1.Impact of Frailty on the Course and Walking Ability after Cardiac Surgery
Tasuku HONDA ; Nobuhiko MUKOHARA ; Hirohisa MURAKAMI ; Hiroshi TANAKA ; Yoshikatsu NOMURA ; Syunsuke MIYAHARA ; Gaku UCHINO ; Jun FUZISUE ; Motoharu KAWASHIMA ; Shuto TONOKI
Japanese Journal of Cardiovascular Surgery 2022;51(2):67-72
Objective: Frailty has been noticed as an important preoperative risk factor for cardiac surgery. The purpose of this study was to evaluate the effect of frailty on the rehabilitation process and walking ability after cardiac surgery. Methods: A total of 213 patients aged 65 years or older who underwent elective cardiac surgery at our hospital between August 2018 and October 2020 and who underwent a preoperative frailty assessment were included. The patients were divided into two groups: group F with frailty and group N without frailty, and the perioperative factors, postoperative course, and walking ability in both groups were examined. Results: Of all patients, 70 (33%) were diagnosed as frail. In the preoperative factors, gait speed and grip strength were significantly lower in group F, and there were more cases of sarcopenia and malnutrition. There was no significant difference in surgical factors between the two groups, except for a bias in the surgical category. In the postoperative course, there were no significant differences in intubation time, ICU stay, postoperative complications, or hospital stay between the two groups, but more patients in group F were transferred to another hospital. In the F group, the start of walking and the day of achieving 100 m walking were significantly delayed, and the number of patients who achieved 300 m walking was 52 (74%), which was significantly lower than 197 (89%) in the N group. The cutoff value of gait speed was 0.88 m/s. Conclusions: Frailty was associated with delayed rehabilitation and reduced walking ability after cardiac surgery, and increased hospital transfers. In addition, the preoperative gait speed was adopted as one of the factors related to the possibility of a 300 m walk after surgery. We believe that preoperative rehabilitation is a promising strategy to improve the condition of frail patients who require cardiac surgery.
2.Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center
Hiroshi MASUYA ; Daiki USUDA ; Hatsumi NAKATA ; Naomi YUHARA ; Keiko KURIHARA ; Yuri NAMIKI ; Shigeru IWASE ; Toyoyuki TAKADA ; Nobuhiko TANAKA ; Kenta SUZUKI ; Yuki YAMAGATA ; Norio KOBAYASHI ; Atsushi YOSHIKI ; Tatsuya KUSHIDA
Laboratory Animal Research 2021;37(1):21-31
Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.
3.Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center
Hiroshi MASUYA ; Daiki USUDA ; Hatsumi NAKATA ; Naomi YUHARA ; Keiko KURIHARA ; Yuri NAMIKI ; Shigeru IWASE ; Toyoyuki TAKADA ; Nobuhiko TANAKA ; Kenta SUZUKI ; Yuki YAMAGATA ; Norio KOBAYASHI ; Atsushi YOSHIKI ; Tatsuya KUSHIDA
Laboratory Animal Research 2021;37(1):21-31
Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.
4.Effects of co-transfection with myostatin-targeting siRNA and ActRIIB-Fc fusion protein on skeletal muscle growth
OD Bayarsaikhan ; NOBUHIKO KAWAI ; HIROYO MORI ; NAO KINOUCH ; TAKESHI NIKAWA ; EIJI TANAKA
Innovation 2018;12(4):52-
Myostatin (Mstn) is a secreted TGF- β family member that controls skeletal muscle growth, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-β family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the combinative effects of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc on murine myoblast in vitro and in vivo.
C2C12 cells were treated by Mstn-siRNA with or without ActRIIB-Fc at 0 and 48 h after differentiation. Myotube size was measured, and gene expression of Mstn, MuRF-1, MyoD and myogenin were analyzed. Furthermore, 11-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc locally into the masseter muscle twice a week. Histological and biochemical analyses were performed using the dissected muscles.
Transfection of Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc resulted in significant increases in the myotube diameter of the C2C12 cells compared with untreated control. Also, treatment with Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc could lead to an upregulation of MyoD and myogenin gene expression and downregulation of Mstn and MuRF-1. In vivo, muscle fibril hypertrophy was observed in both Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc treated groups. Moreover, western blotting analysis showed that the p-Smad2/3 expression level was decreased by treatment of Mstn-siRNA/ActRIIB-Fc. In contrast, MyoD and myogenin protein levels were increased by combined treatment, compared with the other groups.
These suggest that double inhibition of myostain is potentially useful for myogenesis and muscle growth promotion. This may be a good as new treatment remedy for patients with various muscle atrophies, including muscular dystrophy.
5.Co-administration of myostatin-targeting siRNA and ActRIIB-Fc fusion protein increases masseter muscle mass and fiber size
Od Bayarsailhan ; NOBUHIKO KAWAI ; HIROYO MORI ; NAO KINOUCHI ; TAKESHI NIKAWA ; EIJI TANAKA
Innovation 2018;12(4):53-
Myostatin, a member of the TGF-beta superfamily, is a negative regulator of skeletal muscle cell growth and differentiation, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-beta family members in muscle, leading to rapid and marked muscle growth.
The present study was designed to assess the effectiveness of the co-delivery of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc into skeletal muscle as a potential treatment of atrophic myopathies. Eleven-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA with/ without ActRIIB-Fc locally into the masseter muscle twice a week.
Inhibition of myostatin function by the combination of Mstn-siRNA and ActRIIB-Fc increased muscle weight and myofibril size in murine masseter muscle. Real-time RT-PCR analysis revealed significant downregulation of myostatin mRNA expression in both the Mstn-siRNA-treated and the combination treatment group. Furthermore, myogenin mRNA expression was upregulated in the combination treatment group, while MuRF-1 and Atrogin-1 mRNA expression was downregulated compared to administration of each compound alone.
These findings suggest that double inhibition of myostatin is a potentially useful treatment strategy to increase muscle mass and fiber size and could be a useful treatment of patients with various muscle atrophies, including muscular dystrophy.
6.Residual Limb Volume Change in the Early Post-operative Phase after Below-the-knee Amputation : A Report of Three Cases
Yohei Tanaka ; Takaaki Ueno ; Kiyokazu Tanaka ; Nobuhiko Haga
The Japanese Journal of Rehabilitation Medicine 2017;54(11):889-893
For lower limb amputees, good prosthetic fittings are important for wearing prostheses while ensuring gait stability, without skin breakdown. Poor prosthetic fittings tend to occur in the early stage after amputation because of significant changes in residual limb volume. We measured the extent of change in residual limb volume in three below-the-knee amputees by using computed tomography. The measurements were performed before and after inpatient rehabilitation for the first prosthesis. The measurement showed a remarkable change in residual limb volume in a highly active amputee without complications. In contrast, the change in residual limb volume was small in two less active below-the-knee amputees with serious complications, such as heart and renal failures. Generally, to maintain good prosthetic fittings, the first prostheses should be made during inpatient rehabilitation to facilitate maturation of the residual limbs. For the less active below-knee amputees, the prostheses could be made in the outpatient settings because the volume fluctuations of their residual limbs are small and the functional requirements for their daily living are modest.
7.Role of vaginal pallor reaction in predicting late vaginal stenosis after high-dose-rate brachytherapy in treatment-naive patients with cervical cancer.
Ken YOSHIDA ; Hideya YAMAZAKI ; Satoaki NAKAMURA ; Koji MASUI ; Tadayuki KOTSUMA ; Hironori AKIYAMA ; Eiichi TANAKA ; Nobuhiko YOSHIKAWA ; Yasuo UESUGI ; Taiju SHIMBO ; Yoshifumi NARUMI ; Yasuo YOSHIOKA
Journal of Gynecologic Oncology 2015;26(3):179-184
OBJECTIVE: To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. METHODS: We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). RESULTS: More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade > or =2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade > or =2 vaginal stenosis rate at 3 years at 100% (p=0.001). CONCLUSION: High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.
Adult
;
Aged
;
Aged, 80 and over
;
Brachytherapy/*adverse effects/methods
;
Constriction, Pathologic/etiology/pathology
;
Female
;
Humans
;
Iridium Radioisotopes/therapeutic use
;
Middle Aged
;
*Pallor
;
Prognosis
;
Prospective Studies
;
Radiopharmaceuticals/therapeutic use
;
Retrospective Studies
;
Uterine Cervical Neoplasms/*radiotherapy
;
Vaginal Diseases/*etiology/pathology
8.Comparative Analysis of Faculty Development in Japanese Medical Schools from 2003 through 2005
Nobuo NARA ; Masaaki ITO ; Eiji GOTOH ; Nobuhiko SAITO ; Yujiro TANAKA ; Masahiro TANABE ; Osamu FUKUSHIMA ; Saburo HORIUCHI
Medical Education 2007;38(4):275-278
1) The faculty development at each medical school from 2003 through 2005 was analysed.
2) The major themes in faculty development were problem based learning, tutorial, computer based testing, and clinical training.
3) Faculty development is considered an effective way to enhance the contributions of faculty members to medical education.
9.Staged Operation for a Patient with Ischemic Heart Disease and Abdominal Aortic Aneurysm Complicating Idiopathic Thrombocytopenic Purpura
Akiko Tanaka ; Nobuhiko Mukohara ; Hiroya Minami ; Masato Yoshida ; Hidefumi Ohbo ; Tsutomu Shida
Japanese Journal of Cardiovascular Surgery 2006;35(1):29-32
A 62-year-old man, who had been given a diagnosis of chronic idiopathic thrombocytopenic purpura (ITP), was admitted to our hospital for an operation for abdominal aortic aneurysm (AAA). Preoperative coronary angiography revealed severe triple vessel disease, and we chose to treat this first. The platelet count on his first admission was 2.1×104/μl and preoperative immunoglobulin infusion was introduced for 5 days. Off-pump coronary artery bypass grafting (OPCAB) was performed safely with platelet transfusion, and he was discharged on the 14th postoperative day. Thirty-eight days later, graft replacement of AAA was performed with preoperative immunoglobulin infusion and no platelet transfusion, and he was discharged at the 11th postoperative day. Preoperative immunoglobulin infusion therapy and selection of OPCAB were useful to prevent perioperative bleeding complications. This is the first report of staged cardiac and aortic surgery in a patient with ITP.
10.A Case of Successful Transaortic Endovascular Stent Grafting for Distal Aortic Arch Aneurysm with Severely Calcified Chronic Aortic Dissection
Masato Yoshida ; Nobuhiko Mukohara ; Hidefumi Obo ; Hiroya Minami ; Kenichi Kim ; Ayako Maruo ; Kazuhiro Mizoguchi ; Takeshi Inoue ; Akiko Tanaka ; Tsutomu Shida
Japanese Journal of Cardiovascular Surgery 2005;34(4):282-286
A 74-year-old man was admitted to our hospital to undergo an operation for distal aortic arch aneurysm with chronic aortic dissection. The first operation was attempted through left lateral thoracotomy. Since the aorta had a severely calcified false lumen, conventional aortic replacement was considered to entail greater risk and graft replacement was given up. As an another option, endovascular stent grafting via the aortic arch through median sternotomy was selected as a second operation. Deep hypothermic circulatory arrest with selective cerebral perfusion was used during delivery and deployment of the stented graft through the aortotomy site. The distal stented graft was deployed into the true lumen at the ninth thoracic vertebral level. Neither endoleaks nor complications were observed. Postoperative computed tomography showed complete thrombosis of the distal aortic arch aneurysm and the false lumen. The postoperative course was uneventful. Transaortic endovascular stent grafting is an effective and less invasive treatment for aortic arch aneurysms with severely calcified aorta.


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