Freeze-Dried Platelet-Rich Plasma Induces Osteoblast Proliferation via Platelet-Derived Growth Factor Receptor-Mediated Signal Transduction

Hideyuki Kinoshita,Sumihisa Orita,Kazuhide Inage,Kazuki Fujimoto,Yasuhiro Shiga,Koki Abe,Masahiro Inoue,Masaki Norimoto,Tomotaka Umimura,Takeshi Ishii,Tsukasa Yonemoto,Hiroto Kamoda,Toshinori Tsukanis 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.1

Study Design: Controlled laboratory study. Purpose: This study aimed to evaluate the in vitro pharmacological activity of growth factors (GFs) in freeze-dried platelet-rich plasma (FD-PRP) after storage for 4 weeks. Overview of Literature: Freshly prepared PRP is a rich source of many GFs. We reported that FD-PRP stored for 8 weeks accelerated bone union in a rat posterolateral fusion model equally well as fresh-PRP. However, the pharmacological activity of FD-PRP after long-term storage has not been shown in vitro. Methods: Immediately after preparation, as well as 4 weeks after freeze-dried storage, the platelet count was measured. Human osteoblasts were treated with fresh-PRP and FD-PRP, respectively. Western blotting was used to assess the phosphorylation of the platelet-derived growth factor (PDGF) receptor (PDGFR) and its downstream target, extracellular signal-regulated kinase (ERK). The proliferation rates of osteoblasts were investigated by immunocytochemistry and MTT cell viability assays. Furthermore, we used western blotting to evaluate the effect of PDGFR knockdown on the phosphorylation of ERK stimulated with fresh-PRP and FD-PRP. Results: Platelet counts in both the fresh-PRP and FD-PRP samples were approximately 10-fold higher than in peripheral blood samples. The phosphorylation and activation of the PDGFR and ERK were evenly induced by fresh-PRP and FD-PRP stimulation. Both fresh-PRP and FD-PRP significantly induced osteoblast proliferation in MTT cell viability assays. Furthermore, osteoblast PDGFR knockdown attenuated the downstream ERK activation by fresh PRP and FD-PRP. Conclusions: We demonstrated the pharmacological activity of PDGF in FD-PRP in vitro after 4 weeks of storage.

Low-Dose Pegylated Interferon α-2b Plus Ribavirin for Elderly and/or Cirrhotic Patients with Genotype 2 Hepatitis C Virus

Hideyuki Tamai,Naoki Shingaki,Yoshiyuki Mori,Kosaku Moribata,Akira Kawashima,Yoshimasa Maeda,Toru Niwa,Hisanobu Deguchi,Izumi Inoue,Takao Maekita,Mikitaka Iguchi,Jun Kato,Masao Ichinose 거트앤리버 소화기연관학회협의회 2016 Gut and Liver Vol.10 No.4

Background/Aims: This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEGIFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods: Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results: The patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions: Low-dose PEG-IFN plus ribavirin was a safe and costeffective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

Japanese Cancer Association Meeting UICC International Session - What is Cost-effectiveness in Cancer Treatment?

Akaza, Hideyuki,Kawahara, Norie,Roh, Jae Kyung,Inoue, Hajime,Park, Eun-Cheol,Lee, Kwang-Sig,Kim, Sukyeong,Hayre, Jasdeep,Naidoo, Bhash,Wilkinson, Thomas,Fukuda, Takashi,Jang, Woo Ick,Nogimori, Masafum Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized an international session as part of the official program of the 72nd Annual Meeting of the Japanese Cancer Association to discuss the topic "What is cost-effectiveness in cancer treatment?" Healthcare economics are an international concern and a key issue for the UICC. The presenters and participants discussed the question of how limited medical resources can be best used to support life, which is a question that applies to both developing and industrialized countries, given that cancer treatment is putting medical systems under increasing strain. The emergence of advanced yet hugely expensive drugs has prompted discussion on methodologies for Health Technology Assessment (HTA) that seek to quantify cost and effect. The session benefited from the participation of various stakeholders, including representatives of industry, government and academia and three speakers from the Republic of Korea, an Asian country where discussion on HTA methodologies is already advanced. In addition, the session was joined by a representative of National Institute for Health and Care Excellence (NICE) of the United Kingdom, which has pioneered the concept of cost-effectiveness in a medical context. The aim of the session was to advance and deepen understanding of the issue of cost-effectiveness as viewed from medical care systems in different regions.

Rotordynamic Characteristics of Floating Ring Seals in Rocket Turbopumps

Yuichiro Tokunaga,Hideyuki Inoue,Jun Hiromatsu,Tetsuya Iguchi,Yasuhiro Kuroki,Masaharu Uchiumi 한국유체기계학회 2016 International journal of fluid machinery and syste Vol.9 No.3

Floating ring seals offer an opportunity to reduce leakage flows significantly in rotating machinery. Accordingly, they have been applied successfully to rotating machinery within the last several decades. For rocket turbopump applications, fundamental behavior and design philosophy have been revealed. However, further work is needed to explore the rotordynamic characteristics associated with rotor vibrations. In this study, rotordynamic forces for floating ring seals under rotor’s whirling motions are calculated to elucidate rotordynamic characteristics. Comparisons between numerical simulation results and experiments demonstrated in our previous report are carried out. The three-dimensional Reynolds equation is solved by the finite-difference method to calculate hydrodynamic pressure distributions and the leakage flow rate. The entrance loss at the upstream inlet of the seal ring is calculated to estimate the Lomakin effect. The friction force at the secondary seal surface is also considered. Numerical simulation results showed that the rotordynamic forces of this type of floating ring seal are determined mainly by the friction force at the secondary seal surface. The seal ring is positioned almost concentrically relative to the rotor by the Lomakin effect. Numerical simulations agree quite well with the experimental results.

Prediction of a Null Response to Pegylated Interferon α-2b Plus Ribavirin in Patients with High Viral Load Genotype 1b Hepatitis C

( Yuki Wada ),( Hideyuki Tamai ),( Akira Kawashima ),( Naoki Shingaki ),( Yoshiyuki Mori ),( Masanori Kawaguchi ),( Kosaku Moribata ),( Hisanobu Deguchi ),( Kazuki Ueda ),( Izumi Inoue ),( Takao Maeki 대한소화기학회 2014 Gut and Liver Vol.8 No.4

Background/Aims: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. Methods: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. Results: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. Conclusions: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response. (Gut Liver 2014;8:421-427)

Rotordynamic Characteristics of Floating Ring Seals in Rocket Turbopumps

Tokunaga, Yuichiro,Inoue, Hideyuki,Hiromatsu, Jun,Iguchi, Tetsuya,Kuroki, Yasuhiro,Uchiumi, Masaharu Korean Society for Fluid machinery 2016 International journal of fluid machinery and syste Vol.9 No.3

Floating ring seals offer an opportunity to reduce leakage flows significantly in rotating machinery. Accordingly, they have been applied successfully to rotating machinery within the last several decades. For rocket turbopump applications, fundamental behavior and design philosophy have been revealed. However, further work is needed to explore the rotordynamic characteristics associated with rotor vibrations. In this study, rotordynamic forces for floating ring seals under rotor's whirling motions are calculated to elucidate rotordynamic characteristics. Comparisons between numerical simulation results and experiments demonstrated in our previous report are carried out. The three-dimensional Reynolds equation is solved by the finite-difference method to calculate hydrodynamic pressure distributions and the leakage flow rate. The entrance loss at the upstream inlet of the seal ring is calculated to estimate the Lomakin effect. The friction force at the secondary seal surface is also considered. Numerical simulation results showed that the rotordynamic forces of this type of floating ring seal are determined mainly by the friction force at the secondary seal surface. The seal ring is positioned almost concentrically relative to the rotor by the Lomakin effect. Numerical simulations agree quite well with the experimental results.

Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model

Satoshi Sugino,Ken Inoue,Reo Kobayashi,Ryohei Hirose,Toshifumi Doi,Akihito Harusato,Osamu Dohi,Naohisa Yoshida,Kazuhiko Uchiyama,Takeshi Ishikawa,Tomohisa Takagi,Hiroaki Yasuda,Hideyuki Konishi,Yasuko 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4

Background/Aims Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Evaluating Spinal Canal Lesions Using Apparent Diffusion Coefficient Maps with Diffusion-Weighted Imaging

Kanamoto Hirohito,Norimoto Masaki,Eguchi Yawara,Oikawa Yasuhiro,Orita Sumihisa,Inage Kazuhide,Abe Koki,Inoue Masahiro,Kinoshita Hideyuki,Umimura Tomotaka,Matsumoto Koji,Masuda Yoshitada,Furuya Takeo,K 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.3

Study Design: Observational study.Purpose: To evaluate healthy volunteers and patients with spinal canal lesions using apparent diffusion coefficient (ADC) maps with diffusion-weighted imaging.Overview of Literature: Decompression surgery for lumbar spinal stenosis (LSS) is selected on the basis of subjective assessment and cross-sectional magnetic resonance imaging (MRI). However, there is no objective standard for this procedure.Methods: We performed 3T MRI in 10 healthy volunteers and 13 patients with LSS. The ADC values in the spinal canal were evaluated at 46 vertebrae (L4/5 and L5/S1 for each participant), and the reduced and conventional fields of view were compared.Results: The ADC values were 2.72±0.12 at L4/5 in healthy volunteers, 2.76±0.19 at L5/S1 in healthy volunteers, 1.77±0.58 at L4/5 in patients with LSS, and 2.35±0.29 at L5/S1 in patients with LSS. The ADC value at L4/5 in patients with LSS was significantly lower than that at L5/S1 in patients with LSS and that at L4/5 and L5/S1 in healthy volunteers (<i>p</i> <0.05). With an ADC cutoff value of 2.46 to identify LSS, this approach provided an area under the curve of 0.81, sensitivity of 0.92, and specificity of 0.76 (<i>p</i> <0.05).Conclusions: Preoperative examination using ADC maps permits visualization and quantification of spinal canal lesions, thus proving the utility of ADC maps in the selection of decompression surgery for LSS.

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

Seiji Ohtori,Sumihisa Orita,Masaomi Yamashita,Tetsuhiro Ishikawa,Toshinori Ito,Tomonori Shigemura,Hideki Nishiyama,Shin Konno,Hideyuki Ohta,Masashi Takaso,Gen Inoue,Yawara Eguchi,Nobuyasu Ochiai,Shunj 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.4

Purpose: Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. Materials and Methods:Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman’s correlation coefficient by rank test. Results: Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. Conclusion: PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

Clinical Efficacy of Endocytoscopy for Gastrointestinal Endoscopy

Masashi Misawa,Shin-ei Kudo,Yuki Takashina,Yoshika Akimoto,Yasuharu Maeda,Yuichi Mori,Toyoki Kudo,Kunihiko Wakamura,Hideyuki Miyachi,Fumio Ishida,Haruhiro Inoue 대한소화기내시경학회 2021 Clinical Endoscopy Vol.54 No.4

Endocytoscopy (EC) is a contact-type optical endoscope that allows in vivo cellular observation during gastrointestinal endoscopyand is now commercially available not only in Japan but also in Asian, European Union, and Middle Eastern countries. EC helpsconduct a highly accurate pathological prediction without biopsy. Initially, EC was reported to be effective for esophageal diseases. Subsequently, its efficacy for stomach and colorectal diseases has been reported. In this narrative review, we searched for clinicalstudies that investigated the efficacy of EC. EC seems to accurately diagnose gastrointestinal diseases without biopsy. Most of thestudies aimed to clarify the relationship between endocytoscopic findings of gastrointestinal neoplasia and pathological diagnosis. Some studies have investigated non-epithelial lesions or diseases, such as inflammatory bowel disease or infectious diseases. However, there are few high-level pieces of evidence, such as randomized trials; thus, further studies are needed.