Effect of repeated Waon therapy on exercise tolerance and pulmonary function in patients with chronic obstructive pulmonary disease: a pilot controlled clinical trial

Purpose: Controlled clinical trials evaluating the efficacy of repeated Waon therapy for patients with chronic obstructive pulmonary disease (COPD) have yet to be conducted. The purpose of the present study was to evaluate whether repeated Waon therapy exhibits an adjuvant effect on conventional therapy for COPD patients. Patients and methods: This prospective trial comprised 20 consecutive COPD patients who satisfied the criteria of the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines, stages 1–4. They were assigned to either a Waon or control group. The patients in the Waon group received both repeated Waon therapy and conventional therapy, including medications, such as long-acting inhaled β2 agonists, long-acting anticholinergics and xanthine derivatives, and pulmonary rehabilitation. The Waon therapy consisted of sitting in a 60°C sauna room for 15 minutes, followed by 30 minutes of being warmed with blankets once a day, 5 days a week, for a total of 20 times. The patients in the control group received only conventional therapy. Pulmonary function and the 6-minute walk test were assessed before and at 4 weeks after the program. Results: The change in vital capacity (0.30 ± 0.4 L) and in peak expiratory flow (0.48 ± 0.79 L/s) in the Waon group was larger than the change in the vital capacity (0.02 ± 0.21 L) (P=0.077) and peak expiratory flow (−0.11 ± 0.72 L/s) (P=0.095) in the control group. The change in forced expiratory flow after 50% of expired forced vital capacity in the Waon group, 0.08 (0.01–0.212 L/s), was larger than that in the control group, −0.01 (−0.075–0.04 L/s) (P=0.019). Significant differences were not observed in the change in any parameters in the 6-minute walk test. Data are presented as means ± standard deviation or median (25th–75th percentile). Conclusion: The addition of repeated Waon therapy to conventional therapy for COPD patients can possibly improve airway obstruction

Molecular Approach to Uterine Leiomyosarcoma: LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma

Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker which distinguishes malignant LMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, in order to establish a treatment method. LMP2-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2 expression to be absent in human LMS, but present in human LMA. Therefore, defective LMP2 expression may be one of the risk factors for LMS. LMP2 is a potential diagnostic-biomarker for uterine LMS, and may be targeted-molecule for a new therapeutic approach

Tumor Immunoediting, from T Cell-Mediated Immune Surveillance to Tumor-Escape of Uterine Leiomyosarcoma

The majority of smooth muscle tumors found in the uterus are benign, but uterine leiomyosarcomas (LMSs) are extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not clearly understood. The presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules is important for tumor rejection by cytotoxic T-lymphocytes (CTLs). Such antigenic peptides are generated as a result of the degradation of intracellular proteins by the proteasome pathway, a process that is influenced by the interferon (IFN)-γ-inducible low molecular mass polypeptide-2 (LMP2) subunit of the 20S proteasome. Homozygous deficient mice for LMP2 are now known to spontaneously develop uterine LMS. LMP2 expression is reportedly absent in human uterine LMS, but present in human myometrium. Further studies revealed a few infiltrating CD56+ NK cells in human uterine LMS tissues. This review aims at summarizing recent insights into the regulation of NK cell function and the T cell-mediated immune system as tumor immune surveillance, first attempts to exploit NK cell activation to improve immunity to tumors

A systematic review of nonrandomized controlled trials on the curative effects of aquatic exercise

Hiroharu Kamioka1, Kiichiro Tsutani2, Yoshiteru Mutoh3, Hiroyasu Okuizum4, Miho Ohta5, Shuichi Handa4, Shinpei Okada6, Jun Kitayuguchi7, Masamitsu Kamada7, Nobuyoshi Shiozawa8, Sang-Jun Park4, Takuya Honda4, Shoko Moriyama41Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, 3Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan; 4Mimaki Onsen (Spa) Clinic, Tomi City, Japan; 5Laboratory of Aqua, Health, and Sports Medicine, 6Physical Education and Medicine Research Foundation, Nagano, Japan; 7Physical Education and Medicine Research Center Unnan, Unnan City, Japan; 8Department of Longevity and Social Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanBackground: The objectives of this review were to integrate the evidence of curative effects through aquatic exercise and assess the quality of studies based on a review of nonrandomized controlled trials (nRCTs).Methods: Study design was a systematic review of nonrandomized controlled trials. Trials were eligible if they were nonrandomized clinical trials. Studies included one treatment group in which aquatic exercise was applied. We searched the following databases from 2000 up to July 20, 2009: MEDLINE via PubMed, CINAHL, and Ichushi-Web.Results: Twenty-one trials met all inclusion criteria. Languages included were English (N = 9), Japanese (N = 11), and Korean (N = 1). Target diseases were knee and/or hip osteoarthritis, poliomyelitis, chronic kidney disease, discomforts of pregnancy, cardiovascular diseases, and rotator cuff tears. Many studies on nonspecific disease (healthy participants) were included. All studies reported significant effectiveness in at least one or more outcomes. However results of evaluations with the TREND and CLEAR-NPT checklists generally showed a remarkable lack of description in the studies. Furthermore, there was the problem of heterogeneity, and we were therefore not able to perform a meta-analysis.Conclusion: Because there was insufficient evidence on aquatic exercise due to poor methodological and reporting quality and heterogeneity of nRCTs, we were unable to offer any conclusions about the effects of this intervention. However, we were able to identify problems with current nRCTs of aquatic exercise, and propose a strategy of strengthening study quality, stressing the importance of study feasibility as a future research agenda objective.Keywords: aquatic exercise, systematic review, nonrandomized controlled trials&nbsp

Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: Morphological significance of calponin h1

Uterine leiomyosarcoma (LMS) is a highly metastatic smooth muscle neoplasm for which calponin h1 is suspected to have a biological role as a tumor-suppressor. We earlier reported that LMP2-null mice spontaneously develop uterine LMS through malignant transformation of the myometrium, thus implicating this protein as an anti-tumorigenic candidate as well. In the present study, we show that LMP2 may negatively regulate LMS independently of its role in the proteasome. Moreover, several lines of evidence indicate that although calponin h1 does not directly influence tumorigenesis, it clearly affects LMP2-induced cellular morphological changes. Modulation of LMP2 may lead to new therapeutic approaches in human uterine LMS.ArticleFEBS LETTERS. 586(13):1824-1831 (2012)journal articl

Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy

Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. We earlier reported that mice with a homozygous deficiency for LMP2, an interferon (IFN)-gamma-inducible factor, spontaneously develop uterine LMS. The IFN-gamma pathway is important for control of tumor growth and invasion and has been implicated in several cancers. In this study, experiments with human and mouse uterine tissues revealed a defective LMP2 expression in human uterine LMS that was traced to the IFN-gamma pathway and the specific effect of JAK-1 somatic mutations on the LMP2 transcriptional activation. Furthermore, analysis of a human uterine LMS cell line clarified the biological significance of LMP2 in malignant myometrium transformation and cell cycle, thus implicating LMP2 as an anti-tumorigenic candidate. This role of LMP2 as a tumor suppressor may lead to new therapeutic targets in human uterine LMS.ArticleSCIENTIFIC REPORTS. 1:180 (2011)journal articl

リンショウケンキュウ ト エキガクケンキュウ ニ オケル ロンブン ノ シツ ヲ タカメルタメ ノ コクサイドウコウ ヒト ヲ タイショウ ト シタ ケンキュウデザイン ノ エビデンス・グレーディング

本研究は,人を対象とした治療や健康増進の効果を明らかにする研究のエビデンスを示す方法をレビューすることを目的とした。疫学や臨床研究においては,研究デザインによって,エビデンスのグレーディング(grading : 格付け)が行われている。各種の研究デザインにおける論文を評価したり,論文の質を高めるためにチェックリストや声明が開発されている。また,人を対象とした介入研究を実施する場合には,パブリケーション・バイアスの減少,研究の倫理,臨床試験参加の推進につながるため,事前の臨床試験登録(clinical trial registry : CTR)が必要である。世界的な11の医学雑誌からなる「国際医学雑誌編集者委員会(International Committee of Medical Journal Editors : ICMJE)」は,臨床試験の登録(clinical trial registry : CTR)を論文投稿の条件としている。疫学研究や臨床研究を実施する場合には,こうした動向を理解する必要がある。This narrative reviews the means of effectively evaluating evidence in the outcome of clinical trial and quality of health care. The grading of evidence in clinical and epidemiologic studies has been provided to improve the study design and to raise the quality of publications. Check lists and guidelines are developed to reduce publication bias, and clinical trial registry has the potential to facilitate ethics and to increase participation of clinical trials. The International Committee of Medical Journal Editors has proposed that only clinical trials are published that are registered at inception. These trends are to be appreciated when epidemiologic or clinical study is conducted

ソクヨク ニ オケル ジンコウ ボウショウセン ガ ジリツシンケイカツドウ ニ アタエル エイキョウ

本研究は人工芒硝泉による足浴が自律神経活動に及ぼす影響について検討することを目的とした。健康な若年男女計6名(男性3名 : 20.7±0.6歳,女性3名 : 21.3±0.6歳)を対象に,人工芒硝泉浴,淡水浴,湯なし条件(対照座位)の足浴条件を1日1条件,ランダムな順序で施行した。対象者には20分間座位安静をとってもらい,引き続き足浴前値の測定を行った。足浴は座位にて41℃(33L)の温湯に両足膝下約10cmまで15分間浸漬して行った。足浴終了後は対象者自身が水分を拭き取り,両足を毛布で覆い,60分間座位安静を保った。その間,心拍数,心拍変動周波数に基づく自律神経活動,鼓膜温を測定するとともに,体感温度,眠気,疲労感などの主観的評価をVisual Analogue Scale(VAS)を用いて記録した。その結果,人工芒硝泉浴及び淡水浴により体感温度は有意に上昇したが,鼓膜温及び心拍数に有意な変動は見られなかった。また淡水浴後は交感神経活動の有意な亢進が認められたが,人工芒硝泉浴後はそれが見られなかった。本結果から人工芒硝泉による足浴は足浴後の交感神経活動の亢進を抑え,疲労感の低減に寄与する可能性が示唆された。This study was conducted to estimate the effect of a footbath with sodium sulfate (Na2SO4) on autonomic nervous system (ANS) activity. Each of three young healthy males (age, 20.7±0.6 years) and females (age, 21.3±0.6 years) participated in 3 conditions in random order, footbaths with or without Na2SO4, and a sitting position without water as a control. Each subject sat on a chair and kept quiet for 20min with heart rate (HR) stabilized, and subsequently basal measurements were conducted. In a sitting position, they dipped their calves 10cm under their knee joints into hot water (41℃, 33L) for 15min. Immediately after the bathing, they removed moisture, covered their knees with a blanket and sat for 60min thereafter. Counts of HR, ANS activity based on frequency of HR variability, and a core temperature using an eardrum thermometer were measured. The degree of thermal comfort such as relatively hot or relatively cool, sleepiness and fatigue were also estimated using visual analogue scales (VAS). As a result, both footbaths with and without Na2SO4 significantly increased the subjective thermal comfort, while the core temperature and HR counts were unaffected. Sympathetic nervous system (SNS) activity was significantly increased by the footbath without Na2SO4, but not with Na2SO4. These observations suggested that in the footbath, Na2SO4 might have an inhibitory effect on increased SNS activity, and induce some depressive effects on feeling of fatigue