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1Reduced hemoglobin and increased C-reactive protein are associated with upper gastrointestinal bleeding显示文摘AIM: To investigate the early upper gastrointestinal endoscopy(endoscopy) significantly reduces mortality resulting from upper gastrointestinal(GI) bleeding. METHODS: Upper GI bleeding was defined as 1a, 1b, 2a, and 2b according to the Forrest classification. The hemoglobin(Hb), and C-reactive protein(CRP) were examined at around the day of endoscopy and 3 mo prior to endoscopy. The rate of change was calculated as follows:(the result of blood examination on the day of endoscopy- the results of blood examination 3 mo prior to endoscopy)/(results of blood examination 3 mo prior to endoscopy). Receiver operating characteristic curves were created to determine threshold values. RESULTS: Seventy-nine men and 77 women were enrolled. There were 17 patients with upper GI bleeding: 12 with a gastric ulcer, 3 with a duodenal ulcer, 1 with an acute gastric mucosal lesion, and 1 with gastric cancer. The area under the curve(AUC), threshold, sensitivity, and specificity of Hb around the day of endoscopy were 0.902, 11.7 g/dL, 94.1%, and 77.1%, respectively, while those of CRP were 0.722, 0.5 mg/dL, 70.5%, and 73%, respectively. The AUC, threshold, sensitivity, and specificity of the rate of change of Hb were 0.851,-21.3%, 76.4%, and 82.6%, respectively, while those of CRP were 0.901, 100%, 100%, and 82.5%, respectively. CONCLUSION: Predictors for upper GI bleeding were Hb < 11.7 g/dL, reduction rate in the Hb > 21.3% and an increase in the CRP > 100%, 3 mo before endoscopy.Minoru Tomizawa Fuminobu Shinozaki Rumiko Hasegawa Akira Togawa Yoshinori Shirai Noboru Ichiki Yasufumi Motoyoshi Takao Sugiyama Shigenori Yamamoto Makoto Sueishi 2014World Journal of Gastroenterology2014,20,5:13
2Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer显示文摘AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS: All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% ± 2.4% (mean ± SD), 30.9% ± 5.5%, 23.8% ± 3.9%, 37.1% ± 5.3%, 10.4% ± 4.5%, 52.5% ± 4.5% and 22.6% ± 0.4%, at 2 μmol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% ± 7.6%, 32.9% ± 8.2%, 53.9% ± 8.0%, 52.8% ± 4.0%, 32.3% ± 4.2%, 51.8% ± 4.5%, and 30.6% ± 9.4%, at 50 μmol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% ± 0.2%, 0%, 0%, 2.0% ± 0.1%, 5.0% ± 0.2%, 3.0% ± 0.1%, and 5.0% ± 0.2%, respectively (P < 0.05). LY294002 at 50 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% ± 0.2%, 0%, 3.0% ± 0.2%, 0%, 0%, 0% and 3% ± 0.1%, respectively (P < 0.05). PD980509 at 20 μmol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 μmol/L PPP or 50 μmol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 μmol/L PD98059 did not show apoptosis.CONCLUSION: IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer.Minoru Tomizawa Fuminobu Shinozaki Takao Sugiyama Shigenori Yamamoto Makoto Sueishi Takanobu Yoshida 2010World Journal of Gastroenterology2010,16,15:12
3Patient characteristics with high or low blood urea nitrogen in upper gastrointestinal bleeding显示文摘AIM: To examine characteristics of patients with blood urea nitrogen(BUN) levels higher and lower than the normal limit.METHODS: Patient records between April 2011 and March 2014 were analyzed retrospectively. During this time, 3296 patients underwent upper endoscopy. In total, 50 male(69.2 ± 13.2 years) and 26 female(72.3 ± 10.2 years) patients were assessed. Patients were divided into two groups based on BUN levels: higher than the normal limit(21.0 mg/d L)(H) and lower thanthe normal limit(L). One-way analysis of variance was performed to reveal differences in the variables between the H and L groups. Fisher's exact test was used to compare the percentage of patients with gastric ulcer or gastric cancer in the H and L groups.RESULTS: White blood cell count was higher in the H group than in the L group(P = 0.0047). Hemoglobin level was lower in the H group than in the L group(P = 0.0307). Glycated hemoglobin was higher in the H group than in the L group(P = 0.0264). The percentage of patients with gastric ulcer was higher in the H group(P = 0.0002). The H group contained no patients with gastric cancer.CONCLUSION: Patients with BUN ≥ 21 mg/d L might have more severe upper gastrointestinal bleeding.Minoru Tomizawa Fuminobu Shinozaki Rumiko Hasegawa Yoshinori Shirai Yasufumi Motoyoshi Takao Sugiyama Shigenori Yamamoto Naoki Ishige 2015World Journal of Gastroenterology2015,21,24:8
4Sonoporation:Gene transfer using ultrasound显示文摘Genes can be transferred using viral or non-viral vectors.Non-viral methods that use plasmid DNA and short interference RNA(si RNA)have advantages,such as low immunogenicity and low likelihood of genomic integration in the host,when compared to viral methods.Non-viral methods have potential merit,but their gene transfer efficiency is not satisfactory.Therefore,new methods should be developed.Low-frequency ultrasound irradiation causes mechanical perturbation of the cell membrane,allowing the uptake of large molecules in the vicinity of the cavitation bubbles.The collapse of these bubbles generates small transient holes in the cell membrane and induces transient membrane permeabi-lization.This formation of small pores in the cell membrane using ultrasound allows the transfer of DNA/RNA into the cell.This phenomenon is known as sonoporation and is a gene delivery method that shows great promise as a potential new approach in gene therapy.Microbubbles lower the threshold of cavity formation.Complexes of therapeutic genes and microbubbles improve the transfer efficiency of genes.Diagnostic ultrasound is potentially a suitable sonoporator because it allows the real-time monitoring of irradiated fields.Minoru Tomizawa Fuminobu Shinozaki Yasufumi Motoyoshi Takao Sugiyama Shigenori Yamamoto Makoto Sueishi 2013World Journal of Methodology2013,3,4:4
5Assessment of the diagnostic performance and interobserver variability of endocytoscopy in Barrett's esophagus:A pilot ex-vivo study显示文摘AIM:To investigate a classification of endocytoscopy(ECS)images in Barrett’s esophagus(BE)and evaluate its diagnostic performance and interobserver variability.METHODS:ECS was applied to surveillance endoscopic mucosal resection(EMR)specimens of BE ex-vivo.The mucosal surface of specimen was stained with 1%methylene blue and surveyed with a catheter-type endocytoscope.We selected still images that were most representative of the endoscopically suspect lesion and matched with the final histopathological diagnosis to accomplish accurate correlation.The diagnostic performance and inter-observer variability of the new classification scheme were assessed in a blinded fashion by physicians with expertise in both BE and ECS and inexperienced physicians with no prior exposure to ECS.RESULTS:Three staff physicians and 22 gastroenterology fellows classified eight randomly assigned unknown still ECS pictures(two images per each classification)into one of four histopathologic categories as follows:(1)BEC1-squamous epithelium;(2)BEC2-BE without dysplasia;(3)BEC3-BE with dysplasia;and(4)BEC4-esophageal adenocarcinoma(EAC)in BE.Accuracy of diagnosis in staff physicians and clinical fellows were,respectively,100%and 99.4%for BEC1,95.8%and83.0%for BEC2,91.7%and 83.0%for BEC3,and95.8%and 98.3%for BEC4.Interobserver agreement of the faculty physicians and fellows in classifying each category were 0.932 and 0.897,respectively.CONCLUSION:This is the first study to investigate classification system of ECS in BE.This ex-vivo pilot study demonstrated acceptable diagnostic accuracy and excellent interobserver agreement.Yutaka Tomizawa Prasad G Iyer Louis M Wongkeesong Navtej S Buttar Lori S Lutzke Tsung-Teh Wu Kenneth K Wang 2013World Journal of Gastroenterology2013,19,46:2
6Laboratory test variables useful for distinguishing upper from lower gastrointestinal bleeding显示文摘AIM: To distinguish upper from lower gastrointestinal(GI) bleeding. METHODS: Patient records between April 2011 and March 2014 were analyzed retrospectively(3296 upper endoscopy, and 1520 colonoscopy). Seventysix patients had upper GI bleeding(Upper group) and 65 had lower GI bleeding(Lower group). Variables were compared between the groups using one-way analysis of variance. Logistic regression was performed to identify variables significantly associated with the diagnosis of upper vs lower GI bleeding. Receiveroperator characteristic(ROC) analysis was performed to determine the threshold value that could distinguish upper from lower GI bleeding. RESULTS: Hemoglobin(P = 0.023), total protein(P = 0.0002), and lactate dehydrogenase(P = 0.009) were significantly lower in the Upper group than in the Lower group. Blood urea nitrogen(BUN) was higher in the Upper group than in the Lower group(P = 0.0065). Logistic regression analysis revealed that BUN was most strongly associated with the diagnosis of upper vslower GI bleeding. ROC analysis revealed a threshold BUN value of 21.0 mg/d L, with a specificity of 93.0%.CONCLUSION: The threshold BUN value for distinguishing upper from lower GI bleeding was 21.0 mg/d L.Minoru Tomizawa Fuminobu Shinozaki Rumiko Hasegawa Yoshinori Shirai Yasufumi Motoyoshi Takao Sugiyama Shigenori Yamamoto Naoki Ishige 2015World Journal of Gastroenterology2015,21,20:2
7Signaling pathway of insulin-like growth factor-Ⅱ as a target of molecular therapy for hepatoblastoma显示文摘AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation.RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7 (269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211% ± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5% (Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6) and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis.CONCLUSION: IGF-Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.Minoru Tomizawa Hiromitsu Saisho 2006World Journal of Gastroenterology2006,12,40:2
8A child with severe inner ear malformations with favorable hearing utilization and balance functions after wearing hearing aids显示文摘Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recovering hearing, necessitating cochlear implants. We report a case of a 6-year-old boy with congenital deafness and bilateral inner ear malformations(right side, incomplete partition type I [IP-I]; left side, common cavity deformity). Hearing aids had a remarkable effect in this patient, enabling sufficient and favorable hearing recovery such as to allow the patient to engage in daily conversations. Per-rotatory nystagmus was recorded on an electronystagmogram for both right and left rotations in a damped rotational chair test. It is rare for deaf children with severe bilateral inner ear malformation to demonstrate favorable development in hearing and good equilibrium function. Our findings suggest that auditoryevestibular hair cells in this patient may have been partially preserved despite IP-I in the right ear and common cavity deformity of the left ear.Yusuke Kimura Takeshi Masuda Akifumi Tomizawa Hideaki Sakata Kimitaka Kaga 2017Journal of Otology2017,12,1:2
9Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S- 180 -implanted mice 显示文摘Kanno S Tomizawa A Hiura T 2005Biol Pharm Bull2005,28,3:1
10Molecular Features of Neonicotinoid Phannacophore Variants Interacting with the Insect Nicotinic Receptor 显示文摘OHNO I TOMIZAWA M DURKIN K A 2009Chem Res Toxicol2009,22,:1
11Selective toxicity of neonicotinoids attributa- ble to specificity of insect and mammalian nicotinic receptors 显示文摘Tomizawa M Casida J E 2003Annu Rev Entomo12003,48,:1
12Clinicopathological significance of Fhit protein expression in stage I non-small-cell lung carcinoma显示文摘Tomizawa Y Nakajima T Kohno T 1998Cancer Res1998,58,23:1
13Spectrophotometrie method for the determination of an anionic surfactant without liquid-liquid extraction显示文摘MINORI KAMAYA YOKO TOMIZAWA KUNIO NAGASHIMA 1998AnalyLica Chimica Acta1998,362,:1
14Novel poly(vinyl alcohol)-degrading enzyme and the degradation mechanism 显示文摘MATSUMURA S TOMIZAWA N TOKI A NISHIKAWA K TOSHlMA K 1999Macromolecules1999,32,:1
15The max-min Delphi Method and Fuzzy Dslphi Method Via Fuzzy Integration显示文摘Ishikawa A Amagasa M Shiga T Tomizawa G Tatsuta R Mieno H 1993Fuzzy Sets and Systems1993,,5:1
16p53 protein transduction therapy: success -ful targeting and inhibition of the growth of the bladder cancer cells显示文摘Inoue M Tomizawa K 2006Eur Urol2006,49,1:1
17Bergenin: Isocoumarin from the stems of Mallotus repandus 显示文摘Tomizawa S Asuke K Suguro N 1976Phytochemistry1976,15,2:1
18The Neonicotinoid Electronegative Pharmacophore Plays the Crucial Role in the High Affinity and Selectivity for the Drosophila Nicotinic Receptor: An Anomaly for the Nicotinoid Cation-or Interaction Model 显示文摘TOMIZAWA M ZHANG N J DURKIN K A 2003Biochemistry2003,42,25:1
19Epigenetic inactivation of the RUNX3 gene in lung cancer显示文摘Sato K Tomizawa Y lijima H 2006Oncol Rep2006,15,:1
20Neonicotiiloid insecticides: Molecular features conferring selectivity for insect versus mammalian nicotinic receptor显示文摘Tomizawa M Lee D L Casida J E 2000Agric FoodChem2000,48,:1
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