The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 232, Issue 2
February
Displaying 1-10 of 10 articles from this issue
Invited Review
  • Atsushi Masamune
    Article type: Invited Review
    2014 Volume 232 Issue 2 Pages 69-77
    Published: 2014
    Released on J-STAGE: February 07, 2014
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    Chronic pancreatitis is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to malnutrition and diabetes. Alcohol is the leading cause in Western countries, but genetic factors are also implicated. Since the identification of mutations in the cationic trypsinogen (PRSS1) gene as a cause of hereditary pancreatitis in 1996, we have seen great progress in our understanding of the genetics of pancreatitis. It has been established that mutations in the genes related to the activation and inactivation of trypsin(ogen) such as PRSS1, serine protease inhibitor Kazal type 1 (SPINK1) and chymotrypsin C (CTRC) genes are associated with pancreatitis. In 2013, carboxypeptidase A1 (CPA1) was identified as a novel pancreatitis susceptibility gene. Endoplasmic reticulum stress in pancreatic acinar cells resulting from the mis-folding of mutated pancreatic enzymes has been shown to act as a novel mechanism underlying the susceptibility to pancreatitis. In Japan, the nationwide survey revealed 171 patients (96 males and 75 females) with hereditary pancreatitis in 59 families based on the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer criteria. Because about 30% of families with hereditary pancreatitis do not carry mutations in any of the known pancreatitis susceptibility genes, other yet unidentified genes might be involved. Next generation sequencers can perform billions of sequencing reactions with a read length of 150-250 nucleotides. Comprehensive analysis using next generation sequencers will be a promising strategy to identify novel pancreatitis-associated genes and further clarify the pathogenesis of pancreatitis.
Review
  • Yeongcheol Eum, Jongeun Yim, Wonjae Choi
    Article type: Review
    2014 Volume 232 Issue 2 Pages 79-83
    Published: 2014
    Released on J-STAGE: February 07, 2014
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    Recently, the problems of old age have been discussed in terms of two aspects: preventive and therapeutic approach. The previous studies on the preventive aspect have been mostly concerned with the educational preparation for successful approach to elderly, directing focus toward the transitional period of the old age. Most research into the therapeutic aspect on the elderly diseases has focused on organic mental disorders such as dementia and functional mental diseases such as depression. This study aims to suggest the preventive and new therapeutic possibility in old people through combining the elderly health with literature. First, the research results regarding the social background for the elderly problems indicate that geriatric diseases increase in proportion to the increase of the population. Secondly, for the literature therapy, it is initially required to seek a comprehensive understanding about the health of the elderly through the phased consideration for the elderly problems. Thirdly, for the treatment of geriatric diseases by using literature, it is necessary to develop more active and integrative literature therapy than passive bibliotherapy. Literature therapy is the use of literature in the treatment of people with emotional or mental illness. Fourthly, theoretical approach should be considered for the health of the elderly and the literature therapy. From a literary approach, the literature therapy can help the study on geriatric diseases such as dementia and depression. Thus, the program for the health of geriatric issues and literature therapy should be developed as the next step in the future.
Regular Contribution
  • Chaohui Wu, Yunpeng Cao, Zefeng He, Jianbing He, Chao Hu, Hongbing Dua ...
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 85-95
    Published: 2014
    Released on J-STAGE: February 15, 2014
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    MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinum-based chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.
  • Tsubasa Suzuki, Yasuhiko Ono, Hidenori Maeda, Yoshiki Tsujimoto, Yugo ...
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 97-104
    Published: 2014
    Released on J-STAGE: February 15, 2014
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    Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: −4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.
  • Koichi Ogawa, Tadashi Kondo, Takafumi Tamura, Hideki Matsumura, Kiyosh ...
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 105-113
    Published: 2014
    Released on J-STAGE: February 19, 2014
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    Liver steatosis increases the risk of postoperative complications following major liver resection, since the steatotic liver is susceptible to ischemia-reperfusion (IR) injury. However, it is unclear how IR injury changes in relation to the degree of hepatic steatosis. Previously, we reported that interaction between Kupffer cells (KCs) and platelets induced hepatic IR injury. The aim of our present study was to evaluate the relationship between the degree of liver steatosis and IR injury by focusing on the interaction of KCs and platelets. Mild and moderate steatotic liver models were generated in Wistar rats by feeding a choline-deficient diet for 2 and 4 weeks, respectively. The intensity of steatosis was defined based on the proportion of hepatocytes with fatty infiltration: normal (less than 5%), a mild steatosis (5-30%), and moderate steatosis (30-60%). All groups were subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The number of adhesion of KCs to platelets in sinusoids was observed by intravital microscopy. IR injury was evaluated with serum alanine aminotransferase levels, histological findings, and sinusoidal perfusion. Compared to the normal liver, mild steatosis reduced the adhesion of KCs to platelets, inducing the attenuation of IR injury. In contrast, moderate steatosis increased the adhesion of KCs to platelets, aggravating IR injury relative to the normal liver. IR injury in the steatotic liver was not simply proportional to the degree of steatosis. Mild steatosis ameliorates IR injury compared to the normal liver, whereas moderate steatosis increases IR injury.
  • Fumiko Sato, Takanori Ishida, Noriaki Ohuchi
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 115-122
    Published: 2014
    Released on J-STAGE: February 21, 2014
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    Most patients who undergo breast cancer surgery suffer from impairment of upper extremity function. In this study, we investigated the effectiveness of a perioperative educational program for improving upper arm dysfunction in patients with breast cancer. This longitudinal controlled study was conducted between January 2010 and July 2012. Participants comprised 149 patients with primary breast cancer before operation, allocated to intervention and control groups. Intervention comprised a 3-month educational program on monitoring arm function and exercises for preventing shoulder dysfunction and lymphedema. The control group received routine care from on-site staffs. Of the 149 patients analyzed, 69 underwent axillary lymph node dissection (ALND), and 80 underwent sentinel lymph node biopsy (SLNB). The intervention group included 39 patients with ALND and 51 patients with SLNB, while the control group included 30 patients with ALND and 29 patients with SLNB. Arm girth, shoulder range of motion (ROM), and grip strength were measured before surgery and at 1 week, 1 month and 3 months postoperatively. Self-reported questionnaires, the Subjective Perception of Post-Operative Functional Impairment of the Arm (SPOFIA) and the Disabilities of the Arm, Shoulder and Hand (DASH), were administered at the same time points. Among the variables examined, only SPOFIA and grip strength were significantly improved in the intervention group with ALND. In contrast, the perioperative educational program caused no significant improvement for the patients who underwent the surgery with SLNB. Thus, the present program improves the postoperative upper arm function and discomfort in breast cancer patients who undergo surgery with ALND.
  • Yasuhiro Mori, Kousuke Kanemoto, Teiichi Onuma, Masaki Tanaka, Tomohir ...
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 123-128
    Published: 2014
    Released on J-STAGE: February 21, 2014
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    Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.
  • Hui Zhang, Zhuqin Gu, Jing An, Chaodong Wang, Piu Chan
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 129-136
    Published: 2014
    Released on J-STAGE: February 25, 2014
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    Non-motor symptoms (NMS) are important preclinical features of Parkinson’s disease (PD) and have become the leading cause of poor quality of life with disease progression. There are little data on how antiparkinsonian medications influence the NMS in PD at early stage. In this study, we explored the distribution of NMS in treated and untreated PD and investigated the association between NMS and antiparkinsonian medications in Chinese patients with early PD. Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical trials. Face-to-face interviews and evaluations were performed for clinical information. NMS were compared in patients with or without antiparkinsonian treatment, and between subgroups of dopaminergic medications. Eight hundred and sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were free of NMS. PD patients with antiparkinsonian medications had a significantly higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn & Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis revealed that Levodopa Equivalent Dose (LED) was associated with constipation (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in the prodromal stage of PD, antiparkinsonian treatment is associated with increased frequency of some NMS, which may challenge the management for PD.
  • Ahmet Arif Yalcin, Ibrahim Faruk Akturk, Omer Celik, Mehmet Erturk, Ve ...
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 137-144
    Published: 2014
    Released on J-STAGE: February 25, 2014
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    Coronary artery ectasia (CAE) is characterized by inappropriate dilation of the coronary vasculature. The underlying mechanisms of CAE formation are not yet entirely known. A polymorphism in the endothelial nitric oxide synthase (eNOS) gene, which reduces eNOS activity, might be a risk factor for coronary heart diseases. However, its role in CAE is unknown. One of the most studied eNOS gene polymorphisms is a c.894G>T polymorphism that results in the conversion of Glu (GAG) to Asp (GAT) at position 298. In this study, we investigated the potential association between the c.894G>T (Glu298Asp) polymorphism and CAE. The present study included 84 subjects from 2,980 consecutive patients in whom elective diagnostic coronary angiography was performed. Forty patients with isolated CAE and 44 subjects with normal coronary arteries were enrolled. The frequencies of the G allele were 78.4% in the control and 57.5% in CAE patients. The TT genotype was more frequent in patients with CAE than that in the controls (20% vs. 4.5%, p = 0.013). Furthermore, the risk of developing CAE in the presence of the homozygous TT genotype was significantly higher in the patients than that in the controls (OR = 7.7, 95% CI = 1.44-41.3). The presence of an 894T allele increased the risk of CAE 2.8-fold (95% CI = 1.15-6.73; p = 0.027). The frequencies of the T allele were 65% in CAE patients and 38.6% in the controls. In conclusion, the c.894G>T polymorphism in the eNOS gene may be a risk factor for CAE.
  • Olaf Stanger, Irene Aigner, Wolfgang Schimetta, Willibald Wonisch
    Article type: Regular Contribution
    2014 Volume 232 Issue 2 Pages 145-154
    Published: 2014
    Released on J-STAGE: February 27, 2014
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    Ischemia-reperfusion has been reported to be associated with augmented oxidative stress in the course of surgery, which might be causally involved in the onset of atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. We hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty acids (n-3 PUFAs) might lower the incidence of AF following coronary artery bypass graft (CABG) surgery. In the present study, by monitoring oxidative stress in the course of CABG surgery, we analyzed the efficacy of vitamins (ascorbic acid and α-tocopherol) and/or n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid). Subjects (n = 75) were divided into 4 subgroups: control, vitamins, n-3 PUFAs, and a combination of vitamins and n-3 PUFAs. Fluorescent techniques were used to measure the antioxidative capacity, i.e. ability to inhibit oxidation. Total peroxides, endogenous peroxidase activity, and antibodies against oxidized LDL (oLAb) were used as serum oxidative stress biomarkers. Post-operative increase in oxidative stress was associated with the consumption of antioxidants and a simultaneous onset of AF. This was confirmed through an increased peroxide level and a decreased oLAb titer in control and n-3 PUFAs groups, indicating the binding of antibodies to oxidative modified epitopes. In both subgroups that were supplemented with vitamins, total peroxides decreased, and the maintenance of a constant IgG antibody titer was facilitated. However, treatment with vitamins or n-3 PUFAs was inefficient with respect to AF onset and its duration. We conclude that the administration of vitamins attenuates post-operative oxidative stress in the course of CABG surgery.
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