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.

UV-Blue Light Emission from ZnO Nanoparticles

Obuliraj Senthilkumar,Kazuki Yamauchi,Kasilingam Senthilkumar,Takahiro Yamamae,Yasuhisa Fujita,Naoki Nishimoto 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.53 No.1

Gas evaporation was employed to prepare nitrogen-doped ZnO nanoparticles, which showed in- tense UV/blue emission (380 nm) at room temperature. The thin lms were deposited by dip coating with nanoparticles dispersed in isopropanol and water. The PL spectrum showed dominant acceptor bound excitons around 371 nm at low temperatures, which was due to the substitution of nitrogen acceptors in oxygen sites. Nitrogen doping was also conrmed from Raman spectroscopy, which showed a nitrogen-related local vibrational mode (LVMN) at 583 cm-1. Gas evaporation was employed to prepare nitrogen-doped ZnO nanoparticles, which showed in- tense UV/blue emission (380 nm) at room temperature. The thin lms were deposited by dip coating with nanoparticles dispersed in isopropanol and water. The PL spectrum showed dominant acceptor bound excitons around 371 nm at low temperatures, which was due to the substitution of nitrogen acceptors in oxygen sites. Nitrogen doping was also conrmed from Raman spectroscopy, which showed a nitrogen-related local vibrational mode (LVMN) at 583 cm-1.

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.

Does Discontinuing Teriparatide Treatment and Replacing It with Bisphosphonate Maintain the Volume of the Bone Fusion Mass after Lumbar Posterolateral Fusion in Women with Postmenopausal Osteoporosis?

Seiji Ohtori,Sumihisa Orita,Kazuyo Yamauchi,Yawara Eguchi,Yasuchika Aoki,Junichi Nakamura,Miyako Suzuki,Gou Kubota,Kazuhide Inage,Yasuhiro Shiga,Koki Abe,Kazuki Fujimoto,Hirohito Kanamoto,Masahiro Ino 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.2

Study Design: Retrospective case series. Purpose: The purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis. Overview of Literature: Clinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years. Methods: We treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 μg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery. Results: We followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p >0.05). Conclusions: This study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.

The Time Course Changes in Bone Metabolic Markers after Administering the Anti-Receptor Activator of Nuclear Factor-Kappa B Ligand Antibody and Drug Compliance among Patients with Osteoporosis

Kazuhide Inage,Sumihisa Orita,Kazuyo Yamauchi,Yoshihiro Sakuma,Go Kubota,Yasuhiro Oikawa,Takeshi Sainoh,Jun Sato,Kazuki Fujimoto,Yasuhiro Shiga,Kazuhisa Takahashi,Seiji Ohtori 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.3

Study Design: Retrospective study. Purpose: We conducted a study to investigate the time course changes in bone metabolic markers after the administration of the anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody and to assess drug compliance among osteoporotic patients. Overview of Literature: The anti-RANKL antibody is expected to provide an improvement in those with a bone metabolism disorder. However there are only a few clinical reports available on the effect of treatment. Methods: We included 40 post-menopausal osteoporotic patients who received the anti-RANKL antibody. To determine the time course changes in the bone metabolic markers, we measured the serum tartrate-resistant acid phosphatase 5b (TRACP 5b; a bone resorption marker) and the serum N-terminal propeptide of type 1 collagen (P1NP; a bone formation marker) levels prior to and 1 month after administrating the anti-RANKL antibody. To evaluable drug compliance, we assessed the dropout rate during treatment and at 6 months after treatment. Results: The average TRACP 5b level significantly decreased from 574.8 mU/dL before treatment to 153.2 mU/dL 1 month after treatment (p <0.05). There was no significant difference in the average P1NP level, which was 56.9 μG/L and 35.1 μG/L before and 1 month after treatment, respectively (p >0.05). As for drug compliance, we did not have any dropouts during the treatment or after 6 months (dropout rate: 0%). Conclusions: Our study suggests that anti-RANKL antibody treatment suppresses bone resorption and maintains bone formation.

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.

Elevated Levels of Serum Pentosidine Are Associated with Dropped Head Syndrome in Older Women

Yawara Eguchi,Toru Toyoguchi,Kazuhide Inage,Kazuki Fujimoto,Sumihisa Orita,Kazuyo Yamauchi,Miyako Suzuki,Hirohito Kanamoto,Koki Abe,Masaki Norimoto,Tomotaka Umimura,Masao Koda,Takeo Furuya,Yasuchika A 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.1

Study Design: A retrospective observational study was performed. Purpose: We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women. Overview of Literature: AGEs have been implicated in the pathogenesis of sarcopenia. Methods: We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2–C7 sagittal vertical axis (C2–C7SVA), C2–C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined. Results: Sarcopenia (SMI <5.75) was observed at a high prevalence in participants with DHS (77% compared to 22% of healthy controls). Height, weight, femoral bone mineral density, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. Serum and urinary pentosidine, and serum homocysteine were significantly higher in the DHS group compared to controls. Analysis of cervical alignment revealed a significant positive correlation of serum pentosidine with C2–C7SVA and C2S. Conclusions: Sarcopenia was involved in DHS, and high serum pentosidine levels are associated with severity of DHS in older women.

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.

Mini-Open Anterior Retroperitoneal Lumbar Interbody Fusion: Oblique Lateral Interbody Fusion for Lumbar Spinal Degeneration Disease

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.4

Purpose: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. Materials and Methods: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosiswere examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visualanalog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. Results:Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. Conclusion: OLIF surgery produced good surgical results without any major complication.