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World Journal of Gastroenterology 2015年第44期21卷 12722-12728页

作者： Nobuyoshi Takeshita Toru Fukunaga Masayuki Kimura Yuji Sugamoto Kentaro Tasaki Isamu Hoshino Takumi Ota Tetsuro Maruyama Tomohide Tamachi takashi hosokawa Yo Asai Hisahiro Matsubara Department of Surgery Numazu City Hospital Department of Frontier Surgery Chiba University Graduate School of Medicine

A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, c SS, c N0, c H0, c P0, c M0 c Stage Ⅱ, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, p SS, p N3, p H0, p P1, p M1(para-aortic lymph node, dissemination) f Stage Ⅳ. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography(CT) detected an 11 mm of liver metastasis in the posteroinferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of paraaortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in paraaortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine aloneand continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome(Grade 3), we managed

关键词： Rectal cancer Surgical resection Virchow lymph nod

Esophageal intramural pseudodiverticulosis of the residual esophagus after esophagectomy for esophageal cancer

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World Journal of Gastroenterology 2015年第30期21卷 9223-9227页

作者： Nobuyoshi Takeshita Naoki Kanda Toru Fukunaga Masayuki Kimura Yuji Sugamoto Kentaro Tasaki Masaya Uesato Tetsutaro Sazuka Tetsuro Maruyama Naohiro Aida Tomohide Tamachi takashi hosokawa Yo Asai Hisahiro Matsubara Department of Surgery Numazu City Hospital Department of Frontier Surgery Chiba University Graduate School of Medicine

A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer(T3N2M0 Stage Ⅲ) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation,including redness,erosion,edema,bleeding,friability,and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine,gastrografinfilled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly,endoscopic balloon dilatation was performed and antifungal therapy was started in the hospital. Seven weeks later,endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently,the patient was discharged. At the latest follow-up,the patient was symptomfree and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.

关键词： Esophageal intramural pseudodiverticulosis Esophageal cancer Esophageal candidiasis Anastomoticstricture Esophagectomy Residual esophagus

Integration of Droplet Microfluidic Tools for Single-cell Functional Metagenomics:An Engineering Head Start

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Genomics, Proteomics & Bioinformatics 2021年第3期19卷 504-518页

作者： David Conchouso Amani Al-Ma’abadi Hayedeh Behzad Mohammed Alarawi Masahito hosokawa Yohei Nishikawa Haruko Takeyama Katsuhiko Mineta takashi Gojobori Department of Industrial and Mechanical Engineering Universidad de las Américas PueblaPuebla 72810Mexico Computational Bioscience Research Center King Abdullah University of Science and TechnologyThuwal 23955-6900Saudi Arabia Biological and Environmental Sciences and Engineering Division King Abdullah University of Science and TechnologyThuwal 23955-6900Saudi Arabia Research Organization for Nano&Life Innovation Waseda UniversityTokyo 162-0041Japan Department of Life Science and Medical Bioscience Waseda UniversityTokyo 162-8480Japan Institute for Advanced Research of Biosystem Dynamics Waseda Research Institute for Science and EngineeringWaseda UniversityTokyo 169-8555Japan Computational Bio Big-Data Open Innovation Laboratory AIST-Waseda UniversityTokyo 169–0072Japan Computer Electricaland Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and TechnologyThuwal 23955-6900Saudi Arabia

Droplet microfluidic techniques have shown promising outcome to study single cells at high ***,their adoption in laboratories studying“-omics”sciences is still irrelevant due to the complex and multidisciplinary nature of the *** facilitate their use,here we provide engineering details and organized protocols for integrating three droplet-based microfluidic technologies into the metagenomic pipeline to enable functional screening of bioproducts at high ***,a device encapsulating single cells in droplets at a rate of~250 Hz is described considering droplet size and cell ***,we expand on previously reported fluorescence-activated droplet sorting systems to integrate the use of 4 independent fluorescence-exciting lasers(i.e.,405,488,561,and 637 nm)in a single platform to make it compatible with different fluorescence-emitting *** this sorter,both hardware and software are provided and optimized for effortlessly sorting droplets at 60 ***,a passive droplet merger is also integrated into our pipeline to enable adding new reagents to already-made droplets at a rate of 200 ***,we provide an optimized recipe for manufacturing these chips using silicon dry-etching *** of the overall integration and the technical details presented here,our approach allows biologists to quickly use microfluidic technologies and achieve both single-cell resolution and high-throughput capability(>50,000 cells/day)for mining and bioprospecting metagenomic data.

关键词： Droplet microfluidics Single cell Metagenomics Droplet sorter Biotechnology

Long-term dexamethasone treatment diminishes store-operated Ca^(2+) entry in salivary acinar cells

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International Journal of Oral Science 2019年第1期11卷 25-32页

作者： Yuichiro Kusuda Yusuke Kondo Yuta Miyagi takashi Munemasa Yusuke Hori Fumiko Aonuma Shintaro Tsuka Taro Mukaibo Chihiro Masaki Ryuji hosokawa Division of Oral Reconstruction and Rehabilitation Kyushu Dental University

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol(CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na^+-K^+-2 Cl-cotransporter, transmembrane member 16 A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca^(2+) in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca^(2+) and Ca^(2+) ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment ***, salivation induced by the Ca^(2+) -ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca^(2+) entry, resulting in hyposalivation in mouse submandibular glands.

关键词： Corticosteroids carbachol(CCh)induced

Serotonin 2C Receptor Alternative Splicing in a Rat Model of Orofacial Neuropathic Pain

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Neuroscience & Medicine 2012年第1期3卷 69-74页

作者： Aya Nakae Kunihiro Nakai Tatsuya Tanaka Ko hosokawa takashi Mashimo Center for Medical Research and Education Osaka University Graduate School of Medicine Department of Anesthesiology & Intensive Care Osaka University Graduate School of Medicine Department of Plastic Surgery Osaka University Graduate School of Medicine

Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA;the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.

关键词： Orofacial Neuropathic Pain Prader-Willi Syndrome Serotonin 2C Receptor Alternative Splicing SnoRNA RBII-52 RNA Editing Spinal Cord

Stress Distribution in Maxillary Central Incisors without Ferrules: A Finite Element Analysis of Post and Core Systems

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Open Journal of Stomatology 2021年第7期11卷 251-262页

作者： Akihiro Tagahara Chihiro Masaki Tomotaka Nodai takashi Munemasa Taro Mukaibo Yusuke Kondo Ryuji hosokawa Division of Oral Reconstruction and Rehabilitation Kyushu Dental University Kitakyushu Japan

Purpose: The purpose of this study was to identify optimal post and core materials for central incisors without ferrules using three-dimensional finite element analysis and three-point bending tests. Methods: Stress analyses were performed with six models: cast metal post and core (MP), composite resin core alone, straight fiber-reinforced post-composite resin core (FSR), tapered fiber-reinforced post-composite resin core, straight titanium post-composite resin core (TSR), and tapered titanium post-composite resin core (TTR). A 100-N load was applied to the lingual surface at a 45° angle to the long axis of the tooth. Maximum von Mises stress distributions were calculated with finite element analysis software. Five samples each of composite resin, straight fiber-reinforced post, straight titanium post, straight fiber-reinforced post and composite resin, and straight titanium post and composite resin were subjected to three-point bending tests, followed by analysis of variance and Tukey’s multiple comparison test. Results: Stress distribution was optimal on TTR. Maximum von Mises stress on the cervical side of the post was greatest in TSR (693 MPa) and TTR (556 MPa). Maximum stress on the apical side of the post was greatest in MP (110 MPa). Maximum stress in surrounding dentin was lowest in MP (203 MPa) and TTR (250 MPa). Gap distance was smallest in MP (0.09 mm) and largest in FSR (0.26 mm). Mean maximum three-point bending force was lowest in composite resin (26.9 N/mm) and highest in titanium post and composite resin (97.1 N/mm). Titanium post bending strength was consistently greater than that of the fiber-reinforced post (p Conclusion: These results revealed optimal stress distribution and high bending strength with the tapered titanium post and resin combination, suggesting that this combination can most effectively prevent root or post fracture in an anterior tooth without a ferr

关键词： Fiber Post Titanium Post Ferrule Three-Dimensional Finite Element Analysis Three-Point Bending Test

Effects of Beverage Ingredients on Salivary Fluid Secretion with an <i>ex Vivo</i>Submandibular Gland Perfusion System: Tannic Acid as a Key Component for the Inhibition of Saliva Secretion

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Open Journal of Stomatology 2015年第1期5卷 12-18页

作者： Atsushi Imamura Tetsuji Nakamoto Taro Mukaibo takashi Munemasa Yusuke Kondo Manami Kidokoro Chihiro Masaki Ryuji hosokawa Department of Oral Reconstruction and Rehabilitation Kyushu Dental University Kitakyushu Japan

Tannic acid (TA) and TA containing beverage have been proved to inhibit Ca2+-activated Cl- channel located apical membrane of the secretory cells. However, their effect on salivary fluid secretion is not well investigated. We used mouse ex Vivo submandibular gland perfusion technique to identify the general effect of TA and related beverage samples on muscarinic agonist carbachol induced fluid secretion. Green tea inhibited fluid secretion by 64% from the control, where oolong tea was by 53%, and red wine by 43% which was linked with their TA concentration. On the other hand, though TA was contained at 4.7 μM in white wine sample and 33 μM in coffee extract, no adverse effect was observed. In addition, coffee induced salivation in the absence of carbachol. TA had a negative effect on fluid secretion with a concentration dependent manner. The effects of TA on carbachol induced calcium increase showed identical as fluid secretion, which was initially no effect, and then gradually decreased over the time. These results demonstrate that TA directly inhibits the salivary fluid secretion and it affects not only Ca2+-activated Cl- channel but also intracellular Ca2+ increasing mechanisms.

关键词： Saliva Secretion Red Wine Tannic Acid Ca2+ Activated Cl- Channel

Production of the Blood Pressure Lowing Peptides from Brown Alga(Undaria pinnatifida)

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Journal of Ocean University of China 2005年第3期4卷 209-213页

作者： Sato Minoru Oba takashi hosokawa Takao Yamaguchi Toshiyasu Nakano Toshiki Saito Tadao Muramoto Koji Kahara takashi Funayama Katsura Kobayashi Akio Nakano Takahisa Graduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanGraduate School of Agricultural Science Tohoku University Aoba-Ku Sendai Miyagi 981-8555 JapanRiken Vitamin Co. Ltd. 2-9-18 Misaki-Cho Chiyoda-Ku Tokyo 101-8370 JapanRiken Vitamin Co. Ltd. 2-9-18 Misaki-Cho Chiyoda-Ku Tokyo 101-8370 JapanRiken Vitamin Co. Ltd. 2-9-18 Misaki-Cho Chiyoda-Ku Tokyo 101-8370 JapanRiken Vitamin Co. Ltd. 2-9-18 Misaki-Cho Chiyoda-Ku Tokyo 101-8370 Japan

Brown alga (Undaria pinnatifida) was treated with alginate lyase and hydrolyzed using 17 kinds of proteases andthe inhibitory activity of the hydrolysates for the angiotensin-I-converting enzyme (ACE) was measured. Four hydrolysateswith potent ACE-inhibitory activity were administered singly and orally to spontaneously hypertensive rats (SHRs). The sys-tolic blood pressure of SHRs decreases significantly after single oral administration of the brown alga hydrolysates by pro-tease S ’Amano’ (from Bacillus stearothermophilus) at the concentration of 10 (mg protein) (kg body weight)-1. In the 17weeks of feeding experiment, 7-week-old SHRs were fed standard diet supplemented with the brown alga hydrolysates for 10weeks. In SHRs fed 1.0 and 0.1% brown alga hydrolysates, elevating of systolic bloodpressure was significantly suppressedfor 7 weeks. To elucidate the active components, the brown alga hydrolysates were fractionated by 1-butanol extraction andHPLC on a reverse-phase column. Seven kinds of ACE-inhibitory peptides were isolated and identified by amino acid compo-sition analysis, sequence analysis, and LC-MS with the results Val-Tyr, Ile-Tyr, Ala-Trp, Phe-Tyr, Val-Trp, Ile-Trp, andLeu-Trp. Each peptide was determined to have an antihypertensive effect after a single oral administration in SHRs. Thebrown alga hydrolysates were also confirmed to decrease the blood pressure in humans.

关键词：海藻缩氨酸抗血压药物藻酸盐水解工艺

Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy

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World Journal of Gastroenterology 2013年第2期19卷 249-257页

作者： Takanori hosokawa Masayuki Kurosaki Kaoru Tsuchiya Shuya Matsuda Masaru Muraoka Yuichiro Suzuki Nobuharu Tamaki Yutaka Yasui Toru Nakata takashi Nishimura Shoko Suzuki Ken Ueda Hiroyuki Nakanishi Jun Itakura Yuka Takahashi Namiki Izumi Division of Gastroenterology and Hepatology Musashino Red Cross HospitalTokyo 180-8610Japan

AIM:To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma(HCC) and survival after curative ***:This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation(RFA) *** mean age was 67.6 years and the mean observation period was 4.04 *** etiological background of liver disease was hepatitis B virus infection in 30,hepatitis C virus infection in 278,excessive alcohol drinking in 9,and other in 27 *** Child-Pugh classification grade was A(n = 307) or B(n = 37).The number of HCC nodules was one in 260,two in 61,and three in 23 *** surveillance of HCC recurrence after curative therapy with RFA,patients were radiologically evaluated every 3 *** associated with distant recurrence of HCC or survival were ***:Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant *** 1-,2-,and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others:50.6% vs 26.8%,83.5% vs 54.4%,and 93.8% vs 73.0%,respectively(P = 0.0001).Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97(95%CI,1.33-2.91),(P = 0.0007)] after adjustment for other risk factors,such as number of HCC nodules [2.03(95%CI,1.51-2.73),P < 0.0001] and initial level of serum alpha fetoprotein(AFP) [1.43(95%CI,1.04-1.97),P = 0.028].Obesity was not an independent predictor of *** incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic *** 232 patients who had HCC recurrence,138 had a second *** 1-,2-,and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others:9.0% vs 5.9%,53.1

关键词： Hyperglycemia Hepatocellular carcinoma Recurrence Radio frequency ablation Survival