The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 236, Issue 4
August
Displaying 1-10 of 10 articles from this issue
Regular Contribution
  • Masashi Kanezaki, Teruhiro Ogawa, Tadafumi Izumi
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 241-245
    Published: 2015
    Released on J-STAGE: June 26, 2015
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    Contraction of the genioglossus affects either tongue protrusion strength or dilating forces of the upper airway. The upper airway in patients with obstructive sleep apnea (OSA) is thought to collapse during sleep, at least in part because of a sleep related reduction in genioglossus muscle activity. Thus, although tongue protrusion strength by genioglossus activity during sleep contributes to the maintenance of airway patency in patients with OSA, the relationship between tongue protrusion strength in the arousal state and obstructive sleep apnea has not been fully elucidated. Conventional method of tongue protrusion strength cannot be used to evaluate in edentulous subjects and/or subjects with the decreased biting force. In this study, employing a novel measurement method that does not require biting a transducer, we investigated relationships between the tongue protrusion strength and polysomnographic findings. We enrolled twenty normal subjects and 26 subjects with OSA. All subjects completed the measurement of tongue protrusion strength. Each subject with OSA was evaluated by full polysomnography. The degree of tongue protrusion strength was assessed by maximum voluntary contraction against the tongue depressor connected with a strain gauge dynamometer. The tongue protrusion strength was negatively correlated with obstructive apnea time, apnea index (AI) and the percent of sleep stage 2 (r = −0.61, p < 0.0001, r = −0.41 p = 0.03 and r = −0.39 p = 0.04, respectively). Tongue protrusion strength measured in the arousal state is predictive of the airway patency during sleep in OSA.
  • Bang-Gee Hsu, Ming-Hui Shih, Yen-Cheng Chen, Guan-Jin Ho, Teng-Yi Lin, ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 247-253
    Published: 2015
    Released on J-STAGE: July 03, 2015
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    Osteoprotegerin (OPG) is a cytokine that regulates bone resorption by inhibiting osteoclastogenesis, and OPG has been implicated in the process that causes vascular stiffness. An increase in serum OPG level has been associated with the development of arterial stiffness. Kidney transplant (KT) patients are susceptible to aortic stiffness, which is considered to be a predictor of cardiovascular events in this patient population. Carotid-femoral pulse wave velocity (cfPWV) has emerged as a gold standard for non-invasive evaluation of aortic stiffness. The aim of this study was to evaluate the relationship between serum OPG concentration and cfPWV among KT patients. Fasting blood samples were obtained from 57 KT patients and their cfPWV was measured using applanation tonometry. The serum OPG levels were measured using an enzyme-linked immunosorbent assay. Univariable linear regression analysis showed that the cfPWV in KT patients was significantly and positively correlated with age, body weight, waist circumference, body mass index, log-creatinine, systolic blood pressure, diastolic blood pressure, pulse pressure, and the log-OPG concentration. KT patients with metabolic syndrome had higher cfPWV values than those without metabolic syndrome (P = 0.036), which indicates a higher incidence of aortic stiffness in this patient population. Multivariable forward stepwise linear regression analysis of the significant variables showed that the log-OPG (P = 0.001), the log-creatinine (P = 0.004), and the SBP (P = 0.005) remained as independent and positive predictors of cfPWV values. These findings indicate that serum OPG levels are positively associated with cfPWV in KT patients.
  • Chuanxi Chen, Xiangdong Guan, Deborah A. Quinn, Bin Ouyang
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 255-261
    Published: 2015
    Released on J-STAGE: July 08, 2015
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    Mechanical ventilation is the most important life supportive therapy for patients with acute respiratory distress syndrome (ARDS). However, increasing evidence from clinical studies suggests that mechanical ventilation can cause lung fibrosis, which may significantly contribute to morbidity and mortality. Recent studies also found fibroproliferation occurred in early stage of ARDS with poor outcome. We have hypothesized that mechanical ventilation-induced lung injury may be a major contributor to lung fibrosis, and antioxidant could be a potential therapeutic agent for the treatment to mechanic ventilation induced fibroproliferation. We therefore used Sprague-Dawley rats that were ventilated with large tidal volume (20 ml/kg) or low tidal volume (7 ml/kg). We analyzed the time course of collagen level in the lung and the effect of N-acetylcysteine (NAC), a thiol antioxidant, on mechanical ventilation-induced collagen accumulation. In addition, normal human lung fibroblasts (NHLF) were exposed to mechanical stretch, which mimics ventilator-induced lung inflation, to evaluate the collagen secretion in culture medium. We found that ventilation-induced collagen accumulation occurred even after 2-hour ventilation. Pretreatment with NAC (140 mg/kg) inhibited collagen accumulation in lungs of rats ventilated with large tidal volume. Moreover, mechanical stretch caused the accumulation of collagen in the culture medium of NHLF, the magnitude of which was decreased with the pretreatment with NAC (1 mM). These results indicate that mechanical ventilation can induce collagen accumulation within 2 hours. NAC alleviated the collagen accumulation induced by mechanical ventilation with high tidal volume. Therefore, NAC can be considered as a good candidate in preventing ventilation-induced lung fibrosis.
  • Yasuyuki Yazaki, Kenji Sugawara, Mitsunori Honda, Hiroshi Ohnishi, Shi ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 263-271
    Published: 2015
    Released on J-STAGE: July 28, 2015
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    Autochthonous hepatitis E is increasingly being recognized in industrialized countries, including Japan. Although neurological abnormalities have been sporadically reported as an extrahepatic manifestation of hepatitis E virus (HEV) infection, it is rare and has not been reported in Japan. The present study aimed to characterize a total of 20 patients consecutively diagnosed with sporadic acute hepatitis E at a city hospital in Hokkaido, Japan, during 2001-2014, focusing on a patient complicated with neuropathy. Seventeen patients were infected with genotype 4 HEV, while the remaining three patients were with genotype 3 HEV. Although a 67-year-old male with severe hepatitis did not have predisposing factors associated with the development of neurological disorders, such as diabetes mellitus and the use of immunosuppressive agents, he developed bilateral peripheral facial palsy six days after admission. A neurological examination revealed the inability to smile, frown, close his eyes completely or puff out his cheeks. MRI brain scans were considered to be normal. Although it took 83 days after admission for the total bilirubin levels to normalize, his neurological symptoms resolved gradually within three weeks without any sequelae following conservative therapy. A full-length genomic analysis of the HEV strain (HE-JA30) isolated from the patient belonged to genotype 4 and was closest to that currently circulating in Hokkaido, Japan. This is the first report of HEV-associated neuropathy in Japan. While all of previous reports on HEV-related neuropathy involve genotype 3 HEV, the present report is unique in that genotype 4 HEV is responsible for the neuropathy.
  • Ki Hun Cho, Min Kyu Kim, Hwang-Jae Lee, Wan Hee Lee
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 273-280
    Published: 2015
    Released on J-STAGE: July 31, 2015
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    Virtual reality training is considered as an effective intervention method of stroke patients, and the virtual reality system for therapeutic rehabilitation has emphasized the cognitive factors to improve walking function. The purpose of current study was to investigate the effect of virtual reality training with cognitive load (VRTCL) on walking function of chronic stroke. Chronic stroke patients were randomly assigned to the VRTCL group (11 patients, including 5 men; mean age, 60.0 years; post-stroke duration, 273.9 days) or control group (11 patients, including 2 men; mean age, 58.6 years; post-stroke duration, 263.9 days). All subjects participated in the standard rehabilitation program that consisted of physical and occupational therapies. In addition, VRTCL group participated in the VRTCL for 4 weeks (30 min per day and five times a week), while those in the control group participated in virtual reality treadmill training. Walking function under single (walking alone) and dual task (walking with cognitive tasks) conditions was assessed using an electrical walkway system. After the 4-week intervention, under both single and dual task conditions, significant improvement on walking function was observed in VRTCL and control groups (P < 0.05). In addition, in the dual task condition, greater improvement on walking function was observed in the VRTCL group, compared with the control group (P < 0.05). These findings demonstrated the efficacy of VRTCL on the walking function under the dual task condition. Therefore, we suggest that VRTCL may be an effective method for the achievement of independent walking in chronic stroke patients.
  • Chih-Chung Shiao, Hsiu-Chuan Hsu, I-Ling Chen, Ching-Yi Weng, Jui-Chu ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 281-288
    Published: 2015
    Released on J-STAGE: August 05, 2015
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    Pneumonia is an important infectious entity that affects residents in long-term care facilities (LTCFs), whereas hospitalization-requiring pneumonia (HRP) represents a more critical patient condition with worse outcomes. The evidence addressing the association between Barthel index and risk of HRP among LTCF residents is lacking. A multicenter, retrospective cohort study was conducted in three LTCFs enrolling adult patients who resided for 3 months or more and ever underwent Barthel index evaluation within a study period of January 1 to December 31, 2010. The endpoint was HRP after enrollment. A total of 299 patients (169 women; age, 79.0 ± 12.2 years) were enrolled and categorized into HRP Group (n = 68; 36 women; age, 79.1 ± 11.3 years) and Non-HRP Group (n = 231; 133 women; age, 79.0 ± 12.4 years) by the endpoint. The patients in HRP Group had significantly lower Barthel index (8.6 versus 25.8 points, p < 0.001) but higher proportion of chronic obstructive pulmonary disease (13.2% versus 3.9%, p = 0.004). By the multivariate analysis of logistic regression, we found that lower Barthel index (odds ratio (OR), 0.967; p < 0.001), existence of chronic obstructive pulmonary disease (OR, 4.192; p = 0.015), and feeding route (percutaneous endoscopic gastrostomy comparing with oral feeding; OR, 0.177; p = 0.012) were independently associated with HRP. In conclusion, a lower Barthel index is significantly associated with the occurrence of pneumonia that requires hospitalization in long-term care residents. Barthel index is a useful and reliable tool for risk evaluation in this population.
Case
  • Yoshinobu Konishi, Satoshi Takahashi, Katsuyuki Nishi, Taro Sakamaki, ...
    Article type: Case
    2015 Volume 236 Issue 4 Pages 289-295
    Published: 2015
    Released on J-STAGE: August 05, 2015
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    Multicentric Castleman’s disease is a systemic inflammatory disorder characterized by lymphadenopathy and excessive interleukin-6 production. A unique clinicopathologic variant of multicentric Castleman’s disease, TAFRO (i.e., thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly) syndrome, was recently proposed in Japan. Despite the successful use of anti-interleukin-6 therapy in some patients with TAFRO syndrome, not all patients achieve remission. The pathophysiological etiology of and suitable therapeutic strategies for this variant have not been established. Here, we present our experience of a unique case of TAFRO syndrome in a 78-year-old woman whose symptoms responded differently to several therapies. Tocilizumab, an anti-interleukin-6 receptor antibody, successfully induced remission of fever and lymphadenopathy. However, severe thrombocytopenia persisted and she developed anasarca, ascites, and pleural effusion shortly thereafter. Rituximab, an anti-CD20 antibody, and glucocorticoid therapy provided no symptom relief. In contrast, cyclosporine A, an immunosuppressive agent that blocks T cell function by inhibiting interleukin-2, yielded immediate improvements in systemic fluid retention and a gradual increase in platelet count, with complete resolution of disease symptoms. Excessive serum interleukin-2, when used as an anti-cancer agent, has been reported to cause side effects such as fluid retention, thrombocytopenia, and renal failure. Our case was unique because the anti-interleukin-2 therapy successfully improved symptoms that were not relieved with anti-interleukin-6 therapy. The present report therefore provides insight into the possible role of interleukin-2, in addition to interleukin-6, in TAFRO syndrome. This report will certainly help to clarify the pathogenesis of and optimal treatment strategies for TAFRO syndrome.
Regular Contribution
  • Xuan Hong, Baohong Cui, Meng Wang, Zhaoyang Yang, Li Wang, Qingyong Xu
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 297-304
    Published: 2015
    Released on J-STAGE: August 05, 2015
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    Small cell lung cancer (SCLC) is an aggressive disease characterized by rapid growth and metastases. It has been recognized that the inflammation of the microenvironment plays a critical role in the development of malignancies. However, little is known about the role of multiple inflammatory and hematological markers in the prognosis of SCLC. The aim of this study was to determine the clinical significance of pre-treatment inflammation-based scores and characteristics as prognostic indicators for the survival of SCLC patients. A retrospective analysis of 919 SCLC cases was performed. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. The univariate analysis of all SCLC patients indicated that favorable prognostic factors were age ˂ 70 years, non-smokers, good performance status, limited disease and response to treatment. Moreover, univariate analysis of inflammation-based scores and other blood parameters showed that neutrophil-lymphocyte ratio ≥ 5, platelet-lymphocyte ratio ≥ 250, systemic immune-inflammation index (SII) ≥ 1,600 × 109/L, prognostic nutritional index (albumin + 5 × lymphocyte) < 45, and elevated serum lactate dehydrogenase (LDH) predicted poor prognosis in SCLC patients. SII represents the score that is calculated as follows: platelet count × neutrophil count/lymphocyte count. In the multivariate analysis, SII, together with serum LDH, stage and response to therapy, were associated with overall survival (OS). This study demonstrated that the combination of platelet count and neutrophil-lymphocyte ratio could help to predict poor prognosis in SCLC. Our findings will facilitate the understanding of survival differences in SCLC patients in clinical practice.
    Editor's pick

    Original Article: Small Cell Lung Cancer
    The TJEM Best Citation Award 2021

  • Cai-Lian Zhang, Sheng-Li Ge, Ning Yang, Jin-Ran Zhang, Dong-Dong Tian
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 305-309
    Published: 2015
    Released on J-STAGE: August 13, 2015
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    Small cell lung cancer (SCLC) is a fast-growing cancer with poor prognosis. Patients with extensive-stage SCLC are generally treated with chemotherapy. Thus, it is essential to identify a predictor of efficacy and prognosis for SCLC. Angiopoietin-2 promotes vascular remodeling and angiogenesis. Increasing evidence reveals that angiopoietin-2 is preferentially expressed in cancer cells, and elevated angiopoietin-2 expression is related to invasive and metastatic phenotypes in various cancers. However, serum angiopoietin-2 level and its prognostic potential in SCLC have not been investigated. The aim of this study was to determine the usefulness of angiopoietin-2 level as a predictor of efficacy and prognosis for SCLC. This study consisted of sixty patients with SCLC. Each patient received four cycles of cisplatin-etoposide chemotherapy, and was followed for 36 months. Serum angiopoietin-2 levels were measured by Enzyme-linked immunosorbent assays. The angiopoietin-2 levels were significantly higher in SCLC patients than those in healthy subjects (P < 0.001). The patients were divided into high-level group (32 patients, 2,923.9 ± 294.7 pg/ml) and low-level group (28 patients, 1,789.5 ± 355.1 pg/ml) according to the mean value of the angiopoietin-2 level (2,400 pg/ml). Compared with the patients in the high-level group, the patients in the low-level group showed remarkably survival advantage (P = 0.002). During chemotherapy, the patients in the low-level group showed better treatment response than the patients in the high-level group (P < 0.05). Therefore, angiopoietin-2 might be useful as a prognostic factor for SCLC and for predicting SCLC response to chemotherapy.
  • Qinli Sun, Ping Lin, Jingyu Zhang, Xiaoyan Li, Liguang Yang, Jianguo H ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 4 Pages 311-318
    Published: 2015
    Released on J-STAGE: August 13, 2015
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    Fibroblast growth factor receptor 2 (FGFR2) has been proved to be a significant prognostic factor and a potential therapeutic target in several types of cancer, including gastric cancer. FGFR2 consists two isoforms: FGFR2-IIIb and FGFR2-IIIc, which can be stimulated by different ligands and trigger different downstream signaling pathways. As a specific ligand to FGFR2-IIIb, fibroblast growth factor 10 (FGF10) is expressed in the gastric mesenchyme cell and is involved in stomach development and morphogenesis, but its expression and clinical significance is not well elucidated in gastric cancer. We analyzed FGF10 expression by immunohistochemistry in 178 samples of gastric adenocarcinoma (134 male and 44 female patients, with the average age of 63.2 years old and the average follow-up of 21.6 months). Using the arbitrarily scoring method based on positive cell percentage and staining intensity, we sub-divided the patients into FGF10 high-expression group (58 patients) and low-expression group (120 patients). We thus found that FGF10 expression is significantly associated with lymph node invasion (P = 0.004) and distant metastasis (P = 0.032). Importantly, FGF10 expression is an independent unfavorable prognostic factor (P = 0.042). Moreover, FGF10 knockdown significantly decreased the migration of cultured gastric adenocarcinoma cells, suggesting that FGF10 could promote the invasion of gastric adenocarcinoma. In conclusion, FGF10 expression was identified as a poor prognostic biomarker in gastric adenocarcinoma, and FGF10 could promote the invasion of gastric cancer cells. We suggest that FGF10 could be a potential and promising drug target in gastric adenocarcinoma.
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