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Watanabe R.,Institute for Virus Research | Nakamura H.,The Tazuke Kofukai Medical Research Institute Kitano Hospital | Masutani H.,Institute for Virus Research | Yodoi J.,Institute for Virus Research
Pharmacology and Therapeutics | Year: 2010

Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is mediated by the dithiol-disulfide exchange in the active site. Trx 1 is able to interact with certain molecules, one of which is thioredoxin-binding protein-2 (TBP-2)/Vitamin D3 upregulated protein 1 (VDUP1)/thioredoxin interacting protein (TXNIP). TBP-2 was originally identified as a negative regulator of Trx 1 and acts as a cell growth suppressor and a regulator in lipid/glucose metabolism. Trx 1 and TBP-2 play crucial roles in pathophysiological mechanisms in metabolic disorders, cancer and inflammation. Here we discuss pharmacological aspects of Trx 1 and TBP-2 in these diseases and propose potential therapeutic approaches for intractable oxidative stress-related disorders. © 2010 Elsevier Inc.


Song J.,Kunming University of Science and Technology | Song J.,Henan University of Traditional Chinese Medicine | Dong X.,Kunming University of Science and Technology | Dong X.,First Peoples Hospital of Yunnan Province | And 6 more authors.
Redox Report | Year: 2012

Preterm delivery (PTD) is the leading cause of infant mortality and morbidity. However, the mechanism at the molecular level is still unknown. Placental inflammatory response and oxidative stress are associated with PTD. Thioredoxin-1 (TRX-1) regulates oxidative stress, inflammation, and the activities of transcription factors. Objectives: The objective was to detect in placental tissues the expressions of TRX-1 and the TRX-1-related molecules: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), thioredoxin-1-binding protein-2 (TBP-2), hypoxia inducible transcription factor 1α (HIF-1α), and forkhead box protein O3A (FoxO3A). Methods: PTD was defined as gestation of <37 weeks and term delivery (TD) as ≥37 weeks. The expressions of TRX-1 and TRX-1-related molecules were examined in placental tissues by real-time polymerase chain rection and western blot. Results: The expressions of TRX-1, TNF-α, COX-2, HIF-1α, and FoxO3A in the placenta of PTD were significantly higher as compared with TD, but no difference was observed in TBP-2 expression. Discussion: These results indicate that TRX-1 may be adaptively induced by the effects of inflammation and oxidative stress, suggesting protective roles for TRX-1 against these effects in the placenta of PTD. © W.S. Maney & Son Ltd 2012.


Futamura K.,Sony Corporation | Sekino M.,Sony Corporation | Hata A.,Kyoto University | Ikebuchi R.,Kyoto University | And 9 more authors.
Cytometry Part A | Year: 2015

Flow cytometric analysis with multicolor fluoroprobes is an essential method for detecting biological signatures of cells. Here, we present a new full-spectral flow cytometer (spectral-FCM). Unlike conventional flow cytometer, this spectral-FCM acquires the emitted fluorescence for all probes across the full-spectrum from each cell with 32 channels sequential PMT unit after dispersion with prism, and extracts the signals of each fluoroprobe based on the spectral shape of each fluoroprobe using unique algorithm in high speed, high sensitive, accurate, automatic and real-time. The spectral-FCM detects the continuous changes in emission spectra from green to red of the photoconvertible protein, KikGR with high-spectral resolution and separates spectrally-adjacent fluoroprobes, such as FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral-FCM can measure and subtract autofluorescence of each cell providing increased signal-to-noise ratios and improved resolution of dim samples, which leads to a transformative technology for investigation of single cell state and function. These advances make it possible to perform 11-color fluorescence analysis to visualize movement of multilinage immune cells by using KikGR-expressing mice. Thus, the novel spectral flow cytometry improves the combinational use of spectrally-adjacent various FPs and multicolor fluorochromes in metabolically active cell for the investigation of not only the immune system but also other research and clinical fields of use. © 2015 International Society for Advancement of Cytometry.


PubMed | Red Cross, Kyoto Katsura Hospital, Kobe City Hospital Organization, National Hospital Organization Kyoto Medical Center and 4 more.
Type: | Journal: Gastrointestinal endoscopy | Year: 2016

The efficacy of ERCP for histologic diagnosis of malignant biliary strictures is disappointingly low. The aim of this study was to investigate the diagnostic performance of a newly developed endoscopic device with scraping loops in combination with conventional biopsy forceps.We performed a multicenter single-arm prospective study. Between February 2013 and December 2014, 123 patients with suspected malignant biliary strictures were enrolled in the study. The new device and conventional biopsy forceps were applied for histologic diagnosis by ERCP. The primary outcome was to evaluate cancer detectability by biopsy forceps, the new device, and their combined use.Of the 123 patients, 119 were diagnosed with a malignant stricture. Sufficient samples were collected in 83.7% (103/123), 93.5% (115/123), and 95.9% (118/123) of patients using biopsy forceps, the new device, and their combination, respectively. Cancer detectability of forceps biopsy, the new device, and their combination were 51.3% (61/119), 64.7% (77/119), and 74.8% (89/119), respectively. The new device had a significantly higher sample yield and cancer detectability than biopsy forceps (P< .01 and P= .018, respectively, McNemar test). Complementary use of the new device with biopsy forceps demonstrated a significantly additive effect in both sample yield and cancer detection (P< .01 each, McNemar test). The new device detected 48.3% (28/58) of cancers that were not diagnosed as malignant by biopsy forceps.The new endoscopic scraper demonstrated a large sample yield and high cancer detectability. It could be a first-line tissue-sampling device for biliary strictures. (University Hospital Medical Information Network Clinical Trial Registry [UMIN-CTR] (http://www.umin.ac.jp/ctr/index.htm) registration number: UMIN000009895.).


PubMed | Red Cross, Kyoto Katsura Hospital, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Kyoto Police Hospital and 6 more.
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2015

Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (5 mm) than in healthy subjects.Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.


Kurosaki Y.,The Tazuke Kofukai Medical Research Institute Kitano Hospital | Yoshida K.,Kyoto University | Ohta T.,The Tazuke Kofukai Medical Research Institute Kitano Hospital | Toda H.,The Tazuke Kofukai Medical Research Institute Kitano Hospital | And 2 more authors.
Japanese Journal of Neurosurgery | Year: 2011

The usefulness of the carotid Black-blood (BB) MRI to evaluate plaque vulnerability has been reported. However, 2D spin-echo sequence at 1.5 tesla MRI, high-resolution BB MRI, need long scanning time and is restricted scanning range. We report two symptomatic carotid stenosis cases that underwent BB MRI at 3 tesla using 3D turbo spin-echo sequence. The scanning time was 4 minutes 30 seconds, and the lumen from the common carotid artery to the intra-cranial internal carotid artery was detected. In addition to the plaque morphology and the extent of the plaque, we could evaluate the lumen of the distal portion of the plaque in the near occlusion case. BB MRI at 3 tesla using 3D turbo spin-echo sequence may be a useful tool for detection of carotid plaque.

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