was to determine whether cardiac Gsalpha overexpression alters autonomic cardiovascular control, which could shed light on the mechanism responsible for the later development of cardiomyopathy. Mean arterial pressure was increased (P<.05) in conscious, chronically instrumented TG mice (123+/-1 mm Hg) compared with age-matched wild-type (WT) control mice (103+/-1 mm Hg). Respiratory frequency was increased (P<.05) in TG mice (269+/-26/min) compared with WT mice (210+/-20/min). By use of telemetric techniques, baseline heart rate (HR) was elevated (P<.05) in conscious, untethered TG mice (696+/-13 bpm) compared with WT mice (568+/-28 bpm). Intrinsic HR, after propranolol and atropine or after ganglionic blockade with hexamethonium, was not different between TG and WT mice. Both the normal minute-to-minute and circadian variations of HR observed in WT mice were markedly blunted in TG mice. HR variability was assessed by the time-domain and frequency-domain methods. At baseline, time-domain analysis indices were reduced (P<.05) in TG mice compared with WT mice. Although the low frequency (LF) component was higher (P<.05) than the high frequency (HF) component in WT mice, the LF component was less (P<.05) than the HF component in TG mice. In addition, arterial baroreflex regulation of HR was markedly blunted in TG mice in response to both nitroglycerin-induced hypotension and phenylephrine-induced hypertension. The reduced LF/HF ratio in TG mice was surprising in view of enhanced beta-adrenergic signaling and may be due to reduced neural tone secondary to the elevated arterial pressure or alterations in arterial baroreflex control. Dobutamine infusion in WT mice also resulted in depressed HR variability. The combination of elevated baseline HR, arterial pressure, and respiratory frequency suggests that enhanced beta-adrenergic signaling in TG mice results in reduced HR variability, in terms of both minute-to-minute variability and the lack of circadian variations in HR. The lack of normal HR variability in general and the failure of HR to decline, even during sleep, may actually be critical mechanisms contributing to the ultimate development of cardiomyopathy in these animals.

Adrenergic beta-Agonists↗
PubMed1998

Oligomeric forms of the 90-kDa heat shock protein.

Two isoforms of the 90-kDa heat shock protein, HSP90alpha and HSP90beta, are present in the cytosol of mammalian cells. Analysis by polyacrylamide gel electrophoresis under nondenaturing conditions (native PAGE) revealed that HSP90alpha predominantly exists as a homodimer and that HSP90beta is present mainly as a monomer [Minami, Kawasaki, Miyata, Suzuki and Yahara (1991) J. Biol. Chem. 266, 10099-10103]. However, only the dimeric form has been observed under other analytical conditions such as gradient centrifugation. In this study, therefore, we investigated native forms of HSP90 by use of immunochemical techniques with isoform-specific monoclonal antibodies recently developed in our laboratory. Glycerol gradient centrifugation at the physiological salt concentration as well as native PAGE analysis of rat liver cytosol revealed oligomeric forms of HSP90alpha sedimenting at 8-10S as predominant ones. On the other hand, the glycerol gradient centrifugation revealed multiple forms of HSP90beta oligomers sedimenting at 6-12S. All of the HSP90beta oligomers, however, migrated at 100-kDa monomer and 190-kDa dimer positions on native PAGE. A novel two-dimensional double native PAGE revealed that the entity was converted from the HSP90beta dimer to monomers during the electrophoresis. The same PAGE further revealed that the HSP90alpha oligomer also dissociated into dimers during the electrophoresis. Full-length form of bacterially-expressed human HSP90alpha migrated as dimers, but a considerable amount did not penetrate into the gel under native PAGE conditions, indicating the existence of oligomeric forms. Electrophoretic studies of deletion mutants of HSP90 demonstrated that the C-terminal 200 amino acids were capable of forming oligomers. Taken together, we conclude that both of the HSP90 isoforms predominantly exist as oligomeric forms in the cytosol even under unstressed conditions but that they artificially dissociate into smaller forms when subjected to native PAGE.

Animals↗
PubMed1998

Risk analysis of pancreatic fistula after pancreatic head resection.

OBJECTIVE: To evaluate the risk factors for pancreatic fistula after pancreatic head resection. DESIGN: Retrospective review. SETTING: University hospital, in the 71-month period from January 1992 through November 1997. PATIENTS AND INTERVENTION: Sixty-two patients who underwent pancreatic head resection with pancreatojejunostomy. We performed an extensive analysis of preoperative and perioperative risk factors for pancreatic fistula. MAIN OUTCOME MEASURES: Pancreatic fistula was defined as high amylase level (> 1000 U/L) in the drainage fluid collected from the peripancreatic drains and/or anastomotic disruption demonstrated radiographically. RESULTS: Nine (15%) of the 62 patients developed pancreatic fistula, and 1 (1.6%) died of intra-abdominal hemorrhage related to the pancreatic fistula. A preoperative normal N-benzoyl-L-tyrosyl-p-aminobenzoic acid test result (P=.01), soft or intermediate pancreatic consistency (P=.04), duodenum-preserving pancreatic head resection for the normal exocrine pancreas (P=.002), and a larger amount of postoperative pancreatic juice output (P=.02) were significant risk factors for pancreatic fistula formation. CONCLUSIONS: Careful attention should be paid to the preoperative exocrine pancreatic function, pancreatic consistency at surgery, and postoperative pancreatic juice output to predict and prevent pancreatic fistula after pancreatic head resection.

Adult↗
PubMed1998

Coil embolization of bleeding visceral pseudoaneurysms following pancreatectomy: the importance of early angiography.

OBJECTIVE: To evaluate the efficacy of early angiography in the diagnosis and treatment of delayed arterial hemorrhage as a significant complication following pancreatectomy. DESIGN: Retrospective case series. SETTING: University hospital; 6-year period between January 1992 and December 1997. PATIENTS AND INTERVENTION: Of a total of 81 patients undergoing pancreatic head resection, 10 (12%) developed massive arterial hemorrhage after surgery. All 10 patients underwent an emergency angiography and 8 of these were managed by transcatheter arterial embolization. RESULTS: Before onset of major bleeding, 9 patients (90%) had developed intra-abdominal abscess resulting from pancreatic fistula or other anastomotic leak, and all 10 patients had had preliminary minor bleeding. The angiogram demonstrated an exact site of bleeding as a pseudoaneurysm in all 10 patients. Transcatheter arterial embolization achieved temporary control of bleeding in all 8 patients for whom embolization was attempted and complete hemostasis in 5 of the 8 subsequently, yielding a success rate of 63%. Overall, 4 patients (40%) died of complications related directly to the major hemorrhage or the transcatheter arterial embolization technique. CONCLUSIONS: An emergency angiography should be considered in all patients who develop either a sentinel or massive gastrointestinal bleed following pancreatectomy irrespective of suspected intra-abdominal sepsis. Transcatheter arterial embolization allows temporary control of massive hemorrhage and hemodynamic stabilization in most cases, and prevents the need for high-risk emergency surgery.

Aged↗
PubMed1998

Computerized nuclear morphometry of hepatocellular carcinoma and its relation to proliferative activity.

BACKGROUND AND OBJECTIVES: Nuclear profiles have been reported as useful prognostic predictor in various cancers. Data from computerized morphometries are objective and can be quickly derived using conventional microscopic analysis. However, it remains to be shown what types of pathological and biological factors influence the nuclear features. The aim of this study was to evaluate the correlation between the morphological nuclear features and clinicopathological parameters in patients with hepatocellular carcinoma (HCC). METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 76 patients with hepatocellular carcinoma who underwent hepatectomy at our hospital. In each case, 300 cancer nuclei were analyzed randomly on routine hematoxylin&eosin-stained slides through the use of a computer-assisted image analysis system that allowed us to trace the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, and the proliferative activity of cancer cells. RESULTS: The mean nuclear area of poorly differentiated carcinoma was significantly larger than that of moderately and well differentiated carcinoma (P = 0.0003). Significant correlation was detected between the nuclear area of cancer cells and proliferative activity associated with proliferating cell nuclear antigen labeling index (PCNA LI) of cancer cells (r = 0.372, P = 0.0008). Moreover, blood vessel invasion of cancer cells or intrahepatic metastasis were more frequently detected in patients with large nuclear areas. Even though the nuclear area was not an independent prognostic factor in the multivariate analysis, the 5-year survival rate of the 35 patients who had tumors with large nuclear areas (>50 microm2, 25.9%) was significantly lower than that of the 36 patients who had tumors with small nuclear areas (< or =50 microm2, 63.3%, P = 0.001). CONCLUSIONS: The nuclear area of HCC correlates with cell differentiation and cell proliferative activity. Moreover, HCC with a large nuclear area has high potential for blood vessel invasion and intrahepatic metastasis. Thus, nuclear morphometry can be used as an useful morphological predictor for malignant potential in patients with HCC.

Adolescent↗
PubMed1998

Do the level of nodal disease according to the TNM classification and the number of involved cervical nodes reflect prognosis in patients with differentiated carcinoma of the thyroid gland?

BACKGROUND AND OBJECTIVES: The importance of nodal involvement as a prognostic factor in differentiated carcinoma of the thyroid gland remains controversial. We therefore attempted to confirm the prognostic factors in differentiated thyroid carcinoma, with special reference to nodal status. PATIENTS AND METHODS: A total of 139 patients with differentiated thyroid cancer followed for 2-27 years, with a median follow-up of 7 years were studied. All patients underwent surgical resection, either subtotal, total, or lobectomy, with modified radical neck dissection. Survival was calculated using the Kaplan-Meier method. RESULTS: Ten (7%) patients have died from thyroid cancer. Adverse prognostic factors included age >45 years (P=0.0120), the presence of distant metastases (P=0.0006), and TNM stage (P=0.0002). The number of lymph nodes dissected ranged from 6 to 92, with an average of 26. Lymph node metastases were found in 102 (73%) patients. There was no difference in survival according to the level of nodal disease by the TNM classification. Furthermore, the number of cervical lymph nodes involved had no effect on the survival. CONCLUSION: Our results suggest that the presence of histologically confirmed lymph node metastases is not an important prognostic factor in patients with differentiated thyroid carcinoma.

Adult↗
PubMed1998

Infrequent frameshift mutations of polynucleotide repeats in multiple primary cancers affecting the esophagus and other organs.

Frequent frameshift mutations of simple nucleotide repeats in the protein-encoding regions, as well as replication errors (RERs) at microsatellite loci, have recently been demonstrated in gastrointestinal tumors. These genetic instabilities have been considered indicative of an increased risk of accumulating mutations in cancer-associated genes and of developing multiple cancers. We studied frameshift (or insertion/deletion) mutations of simple nucleotide repeats in five genes (TGFbeta type II receptor [TGFbetaRII], E2F4, MSH2, MSH3, and MSH6) in 23 tumors from 12 patients who had synchronous cancers of the esophagus and other organs. Genetic instability at four microsatellite loci, as well as mutations in the TP53, APC, and KRAS2 genes, were also studied. No frameshift mutations were observed in the TGFbetaRII, MSH3, and MSH6 genes. RER and a deletion mutation of BAT26 in MSH2 were present in one (1/23; 4%) gastric cancer. This tumor also carried a deletion mutation in the serine (AGC) repeat of the E2F4 gene. Mutation screening of the TP53, APC, and KRAS2 genes revealed that the synchronous cancers did not carry the same mutations. Our results suggested that genetic instability, such as insertion/deletion mutations in simple nucleotide repeats, is not significantly associated with the development of multiple primary cancers of the esophagus and other organs, and that these synchronous cancers developed independently according to their different environmental factors.

Colonic Neoplasms↗
PubMed1998

Induction of midkine expression in reactive astrocytes following rat transient forebrain ischemia.

Midkine (MK), a retinoic acid-responsive gene product, is a 13-kDa heparin-binding protein with neurotropic activity. Previous studies demonstrated the expression of MK in embryonal and neonatal brains and its potent neurotropic activities in vitro. Data concerning its role in the mature central nervous system, however, are still limited. We examined the changes of MK expression in the adult rat brain following transient forebrain ischemia, by Northern blot, in situ hybridization and immunohistochemical analyses. In the control brain, MK mRNA was expressed in the cortical and hippocampal neurons. Following the ischemia, up-regulation of MK mRNA and a corresponding increase of its protein products were found in the hippocampal CA1 subfield. The maximal expression was demonstrated on day 4 after the insult. The cells expressing MK were distributed around the depleted CA1 pyramidal cells and identified as reactive astrocytes by double immunostaining. These data suggest that MK may be an insult-induced molecule which participates in the reparative processes following neuronal injury.

Animals↗
PubMed1998

A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses.

We have established a novel strategy for introducing exogenous Bcl-2 into neuronal cells that is mediated by Cre/loxP recombination using recombinant adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant adenovirus producing recombinase Cre (AxCANCre). Dual infection with both AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of motoneurons in medium either containing or lacking trophic support. Thus, this strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal death as well as for introducing foreign genes into postmitotic neurons under the control of recombinase Cre.

Adenoviridae↗
PubMed1998

Imaging of intraperitoneal tumors with technetium-99m GSA.

99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3 %ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity of 99mTc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors.

Animals↗
PubMed1998

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes.

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.

Aged↗
PubMed1998

Assessing the suitability of gastric carcinoma for limited resection: histologic differentiation of endoscopic biopsy.

Histologically differentiated adenocarcinoma satisfies one of the criteria for limited surgery for mucosal carcinoma of the stomach: however, the histology of the endoscopic biopsy specimen is often different from that of the resected specimen. The medical records of 1018 early gastric carcinomas were retrospectively analyzed to investigate the relation between the histologies of biopsy and resected specimens. Regression analysis showed that the histologies of biopsy specimens were significantly related to those of resected specimens (r = 0.677, n = 5, p = 0.0288) for the mucosal carcinomas, but their relation was not significant for the submucosal carcinomas (r = 0.677, n = 5, p = 0.2091). By analyzing the 344 differentiated mucosal carcinomas, moderately differentiated tubular adenocarcinomas were seen to be frequently less differentiated at resection. The histology of the biopsy specimens from mucosal carcinoma of the stomach grossly satisfies one of the criteria for limited surgery, but moderately differentiated adenocarcinoma may not be suitable for this treatment.

Adenocarcinoma↗
PubMed1998

Presence of the CO2-concentrating mechanism in some species of the pyrenoid-less free-living algal genus Chloromonas (Volvocales, Chlorophyta).

Physiological and morphological characteristics related to the CO2-concentrating mechanism (CCM) were examined in several species of the free-living, unicellular volvocalean genus Chloromonas (Chlorophyta), which differs morphologically from the genus Chlamydomonas only by lacking pyrenoids. The absence of pyrenoids in the chloroplasts of Chloromonas (Cr.) rosae UTEX 1337, Cr. serbinowii UTEX 492, Cr. clatharata UTEX 1970, Cr. rosae SAG 26.90, and Cr. palmelloides SAG 32.86 was confirmed by light and electron microscopy. In addition, immunogold electron microscopy demonstrated that ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) molecules were distributed almost evently throughout the chloroplasts in all five Chloromonas strains. However, Chloromonas exhibited two types of physiological characteristics related to the CCM depending on the species or strains examined. Chloromonas rosae UTEX 1337 and Cr. serbinowii had high photosynthetic affinities for CO2 in cells grown in culture medium bubbled with air (low-CO2 cells), compared with those grown in medium bubbled with 5% CO2 (high-CO2 cells), indicating the presence of the low-CO2-inducible CCM. In addition, these two Chloromonas strains exhibited low-CO2-inducible carbonic anhydrase (CA; EC 4.2.1.1) activity and seemed to have small intracellular inorganic carbon pools. Therefore, it appears that Cr. rosae UTEX 1337 and Cr. serbinowii possess the CCM as in pyrenoid-containing microalgae such as Chlamydomonas reinhardtii. By contrast, Cr. clatharata, Cr. rosae SAG 26.90 and Cr. palmelloides showed low photosynthetic affinities for CO2 when grown under both CO2 conditions. Moreover, these three strains exhibited an apparent absence of intracellular inorganic carbon pools and lacked low-CO2-inducible CA activity. Thus, Cr. clatharata, Cr. rosae SAG 26.90 and Cr. palmelloides, like other pyrenoid-less algae (lichen photobionts) reported previously, seem to lack the CCM. The present study is the first demonstration of the CCM in pyrenoid-less algae, indicating that pyrenoids or accumulation of Rubisco in the chloroplasts are not always essential for the CCM in algae. Focusing on this type of CCM in pyrenoid-less algae, the physiological and evolutionary significance of pyrenoid absence is discussed.

Carbon Dioxide↗
PubMed1998

Effects of teprenone on gastric epithelial restoration in a rabbit cultured cell model.

The mechanism of action of gastrocytoprotective agents is not fully understood. We assessed the effects of an anti-ulcer agent, teprenone, and bile acid on epithelial restoration. Teprenone with or without deoxycholic acid was added to a complete confluent cultured gastric epithelial cell sheet after wounding. Restoration was monitored for 48 h, and the wound size was assessed. Migration velocity was measured, and proliferation was detected by sequential staining with bromodeoxyuridine. The labeling index was calculated. Restoration was completed within 48h in controls, whereas deoxycholic acid retarded repair. The migration velocity was suppressed by deoxycholic acid treatment. The number of proliferative cells peaked at 36 h (labeling index, 1.7%) in controls. In the deoxycholic acid group, the maximal labeling index was 0.5% at 48 h. Teprenone abolished the bile acid-induced retardation. Teprenone showed cytoprotective effects against deoxycholic acid-induced inhibition of epithelial cell migration and proliferation.

Animals↗
PubMed1998

Relapsed duodenal ulcer after cure of Helicobacter pylori infection.

We report a patient--a 42-year-old man--who had suffered from recurrent duodenal ulcer for about 20 years. Successful curative therapy for Helicobacter pylori infection was performed for 2 weeks with new triple omeprazole, anoxicillin, clarithromycin (OAC) treatment in October 1995, and cure of the infection was repeatedly confirmed by histology, culture, and the 13C urea breath test. One month after the curative therapy, recurrence of a small duodenal ulcer was observed and in February another duodenal ulcer and reflux esophagitis occurred, with severe symptoms, despite the continuous administration of ranitidine. None of the examinations to reconfirm cure of the infection revealed the presence of H. pylori. As the patient experienced continual psychological stress and smoked more frequently during the recurrent episode and had not used nonsteroidal anti-inflammatory drugs, stress and smoking appeared to play important roles in the relapse of duodenal ulcer in this patient after cure of H. pylori infection.

Adult↗