The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 227, Issue 4
Displaying 1-11 of 11 articles from this issue
Regular Contributions
  • Atsuhiko Murata, Kohji Okamoto, Shinya Matsuda, Kazuaki Kuwabara, Yuka ...
    2012 Volume 227 Issue 4 Pages 237-244
    Published: 2012
    Released on J-STAGE: July 12, 2012
    Acute cholecystitis is one of the most frequently encountered conditions in daily practice in Japan. However, there is a shortage of detailed data about treatments that have been performed according to the clinical practice guidelines (CPGs) for acute cholecystitis. We therefore examined the management of acute cholecystitis for adherence to the appropriate CPGs using the Japanese administrative database associated with the Diagnosis Procedure Combination (DPC) system. We collected data from 6,070 patients with acute cholecystitis, examining for the application of four recommended treatments (administration of antimicrobial drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) and performance of early and laparoscopic cholecystectomy). The patients were classified according to the procedures documented for each case: no gallbladder drainage (n = 4,333), gallbladder drainage without supportive care (ventilation or hemodiafiltration or the use of vasopressor) (n = 1,591) and gallbladder drainage and supportive care (n = 146). Multiple logistic regression models revealed that patients with gallbladder drainage without supportive care and those with gallbladder drainage and supportive care significantly higher received administration of antimicrobial drugs and NSAIDs, while these patients underwent less early or laparoscopic cholecystectomy than did patients without gallbladder drainage, after adjusting for potential confounding effects of the clinical variables. This study demonstrated that there were various differences with regard to the performance of recommended treatments between the levels of procedures required for acute cholecystitis. In addition, this administrative database was a feasible tool for the evaluation of care processes and will provide useful information contributing to improved quality of medical care.
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  • Xiao-ye He, Xiao-long Zhao, Qian Gu, Ji-ping Shen, Yu Hu, Ren-ming Hu
    2012 Volume 227 Issue 4 Pages 245-252
    Published: 2012
    Released on J-STAGE: July 13, 2012
    Calorie restriction (CR) is a simple method for delaying aging process, extending lifespan, and preventing the onset of aging-related diseases, such as diabetes. However, the mechanism, by which CR influences β-cell functions during the aging process, still remains unclear. In this study, sixteen 8-week-old male Sprague-Dawley rats were randomized to control group with food intake ad libitum and CR group fed with 70% of food intake of the control group. Twenty-four weeks later, the body weights of the rats with CR were significantly lower with the smaller amounts of perirenal and epididymal fats, compared to those of control rats. The β-cell activity, as judged by the early insulin secretion in the intraperitoneal glucose tolerance test, was significantly higher in the CR group than that in control animals. Moreover, CR animals showed the increased β-cell mass and proliferation of β-cells in pancreas. The plasma level of malondialdehyde was lower in CR rats than that in control rats, while the activities of superoxide dismutase, catalase and glutathione peroxidase in plasma were higher in CR rats than control rats. These results indicate that aging is associated with the increases in oxidative stress, which was, however, alleviated by CR. In conclusion, CR from a young age preserves the principal β-cell function of early insulin secretion in rats probably by stimulating the β-cell proliferation. Our observations provide the evidence for clinical significance of CR in preventing β-cell dysfunction during the aging process, which may delay the onset of aging-related disease, including diabetes in humans.
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  • Chuang-Yu Cao, Yu-Yuan Li, Yong-Jian Zhou, Yu-Qiang Nie, Yu-Jui Yvonne ...
    2012 Volume 227 Issue 4 Pages 253-262
    Published: 2012
    Released on J-STAGE: July 18, 2012
    Non-alcoholic fatty liver disease (NAFLD) is defined as excessive accumulation of fatty acid in the liver, a common disease in the world. The research of single nucleotide polymorphisms (SNPs) provides a new approach for managing NAFLD. SNPs may increase or decrease the functions of the target genes and their encoding proteins. Peroxisome proliferator-activated receptor (PPAR) plays a key role in modulating metabolism of hepatic triglycerides and consequently magnitude of NAFLD. In this study, we investigated the effect of three SNPs in the PPAR-γ gene i.e. rs10865710 (C-681G), rs7649970 (C-689T) and rs1801282 (C34G, also termed Pro12Ala) on susceptibility to NAFLD. The participants were selected from our epidemiological survey. Totally 169 participants were enrolled in NAFLD group, and 699 healthy subjects were included as controls. PCR-RFLP was applied to detect the SNPs. The G allele frequency of rs10865710 in NAFLD group (41.1%) was significantly higher than that (34.8%) in controls (p = 0.03). Differences in other two loci (rs7649970 and rs1801282) were not statistically significant between the two groups (p > 0.05). This result was confirmed by haplotype analysis. The GCC haplotype (a set of 3 adjacent SNPs in linkage disequilibrium, corresponding to the three alleles of above polymorphisms in order) was a risk factor for the susceptibility to NAFLD (p = 0.03). This study has revealed that the G allele of rs10865710 in the PPAR-γ gene is associated with the increased susceptibility to NAFLD. Our findings may provide novel diagnostic biomarkers and therapeutic targets for NAFLD.
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  • Yuji Hatakeyama, Naohisa Miyakoshi, Yuji Kasukawa, Arata Watanabe, Mas ...
    2012 Volume 227 Issue 4 Pages 263-267
    Published: 2012
    Released on J-STAGE: July 14, 2012
    Vertebral fractures are an under-recognized problem in children with glucocorticoid-induced osteoporosis (GIO). They cause severe back pain and spinal column deformity with a decrease of quality of life. For evaluating the bone mass, bone mineral density measurements have been widely carried out using dual energy X-ray absorptiometry. However, bone histomorphometric analyses of GIO in children are scarce. Bone histomorphometric analyses of vertebral bodies have not been reported. Our aim is to report the first bone histomorphometric data for vertebrae from an autopsied child with GIO. A 15-year-old girl with systemic lupus erythematosus was started on a daily oral dose of 10 mg of prednisolone at 6 years of age. She presented with back pain from 12 years of age. Magnetic resonance imaging at 14 years of age showed a compression fracture of the first lumbar (L1) vertebral body. At 15 years of age, she died of heart failure owing to pulmonary hypertension. Collapsed (L1) and non-collapsed (seventh thoracic vertebrae; T7) vertebral bodies were autopsied for bone histomorphometry and compared. T7 showed severe osteoporosis (bone volume, 4.99%; trabecular thickness, 59 μm; trabecular separation, 1,134 μm). Compared with T7, L1 showed increased bone volume (33.9%) and trabecular thickness (77 μm), and decreased trabecular separation (156 μm) owing to the impact of the vertebral fracture. The bone formation and bone resorption parameters were comparable between the two vertebrae. These histological findings suggest that severe osteoporosis developed after long-term glucocorticoid administration, and that the remodeling activities were similar in the fractured and non-fractured vertebrae.
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  • Hansheng Liu, Aiqun Zhang, Niansong Qian, Lijie Gao, Lining Xu, Wenzhi ...
    2012 Volume 227 Issue 4 Pages 269-280
    Published: 2012
    Released on J-STAGE: July 20, 2012
    Hepatocellular carcinoma (HCC) is the most common liver tumor in Asian countries, and hepatectomy is currently regarded as the optimal curative treatment for HCC; however, the postoperative outcome remains unsatisfactory. Aiming at further clarification of prognostic factors after hepatectomy, we adopted a detailed stratification on survival periods. A total of 428 HCC patients undergoing curative hepatectomy were firstly divided into two groups using 2-year survival as cutoff point. Multivariate analysis showed that tumor-related factors, including vascular invasion (P < 0.001), high Edmondson grade (P < 0.001), large tumor size (P < 0.001) and high serum alpha-fetoprotein level (P = 0.001), were significant determinants for early death within 2 years, while postoperative transarterial chemoembolization (TACE) was demonstrated a protective factor (P = 0.013). Then the 281 patients with survival > 2 years were divided into two subgroups according to survival or death during follow-up to examine the late death related factors. We found that high serum γ-glutamyl transpeptidase (GGT), indicating severity of underlying liver disease, was significantly linked to death in this stage (P = 0.006). In further comparison of survival rates between subgroups stratified by early- and late-death indictors, we found the long-term outcomes of patients with high serum GGT were poor, regardless of the factors related with primary tumor. Furthermore, postoperative TACE decreased late death rate of patients with high GGT levels. In conclusion, despite the overwhelmed effects of primary tumor in the early stage after hepatectomy, postoperative TACE is beneficial for HCC patients with poor liver status.
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  • Jin Deng, Dongmei Huo, Qiaoyuan Wu, Zhenhua Yang, Yunhua Liao
    2012 Volume 227 Issue 4 Pages 281-288
    Published: 2012
    Released on J-STAGE: July 21, 2012
    Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). As a standard treatment regimen for remission induction of proliferative LN, intravenous cyclophosphamide (IVCYC) and corticosteroids has been widely accepted. However, cyclophosphamide (CYC) is associated with significant adverse effects. Tacrolimus, a T-cell-specific calcineurin inhibitor, shares similar immunosuppressive actions with cyclosporine. We performed a meta-analysis of randomized controlled trials (RCTs) to compare efficacy and safety between tacrolimus (oral administration and/or IV injection) and IVCYC in the induction treatment for LN. We identified 5 trials, including 225 patients. Meta-analysis showed that tacrolimus could significantly increase complete remission (RR 1.61, 95% CI, 1.17 to 2.23; P = 0.004), response rate (RR 1.25, 95% CI, 1.09 to 1.44; P = 0.001), serum albumin level (SMD 1.11, 95% CI, 0.17 to 2.06; P = 0.02) and anti-dsDNA negative conversion rate (RR 1.34, 95% CI, 1.01 to 1.78; P = 0.04), and decrease urine protein (SMD −0.52, 95% CI, −0.83 to −0.22; P = 0.0008), systemic lupus erythematosus disease activity index (SLE-DAI) (SMD −0.59, 95% CI, −1.00 to −0.19; P = 0.004) compared with that of IVCYC. The rates of gastrointestinal symptoms and irregular menstruation (or amenorrhea) were significantly lower in tacrolimus group than IVCYC group (RR 0.46, 95% CI, 0.22 to 0.93; P = 0.03 and RR 0.14, 95% CI, 0.04 to 0.50; P = 0.003). In conclusion, tacrolimus was found to be more effective and safer than IVCYC as an induction therapy for Chinese LN patients.
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  • Jing Li, Wen Zhang, Qi Guo, Xiaoxuan Liu, Qiumei Zhang, Rongna Dong, H ...
    2012 Volume 227 Issue 4 Pages 289-296
    Published: 2012
    Released on J-STAGE: July 26, 2012
    Exercise duration and intensity are important parameters in exercise prescription and play a major role in improving insulin sensitivity (including transient and persistent improvement effects following cessation of training) in patients with type 2 diabetes mellitus (T2DM). However, whether duration or intensity of exercise is the more important factor has yet to be established. Therefore, we aimed to determine whether exercise prescriptions differing in duration and intensity differ in their ability to aid T2DM patients to retain insulin sensitivity following the conclusion of a period of training. Sedentary T2DM patients (age 51.2 ± 1.3 years) were assigned to either a low-intensity (50% VO2peak, n = 27) or a high-intensity exercise group (75% VO2peak, n = 28), and followed a 12-week exercise program of 5 sessions/week and 240 kcal/session. Insulin sensitivity (oral glucose tolerance test, ISI) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. The low-intensity group spent more training time to training per exercise session than the high-intensity group (56.1 ± 3.0 min/session vs. 34.3 ± 2.4 min/session) (P < 0.01), but the total amount of energy expended was the same. ISI was increased in both groups 16-24 h after the final training session, but only the low-intensity group still had elevated ISI 15 days after the cessation of training. These findings suggest that in T2DM patients, the persistent training-induced improvements in insulin sensitivity may be more dependent on exercise duration than exercise intensity in regimens with the same level of energy expenditure.
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  • Rina So, Hiroyuki Sasai, Tomoaki Matsuo, Takehiko Tsujimoto, Miki Eto, ...
    2012 Volume 227 Issue 4 Pages 297-305
    Published: 2012
    Released on J-STAGE: July 26, 2012
    The association between visceral adipose tissue (VAT) with cardiovascular disease (CVD) has been clearly demonstrated. Although typical VAT area at 4th and 5th lumbar vertebrae (L4-L5) is used to approximate VAT volume, growing evidence has suggested that this measurement site may not be ideal. However, these findings for Asian people remain unclear. Thus, we searched for the better VAT measurement sites associated with CVD risk factors in obese, Japanese men. Eighty-two obese men were included in a cross-sectional study. Among these participants, 37 men completed the 12-week intervention (90 min and 3 d/week) were used for addressing longitudinal association between the VAT measurement sites and CVD risk factors. Consecutive MRI images (from 3 cm below L4-L5 to 20 cm above L4-L5) were used to explore the relationship between each VAT area and CVD risk factors (total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and blood pressure). The images located only 5-9 cm above L4-L5 had significant correlations with HDL cholesterol and triglycerides, but L4-L5 site did not in the cross-sectional analysis. In response to exercise, the image located 5 cm above L4-L5 showed the highest correlations with changes in total cholesterol (r = 0.46) and glucose (r = 0.36). Also, the image located 6 cm above L4-L5 showed highest correlations with changes in triglycerides (r = 0.37) and insulin (r = 0.37). Thus, the range of VAT images located 5-6 cm above L4-L5 may be optimal for identifying CVD risk factors compared to a typical site of L4-L5.
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  • Yuichi Sakamoto, Yasushi Mariya, Kohmei Kubo
    2012 Volume 227 Issue 4 Pages 307-311
    Published: 2012
    Released on J-STAGE: July 27, 2012
    Chronic active Epstein-Barr virus infection (CAEBV) presents with chronic or recurrent infectious mononucleosis-like symptoms, such as low-grade fever, liver dysfunction, lymphadenopathy, and hepatosplenomegaly. Immunological methods are useful for the diagnosis of viral infections. However, CAEBV patients do not necessarily have high titers of Epstein-Barr virus (EBV)-specific antibodies. Hosts that are immunocompromised after hematopoietic stem cell transplantations sometimes suffer from systemic EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and EBV-positive lymphoma. Patients with EBV-associated diseases are often diagnosed by analyses of bone marrow. Cytomegalovirus (CMV) can cause serious pneumonia or retinitis in immunocompromised hosts. In order to noninvasively understand the clinical status of patients with EBV-associated diseases, we conducted real-time polymerase chain reaction (PCR) methods in their peripheral blood in order to quantify EBV and CMV DNA levels, which reflect viral activity. Here, we describe a 30-year-old Japanese female patient with CAEBV. The patient had repeated fever, fatigue, and liver dysfunction. The histopathological results of liver biopsies were positive for EBV-encoded RNA-1. Acute hepatitis was associated with the EBV infection. The whole-blood EBV DNA levels were high and above 1.0 × 107 copies/mL. After immunosuppressive and antiviral therapies, EBV DNA levels lowered. However, she had to receive bone marrow transplantation because of her EBV-HLH. As the number of lymphocytes increased in the post-transplantation period, EBV DNA levels gradually increased again. The simultaneous detection of CMV DNA was more sensitive than the CMV antigenemia test that is often used to diagnose CMV infections. Unfortunately, the patient died due to a fungal infection. Observing EBV DNA levels closely with real-time quantitative PCR methods is helpful for evaluating the changes in the clinical course.
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  • Tae-Won Jang, Shin-Goo Park, Hyoung-Ryoul Kim, Jung-Man Kim, Young-Seo ...
    2012 Volume 227 Issue 4 Pages 313-319
    Published: 2012
    Released on J-STAGE: July 28, 2012
    Maximal oxygen uptake is generally accepted as the most valid and reliable index of cardiorespiratory fitness and functional aerobic capacity. The exercise test for measuring maximal oxygen uptake is unsuitable for screening tests in public heath examinations, because of the potential risks of exercise exertion and time demands. We designed this study to determine whether work-related physical activity is a potential predictor of maximal oxygen uptake, and to develop a maximal oxygen uptake equation using a non-exercise regression model for the cardiorespiratory fitness test in Korean adult workers. Study subjects were adult workers of small-sized companies in Korea. Subjects with history of disease such as hypertension, diabetes, asthma and angina were excluded. In total, 217 adult subjects (113 men of 21-55 years old and 104 women of 20-64 years old) were included. Self-report questionnaire survey was conducted on study subjects, and maximal oxygen uptake of each subject was measured with the exercise test. The statistical analysis was carried out to develop an equation for estimating maximal oxygen uptake. The predictors for estimating maximal oxygen uptake included age, gender, body mass index, smoking, leisure-time physical activity and the factors representing work-related physical activity. The work-related physical activity was identified to be a predictor of maximal oxygen uptake. Moreover, the equation showed high validity according to the statistical analysis. The equation for estimating maximal oxygen uptake developed in the present study could be used as a screening test for assessing cardiorespiratory fitness in Korean adult workers.
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  • Eun-Kyung Kim, Ji-Hyun Lee, Hye-Cheol Jeong, Doyeon Oh, Seong-Gyu Hwan ...
    2012 Volume 227 Issue 4 Pages 321-331
    Published: 2012
    Released on J-STAGE: July 31, 2012
    Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.
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