19 results on '"Takahiro Shimizu"'
Search Results
2. Polycystic kidney disease 2-like 1 channel contributes to the bitter aftertaste perception of quinine
- Author
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Takahiro Shimizu, Takuto Fujii, Keisuke Hanita, Ryo Shinozaki, Yusaku Takamura, Yoshiro Suzuki, Teppei Kageyama, Mizuki Kato, Hisao Nishijo, Makoto Tominaga, and Hideki Sakai
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Multidisciplinary - Abstract
Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells. The PKD2L1 channel showed rebound activation after the washout of quinine, a bitter tastant, in electrophysiological whole-cell recordings of the PKD2L1-expressing HEK293T cells and Ca2+-imaging analysis of Type III taste cells isolated from wild-type PKD2L1 mice. In the short-term two-bottle preference and lick tests in vivo, the wild-type mice avoided normal water while the PKD2L1-knockout mice preferred normal water after they ingested the quinine-containing water. These results may explain the new mechanism of the quinine-triggered bitter aftertaste perception in Type III taste cells.
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- 2023
3. Quantitative Evaluation of Cerebellar Function in Multiple System Atrophy with Transcranial Magnetic Stimulation
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Shoji Tsuji, Yuichiro Shirota, Yasuo Terao, Yoshikazu Ugawa, Ritsuko Hanajima, and Takahiro Shimizu
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medicine.medical_specialty ,Ataxia ,Neurology ,medicine.medical_treatment ,Stimulation ,050105 experimental psychology ,Multiple system atrophy (MSA) ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,medicine ,0501 psychology and cognitive sciences ,Evoked potential ,business.industry ,05 social sciences ,medicine.disease ,Transcranial magnetic stimulation ,nervous system ,Neurology (clinical) ,medicine.symptom ,Primary motor cortex ,business ,human activities ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Objective evaluation of cerebellar dysfunction in neurodegenerative disorders is often difficult because of other overlapping symptoms. Cerebellar inhibition (CBI) tested by dual-coil transcranial magnetic stimulation (TMS) is anticipated as a promising measure to estimate cerebellar function. Cerebellar TMS inhibits the primary motor cortex (M1), which can be measured as the decrease of motor evoked potential (MEP) elicited by a single-pulse TMS over the M1. This study was conducted to quantify cerebellar dysfunction using CBI in cerebellar type multiple system atrophy (MSA-C) patients. First, CBI was measured using MEP elicited from a hand muscle by stimulating the hand motor area of M1. The amount of CBI was defined as the degree of decrease in the MEP amplitude in the presence of cerebellar stimulation compared with the condition of M1 stimulation alone. Results of the MSA-C patients were compared with those of healthy volunteers. Correlation between amounts of CBI and a clinical scale of ataxia, the International Cooperative Ataxia Scale Rating (ICARS), was assessed. Healthy volunteers showed more inhibition than MSA-C patients. Moreover, ICARS showed that the CBI amount in the patients is correlated with the degree of ataxia significantly. Results suggest that CBI can be a good marker of disease progression in MSA-C patients.
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- 2021
4. Texture analysis of [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography for predicting the treatment response of postoperative recurrent or metastatic oral squamous cell carcinoma treated with cetuximab
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Takahiro Shimizu, Mai Kim, Takahiro Yamaguchi, Masaru Ogawa, Yoshito Tsushima, Takahito Nakajima, Wenchao Gu, Satoshi Yokoo, Ayako Takahashi, and Tetsuya Higuchi
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Treatment response ,medicine.diagnostic_test ,Cetuximab ,business.industry ,Area under the curve ,Computed tomography ,General Medicine ,Metabolic tumor volume ,030218 nuclear medicine & medical imaging ,stomatognathic diseases ,03 medical and health sciences ,0302 clinical medicine ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,medicine ,Radiology, Nuclear Medicine and imaging ,Basal cell ,Tomography ,Nuclear medicine ,business ,medicine.drug - Abstract
To assess the value of the texture analysis of fluorine-18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in predicting the treatment response of postoperative recurrent or metastatic oral squamous cell carcinoma (POR/M-OSCC) treated with cetuximab. A total of 14 patients undergoing 18F-FDG-PET/CT with POR/M-OSCC were divided into the responder and non-responder groups according to cetuximab response by Response Evaluation Criteria in Solid Tumors (RECIST). The regions of interest (ROI) were set at the POR/M-OSCC lesions with the highest uptake of 18F-FDG, and the volumetric and texture features were analyzed. The features with correlation coefficient of 0.6 or more were further evaluated using the logistic regression analysis to create a model. The SHAPEVolume(vx), SHAPEVolume(mL), metabolic tumor volume (MTV), and gray-level run-length matrix run-length nonuniformity (GLRLMRLNU) were significantly different between the responder (n = 6) and non-responder (n = 8) groups (p = 0.044, 0.042, 0.047, and 0.012, respectively). The model’s area under the curve (AUC) was found to be 0.83, 0.83, 0.79, and 0.92, respectively. The heatmap with PET feature dendrogram showed four distinct clusters including them in patient’s responder and non-responder groups. Higher MTV, GLRLMRLNU, SHAPEVolume(vx), and SHAPEVolume(mL) in 18F-FDG-PET images may have the prediction values for treatment response with POR/M-OSCC treated with cetuximab.
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- 2021
5. Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations
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Yoshihiro Yamamoto, Kazutaka Obama, Sachiko Minamiguchi, Takahiro Shimizu, Tomonori Hirano, Takeshi Setoyama, Yukari Kato, Shin'ichi Miyamoto, Yasuhide Takeuchi, Mitsuhiro Nikaido, Hiroshi Seno, Seishi Ogawa, Nobuyuki Kakiuchi, Tatsuki Ogasawara, Akira Yokoyama, Taro Funakoshi, Atsushi Yamada, Tsutomu Chiba, Takaki Sakurai, Manabu Muto, Yoshiharu Sakai, and Suguru Uose
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Stomach neoplasm ,Cancer Research ,medicine.medical_specialty ,biology ,Signet ring cell ,business.industry ,Gastroenterology ,Cancer ,General Medicine ,Mutation Accumulation ,Helicobacter pylori ,medicine.disease ,biology.organism_classification ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Oncology ,030220 oncology & carcinogenesis ,Signet ring cell carcinoma ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,business ,Exome - Abstract
In Helicobacter pylori (Hp)-uninfected individuals, diffuse-type gastric cancer (DGC) was reported as the most common type of cancer. However, the carcinogenic mechanism of Hp-uninfected sporadic DGC is largely unknown. We performed whole-exome sequencing of Hp-uninfected DGCs and Hp-uninfected normal gastric mucosa. For advanced DGCs, external datasets were also analyzed. Eighteen patients (aged 29–78 years) with DGCs and nine normal subjects (28–77 years) were examined. The mutation burden in intramucosal DGCs (10–66 mutations per exome) from individuals aged 29–73 years was not very different from that in the normal gastric glands, which showed a constant mutation accumulation rate (0.33 mutations/exome/year). Unbiased dN/dS analysis showed that CDH1 somatic mutation was a driver mutation for intramucosal DGC. CDH1 mutation was more frequent in intramucosal DGCs (67%) than in advanced DGCs (27%). In contrast, TP53 mutation was more frequent in advanced DGCs (52%) than in intramucosal DGCs (0%). This discrepancy in mutations suggests that CDH1-mutated intramucosal DGCs make a relatively small contribution to advanced DGC formation. Among the 16 intramucosal DGCs (median size, 6.5 mm), 15 DGCs were pure signet ring cell carcinoma (SRCC) with reduced E-cadherin expression and a low proliferative capacity (median Ki-67 index, 2.4%). Five SRCCs reviewed endoscopically over 2–5 years showed no progression. Impaired E-cadherin function due to CDH1 mutation was considered as an early carcinogenic event of Hp-uninfected intramucosal SRCC. Genetic and clinical analyses suggest that Hp-uninfected intramucosal SRCCs may be less likely to develop into advanced DGCs.
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- 2021
6. Predictive factors for dental inflammation with exacerbation during cancer therapy with FDG-PET/CT imaging
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Takahiro Yamaguchi, Masaru Ogawa, Takuya Asami, Keisuke Suzuki, Jun Kurihara, Satoshi Yokoo, Trang Thuy Dam, Takahiro Shimizu, and Mai Kim
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Male ,medicine.medical_specialty ,Cancer therapy ,Exacerbation ,Periodontal examination ,Bleeding on probing ,PET accumulation of dental lesion grading ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Risk Factors ,Neoplasms ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,030212 general & internal medicine ,Risk factor ,Aged ,Fluorodeoxyglucose-positron emission tomography/computed tomography ,Inflammation ,Univariate analysis ,business.industry ,Cancer ,Odds ratio ,Perioperative ,Middle Aged ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Female ,Original Article ,Oral adverse event ,Radiology ,medicine.symptom ,Dental inflammation exacerbation during cancer therapy ,business - Abstract
Purpose Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation. Methods We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system. Results Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8–19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2–41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT. Conclusion Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.
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- 2021
7. Correction to: Cathepsin C promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca2+-dependent PKC/p38MAPK/NF-κB pathway
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Qing Liu, Yanli Zhang, Shuang Liu, Yanna Liu, Xiaohan Yang, Gang Liu, Takahiro Shimizu, Kazuhiro Ikenaka, Kai Fan, and Jianmei Ma
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Lipopolysaccharides ,Male ,Immunology ,Mice, Transgenic ,Protein Aggregation, Pathological ,Cathepsin C ,Mice ,Cellular and Molecular Neuroscience ,Animals ,RC346-429 ,Cells, Cultured ,Learning Disabilities ,General Neuroscience ,Calcium-Binding Proteins ,Microfilament Proteins ,NF-kappa B ,Correction ,Cell Polarity ,Enzyme Activation ,Mice, Inbred C57BL ,Gene Expression Regulation ,Neurology ,Encephalitis ,Calcium ,Female ,Neurology. Diseases of the nervous system ,Microglia ,Signal Transduction - Abstract
Microglia-derived lysosomal cathepsins are important inflammatory mediators to trigger signaling pathways in inflammation-related cascades. Our previous study showed that the expression of cathepsin C (CatC) in the brain is induced predominantly in activated microglia in neuroinflammation. Moreover, CatC can induce chemokine production in brain inflammatory processes. In vitro studies further confirmed that CatC is secreted extracellularly from LPS-treated microglia. However, the mechanisms of CatC affecting neuroinflammatory responses are not known yet.CatC over-expression (CatCOE) and knock-down (CatCKD) mice were treated with intraperitoneal and intracerebroventricular LPS injection. Morris water maze (MWM) test was used to assess the ability of learning and memory. Cytokine expression in vivo was detected by in situ hybridization, quantitative PCR, and ELISA. In vitro, microglia M1 polarization was determined by quantitative PCR. Intracellular CaThe LPS-treated CatCOE mice exhibited significantly increased escape latency compared with similarly treated wild-type or CatCKD mice. The highest levels of TNF-α, IL-1β, and other M1 markers (IL-6, CD86, CD16, and CD32) were found in the brain or serum of LPS-treated CatCOE mice, and the lowest levels were detected in CatCKD mice. Similar results were found in LPS-treated microglia derived from CatC differentially expressing mice or in CatC-treated microglia from wild-type mice. Furthermore, the expression of NR2B mRNA, phosphorylation of NR2B, CaThe data suggest that CatC promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca
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- 2022
8. Structure–activity relationships and evaluation of esterified diterpenoid alkaloid derivatives as antiproliferative agents
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Nami Kusanagi, Koji Wada, Takahiro Shimizu, Megumi Mizukami, Yuji Suzuki, Kang-Po Li, Hiroshi Yamashita, Masuo Goto, and Kuo Hsiung Lee
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Stereochemistry ,Antineoplastic Agents ,01 natural sciences ,Article ,Magnoliopsida ,Structure-Activity Relationship ,Alkaloids ,Cell Line, Tumor ,Humans ,Structure–activity relationship ,Potency ,Aconitum ,Cell Proliferation ,biology ,Plant Extracts ,010405 organic chemistry ,Chemistry ,Alkaloid ,Delphinium ,biology.organism_classification ,Terpenoid ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Cell culture ,Antiproliferative Agents ,Molecular Medicine ,Diterpenes - Abstract
Diterpenoid alkaloids with remarkable chemical properties and biological activities are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. However, little information has been reported on the antiproliferative effects of the diterpenoid alkaloid constituents of Aconitum and Delphinium plants. C-1 and 14 esterifications of delcosine (1) were carried out to provide 39 new diterpenoid alkaloid derivatives (3–14, 16–29, 3a–7a, 9a, 13a, 13b, 14a, 14b, 16a, 17a, 24a, 35a). Selected compounds (3–14, 16–29, 3a–7a, 9a, 13a, 13b, 14a, 14b, 16a, 17a, 24a, 35a) were evaluated for antiproliferative activity against three to five human tumor cell lines including triple-negative breast cancer (TNBC) and P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) subline. Several newly synthesized delcosine derivatives (6, 7, 13, 13a, 13b) showed substantial suppressive effects against all human tumor cell lines tested. In contrast, the natural alkaloids (1, 31, 33) showed no effect. Most of the active compounds were delcosine derivatives with two specific substitution patterns—C-1 and C-1,14. In particular, 1-acyldelcosine derivative (5–7) displayed more potency than 1,14-diacyldelcosine derivatives (5a–7a). These acylated alkaloid derivatives caused accumulation of TNBC cells at sub-G1 within 24 h. 1-Acylation of 1 appears to be critical for producing antiproliferative activity in this alkaloid class and a means to provide promising new leads for further development into antitumor agents.
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- 2019
9. Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells
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Kenta Sukegawa, Tsutomu Fujii, Hideki Sakai, Takuya Nagata, Takuto Fujii, Takahiro Shimizu, Tomoyuki Okumura, Shunsuke Kawai, and Isaya Hashimoto
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0301 basic medicine ,Cell physiology ,Patch-Clamp Techniques ,Physiology ,Endogeny ,Membrane Potentials ,03 medical and health sciences ,0302 clinical medicine ,Chloride Channels ,Stomach Neoplasms ,Cell Line, Tumor ,medicine ,Humans ,Cloning, Molecular ,Cell proliferation ,Original Paper ,Gene knockdown ,Cell growth ,Chemistry ,Cancer ,Chloride intracellular channel protein ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Chloride channel ,Cancer research ,Cell Migration Assays ,Gastric cancer ,Intracellular - Abstract
Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl− currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl− channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.
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- 2020
10. Safety and efficacy of diagnostic flexible bronchoscopy in very old patients with lung cancer
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Naozumi Hashimoto, Mitsuo Sato, Naoyuki Imai, Takahiro Shimizu, Kazuyoshi Imaizumi, Tetsunari Hase, Masahiro Morise, Shotaro Okachi, and Yoshinori Hasegawa
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Old patients ,medicine.medical_specialty ,Chemotherapy ,Performance status ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Medical record ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Bronchoscopy ,Internal medicine ,medicine ,030212 general & internal medicine ,Stage (cooking) ,Lung cancer ,business ,Flexible bronchoscopy - Abstract
Although there is a remarkable increase in diagnostic flexible bronchoscopy (FB) in old patients, safety and efficacy of FB in very old patients remain to be elucidated. In this study, we aimed to evaluate the complications and diagnostic yield of FB in patients aged ≥ 80 years with lung cancer compared with those aged
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- 2018
11. The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation
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Masashi Hamada, Yasuo Terao, Takahiro Shimizu, Hiroyuki Enomoto, Ryosuke Tsutsumi, Nobuyuki Tanaka, Mitsunari Abe, Shunsuke Kobayashi, Ritsuko Hanajima, Yoshikazu Ugawa, and Koichiro Nakamura
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Adult ,Male ,0301 basic medicine ,Aging ,medicine.medical_specialty ,medicine.medical_treatment ,Long-Term Potentiation ,Stimulation ,Audiology ,03 medical and health sciences ,0302 clinical medicine ,Neuroplasticity ,Psychophysics ,medicine ,Humans ,Muscle, Skeletal ,Aged ,Analysis of Variance ,Electromyography ,General Neuroscience ,Age Factors ,Motor Cortex ,Long-term potentiation ,Human brain ,Middle Aged ,Evoked Potentials, Motor ,Transcranial Magnetic Stimulation ,Transcranial magnetic stimulation ,030104 developmental biology ,medicine.anatomical_structure ,Brain stimulation ,Synaptic plasticity ,Female ,Primary motor cortex ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.
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- 2017
12. Diagnosing native liver fibrosis and esophageal varices using liver and spleen stiffness measurements in biliary atresia: a pilot study
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Yasushi Fuchimoto, Miwako Nakano, Takahiro Shimizu, Kiyoshi Ohkuma, Akihiro Fujino, Ken Hoshino, Yutaka Tanami, Takumi Fujimura, Naoki Hosoe, Yohei Masugi, Nobuhiro Takahashi, Hirotoshi Ebinuma, Michiie Sakamoto, Mototoshi Kato, Hidetsugu Saito, Tatsuo Kuroda, Hideo Ishihama, and Hirofumi Tomita
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Adolescent ,Pilot Projects ,Spleen ,Esophageal and Gastric Varices ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Esophageal varices ,Biliary Atresia ,Biliary atresia ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Neuroradiology ,Acoustic radiation force impulse imaging ,Receiver operating characteristic ,business.industry ,Ultrasound ,Area under the curve ,Infant ,medicine.disease ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Elasticity Imaging Techniques ,Female ,030211 gastroenterology & hepatology ,Radiology ,business - Abstract
Biliary atresia commonly leads to liver fibrosis and cirrhotic complications, including esophageal varices. To evaluate liver and spleen stiffness measurements using acoustic radiation force impulse (ARFI) imaging for diagnosing grade of liver fibrosis and predicting the presence of esophageal varices in patients treated for biliary atresia. ARFI imaging of the spleen and native liver was performed in 28 patients with biliary atresia. We studied the relation between ARFI imaging values and liver histology findings (n=22), upper gastrointestinal endoscopy findings (n=16) and several noninvasive test results. Diagnostic accuracy was assessed using receiver operating characteristic curve analyses. Liver stiffness measurements exhibited a significant difference among the different grades of liver fibrosis (P=0.009), and showed higher values in patients with high-risk esophageal varices than in the other patients (P=0.04). The areas under the receiver operating characteristic curves of liver stiffness measurements for liver fibrosis grades ≥ F2, ≥F3 and = F4 were 0.83, 0.93 and 0.94, respectively. Patients with high-risk esophageal varices were preferentially diagnosed by the combined liver and spleen stiffness measurements (area under the curve, 0.92). Liver and spleen stiffness measurements using ARFI imaging are potential noninvasive markers for liver fibrosis and esophageal varices in patients treated for biliary atresia.
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- 2016
13. Brain opioid and nociceptin receptors are involved in regulation of bombesin-induced activation of central sympatho-adrenomedullary outflow in the rat
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Motoaki Saito, Youichirou Higashi, Takahiro Shimizu, Keisuke Taniuchi, Shogo Shimizu, Tetsuya Ueba, Toshio Yawata, and Kumiko Nakamura
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0301 basic medicine ,medicine.medical_specialty ,Sympathetic Nervous System ,medicine.drug_class ,Clinical Biochemistry ,(+)-Naloxone ,Pharmacology ,Nociceptin Receptor ,03 medical and health sciences ,chemistry.chemical_compound ,Catecholamines ,0302 clinical medicine ,Opioid receptor ,Naltrindole ,Internal medicine ,medicine ,Animals ,Receptor ,Molecular Biology ,Cyprodime ,Naloxone ,business.industry ,Brain ,Bombesin ,Cell Biology ,General Medicine ,Naltrexone ,Rats ,Nociceptin receptor ,030104 developmental biology ,Endocrinology ,Morphinans ,Opioid ,chemistry ,Adrenal Medulla ,Receptors, Opioid ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Previously, we reported that central administration of bombesin, a stress-related peptide, elevated plasma levels of catecholamines (noradrenaline and adrenaline) in the rat. The sympatho-adrenomedullary system, which is an important component of stress responses, can be regulated by the central opioid system. In the present study, therefore, we examined the roles of brain opioid receptor subtypes (µ, δ, and κ) and nociceptin receptors, originally identified as opioid-like orphan receptors, in the bombesin-induced activation of central sympatho-adrenomedullary outflow using anesthetized male Wistar rats. Intracerebroventricularly (i.c.v.) administered bombesin-(1 nmol/animal) induced elevation of plasma catecholamines was significantly potentiated by pretreatment with naloxone (300 and 1000 µg/animal, i.c.v.), a non-selective antagonist for µ-, δ-, and κ-opioid receptors. Pretreatment with cyprodime (100 µg/animal, i.c.v.), a selective antagonist for µ-opioid receptors, also potentiated the bombesin-induced responses. In contrast, pretreatment with naltrindole (100 µg/animal, i.c.v.) or nor-binaltorphimine (100 µg/animal, i.c.v.), a selective antagonist for δ- or κ-opioid receptors, significantly reduced the elevation of bombesin-induced catecholamines. In addition, pretreatment with JTC-801 (30 and 100 µg/animal, i.c.v.) or J-113397 (100 µg/animal, i.c.v.), which are selective antagonists for nociceptin receptors, also reduced the bombesin-induced responses. These results suggest that brain µ-opioid receptors play a suppressive role and that brain δ-, κ-opioid, and nociceptin receptors play a facilitative role in the bombesin-induced elevation of plasma catecholamines in the rat. Thus, in the brain, these receptors could play differential roles in regulating the activation of central sympatho-adrenomedullary outflow.
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- 2015
14. Influence of extracellular zinc on M1 microglial activation
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Shogo Shimizu, Takaaki Aratake, Kumiko Nakamura, Tetuya Ueba, Motoaki Saito, Masayuki Tsuda, Youichirou Higashi, Takahiro Shimizu, and Toshio Yawata
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Lipopolysaccharides ,Male ,0301 basic medicine ,Necrosis ,Lipopolysaccharide ,chemistry.chemical_element ,Zinc ,Hippocampal formation ,Article ,Brain Ischemia ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chlorides ,Cell Line, Tumor ,medicine ,Extracellular ,Animals ,Humans ,Cells, Cultured ,Neurons ,chemistry.chemical_classification ,Reactive oxygen species ,Multidisciplinary ,Microglia ,Chemistry ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,Zinc Compounds ,Cytokines ,Tumor necrosis factor alpha ,medicine.symptom ,Reactive Oxygen Species ,030217 neurology & neurosurgery - Abstract
Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30–60 μM ZnCl2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia–reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.
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- 2017
15. Regulation of the murine TRPP3 channel by voltage, pH, and changes in cell volume
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Takahiro Shimizu, Bernd Nilius, Thomas Voets, and Annelies Janssens
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Patch-Clamp Techniques ,TRPP Cation Channels ,Physiology ,Clinical Biochemistry ,volume sensitivity ,Gating ,Cell Line ,Membrane Potentials ,TRPC1 ,Mice ,Transient receptor potential channel ,transient receptor potential channels ,taste receptor ,Physiology (medical) ,Animals ,Humans ,Protein Isoforms ,Repolarization ,Ion channel ,Cell Size ,pkd2l1 ,Arachidonic Acid ,Voltage-gated ion channel ,voltage dependency ,Chemistry ,ion channels ,Depolarization ,dependence ,Hydrogen-Ion Concentration ,ph sensitivity ,cations ,inhibition ,Stretch-activated ion channel ,Biochemistry ,polycystins ,Biophysics ,Calcium ,activation ,polycystic kidney-disease ,Ion Channel Gating ,transient receptor ,murine trpp3 ,conductance - Abstract
Transient receptor potential (TRP) polycystin 3 (TRPP3) is a member of the TRP superfamily of cation channels. Murine TRPP3 has been reported to form an acid-activated cation channel on the plasma membrane when coexpressed with the polycystin 1-like protein 3 (PKD1L3); however, the function and biophysical properties of TRPP3-dependent channels have not yet been characterized in detail. Here we show that overexpression of murine TRPP3 channel in HEK293 cells, without coexpression of PDK1-like proteins, leads to robust channel activity. These channels exhibit a high single-channel conductance of 184 pS at negative potentials, are Ca2+-permeable, and relatively nonselective between cations. Whole-cell experiments showed a characteristic form of voltage-dependent gating of TRPP3 channels, whereby repolarization after depolarization caused large transient inward TRPP3 tail currents. Moreover, we found that TRPP3 activity was increased upon cell swelling and by alkalization. Taken together, our results demonstrate that TRPP3, on its own, can act as a voltage-dependent, pH- and volume-sensitive plasma membrane cation channel. ispartof: Pflugers Archiv-European Journal of Physiology vol:457 issue:4 pages:795-807 ispartof: location:Germany status: published
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- 2008
16. Role of acid-sensitive outwardly rectifying anion channels in acidosis-induced cell death in human epithelial cells
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Hai-Yan Wang, Tomohiro Numata, Takahiro Shimizu, and Yasunobu Okada
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Anions ,Physiology ,Phloretin ,Clinical Biochemistry ,Population ,4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ,Ion Channels ,HeLa ,Necrosis ,chemistry.chemical_compound ,Chloride Channels ,Physiology (medical) ,Extracellular ,Humans ,Propidium iodide ,education ,Cell Size ,education.field_of_study ,Cell Death ,biology ,Caspase 3 ,Epithelial Cells ,Depolarization ,Hydrogen-Ion Concentration ,biology.organism_classification ,Cell biology ,Electrophysiology ,chemistry ,DIDS ,Chloride channel ,Acidosis ,HeLa Cells - Abstract
Recently, a novel type of anion channel activated by extracellular acidification has been found in a variety of mammalian cell types. However, the role of this acid-sensitive outwardly rectifying (ASOR) anion channel is not known. In human epithelial HeLa cells, reduction in extracellular pH below 5 rapidly activated anion-selective whole-cell currents. The currents exhibited strong outward rectification, activation kinetics at positive potentials, low-field anion selectivity, and sensitivity to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and phloretin. When outside-out patches were exposed to acidic bathing solution, single-channel events of the anion channel could be observed. The unitary conductance was 4.8 pS in the voltage range between -80 and +80 mV. The single-channel activity prominently increased with depolarization and was suppressed by DIDS or phloretin. After 1-h incubation in acidic solution (pH 4.5), a significant population of HeLa cells suffered from necrotic cell injury characterized by stainability with propidium iodide and lack of caspase-3 activation. Upon exposure to acidic solution, HeLa cells exhibited immediate, persistent swelling. Both the necrotic volume increase and cell injury induced by extracellular acidification were inhibited by DIDS or phloretin. Therefore, it is concluded that the ASOR anion channel is involved in the genesis of necrotic cell injury induced by acidosis in human epithelial cells.
- Published
- 2006
17. Angiotensin II acting on brain AT1 receptors induces adrenaline secretion and pressor responses in the rat
- Author
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Fotios Dimitriadis, Takayuki Nemoto, Kumiko Nakamura, Toshio Yawata, Youichirou Higashi, Takahiro Shimizu, Keisuke Taniuchi, Shogo Shimizu, Motoaki Saito, Tetsuya Ueba, and Toshihiko Yanagita
- Subjects
Male ,medicine.medical_specialty ,Angiotensin receptor ,Epinephrine ,Tetrazoles ,Blood Pressure ,Receptor, Angiotensin, Type 1 ,Article ,Norepinephrine ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Neurotransmitter ,Receptor ,Medulla ,Injections, Intraventricular ,Multidisciplinary ,Angiotensin II receptor type 1 ,Chemistry ,Angiotensin II ,Brain ,Valine ,Rats ,Endocrinology ,medicine.anatomical_structure ,Valsartan ,Adrenal Medulla ,cardiovascular system ,Adrenal medulla ,Angiotensin II Type 1 Receptor Blockers ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,medicine.drug - Abstract
Angiotensin II (AngII) plays important roles in the regulation of cardiovascular function. Both peripheral and central actions of AngII are involved in this regulation, but mechanisms of the latter actions as a neurotransmitter/neuromodulator within the brain are still unclear. Here we show that (1) intracerebroventricularly (i.c.v.) administered AngII in urethane-anesthetized male rats elevates plasma adrenaline derived from the adrenal medulla but not noradrenaline with valsartan- (AT1 receptor blocker) sensitive brain mechanisms, (2) peripheral AT1 receptors are not involved in the AngII-induced elevation of plasma adrenaline, although AngII induces both noradrenaline and adrenaline secretion from bovine adrenal medulla cells, and (3) i.c.v. administered AngII elevates blood pressure but not heart rate with the valsartan-sensitive mechanisms. From these results, i.c.v. administered AngII acts on brain AT1 receptors, thereby inducing the secretion of adrenaline and pressor responses. We propose that the central angiotensinergic system can activate central adrenomedullary outflow and modulate blood pressure.
- Published
- 2014
18. Association of apolipoprotein allele ε2 with psoriasis vulgaris in Japanese population
- Author
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Takashi Imamura, Masahiko Muto, Hiroko Furumoto, Takahiro Shimizu, Chidori Asagami, Kazuyuki Nakamura, and Yoshiaki Hamamoto
- Subjects
Adult ,Male ,Apolipoprotein E ,medicine.medical_specialty ,Adolescent ,Apolipoprotein B ,Dermatology ,Biology ,Apolipoproteins E ,Gene Frequency ,Japan ,Internal medicine ,Psoriasis ,medicine ,Humans ,Allele ,Child ,Allele frequency ,Alleles ,Aged ,Isoelectric focusing ,General Medicine ,Middle Aged ,medicine.disease ,Phenotype ,Endocrinology ,Child, Preschool ,Immunology ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Antibody - Abstract
We studied phenotypic variations of apolipoprotein E (apoE) and the corresponding allele frequencies in 100 Japanese patients with psoriasis vulgaris (PV). The phenotypes of apoE were examined using analytical isoelectric focusing followed by immunoblotting with goat anti-apoE antibody and alkaline phosphatase-conjugated rabbit antigoat IgG. The phenotypic frequency of apoE3/2 in PV was significantly higher than in healthy controls, and this elevation was associated with an increased frequency of the epsilon 2 allele. Therefore, it is suggested that the apoE molecule plays an important role in the development of PV.
- Published
- 1997
19. Pneumocephalus as a complication of esophageal carcinoma
- Author
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Yasuhiro Hasegawa, Yoshiaki Tokuyama, Kazuhiro Miura, Kana Shimomura, Takehito Otsubo, Takeharu Enomoto, Toshikazu Hirayama, Tatsuhiro Arai, and Takahiro Shimizu
- Subjects
medicine.medical_specialty ,business.industry ,Fistula ,Head injury ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Pneumocephalus ,Clinical Images ,Emergency Medicine ,medicine ,Carcinoma ,Esophagus ,Subarachnoid space ,Complication ,business ,Rare disease - Abstract
A 73-year-old man presented with a loss of consciousness. He was comatose at the time of admission with a GCS of 5 and no localized neurological signs. Medical records indicated that the patient had undergone surgical treatment for esophageal carcinoma 2 years previously. Metastases developed in the reconstructed stomach tube and middle esophagus 6 months after surgery, and the patient had therefore received radiotherapy. Computed tomography (CT) of the head revealed gaseous distention in the subarachnoid space around the cortex. Some air was visible around the brain stem (Fig.(Fig.1).1). No head injuries and no skull-base fracture were observed. The radiological diagnosis was a pneumocephalus. He died 2 days after admission. Fig. 1 Axial CT of the brain showing profound gaseous attenuation in the subarachnoid space, cortical sulci and ambient cistern Pneumocephalus is a rare disease that has most often been described as a result of skull base fracture or intracranial and spinal operations. A subarachnoid-pleural fistula and intracranial air may occur after lung resection [1]. Willheim reported pneumocephalus as a complication of metastases in sacral carcinoma [2]. This is a very rare eroding tumor that may cause pneumocephalus without either trauma or surgery. We think that the destruction of the esophagus and tissue of the esophageal carcinoma, which was hastened by eroding bone, caused a communication between the subarachnoid space and esophagus. The diagnosis was of pneumocephalus as a complication of esophageal carcinoma.
- Published
- 2010
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