27 results on '"Kojiro Imai"'
Search Results
2. Establishment of optimal exercise therapy using near-infrared spectroscopy monitoring of tissue muscle oxygenation after therapeutic angiogenesis for patients with critical limb ischemia: A multicenter, randomized, controlled trial
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Keisuke Shoji, Kenji Yanishi, Hirokazu Shiraishi, Shiho Yamabata, Arito Yukawa, Satoshi Teramukai, Kojiro Imai, Toshiko Ito-Ihara, Masami Tao, Yukihito Higashi, Tomoaki Ishigami, Yoshihiro Fukumoto, Koichiro Kuwahara, and Satoaki Matoba
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Medicine (General) ,R5-920 - Abstract
Critical limb ischemia (CLI) is a potentially life-threatening condition that involves severely reduced blood flow to the peripheral arteries due to arteriosclerosis obliterans (ASO) of the limbs or a similar condition. CLI patients must undergo revascularization to avoid amputation of the lower limbs and improve their survival prognosis. However, the outcomes of conventional surgical revascularization or endovascular therapy are inadequate; therefore, establishing further effective treatment methods is an urgent task. We perform therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells in clinical practice and demonstrated its safety and efficacy for CLI patients for whom conventional treatments failed or are not indicated. Exercise therapies must be devised for CLI patients who have undergone therapeutic angiogenesis to save their limbs and improve survival. Because evidence regarding the efficacy and safety of exercise therapy for CLI patients is lacking, we plan to perform a prospective trial of the efficacy and safety of optimal exercise therapy following therapeutic angiogenesis for CLI patients.The trial will enroll 30 patients between 20 and 79 years with Rutherford category 4 or 5 CLI caused by ASO who will undergo therapeutic angiogenesis. Participants will be randomly allocated to receive either optimal exercise therapy or fixed exercise therapy. Those receiving optimal exercise therapy will undergo tissue muscle oxygen saturation monitoring using near-infrared spectroscopy while performing exercises and will be prescribed optimal exercise therapy. The optimal amount of exercise will be determined on day 8, 31, 61, 91 and 181 after therapeutic angiogenesis. Ethics and dissemination: This protocol was approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine. In accordance with the Helsinki Declaration, written informed consent has been obtained from all participants prior to enrollment. The results of this trial will be disseminated by publication in a peer-reviewed journal. Trial registration: This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000035288). Keywords: Critical limb ischemia, Arteriosclerosis obliterans, Therapeutic angiogenesis, Optimal exercise therapy, Tissue muscle oxygen saturation, Near-infrared spectroscopy
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- 2020
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3. Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese.
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Masakazu Nakano, Yoko Ikeda, Yuichi Tokuda, Masahiro Fuwa, Natsue Omi, Morio Ueno, Kojiro Imai, Hiroko Adachi, Masaaki Kageyama, Kazuhiko Mori, Shigeru Kinoshita, and Kei Tashiro
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Medicine ,Science - Abstract
BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P
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- 2012
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4. Strategic combination of cultivated oral mucosal epithelial transplantation and postoperative limbal-rigid contact lens-wear for end-stage ocular surface disease: a retrospective cohort study.
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Yulia Aziza, Kojiro Imai, Motohiro Itoi, Hokoru Yoshioka, Seitaro Komai, Koji Kitazawa, Ratna Sitompul, Mayumi Ueta, Hideki Fukuoka, Tsutomu Inatomi, Shigeru Kinoshita, and Chie Sotozono
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Purpose To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy. Design Retrospective cohort. Methods In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively. Results This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed. Conclusion In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure
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Naoki Okumura, Munetoyo Toda, Kohsaku Numa, John Bush, Motomu Tanaka, Noriko Koizumi, Junji Hamuro, Akihisa Yamamoto, Kojiro Imai, Shigeru Kinoshita, Hiroshi Tanaka, Chie Sotozono, Satoshi Teramukai, and Morio Ueno
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medicine.medical_specialty ,Visual acuity ,genetic structures ,business.industry ,Endothelium, Corneal ,Injection therapy ,Endothelial Cells ,Cell Count ,Cell Differentiation ,Cell subpopulations ,Cell sorting ,Post surgery ,eye diseases ,Cornea ,Ophthalmology ,Humans ,Medicine ,Corneal endothelial cell ,sense organs ,medicine.symptom ,business ,Cells, Cultured ,Mature cell - Abstract
PURPOSE To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC)-injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial failure (CEF). DESIGN Comparative, interventional case series. METHODS This study involved 18 eyes with CEF that underwent cultured hCEC-injection therapy, categorized into two groups: 1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs [Group 1 (Gr1)], and 2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs [Group 2 (Gr2)]. From 1-week to 3-years postoperative, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's 'spring constant' was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers. RESULTS At 3-years postoperative, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3,083 cells/mm2; range, 2,182-4,417 cells/mm2) was higher than that in Gr1 (1,349 cells/mm2; range, 746-2,104 cells/mm2) (P < 0.001), and the spring constant verified the superiority of the mature cultured hCECs. From 24-weeks through 3-years postoperative, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < 0.005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed. CONCLUSION Our findings showed that mature cell SPs for hCEC-injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years post surgery.
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- 2022
6. A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans
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Ayumu Fujioka, Kenji Yanishi, Arito Yukawa, Kojiro Imai, Isao Yokota, Kei Fujikawa, Ayumu Yamada, Akari Naito, Keisuke Shoji, Hirofumi Kawamata, Yukihito Higashi, Tomoaki Ishigami, Ken-ichiro Sasaki, Syuhei Tara, Koichiro Kuwahara, Satoshi Teramukai, and Satoaki Matoba
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General Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
7. Attempt to Visualize 'Hidden Curriculum' in Research Activities: Analysis and Consideration by Multiple Regression Analysis
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Yasuaki, Shinomiya, Kengo, Yoshii, Satoshi, Teramukai, Tomomi, Azuma, Masanaga, Yamawaki, Yoko, Watanabe, Kotone, Matsuyama, Kojiro, Imai, Naoto, Kawahara, Yuichi, Minemura, Chiaki, Kageyama, and Koichi, Setoyama
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京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室, 京都府立医科大学大学院医学研究科生命基礎数理学教室, 京都府立医科大学大学院医学研究科生物統計学教室, 京都府立医科大学大学院保健看護学研究科, 東京医科歯科大学臨床医学教育学開発分野, 新潟大学創生学部, 日本医科大学医療管理学, 京都府立医科大学大学院医学研究科医療フロンティア展開学, 九州大学病院ARO次世代医療センター, 群馬パース大学教養部, 本稿では,医学教育分野で注目されている「隠れたカリキュラム(hidden curriculum)」を,医学研究の倫理分野において倫理的意思決定やそれに影響を与える組織の環境に応用し,研究倫理に関する規範意識・行動様式を問う情意領域問題の測定尺度を作成したものを用いて,「あなたならばどう行動するか」と「あなたの周りの人ならばどう行動すると考えるか」についてそれぞれ質問を行い,その得点差を見ることで隠れたカリキュラムの影響を可視化することを試みた。その結果,全体及びすべてのカテゴリーにおいて「あなたならばどう行動するか」の得点が高いこと,属性との関連について調べたところ,一部のカテゴリーと性別,人に関わる研究の有無で有意な得点差がみられた。
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- 2021
8. An Examination of Questions for a Self-Descriptive Scale on Research Ethics: Referring to Discussions in the Development of the Scale
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Chiaki, Kageyama, Satoshi, Teramukai, Tomomi, Azuma, Masanaga, Yamawaki, Yoko, Watanabe, Kotone, Matsuyama, Kengo, Yoshii, Kojiro, Imai, Naoto, Kawahara, Yuichi, Minemura, and Koichi, Setoyama
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京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室, 京都府立医科大学大学院医学研究科生物統計学教室, 京都府立医科大学大学院保健看護学研究科, 東京医科歯科大学臨床医学教育学開発分野, 新潟大学創生学部, 日本医科大学医療管理学, 京都府立医科大学大学院医学研究科生命基礎数理学教室, 京都府立医科大学大学院医学研究科医療フロンティア展開学, 九州大学病院ARO次世代医療センター, 群馬パース大学教養部, AMED研究公正高度化モデル開発支援事業「学際的アプローチによる研究倫理教育のモデル評価プログラムの開発と検証」(瀬戸山班)では、研究活動に関する倫理的意思決定を測定する尺度を開発している。本論文では、この開発中の尺度の質問文に着目し、自己記述式尺度が抱える問題点を克服するため、質問文の作成において検討した内容や、この質問文のオリジナリティ、課題について述べる。
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- 2021
9. Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure
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Koji Kitazawa, Chie Sotozono, Hiroshi Tanaka, Noriko Koizumi, Kojiro Imai, Naoki Okumura, Kohsaku Numa, Morio Ueno, John Bush, Satoshi Teramukai, Junji Hamuro, and Shigeru Kinoshita
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Adult ,Graft Rejection ,Male ,Intraocular pressure ,medicine.medical_specialty ,Visual acuity ,genetic structures ,Anterior Chamber ,Pyridines ,Visual Acuity ,Cell Count ,Regenerative Medicine ,Slit Lamp Microscopy ,03 medical and health sciences ,0302 clinical medicine ,Cell injection ,Ophthalmology ,Prone Position ,Humans ,Medicine ,Prospective Studies ,Protein Kinase Inhibitors ,Cells, Cultured ,Intraocular Pressure ,Aged ,030304 developmental biology ,rho-Associated Kinases ,0303 health sciences ,business.industry ,Corneal Edema ,Endothelium, Corneal ,Fuchs' Endothelial Dystrophy ,Five year follow up ,Injection therapy ,Middle Aged ,Amides ,Combined Modality Therapy ,eye diseases ,Clinical trial ,030221 ophthalmology & optometry ,Female ,sense organs ,Injections, Intraocular ,medicine.symptom ,business ,Corneal endothelial cell density ,Landolt C ,Follow-Up Studies - Abstract
Purpose To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. Design Prospective observational study. Participants This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. Methods All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. Main Outcome Measures The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. Results At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601–2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. Conclusions The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery.
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- 2021
10. Clinical trial to evaluate the therapeutic benefits of limbal-supported contact lens wear for ocular sequelae due to Stevens-Johnson syndrome/toxic epidermal necrolysis
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Kojiro Imai, Ken Ogino, Motohiro Itoi, Satoshi Teramukai, Chie Sotozono, Eriko Sumi, Shigeru Kinoshita, and Mayumi Ueta
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medicine.medical_specialty ,Visual acuity ,genetic structures ,Contact Lenses ,Visual Acuity ,03 medical and health sciences ,0302 clinical medicine ,Ophthalmology ,medicine ,Humans ,In patient ,Adverse effect ,Ocular pain ,Retrospective Studies ,business.industry ,Stevens johnson ,General Medicine ,medicine.disease ,eye diseases ,Toxic epidermal necrolysis ,Contact lens ,Clinical trial ,Stevens-Johnson Syndrome ,030221 ophthalmology & optometry ,sense organs ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Follow-Up Studies ,Optometry - Abstract
Purpose To analyze the therapeutic benefits of limbal-supported contact lens (CL) wear in patients with ocular sequelae due to Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Methods This interventional study enrolled 10 chronic SJS/TEN eyes with a spectacle best-corrected visual acuity (BCVA) of between 0.01 and 0.7 that were fitted with a limbal-supported CL. At baseline and at after 3-months CL use, CL-wear BCVA and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores were measured, and then compared. Incidence rates and severities of adverse events were also analyzed. Results At after 3-months CL use, BCVA with the fitted CL significantly improved compared to that with spectacle correction at baseline (LogMAR: 0.76−0.15) (P = 0.0039), all NEI VFQ-25 scores improved, however, only in ocular pain and mental health showed statistically significant improvement (P = 0.0078 and 0.0039). No serious adverse events were observed during the follow-up. Conclusion Wearing of the limbal-supported CL improved vision compared to spectacles and reduced ocular pain in patients with ocular sequelae due to SJS/TEN.
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- 2020
11. Oral Mucosal Epithelial Transplantation and Limbal-Rigid Contact Lens: A Therapeutic Modality for the Treatment of Severe Ocular Surface Disorders
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Mayumi Ueta, Shigeru Kinoshita, Seitaro Komai, Gaku Ishida, Takahiro Nakamura, Chie Sotozono, Norihiko Yokoi, Yasuko Kimura, Noriko Koizumi, Masanori Fukushima, Hideki Fukuoka, Koji Kitazawa, Kojiro Imai, Tsutomu Inatomi, and Masahiro J. Go
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medicine.medical_specialty ,genetic structures ,Contact Lenses ,Rigid contact lens ,Pemphigoid, Benign Mucous Membrane ,Vision Disorders ,Visual Acuity ,macromolecular substances ,Corneal Diseases ,03 medical and health sciences ,0302 clinical medicine ,Limbal transplantation ,Ophthalmology ,Burns, Chemical ,Humans ,Medicine ,Cells, Cultured ,business.industry ,Corneal opacity ,Epithelium, Corneal ,Mouth Mucosa ,Epithelial Cells ,Combined Modality Therapy ,eye diseases ,Nonsurgical treatment ,Contact lens ,Transplantation ,Eye Burns ,Stevens-Johnson Syndrome ,030221 ophthalmology & optometry ,sense organs ,Stem cell ,business ,Ocular surface ,030217 neurology & neurosurgery ,Stem Cell Transplantation - Abstract
Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal or chemical injury are considered severe ocular surface disorders (OSDs) because they affect the entire ocular surface, including corneal and conjunctival epithelial stem cells. In patients with severe OSDs, the long-term prognosis for limbal transplantation is poor, and the related corneal opacity and cicatrization lead to devastating visual impairment. To date, there is no standardized treatment to improve vision in cases with severe OSD. Investigating novel treatment methods for severe OSDs, our group began cultivated oral mucosal epithelial transplantation in 2002 and developed a limbal-supported rigid-type contact lens that can be applied as a nonsurgical treatment. When used in combination, these treatment methods make it possible to successfully restore vision in cases with severe OSDs.
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- 2020
12. Novel Vertical Cup-to-Disc Classification to Identify Normal Eyes that Maintain Non-Glaucoma Status: A 10-Year Longitudinal Study
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Yoko Ikeda, Kazuhiko Mori, Yuko Maruyama, Morio Ueno, Kengo Yoshii, Yuji Yamamoto, Kojiro Imai, Natsue Omi, Ryuichi Sato, Fumiko Sato, Masakazu Nakano, Junji Hamuro, Kei Tashiro, Chie Sotozono, and Shigeru Kinoshita
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Ophthalmology - Abstract
We propose a new classification model to serve as a control for future genomic studies of glaucoma by distinguishing normal subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio.This study aimed to develop a classification for distinguishing subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio (VCDR).Among 842 volunteers 40 years and older, 421 volunteers participated in the second ophthalmic examination 10 years after their first examination. Each volunteer was diagnosed either as healthy normal or glaucoma suspect (GS) in the first glaucoma screening examinations. The former was further classified into the three grades of N1, N2, and N3. Specifically, N1 represented (1) VCDR0.3; (2) no notching or nerve fiber layer defect; and (3) no undermining, N2 indicated 0.3 ≤ VCDR0.6 and conditions (2) and (3) of N1; and N3 represented 0.3≤VCDR0.6 with undermining and condition (2), or 0.6≤VCDR0.7 and condition (2) of N1. Glaucoma transition rates (GTRs) were evaluated in 421 volunteers who returned to participate after a 10-year period.GTRs were calculated as 1.3% in both N1 and N2, 3.9% in N3, and 18.2% in GS. The ratio of volunteers in the same category maintenance rate increased from N1 to N3.GTRs were lower in N1 and N2 than in N3 or GS during the 10-year study period. This novel classification of healthy non-glaucoma subjects may help identify those, especially Japanese males, who maintain a non-glaucoma status for an extended period of 10 years.
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- 2021
13. Seasonal Variation and Trend of Intraocular Pressure Decrease Over a 20-Year Period in Normal-Tension Glaucoma Patients
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Toshihide Yamasaki, Kengo Yoshii, Natsue Omi, Kojiro Imai, Yoko Ikeda, Yuji Yamamoto, Kei Tashiro, Kazuhiko Mori, Masakazu Nakano, Fumiko Sato, Yuko Maruyama, Ryuichi Sato, Chie Sotozono, Morio Ueno, and Shigeru Kinoshita
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Male ,medicine.medical_specialty ,Intraocular pressure ,genetic structures ,Glaucoma ,Nonlinear multiple regression ,Tonometry, Ocular ,Ophthalmology ,Normal tension glaucoma ,medicine ,Humans ,Intraocular Pressure ,Aged ,Retrospective Studies ,INTRAOCULAR PRESSURE DECREASE ,business.industry ,Retrospective cohort study ,Mean age ,Seasonality ,Middle Aged ,medicine.disease ,eye diseases ,Female ,sense organs ,Seasons ,business - Abstract
To investigate the trend of seasonal variation of intraocular pressure (IOP) in patients with normal-tension glaucoma over a 20-year period by retrospectively analyzing the Kyoto Prefectural University of Medicine Glaucoma Registry database as real-world data.Retrospective cohort study.Data points (n = 49,007) were extracted retrospectively from the medical records of 1774 patients with normal-tension glaucoma (665 male patients and 1109 female patients; mean ± SD age was 59.8 ± 14.4 years; and mean ± SD observation period was 5.6 ± 4.4 years) seen over the 20-year period. We first calculated the mean IOP from all available data of each month from January 1997 through December 2016. The data were then categorized into 5 groups of 4 consecutive years each (1997-2000, 2001-2004, 2005-2008, 2009-2012, and 2013-2016) and the mean IOP of each month within the group was calculated. Seasonal variations of IOP over the 20-year study period and in the 5 consecutive groups were then investigated via nonlinear multiple regression analysis.A continuous decrease of IOP was detected throughout the 20-year period (P.001), with distinct seasonal variation. The annual mean ± SD IOP was highest (13.9 ± 2.7 mm Hg) in the oldest group (1997-2000), with a gradual decrease in each subsequent group, finally becoming lowest (12.3 ± 2.7 mm Hg) in the most recent group (2013-2016) (P.001), and all of them were accompanied by distinct seasonal variation (P.001).Based on the Kyoto Prefectural University of Medicine Glaucoma Registry real-world longitudinal data, our findings revealed a continuous decrease and distinct seasonal variation of IOP in patients with normal-tension glaucoma throughout the 20-year study period.
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- 2021
14. Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol
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Takanori Kawasaki, Isao Yokota, Takashi Okada, Kojiro Imai, Hiroshi Fujita, Naohiko Nakanishi, Ayumu Yamada, Takahisa Sawada, Satoaki Matoba, and Shigeki Takai
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Adult ,medicine.medical_specialty ,Deep vein ,venous thromboembolism ,Cardiovascular Medicine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Rivaroxaban ,Internal medicine ,Neoplasms ,medicine ,Protocol ,Humans ,cancer ,030212 general & internal medicine ,cardiovascular diseases ,Thrombus ,Aged ,business.industry ,Standard treatment ,Cancer ,Thrombosis ,General Medicine ,Middle Aged ,medicine.disease ,Institutional review board ,medicine.anatomical_structure ,Complication ,business ,030217 neurology & neurosurgery ,medicine.drug ,Factor Xa Inhibitors - Abstract
IntroductionAnticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE.Methods and analysisThis study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications.Ethics and disseminationThis study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.Trial registration numberUMIN000027793
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- 2019
15. Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy
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Michio Hagiya, Takahiro Nakamura, Munetoyo Toda, Hiroshi Tanaka, Isao Yokota, Morio Ueno, Naoki Okumura, John Bush, Junji Hamuro, Tsutomu Inatomi, Kojiro Imai, Shigeru Kinoshita, Chie Sotozono, Satoshi Teramukai, Noriko Koizumi, and Yuji Yamamoto
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Male ,0301 basic medicine ,medicine.medical_specialty ,genetic structures ,Endothelial corneal dystrophy ,Corneal hydration ,Corneal Diseases ,Cornea ,Corneal Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Primary outcome ,Ophthalmology ,medicine ,Humans ,Donor cornea ,Protein Kinase Inhibitors ,Rho-associated protein kinase ,Cells, Cultured ,Intraocular Pressure ,Aged ,Aged, 80 and over ,rho-Associated Kinases ,business.industry ,Endothelial Cells ,General Medicine ,Middle Aged ,Combined Modality Therapy ,eye diseases ,Corneal transparency ,030104 developmental biology ,cardiovascular system ,030221 ophthalmology & optometry ,Bullous keratopathy ,Female ,Corneal endothelial cell ,sense organs ,business - Abstract
Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×10At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 μm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98).Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).
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- 2018
16. Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer
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Hideo Shigematsu, Masato Takahashi, Takashi Ishikawa, Teruhisa Sakurai, Hisako Ono, Katsuhiko Nakatsukasa, Kei Koizumi, Koichi Sakaguchi, Masato Suzuki, Eiichi Konishi, Kimito Yamada, Kazutaka Narui, Tetsuya Taguchi, Hisashi Shioya, Shinichiro Taira, Yokota Isao, Kei Fujikawa, Shunji Takahashi, Kojiro Imai, Naoki Niikura, Yoshie Hasegawa, Daishu Miura, and Mana Yoshimura
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Oncology ,Adult ,medicine.medical_specialty ,Side effect ,medicine.medical_treatment ,hormone-sensitive breast cancer ,Osteoporosis ,Breast Neoplasms ,Bone and Bones ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,Fractures, Bone ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Study Protocol Clinical Trial ,Bone Density ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,bone health ,Aromatase ,Neoplasm Staging ,postmenopausal ,biology ,business.industry ,Aromatase Inhibitors ,General Medicine ,Middle Aged ,medicine.disease ,Denosumab ,Normal bone ,Research Design ,030220 oncology & carcinogenesis ,aromatase inhibitor ,biology.protein ,Female ,business ,bone mineral density ,Adjuvant ,Biomarkers ,medicine.drug ,Research Article - Abstract
Background: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. Patients and methods: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I–IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1–L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were (1) rate of change in the lumbar spine (L1–L4) BMD after 2, 3, 4, and 5 years; (2) rate of change in the femoral neck BMD; (3) rate of change in radius BMD (determined using an ultrasonic bone densitometer); (4) changes in calcium and bone metabolism markers (TRAP 5b, bone alkaline phosphatase, and pentosidine); (5) development of pathological fracture within 3 years; (6) disease-free survival; (7) overall survival (OS); (8) adverse events; and (9) quality of life. Ethics and dissemination: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. Trial registration: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.
- Published
- 2019
17. Establishment of optimal exercise therapy using near-infrared spectroscopy monitoring of tissue muscle oxygenation after therapeutic angiogenesis for patients with critical limb ischemia: A multicenter, randomized, controlled trial
- Author
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Satoaki Matoba, Tomoaki Ishigami, Masami Tao, Kenji Yanishi, Koichiro Kuwahara, Toshiko Ito-Ihara, Kojiro Imai, Yukihito Higashi, Hirokazu Shiraishi, Yoshihiro Fukumoto, Arito Yukawa, Satoshi Teramukai, Shiho Yamabata, and Keisuke Shoji
- Subjects
RHI, reactive hyperemia index ,VAS, visual analogue scale ,medicine.medical_treatment ,ΔO2Hb, change in oxygenated hemoglobin concentration ,Helsinki declaration ,law.invention ,0302 clinical medicine ,Tissue muscle oxygen saturation ,Randomized controlled trial ,law ,Informed consent ,030212 general & internal medicine ,BM-MNC, bone marrow-derived mononuclear cells ,StO2, thenar tissue oxygen saturation ,TcPO2, transcutaneous oxygen pressure ,lcsh:R5-920 ,Arteriosclerosis obliterans ,TAO, thromboangiitis obliterans ,ASO, arteriosclerosis obliterans ,NIRS, near-infrared spectroscopy ,Critical limb ischemia ,eNOS, endothelial nitric oxide synthase ,General Medicine ,CT, computed tomography ,WIQ, walking impairment questionnaire ,medicine.symptom ,lcsh:Medicine (General) ,SPP, skin perfusion pressure ,TOI, tissue oxygenation index ,medicine.medical_specialty ,Therapeutic angiogenesis ,Revascularization ,Article ,CLI, critical limb ischemia ,Optimal exercise therapy ,03 medical and health sciences ,Near-infrared spectroscopy ,medicine ,Intensive care medicine ,PAD, peripheral artery disease ,nTHI, normalized tissue hemoglobin index ,Pharmacology ,NO, nitric oxide ,business.industry ,ΔHHb, change in deoxygenated hemoglobin concentration ,medicine.disease ,body regions ,Amputation ,business ,030217 neurology & neurosurgery - Abstract
Critical limb ischemia (CLI) is a potentially life-threatening condition that involves severely reduced blood flow to the peripheral arteries due to arteriosclerosis obliterans (ASO) of the limbs or a similar condition. CLI patients must undergo revascularization to avoid amputation of the lower limbs and improve their survival prognosis. However, the outcomes of conventional surgical revascularization or endovascular therapy are inadequate; therefore, establishing further effective treatment methods is an urgent task. We perform therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells in clinical practice and demonstrated its safety and efficacy for CLI patients for whom conventional treatments failed or are not indicated. Exercise therapies must be devised for CLI patients who have undergone therapeutic angiogenesis to save their limbs and improve survival. Because evidence regarding the efficacy and safety of exercise therapy for CLI patients is lacking, we plan to perform a prospective trial of the efficacy and safety of optimal exercise therapy following therapeutic angiogenesis for CLI patients.The trial will enroll 30 patients between 20 and 79 years with Rutherford category 4 or 5 CLI caused by ASO who will undergo therapeutic angiogenesis. Participants will be randomly allocated to receive either optimal exercise therapy or fixed exercise therapy. Those receiving optimal exercise therapy will undergo tissue muscle oxygen saturation monitoring using near-infrared spectroscopy while performing exercises and will be prescribed optimal exercise therapy. The optimal amount of exercise will be determined on day 8, 31, 61, 91 and 181 after therapeutic angiogenesis. Ethics and dissemination: This protocol was approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine. In accordance with the Helsinki Declaration, written informed consent has been obtained from all participants prior to enrollment. The results of this trial will be disseminated by publication in a peer-reviewed journal. Trial registration: This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000035288). Keywords: Critical limb ischemia, Arteriosclerosis obliterans, Therapeutic angiogenesis, Optimal exercise therapy, Tissue muscle oxygen saturation, Near-infrared spectroscopy
- Published
- 2020
18. Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol.
- Author
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Shigeki Takai, Naohiko Nakanishi, Isao Yokota, Kojiro Imai, Ayumu Yamada, Takanori Kawasaki, Takashi Okada, Takahisa Sawada, Hiroshi Fujita, and Satoaki Matoba
- Abstract
Introduction Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE. Methods and analysis This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications. Ethics and dissemination This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals. [ABSTRACT FROM AUTHOR]
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- 2019
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19. Impact of high myopia and duration of hard contact lens wear on the progression of ptosis
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Akihide Watanabe, Shigeru Kinoshita, and Kojiro Imai
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Adult ,Blepharoplasty ,Male ,Refractive error ,medicine.medical_specialty ,Time Factors ,genetic structures ,Contact Lenses ,medicine.medical_treatment ,Visual Acuity ,Refraction, Ocular ,Cornea ,Ptosis ,Risk Factors ,Ophthalmology ,medicine ,Blepharoptosis ,Humans ,Dioptre ,Aged ,Unilateral ptosis ,business.industry ,High myopia ,General Medicine ,Middle Aged ,medicine.disease ,eye diseases ,Contact lens ,medicine.anatomical_structure ,Myopia, Degenerative ,Disease Progression ,Female ,sense organs ,Eyelid ,medicine.symptom ,business - Abstract
To investigate the impact of myopia and duration of hard contact lens (HCL) wear on the progression of ptosis. This study involved 194 eyes of 98 patients with either bilateral or unilateral ptosis with long-term HCL wear. The ptosis of each eyelid was classified into 1 of 4 grades (no ptosis, mild, moderate and severe), and the average spherical equivalent refractive error (SERE), patient age and the duration of HCL wear were then examined. The average SERE (in diopters) in 99 severe eyes was −8.34, in 47 moderate eyes, −6.28, in 37 mild eyes −5.57 and in 11 no ptosis eyes, −4.80, while the average duration of HCL wear (in years) were 34, 30, 29, and 31, respectively. The average SERE was significantly higher in the severe than in the moderate, mild and no ptosis eyelids, and the average duration of HCL wear was significantly longer in the severe than in the moderate and mild ptosis eyelids. Path analysis showed that the severity of ptosis is significantly influenced by SERE, as well as by patient age and the duration of HCL wear. High myopia, patient age and long-term HCL wear are risk factors associated with the progression of ptosis.
- Published
- 2012
20. Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population
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Kojiro Imai, Natsue Omi, Masaaki Kageyama, Hiroko Adachi, Ryuichi Sato, Yoko Ikeda, Kei Tashiro, Morio Ueno, Yuichi Tokuda, Masakazu Nakano, Shigeru Kinoshita, Masahiro Fuwa, and Kazuhiko Mori
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Male ,Population ,Genome-wide association study ,Locus (genetics) ,Single-nucleotide polymorphism ,Promyelocytic Leukemia Protein ,Exfoliation Syndrome ,Polymorphism, Single Nucleotide ,Article ,Asian People ,Gene Frequency ,Japan ,Meta-Analysis as Topic ,Risk Factors ,Humans ,Medicine ,Genetic Predisposition to Disease ,education ,Gene ,Allele frequency ,Aged ,Aged, 80 and over ,Genetics ,education.field_of_study ,Multidisciplinary ,business.industry ,Tumor Suppressor Proteins ,GTPase-Activating Proteins ,Haplotype ,Nuclear Proteins ,Middle Aged ,eye diseases ,Haplotypes ,Asian population ,Female ,Amino Acid Oxidoreductases ,business ,Genome-Wide Association Study ,Transcription Factors - Abstract
The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and Caucasian populations. Therefore, we newly performed a genome-wide association study using 201 XFS/XFG and 697 controls in Japanese, and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus. These SNPs were confirmed by an independent population consisted of 121 XFS/XFG and 263 controls in Japanese. Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population. Although there still should be other gene(s) in the other region(s) contributing to the disease process, these results suggested that the combination of newly discovered variants in these genes might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.
- Published
- 2014
21. [Active systemic steroid therapy employed in a case of bilateral frosted branch angiitis with acute chorioretinal circulatory insufficiency]
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Junko, Inaba, Kojiro, Imai, Yukiko, Nakano, Toru, Yasuhara, and Rei, Tada
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Male ,Retinal Vasculitis ,Choroid ,Retinal Artery ,Vasodilator Agents ,Prostaglandins ,Humans ,Steroids ,Fluorescein Angiography ,Betamethasone ,Aged - Abstract
Steroid treatment is believed to be effective for frosted branch angiitis, but frosted branch angiitis with retinal circulatory insufficiency does not have a good prognosis by steroid treatment alone. Here, we present a case of a patient that had a good outcome when treated with long-term active systemic betamethasone and vasodilation therapy for bilateral frosted branch angiitis with acute chorioretinal circulatory insufficiency.A 69-year-old male presented with sudden visual loss in his left eye. The visual acuity was 1.0 in the right eye and 0.1 in the left eye. In his left eye, only mild inflammation occurred in the anterior chamber, but extensive inflammation such as sheathing of retinal vessels, retinal hemorrhage, and edema of the optic disc was present. Fluorescein angiography showed a delay of the arm-retinal artery circulation time and severe dye leakage from the retinal vessels. The following day, the visual acuity worsened to 0.1 in the right eye and hand motion in the left eye. Moreover, extensive inflammation was now present in both the anterior and posterior segments, and the sheathing of the retinal vessels developed to frosted branch-like angiitis. Doppler examination showed flow in the bilateral ophthalmic artery but did not show flow in the central retinal artery or posterior ciliary artery. These findings were compatible with the diagnosis of frosted branch angiitis with chorioretinal circulatory insufficiency. We initiated active systemic steroid therapy for 7 months and vasodilation therapy for 3 months. Two years later, the visual acuity improved to 0.5 in both eyes.Long-term active systemic steroid therapy for frosted branch angiitis with severe circulatory insufficiency in the retina and choroid may improve visual function.
- Published
- 2008
22. LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population
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Kazuhiko, Mori, Kojiro, Imai, Akira, Matsuda, Yoko, Ikeda, Shigeta, Naruse, Hisako, Hitora-Takeshita, Masakazu, Nakano, Takazumi, Taniguchi, Natsue, Omi, Kei, Tashiro, and Shigeru, Kinoshita
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Aged, 80 and over ,Lens Capsule, Crystalline ,Glaucoma ,Middle Aged ,Exfoliation Syndrome ,Polymorphism, Single Nucleotide ,eye diseases ,Asian People ,Gene Expression Regulation ,Haplotypes ,Case-Control Studies ,Humans ,Genetic Predisposition to Disease ,Amino Acid Oxidoreductases ,RNA, Messenger ,Aged ,Research Article - Abstract
Purpose We performed genetic association studies using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. We also quantified LOXL1 mRNA expression in the human lens capsule to examine the possible correlation between LOXL1 expression and XFG pathogenesis. Methods We performed a case-control study using 95 Japanese XFG patients and 190 controls. Real-time polymerase chain reaction (PCR) analysis was performed using lens capsules obtained during surgery. Results The TT genotype in the single nucleotide polymorphism (SNP) rs1048661 and the GG genotype in the SNP rs3825942 in exon 1 of LOXL1 were significantly associated with an increased risk of XFG under recessive models (χ2 test, p=5.34×10−34 and p=2.1×10−8, respectively). Quantification of LOXL1 mRNA expression demonstrated no significant difference between XFG and senile cataract samples. Conclusions Although the functional effects of the LOXL1 SNP appear to be qualitative rather than quantitative, the amino acid substitution (R141L) caused by SNP rs1048661 is not a simple decisive factor for XFG due to the inverted allele frequency between Japanese XFG and Caucasian XFG patients. Further genetic and functional studies are essential for clarifying XFG pathogenesis.
- Published
- 2008
23. Relationship between frequent swimming pool use and lacrimal duct obstruction
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Kojiro Imai, Biji Araki, Eri Kondoh, Akihide Watanabe, Dinesh Selva, Shigeru Kinoshita, and Koichi Wakimasu
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,MEDLINE ,Young Adult ,Age Distribution ,Swimming Pools ,Text mining ,Japan ,Risk Factors ,Lacrimal Duct Obstruction ,Surveys and Questionnaires ,Humans ,Medicine ,Young adult ,Child ,Swimming ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Follow up studies ,Retrospective cohort study ,General Medicine ,Middle Aged ,Surgery ,Ophthalmology ,LACRIMAL DUCT OBSTRUCTION ,Female ,Age distribution ,business ,Follow-Up Studies - Published
- 2013
24. Involvement of Plasminogen Activator Inhibitor-1 in the Pathogenesis of Atopic Cataracts
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Yasuo Watanabe, Osamu Matsuo, Satoru Nakatani, Kanji Hori, Akira Matsuda, Akira Murakami, Nobuyuki Ebihara, Kiyotaka Okada, Kazuhiko Mori, Toshinari Funaki, and Kojiro Imai
- Subjects
Pathology ,medicine.medical_specialty ,genetic structures ,Blotting, Western ,Biology ,Cataract ,Transforming Growth Factor beta1 ,Lesion ,Pathogenesis ,Interferon-gamma ,chemistry.chemical_compound ,Cataracts ,Lens, Crystalline ,Plasminogen Activator Inhibitor 1 ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Cells, Cultured ,Gene knockdown ,Reverse Transcriptase Polymerase Chain Reaction ,Epithelial Cells ,medicine.disease ,Immunohistochemistry ,eye diseases ,body regions ,Microscopy, Electron ,Gene Expression Regulation ,chemistry ,Plasminogen activator inhibitor-1 ,sense organs ,medicine.symptom ,Plasminogen activator ,Immunostaining - Abstract
PURPOSE Further to our previous report of a genetic association between interferon-gamma (IFN-γ) receptor 1 gene and atopic cataract, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1), a fibrosis-related, IFN-γ downstream molecule, in the pathogenesis of atopic cataracts. METHODS Cultured lens epithelial cells (LECs) were stimulated by IFN-γ and quantified by PAI-1 mRNA/protein expression. PAI-1 and TGF-β mRNA expression was quantified using cDNA samples obtained from the lens epithelium of atopic cataract patients (n = 7) and of senile cataract patients (n = 8). The anterior capsules obtained from atopic cataracts (n = 9) were immunostained with anti-PAI-1 and anti-alpha smooth muscle actin (α-SMA) antibodies. PAI-1 gene expression was knocked down by PAI-1 siRNA, and α-SMA expression was examined under TGF-β1 stimulation. Expression of α-SMA was examined as a pathological hallmark of anterior subcapsular cataracts, commonly observed in atopic cataracts. RESULTS The IFN-γ stimulation induced PAI-1 mRNA/protein expression in the LECs from 24 to 48 hours after stimulation. The expression of PAI-1 mRNA and TGF-β1 mRNA was significantly higher in the cDNA samples obtained from the atopic cataracts than those obtained from the senile cataracts. PAI-1-positive immunostaining was observed at the fibrotic lesion of the atopic cataracts, and α-SMA-positive myofibroblasts were observed at the vicinity of the PAI-1-positive lesion in all nine samples examined. PAI-1 gene knockdown resulted in reduced α-SMA expression in the LECs. CONCLUSIONS The findings of this study suggest that the IFN-γ, PAI-1, and TGF-β1 are involved in the pathophysiology of atopic cataracts.
- Published
- 2012
25. Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese
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Yuichi Tokuda, Kei Tashiro, Kojiro Imai, Natsue Omi, Yoko Ikeda, Hiroko Adachi, Shigeru Kinoshita, Masahiro Fuwa, Kazuhiko Mori, Morio Ueno, Masaaki Kageyama, and Masakazu Nakano
- Subjects
Intraocular pressure ,Heredity ,RNA, Untranslated ,genetic structures ,lcsh:Medicine ,Glaucoma ,Genome-wide association study ,Bioinformatics ,0302 clinical medicine ,Japan ,Polymorphism (computer science) ,Prevalence ,lcsh:Science ,Genetics ,0303 health sciences ,Multidisciplinary ,Genomics ,Optic nerve ,Medicine ,RNA, Long Noncoding ,Chromosomes, Human, Pair 9 ,Research Article ,Genotype ,Clinical Research Design ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Genome Analysis Tools ,Genetic variation ,medicine ,Humans ,Genetic Predisposition to Disease ,Genotyping ,Intraocular Pressure ,030304 developmental biology ,Population Biology ,lcsh:R ,Case-control study ,Computational Biology ,Human Genetics ,Optic Nerve ,medicine.disease ,eye diseases ,Ophthalmology ,Case-Control Studies ,030221 ophthalmology & optometry ,lcsh:Q ,sense organs ,Population Genetics ,Genome-Wide Association Study - Abstract
BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P
- Published
- 2012
26. Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population.
- Author
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Masakazu Nakano, Yoko Ikeda, Yuichi Tokuda, Masahiro Fuwa, Morio Ueno, Kojiro Imai, Ryuichi Sato, Natsue Omi, Hiroko Adachi, Masaaki Kageyama, Kazuhiko Mori, Shigeru Kinoshita, and Kei Tashiro
- Subjects
LYSYL oxidase ,SINGLE nucleotide polymorphisms ,EXFOLIATION syndrome ,GLAUCOMA ,ALLELES - Abstract
The article discusses a study on the common variants in lysyl oxidase-like 1 gene (LOXL1) associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). It notes the risk allele of a variant in LOXL1 which has been discovered to be inverted between Asian and Caucasian population. The authors performed a genome-wide association study using 201 XFS/XFG and 697 controls and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs).
- Published
- 2014
- Full Text
- View/download PDF
27. Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.
- Author
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Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, Bush, John, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro, Kinoshita, Shigeru, Koizumi, Noriko, Ueno, Morio, and Okumura, Naoki
- Subjects
- *
CORNEA surgery , *PROTEIN kinase inhibitors , *CELL culture , *COMBINED modality therapy , *COMPARATIVE studies , *CORNEA , *CORNEA diseases , *CORNEAL transplantation , *EPITHELIAL cells , *INTRAOCULAR pressure , *RESEARCH methodology , *MEDICAL cooperation , *PHOSPHOTRANSFERASES , *RESEARCH , *EVALUATION research , *CHEMICAL inhibitors , *TRANSPLANTATION of organs, tissues, etc. , *ANATOMY , *THERAPEUTICS - Abstract
Background: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.Methods: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 μl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 μm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection.Results: At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 μm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98).Conclusions: Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .). [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
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