FLAME SPREAD EXPERIMENT OF A FUEL DROPLET ARRAY IN HIGH-PRESSURE AMBIENCE

Shinichiro Kato,Hiroyuki Mizuno,Hideaki Kobayashi,Takashi Niioka 대한기계학회 1996 KSME/JSME THERMAL and FLUID Engineering Conference Vol.2 No.1

Infl iximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn`s Disease

( Kyoichi Kato ),( Ken Fukunaga ),( Koji Kamikozuru ),( Shinichiro Kashiwamura ),( Nobuyuki Hida ),( Yoshio Ohda ),( Naohisa Takeda ),( Koji Yoshida ),( Masaki Iimuro ),( Yoko Yokoyama ),( Risa Kikuya 대한소화기기능성질환·운동학회 2011 Gut and Liver Vol.5 No.1

Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has effi cacy in treating Crohn`s disease (CD). However, knowledge of the potential effects of IFX on patients` immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI) of 194.2±92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/ CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results: CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-β1 (p<0.01), and ``regulated on activation, normal T cell expressed and secreted`` (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ (p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1β (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-γ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance. (Gut Liver 2011;5:37-45)

Infl iximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naïve Patients with Crohn’s Disease

Kyoichi Kato,Ken Fukunaga,Koji Kamikozuru,Shinichiro Kashiwamura,Nobuyuki Hida,Yoshio Ohda,Naohisa Takeda,Koji Yoshida,Masaki Iimuro,Yoko Yokoyama,Risa Kikuyama,Hiroto Miwa,Takayuki Matsumoto 거트앤리버 소화기연관학회협의회 2011 Gut and Liver Vol.5 No.1

Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has effi cacy in treating Crohn’s disease (CD). However, knowledge of the potential effects of IFX on patients’ immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI)of 194.2±92.9 and an average duration of disease of 3.26months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results:CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13(p<0.01), transforming growth factor-β1 (p<0.01), and ‘regulated on activation, normal T cell expressed and secreted’(RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ(p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1β (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01)and a decrease in the Th1 (IFN-γ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naïve Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection

Kazuyuki Matsumoto,Hironari Kato,Shigeru Horiguchi,Takeshi Tomoda,Akihiro Matsumi,Yuki Ishihara,Yosuke Saragai,Saimon Takada,Shinichiro Muro,Daisuke Uchida,Hiroyuki Okada 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.5

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution.

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer

Yukiharu Todo,Hidenori Kato,Kazuhira Okamoto,Shinichiro Minobe,Katsushige Yamashiro,Noriaki Sakuragi 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.1

Objective: The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. Methods: In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. Results: Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). Conclusions: It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy:a retrospective analysis in a Japanese cohort

Daisuke Endo,Yukiharu Todo,Kazuhira Okamoto,Shinichiro Minobe,Hidenori Kato,Noriaki Nishiyama 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.1

Objective: Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT. Methods: We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models. Results: Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes. Conclusion: New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.

Diagnostic Ability of Convex-Arrayed Endoscopic Ultrasonography for Major Vascular Invasion in Pancreatic Cancer

Yuki Fujii,Kazuyuki Matsumoto,Hironari Kato,Yosuke Saragai,Saimon Takada,Sho Mizukawa,Shinichiro Muro,Daisuke Uchida,Takeshi Tomoda,Shigeru Horiguchi,Noriyuki Tanaka,Hiroyuki Okada 대한소화기내시경학회 2019 Clinical Endoscopy Vol.52 No.5

Background/Aims: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascularinvasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. Methods: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUSimage findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion,types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors andevaluated vessels. Results: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in theveins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings weresignificantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0–742] µmvs. 2,833 [1,076–5,694] µm, p=0.012) and arteries (623 [0–854] µm vs. 3,097 [1,396–6,000] µm, p=0.0061). All cases with a distance of≥1,000 µm between the tumors and main vessels were correctly diagnosed. Conclusions: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.

Therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma

Hiroyuki Yamazaki,Yukiharu Todo,Chisa Shimada,Sho Takeshita,Shinichiro Minobe,Kazuhira Okamoto,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.2

Objectives: This study evaluated the therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC). Methods: We retrospectively reviewed records of 127 consecutive patients with pT1/pT2 and M0 OCCC who were treated between January 1995 and December 2015. We compared survival outcomes between those who did and did not undergo para-aortic lymph node dissection (PAND), and analyzed independent prognostic factors (Cox proportional hazards model with backward stepwise elimination). Results: Of the 127 patients, 36 (28%) did not undergo lymphadenectomy; 12 (10%) patients underwent pelvic lymph node dissection (PLND) only; and 79 (62%) patients underwent both PLND and PAND. Of the 91 patients with lymphadenectomy, 11 (12%) had lymph node metastasis (LNM). The PAND− and PAND+ groups did not significantly differ in age, distribution of pT status, radiologically enlarged lymph nodes, positive peritoneal cytology, capsule rupture, peritoneal involvement, and combined chemotherapy. Cox regression multivariate analysis confirmed that older age (hazard ratio [HR]=2.1; 95% confidence interval [CI]=1.0–4.3), LNM (HR=4.4; 95% CI=1.7–11.6), and positive peritoneal cytology (HR=4.2; 95% CI=2.1–8.4) were significantly and independently related to poor disease-specific survival (DSS), but implementation of both PLND and PAND (HR=0.4; 95% CI=0.2–0.8) were significantly and independently related to longer DSS. Conclusion: Although few in number, there are some patients with early-stage OCCC who can benefit from full lymphadenectomy. Its therapeutic role should be continuously investigated in OCCC patients at potential risk of LNM.

A2E, a pigment of the lipofuscin of retinal pigment epithelial cells, is an endogenous ligand for retinoic acid receptor.

Iriyama, Aya,Fujiki, Ryoji,Inoue, Yuji,Takahashi, Hidenori,Tamaki, Yasuhiro,Takezawa, Shinichiro,Takeyama, Kenichi,Jang, Woo-Dong,Kato, Shigeaki,Yanagi, Yasuo American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.18

<P>Lipofuscin contains fluorophores, which represent a biomarker for cellular aging. Although it remains unsubstantiated clinically, experimental results support that the accumulation of lipofuscin is related to an increased risk of choroidal neovascularization due to age-related macular degeneration, a leading cause of legal blindness. Here, we report that a major lipofuscin component, A2E, activates the retinoic acid receptor (RAR). In vitro experiments using luciferase reporter assay, competitional binding assay, analysis of target genes, and chromatin immunoprecipitation (ChIP) assay strongly suggest that A2E is a bona fide ligand for RAR and induces sustained activation of RAR target genes. A2E-induced vascular endothelial growth factor (VEGF) expression in a human retinal pigment epithelial cell line (ARPE-19) and RAR antagonist blocked the up-regulation of VEGF. The conditioned medium of A2E-treated ARPE-19 cells induced tube formation in human umbilical vascular endothelial cells, which was blocked by the RAR antagonist and anti-VEGF antibody. These results suggest that A2E accumulation results in the phenotypic alteration of retinal pigment epithelial cells, predisposing the environment to choroidal neovascularization development. This is mediated through the agonistic function of A2E, at least in part. The results of this study provide a novel potential therapeutic target for this incurable condition.</P>