Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint Leading to Degenerative Changes via Interleukin-6 Secretion

Kazuki Sugimoto,Takayuki Nakamura,Takuya Tokunaga,Yusuke Uehara,Tatsuya Okada,Takuya Taniwaki,Toru Fujimoto,Yuichi Oike,Eiichi Nakamura 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.3

Study Design: Experimental human study. Purpose: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. Overview of Literature: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. Methods: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription–polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. Results: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. Conclusions: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.

Individual Identification by Gait Vibration Data Transmitted Floor

Yuichi Nakamura,Kazuki Ito,Tatsuo Hasegawa,Shin Itami,Yohei Saika,Masahiro Nakagawa 제어로봇시스템학회 2016 제어로봇시스템학회 국제학술대회 논문집 Vol.2016 No.10

The establishment of variety methods in the individual identification technology is desirable. In this study, it is considered that the method of individual identification from vibration data generated in gait. In the walking motion, the unique information such as the individual’s body type and habit is contained. It is assumed that the unique information is reflected in the gait vibration data transmitted in the floor. The potential for application to individual identification is shown by extracting one step and analyzing the unique information from the gait vibration data. The Adaboost method is applied to the extraction of one step of the walking. In order to represent the characteristics of each individual and analyzed using the Principal Component Analysis.

Ultrasonic Investigation of the Eu-based Intermetallic System EuZn₂Ge₂

Shinya Kudo,Kazuki Saito,Takuto Sato,Mitsuteru Nakamura,Masahito Yoshizawa,Kazuhei Wakiya,Yoshiki Nakanishi,Hikaru Hirabayashi,Shinji Michimura,Masashi Kosaka 한국물리학회 2023 새물리 Vol.73 No.12

In this study, an elastic property of EuZn₂Ge₂ with the tetragonal ThCr₂Si₂-type structure has been investigated by ultrasonic measurements. Elastic constants C<SUB>33</SUB> and C<SUB>44</SUB> were measured as a function of temperature and magnetic _eld applied along the [001] direction. A previous study reported that EuZn₂Ge₂ exhibited three magnetic phase transitions at T<SUB>N1</SUB> = 14.9 K, T<SUB>N2</SUB> = 8.4 K, and T<SUB>t</SUB> = 5 K. We found that an elastic anomaly appeared in the temperature dependence of both of C<SUB>33</SUB> and C<SUB>44</SUB> at T<SUB>N2</SUB>. On the other hand, the corresponding anomaly was hardly visible at T<SUB>N1</SUB> and T<SUB>t</SUB>. These results suggest that a magneto-elastic coupling at T<SUB>N2</SUB> may be relatively large compared with those at T<SUB>N1</SUB> and T<SUB>t</SUB>.

전기이중층 캐패시터 상대전극을 활용한 전기변색소자의 순환안정성 향상

Zhuang Liang,Yuichi Watanabe,Kazuki Nakamura,Norihisa Kobayashi 한국화상학회 2019 한국화상학회지 Vol.25 No.1

일반적으로 전기변색소자들은 전기변색물질, 전해질 그리고 상대전극물질로 구성되어 있다. 그 중에서, 상대전극물질은 소자의 장기전환 안정성 및 낮은 작동 전압 등과 같은 전기변색소자들의 성능을 향상하는데 매우 중요하다. 본 연구에서는 다이메틸 프탈레이트 기반 전기변색소자에 페로센과 카본 전극을 적용하고 그 성능을 테스트 하였다. 특히 카본 전극에서 우수한 장기전환 안정성이 구현되었다. Normally, electrochromic devices (ECDs) consist of EC materials, an electrolyte, and counter electrode materials. The counter material is essential for improving ECD properties such as long-term switching stability and low voltage operation. In this paper, we used and compared the counter materials of ferrocene and carbon electrode for the dimethyl terephthalate-based ECD, and the long-term switching stability was achieved with carbon electrode.

A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B

Yamauchi, Toshimasa,Hara, Kazuo,Maeda, Shiro,Yasuda, Kazuki,Takahashi, Atsushi,Horikoshi, Momoko,Nakamura, Masahiro,Fujita, Hayato,Grarup, Niels,Cauchi, Stephane,Ng, Daniel P K,Ma, Ronald C W,Tsunoda, Nature Publishing Group, a division of Macmillan P 2010 Nature genetics Vol.42 No.10

We conducted a genome-wide association study of type 2 diabetes (T2D) using 459,359 SNPs in a Japanese population with a three-stage study design (stage 1, 4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3, 3,622 cases and 2,356 controls). We identified new associations in UBE2E2 on chromosome 3 and in C2CD4A-C2CD4B on chromosome 15 at genome-wide significant levels (rs7612463 in UBE2E2, combined P = 2.27 ? 10<SUP>??9</SUP>; rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 ? 10<SUP>??9</SUP>). The association of these two loci with T2D was replicated in other east Asian populations. In the European populations, the C2CD4A-C2CD4B locus was significantly associated with T2D, and a combined analysis of all populations gave P = 8.78 ? 10<SUP>??14</SUP>, whereas the UBE2E2 locus did not show association to T2D. In conclusion, we identified two new loci at UBE2E2 and C2CD4A-C2CD4B associated with susceptibility to T2D.

Robotic Double Bipolar LND in Japan: Pros and Cons

Koichi Suda,Susumu Shibasaki,Masaya Nakauchi,Kenichi Nakamura,Tsuyoshi Tanaka,Kazuki Inaba,Ichiro Uyama 대한외과학회 2020 대한외과학회 학술대회 초록집 Vol.2020 No.11

Do Physical Symptoms Predict the Outcome of Surgical Fusion in Patients with Discogenic Low Back Pain?

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Masayuki Miyagi,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sato,Yasuhiro Shiga,Koki Abe,Kazuki 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.3

Study Design: Retrospective case series. Purpose: To determine whether symptoms predict surgical outcomes for patients with discogenic low back pain (DLBP). Overview of Literature: Specific diagnosis of DLBP remains difficult. Worsening of pain on flexion is a reported symptom of DLBP. This study sought to determine whether symptoms predict surgical outcomes for patients with DLBP. Methods: We investigated 127 patients with low back pain (LBP) and no dominant radicular pain. Magnetic resonance imaging was used to select patients with disc degeneration at only one level. If pain was provoked during discography, we performed fusion surgery (87 patients). Visual analogue scale score and responses to a questionnaire regarding symptoms including worsening of pain on flexion or extension were assessed. Symptom sites before surgery were categorized into LBP alone, or LBP plus referred inguinal or leg pain. We followed 77 patients (average 3.0 years) and compared symptoms before surgery with surgical outcome. Results: Sixty-three patients with a good outcome showed postsurgical pain relief (≥60% pain relief) and 14 patients with a poor outcome did not (<60% pain relief). In patients with good outcomes, worsening of LBP was evident in 65% of cases on flexion and in 35% on extension. However, these findings were not significantly different from those in patients with poor outcomes. The percentage of patients with LBP alone was significantly lower and the percentage of patients with LBP plus referred inguinal or leg pain was significantly higher in the group with good surgical outcome compared with patients in the group with poor surgical outcome (p <0.05). Conclusions: Worsening of pain on extension may be a symptom of DLBP. Surgical outcomes were superior in patients with both LBP and either referred inguinal or leg pain compared with those having LBP alone.

Change of Lumbar Ligamentum Flavum after Indirect Decompression Using Anterior Lumbar Interbody Fusion

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Masayuki Miyagi,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.1

Study Design: Retrospective case series. Purpose: The purpose of this study was to examine changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a 10-year follow-up. Overview of Literature: Extreme lateral interbody fusion provides minimally invasive treatment of the lumbar spine; this anterior fusion without direct posterior decompression, so-called indirect decompression, can achieve pain relief. Anterior fusion may restore disc height, stretch the flexure of the ligamentum flavum, and increase the spinal canal diameter. However, changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a long follow-up have not yet been reported. Methods: We evaluated 10 patients with L4 spondylolisthesis who underwent stand-alone anterior interbody fusion using the iliac crest bone. Magnetic resonance imaging was performed 10 years after surgery. The cross-sectional area (CSA) of the dural sac and the ligamentum flavum at L1–2 to L5–S1 was calculated using a Picture Archiving and Communication System. Results: Spinal fusion with correction loss (average, 4.75 mm anterior slip) was achieved in all patients 10 years postsurgery. The average CSAs of the dural sac and the ligamentum flavum at L1–2 to L5–S1 were 150 mm2 and 78 mm2, respectively. The average CSA of the ligamentum flavum at L4–5 (30 mm2) (fusion level) was significantly less than that at L1–2 to L3–4 or L5–S1. Although patients had an average anterior slip of 4.75 mm, the average CSA of the dural sac at L4–5 was significantly larger than at the other levels. Conclusions: Spinal stability induced a lumbar ligamentum flavum change and a sustained remodeling of the spinal canal, which may explain the long-term pain relief after indirect decompression fusion surgery.

More than 6 Months of Teriparatide Treatment Was More Effective for Bone Union than Shorter Treatment Following Lumbar Posterolateral Fusion Surgery

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Nobuyasu Ochiai,Kazuki Kuniyoshi,Yasuchika Aoki,Junichi Nakamura,Masayuki Miyagi,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Takeshi Sainoh,Jun Sa 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.4

Study Design: Retrospective case series. Purpose: To examine the most effective duration of teriparatide use for spinal fusion in women with postmenopausal osteoporosis. Overview of Literature: We reported that daily subcutaneous injection of teriparatide (parathyroid hormone) significantly improved bone union after instrumented lumbar posterolateral fusion (PLF) in women with postmenopausal osteoporosis when compared with oral administration of bisphosphonate. However, the most effective duration of teriparatide use for spinal fusion has not been explored. Methods: Forty-five women with osteoporosis diagnosed with degenerative spondylolisthesis from one of the three treatment groups were evaluated based on: short-duration treatment (average, 5.5 months; n=15; daily subcutaneous injection of 20 μg teriparatide), long-duration treatment (average, 13.0 months; n=15; daily subcutaneous injection of 20 μg teriparatide), and bisphosphonate treatment (average, 13.0 months; n=15; weekly oral administration of 17.5 mg risedronate). All patients underwent PLF with a local bone graft. Fusion rate and duration of bone union were evaluated 1.5 years after surgery. Results: Bone union rate and average duration for bone union were 92% and 7.5 months in the long-duration treatment group, 80% and 8.5 months in the short-duration treatment group, and 70% and 10.0 months in the bisphosphonate treatment group, respectively. Results of bone union rate and average duration for bone union in the teriparatide treatment groups were significantly superior to those in the bisphosphonate treatment group (p <0.05); whereas, significantly superior results were observed in long-duration treatment group when compared with short-duration treatment group (p <0.05). Conclusions: Daily injection of teriparatide for bone union was more effective than oral administration of bisphosphonate. Furthermore, a longer period of teriparatide treatment for bone union was more effective than a shorter period of same treatment.

Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Nobuyasu Ochiai,Shunji Kishida,Kazuki Kuniyoshi,Yasuchika Aoki,Junichi Nakamura,Tetsuhiro Ishikawa,Masayuki Miyagi,Hiroto Kamoda,Miyako Suzuki 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.5

Purpose: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensorynerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-α (TNFα) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFα inhibitor, for pain in knee OA. Materials and Methods: Thirty-nine patients with knee OA and a 2–4 Kellgren-Lawrence grading were evaluated in this prospectivestudy. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injectioninto the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. Results: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. Conclusion: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFα is one factor that induces OA pain.