The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 228, Issue 2
Displaying 1-12 of 12 articles from this issue
Regular Contributions
  • Douglas Kazutoshi Sato, Ichiro Nakashima, Toshiyuki Fukazawa, Yuko Shi ...
    2012 Volume 228 Issue 2 Pages 85-92
    Published: 2012
    Released on J-STAGE: August 31, 2012
    Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system. Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects. Intramuscular IFN-β 1a and subcutaneous IFN-β 1b are currently available in Japan, but large-scale studies evaluating the prevalence and clinical implications of NAbs against these IFN-β preparations in MS patients have only been performed in Caucasian populations. NAbs positivity has been reported to be associated with HLA-DRB1 alleles, suggesting that the positivity might differ among populations with distinct genetic backgrounds. Clinical information and sera were collected from 229 consecutive MS patients treated with IFN-β in 4 centers in Japan. Sera were tested for NAbs using a luciferase reporter gene assay. In total, 5.2% of IFN-β-1a-treated patients (4/77) and 30.3% of IFN-β-1b-treated patients (46/152) were positive for Nabs. The frequency of NAbs was highest in patients treated for 13 to 24 months. Clinical relapse and contrast-enhancing lesions in the magnetic resonance imaging increased together with NAbs titers in this group. In conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in Caucasian populations and is associated with an increase in disease activity. Therefore, routine NAbs testing is recommended also in Asian populations to ensure the early identification of patients who would benefit from a change in therapy.
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  • Misa Miura, Kazunori Seki, Osamu Ito, Yasunobu Handa, Masahiro Kohzuki
    2012 Volume 228 Issue 2 Pages 93-101
    Published: 2012
    Released on J-STAGE: September 04, 2012
    Abdominal muscle strength declines easily with the process of aging and/or disuse, and it is difficult to strengthen weak abdominal muscles in the inactive elderly. In the present study, we applied surface electrical stimulation (ES) to the abdomen of inactive elderly people to investigate its chronic effects. Twenty inactive elderly people (65-89 years) who spent most of the day in their bedroom participated in the study. The subjects were assigned to ES and non-ES groups in a random order. In addition to conventional physical therapy and occupational therapy, ES was applied to both sides of the flank of 10 subjects (ES group) for 8 weeks. For evaluation of the abdominal muscles, the cross-sectional area (CSA) was measured with computed tomography and the electrical muscle activity (iEMG) was measured by electromyography. Functional examinations were performed at 2, 4, and 8 weeks after the beginning of the study with the following parameters: grip strength; maximum walking speed (WS); movement time for sitting up (MSU); number of trunk flexions (NTF); flexibility of the trunk; sit-to-stand time (STS); and Barthel index (BI) score. In the ES group, the NTF and MSU were significantly improved at 4 weeks and thereafter. Furthermore, the STS and WS were also improved significantly after 8 weeks (p < 0.05). The CSA and iEMG both increased significantly (p < 0.05). However, the flexibility of the trunk and BI score did not change. In conclusion, ES to the abdomen has the potential to improve motor function in the inactive elderly.
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  • Hidekazu Abe, Eiji Itoi, Nobuyuki Yamamoto, Hiroshi Minagawa, Tatsuru ...
    2012 Volume 228 Issue 2 Pages 103-108
    Published: 2012
    Released on J-STAGE: September 04, 2012
    Traumatic dislocation most commonly occurs at the shoulder joint. After an initial dislocation of the shoulder, the labrum is usually detached from the glenoid (Bankart lesion). If this lesion fails to heal, surgical repair is necessary. The purpose of this study was to determine the histological and biomechanical healing process of a simulated Bankart lesion created in rabbits. A labral injury was surgically created in 40 Japanese White rabbits. The labrum was sharply dissected from the glenoid rim simulating a Bankart lesion, and was repositioned without sutures. The joint capsule, the supraspinatus and infraspinatus tendons, and the deltoid were anatomically repaired with sutures. Eight rabbits each were sacrificed at 1, 2, 3, 4, and 5 weeks after the surgery for histological and biomechanical examinations (4 animals each). The histology and biomechanical properties of the normal capsulolabral structure was examined in 8 control rabbits. Inflammatory cell infiltration into the gap between the glenoid and the labrum was noted from 1 week. The gap was covered with fibrous connective tissue accompanied by the collagen fibers by 3 weeks. The healing process was completed histologically by 3 weeks. Biomechanically, the tensile load, which decreased significantly at 1 week, gradually increased and returned to the level of intact shoulder at 4 weeks. At least four weeks are necessary for the healing of the labral injury in rabbits. Considering the difference between humans and rabbits, it seems reasonable to let the patients go back to sports 2 to 3 months after dislocation or surgical repair.
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  • Sejoong Kim, Jiyoon Sung, Woong Chul Kang, Shin Young Ahn, Dong Ki Kim ...
    2012 Volume 228 Issue 2 Pages 109-117
    Published: 2012
    Released on J-STAGE: September 05, 2012
    Contrast-induced acute kidney injury (CIAKI) is a common complication after percutaneous coronary artery intervention (PCI). It is urgent to find a novel, easily measurable and accurate predictor for the early detection of CIAKI. Hyperosmolarity and large amounts of contrast media are risk factors for CIAKI. However, there is no study on plasma osmolar gap as a predictor of CIAKI. We enrolled 89 patients undergoing elective PCI and tested changes of serum sodium, osmolar gap, and renal function at 0, 6, 12 and 24 hours. Plasma osmolar gap was calculated using the following formula: measured plasma osmolarity - [2(Na) + serum urea nitrogen/2.8 + glucose/18]. CIAKI was defined as follows: increase in serum creatinine of ≥ 50%, increase in serum creatinine of ≥ 0.3 mg/dL, or decrease in estimated glomerular filtration rate of ≥ 25% within 24 hours after PCI. The incidence of CIAKI was 13.5% (12/89 patients). The CIAKI group had higher plasma osmolar gaps 6 hours after PCI. The adjusted hazard ratio of the plasma osmolar gap from hour 6 (1-mOsm/L increments) to the development of CIAKI was 1.12 (95% confidence interval [CI], 1.01-1.26; P = 0.041). Sensitivity and specificity of 7 mOsm/L or higher plasma osmolar gap at hour 6 were 70.0% and 76.6%, respectively (area under the ROC curve = 0.77 [95% CI, 0.65-0.89]). Increased plasma osmolar gap may precede the development of CIAKI in patients undergoing PCI. In conclusion, plasma osmolar gap may be a useful predictor for the development of CIAKI.
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  • Baris Kilicaslan, Oner Ozdogan, Mehmet Aydin, Huseyin Dursun, Ibrahim ...
    2012 Volume 228 Issue 2 Pages 119-124
    Published: 2012
    Released on J-STAGE: September 06, 2012
    Epicardial fat tissue is a visceral fat depot with anatomical and functional contiguity to the myocardium and coronary arteries. The objective of this study was to evaluate the association between epicardial fat thickness (EFT) and cardiac changes in healthy female subjects. The study population consisted of ninety-six consecutive healthy female (mean age 31.1 ± 6.7 years) who underwent transthoracic echocardiography. EFT was measured by echocardiography. Subjects were divided into two groups according to the EFT; EFT < 6 mm and EFT ≥ 6 mm. The cardiac structural changes, increased left atrial volume indices (LAVI) (41.2 ± 9.9 vs. 52.6 ± 12.5, p = 0.001) and left ventricular mass indices (LVMI) (129.6 ± 32.1 vs. 155.6 ± 31.6 p < 0.05), were observed in patients with increased EFT. Myocardial tei index (MTI), which was used to evaluate both systolic and diastolic functions, was higher with increased EFT (0.44 ± 0.07 vs. 0.48 ± 0.08, p = 0.02). The correlation analysis revealed significant correlation between EFT and each of LAVI (r = 0.312, p = 0.002), LVMI (r = 0.301, p = 0.003), body mass index (BMI) (r = 0.8, p < 0.001), and MTI (r = 0.27, p = 0.005). Multivariate regression analysis demonstrated that EFT was associated with BMI (t = 5.28, p = 0.001), MTI (r = 2.39, p = 0.019), LVMI (r = 2.16, p = 0.01), and LAVI (r = 3.21, p = 0.002). In conclusion, EFT is an important predictor of cardiac alterations in women who are prone to obesity.
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  • Sejoong Kim, Jiyoon Sung, Eun Sook Jung, Hayne Cho Park, Hajeong Lee, ...
    2012 Volume 228 Issue 2 Pages 125-133
    Published: 2012
    Released on J-STAGE: September 13, 2012
    Subtle fluid imbalance can cause poor clinical outcomes among hemodialysis patients. However, the traditional subjective assessment of fluid status may be inadequate. We evaluated whether the objective measurement and optimization of fluid status could be beneficial for hemodynamic and biochemical parameters in hemodialysis patients. We enrolled 120 hemodialysis patients, who were clinically euvolemic for at least 3 months. Based on the results of a body composition monitor, we divided the patients into the following two groups: the hyperhydrated group (post hemodialysis fluid overload ≥ 1.1 L) and the dehydrated group (post hemodialysis fluid overload < −1.1 L). We reduced the patient's body weight in the hyperhydrated group and raised the body weight in the dehydrated group towards normohydration (−1.1 L ≤ fluid overload < 1.1 L) for 16 weeks. Forty-four of 120 patients were in the hyperhydrated group, and 18 of 120 patients in the dehydrated group. After 16 weeks, systolic blood pressure and pulse pressure decreased in the hyperhydrated group, while there was no increase in blood pressure in the dehydrated group after the intervention. Serum levels of monocyte chemotactic protein-1, an inflammatory marker, gradually decreased in the hyperhydrated group, and serum adiponectin levels, an anti-atherogenic biomarker, increased in the two groups. We found that hyperhydrated patients contributed over 1/3 of the participants despite enrolling clinically euvolemic patients and that body composition monitor-guided optimization of body fluid status may lead to improvement of inflammatory markers and anti-atherogenic adipokines as well as hemodynamic parameters in hemodialysis patients.
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  • Sumiko Maeda, Satomi Takahashi, Masami Sato
    2012 Volume 228 Issue 2 Pages 135-141
    Published: 2012
    Released on J-STAGE: September 14, 2012
    Postoperative lung injury after lung cancer resection is still a difficult problem to be solved. Thrombomodulin (TM) is a membrane-bound glycoprotein of endothelial cells, and its serum level is elevated in patients with acute lung injury or acute respiratory distress syndrome. In fact, TM is abundant in the pulmonary capillary vessels. Lung resection reduces the volume of pulmonary capillary vessels; however, the change in the serum levels of TM after lung resection remains to be investigated. We therefore analyzed the postoperative changes in the serum TM levels in 60 patients who underwent thoracotomy without lung resection (n = 3), partial resection of the lung (n = 15), or lobectomy (n = 42). Preoperative and postoperative day-1 laboratory data including the serum levels of TM and KL-6, a sialylated carbohydrate antigen (a biomarker for pulmonary fibrosis), and oxygenation index were collected. Unexpectedly, the postoperative serum levels of TM were lower than preoperative values in lobectomy group, whereas they remained unchanged after thoracotomy without lung resection and after partial resection of the lung. In addition, the serum TM level decreased proportional to the resected lung volume. Eight out of 42 patients with lobectomy presented high postoperative serum levels of TM, and 3 out of these 8 patients presented postoperative impaired oxygenation. Postoperative impaired oxygenation occurred only in patients with elevated TM levels; namely, an increase of serum TM is associated with impaired oxygenation after lung resection. In conclusion, serum TM is a possible biomarker for predicting the occurrence of postoperative lung injury.
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  • Yosuke Kakisaka, Tomoichiro Ohara, Hideo Tozawa, Shun Sato, Saori Kata ...
    2012 Volume 228 Issue 2 Pages 143-145
    Published: 2012
    Released on J-STAGE: September 22, 2012
    Gynecomastia or benign proliferation of the male breast glandular tissue is not uncommon for adolescent males. Its pathogenesis has been attributed to a transient imbalance between estrogens and androgens. Ginseng is a popular herb with a long history of medicinal use. Oriental folk medicine describes it as both a tonic for restoring strength and a panacea. The term “ginseng” generally refers to a plant, Panax ginseng. Based on estrogen-like actions of Panax ginseng due to its structural similarity with estradiol, this agent could be speculated to cause gynecomastia. Here we report a 12-year-old Korean-Japanese boy with bilateral enlargement of the breasts with tenderness in the right breast, which was noticed about 1 month before his first visit to our outpatient clinic. He was diagnosed with gynecomastia based on physical, laboratory, and ultrasound examinations. Detailed questioning about his medications and supplements revealed that he had been given red ginseng extract daily to enhance his performance for 1 month before his clinical presentation. He wanted to make his body stronger as an athlete. He was recommended from his grandmother to take Panax ginseng for his purpose. After stopping this, there was no further growth of the masses and no pain when his right breast was pressed. In conclusion, physicians should consider ginseng in the investigation of gynecomastia.
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  • Xin Liu, Jing Peng, Wenchang Sun, Shufeng Yang, Guoying Deng, Fang Li, ...
    2012 Volume 228 Issue 2 Pages 147-156
    Published: 2012
    Released on J-STAGE: September 26, 2012
    Prostate cancer is the most common malignancy in Western countries. Chemokine C-X-C motif receptor 1 (CXCR1) and CXCR2 play a key role in generation and regulation of CXC chemokine signaling. CXCR1 is a receptor for interleukin 8 (IL8), a pro-inflammatory chemokine, and CXCR1/2 are crucially involved in the prostate cancer development and progression. Thus, we generated a high-affinity human CXCR1/CXCR2 inhibitor, CXCL8 (3-72) K11R/G31P, named G31P, which is a synthetic derivative of the human cytokine, IL-8. In this study, we investigated the effects of G31P on regulation of prostate cancer cell growth in vitro and in nude mouse xenografts. Cell viability, adhesion, and wound healing assays were used to assess the effects of G31P on growth, adhesion, and migration of PC-3 human prostate cancer cells in vitro, respectively. Nude mouse xenografts and xenograft implantation assays were performed to determine the effect of G31P on PC-3 cells in vivo. Immunohistochemistry was used to detect gene expression, and fluorescence imaging was used to detect tumor volume and microvessel density in tumor xenografts. The data showed that G31P treatment significantly reduced PC-3 cell viability, adhesion and migration capacity in a dose-dependent manner (up to 100 ng/ml). Additionally, G31P treatment of nude mice suppressed the growth of orthotopically transplanted tumor xenografts. G31P also inhibited tumor tissue vascularization, which was associated with the decreased expression of vascular endothelial growth factor and nuclear transcription factor (NF)-κB in orthotopic xenograft tissues. This study provides evidence that G31P, a CXCR1/2 inhibitor, may effectively control prostate cancer.
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  • Hiroki Saitoh, Yugo Ashino, Haorile Chagan-Yasutan, Toshiro Niki, Mits ...
    2012 Volume 228 Issue 2 Pages 157-161
    Published: 2012
    Released on J-STAGE: October 02, 2012
    Acute HIV-1 infection is often diagnosed as infectious mononucleosis and the symptoms resolve spontaneously after varying periods of time. After the infection of HIV-1 through the mucosa, the characteristic clinical symptoms and laboratory markers of acute HIV-1 infection appear in each patient through a complicated virus-host interaction. To understand the host responses, we measured two unique proinflammatory cytokines, galectin-9 (Gal-9) and osteopontin (OPN). A β-galactoside-binding mammalian lectin, Gal-9, reduces pro-inflammatory type-1 helper T (Th1) cells and Th17 cells and increases anti-inflammatory regulatory T cells. The plasma level of Gal-9 is known to be associated with HIV-1 viral load in chronic HIV-1 infection. On the contrary, osteopontin induces Th1/Th17 cells and promotes tissue inflammation. OPN is synthesized by variety of cells in the body, and dendritic cells are known to synthesize OPN in HIV-1 infected individuals. It was hypothesized that Gal-9 and/or OPN could be not only immune-modulators but also novel biomarkers of acute HIV-1 infection. We experienced 3 patients with acute HIV-1 and measured the levels of Gal-9 and OPN periodically before and after antiretroviral treatment. The results showed that the plasma levels of Gal-9 were extremely elevated [more than 2,300 pg/ml (normal range < 46 pg/ml)] in all three acute HIV-1 infected individuals and decreased rapidly after treatment. The changes in the OPN levels were less marked. In conclusion, the plasma levels of Gal-9 may be predictive of a severe inflammation status during the acute phase of HIV-1 infection and could be a potential biomarker during acute infection.
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  • Mikiko Hashisako, Kentarou Wakamatsu, Satoshi Ikegame, Hiroyuki Kumazo ...
    2012 Volume 228 Issue 2 Pages 163-168
    Published: 2012
    Released on J-STAGE: October 03, 2012
    The skeleton is the most common site for distant metastasis in patients with cancer. To detect bone metastasis and evaluate the efficacy of treatment, we usually use bone scintigraphy and check serum alkaline phosphatase (ALP). However, such evaluation is sometimes difficult due to flare phenomenon. A 61-year-old male was referred to our department with a suspected diagnosis of lung cancer. Following thorough examinations, he was diagnosed with primary lung cancer (adenocarcinoma, Stage IV) and found to have a mutation in the epidermal growth factor receptor gene at exon 21 (L858R). After initiating treatment with oral gefitinib, ALP increased and peaked at 3,592 U/L by 3 weeks and decreased thereafter. At 4 weeks following treatment initiation, bone scintigraphy revealed a marked increase in abnormal accumulation of 99mTc-polyphosphate, but the primary tumor and metastases in regions other than the bone were reduced. At 9 weeks after treatment initiation, abnormal accumulations was improved in bone scintigraphy, and computed tomography revealed osteoblastic changes consistent with the accumulated lesion observed by bone scintigraphy. After initiating cancer treatment for bone metastasis, it is not uncommon to observe transient asynchronous accumulation in bone scintigraphy or transient increases in ALP in patients who ultimately respond to the treatment. These changes are called flare phenomenon, and documented in patients with prostate cancer or breast cancer receiving treatment. When determining the efficacy of treatments that target carcinomas with bone metastases, it is important to note that flare phenomenon is often indistinguishable from disease progression indicators.
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Letter to the Editor