The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 223, Issue 3
March
Displaying 1-11 of 11 articles from this issue
Regular Contributions
  • Chia-Chao Wu, Jen-Hung Chang, Chun-Chi Chen, Shih-Bin Su, Lai-King Yan ...
    2011 Volume 223 Issue 3 Pages 153-159
    Published: 2011
    Released on J-STAGE: February 23, 2011
    JOURNAL FREE ACCESS
    Hemodialysis patients with secondary hyperparathyroidism (SHP) suffer from excessive oxidative stress and inflammation. Vitamin D analogues are currently the first line therapy for SHP, but the influence of vitamin D treatment on inflammation and oxidative stress remains unknown. This study investigated the influence of vitamin D therapy on oxidative stress and inflammatory markers in hemodialysis patients with SHP. Twenty-five patients (mean age 58 ± 12 years, 13 males and 12 females) were enrolled in the study to receive calcitriol treatment for 16 weeks. We evaluated changes in the serum biochemical parameters, inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6) levels], serum oxidative stress condition [total antioxidant status (TAS)], and CD4+ T-lymphocyte intracellular cytokines [interferon γ (IFN-γ) and interleukin-4 (IL-4)] before and at the end of the 16-week calcitriol treatment. Correlations between each of these factors were also studied. All patients with SHP had low serum 1,25-dihydroxyvitamin D3 levels and elevated serum levels of intact parathyroid hormone (iPTH), CRP and IL-6. Twenty patients (10 males and 10 females) responded to the calcitriol therapy, with significant decrements in serum iPTH. Our results showed that calcitriol can effectively suppress iPTH secretion, reduce inflammatory markers (CRP and IL-6) and oxidative stress. It can also effectively reduce inflammatory cytokine (CD4+ IFN-γ) and increase anti-inflammatory cytokine (CD4+ IL-4). Interestingly, significant correlations between CD4+ IFN-γ levels and serum iPTH levels, as well as between TAS and iPTH levels were noted. Overall, our study has demonstrated calcitriol treatment significantly attenuates inflammation and oxidative stress in hemodialysis patients with SHP.
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  • Jian-Guo Hu, Yan-Xia Wang, Jian-Sheng Zhou, Chang-Jie Chen, Feng-Chao ...
    2011 Volume 223 Issue 3 Pages 161-176
    Published: 2011
    Released on J-STAGE: March 01, 2011
    JOURNAL FREE ACCESS
    Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.
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  • Bin Zhang, Ying Li, Qiang Zhou, Yin Ding
    2011 Volume 223 Issue 3 Pages 177-186
    Published: 2011
    Released on J-STAGE: March 01, 2011
    JOURNAL FREE ACCESS
    Estrogen deficiency in post-menopausal women is considered as one of the risk factors for periodontal diseases. The periodontal ligament is a connective tissue that connects cementum and alveolar bone to constrain teeth within the jaw. Periodontal ligament stem cells (PDLSCs) isolated from the periodontal ligament can differentiate into many types of specialized cells, including osteoblast-like cells that can be used to regenerate alveolar bone. However, little is known about the effect of estrogen-deficient microenvironment on the osteogenic differentiation of PDLSCs. The aim of this study was to explore the role of estrogen on the potential for osteogenic differentiation of PDLSCs using a rat model of osteoporosis. Three-month-old female Sprague-Dawley rats were divided into two groups (n = 6 for each): ovariectomized (OVX) and sham-operated rats (Sham). Then the characteristics of PDLSCs isolated from these rats were investigated. Real-time PCR analysis showed the lower expression levels of estrogen receptors (ERα and ERβ) mRNAs in PDLSCs of OVX animals compared to Sham control. Mineralization assay demonstrated fewer calcium deposits in PDLSCs from OVX group than those from Sham group. Treatment with 17β-estradiol (E2) significantly enhanced the osteogenic differentiation of PDLSCs from both groups in vitro. Furthermore, by means of lentivirus-mediated siRNA targeting ERα or ERβ, the expression of ERα or ERβ was down-regulated (> 50% reduction), which impaired the estrogen-induced osteogenic differentiation of PDLSCs from both groups (> 50% reduction). These results indicate that estrogen plays an important role in maintaining osteogenic differentiation of PDLSCs, which acts through both ERα and ERβ.
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  • Akane Izu, Hidehiko Yanagida, Keisuke Sugimoto, Shinsuke Fujita, Naoki ...
    2011 Volume 223 Issue 3 Pages 187-192
    Published: 2011
    Released on J-STAGE: March 01, 2011
    JOURNAL FREE ACCESS
    Focal segmental glomerular sclerosis (FSGS) is a leading cause of the nephrotic syndrome and characterized by the sclerosing lesions that affect one or more segments of some glomeruli. We encountered a female patient with a partial deletion of chromosome 6p, who presented proteinuria at age 3 years. Detailed chromosomal analysis disclosed an interstitial deletion of 6p: del(6)(p22.1p22.3). No abnormality such as hydronephrosis or renal agenesis was disclosed by imaging, but FSGS was present in a renal biopsy specimen. The patient is currently 11 years old and shows mental retardation with mild deterioration in the renal function. To address the defective genes in the present patient, we carried out comparative genomic hybridization (CGH), showing that E2F3 on chromosome 6p is absent in this patient. E2F3, a member of the E2F family transcription factors, inhibits expression of vascular endothelial growth factor (VEGF) and induces apoptosis during vascular development. The deletion of E2F3 was also detected by employing a PCR method, suggesting that glomerular architecture had been compromised in this patient. Serum VEGF concentrations were elevated to 177 ± 21.4 pg/mL (upper limit of 33.3 pg/mL), when she was 6 years old, associated with the enhanced expression of VEGF in glomeruli. These findings suggest that the dysregulation of VEGF synthesis caused by the deletion of E2F3 may be associated with development of FSGS. In conclusion, among patients with idiopathic FSGS, an abnormality of E2F3 may exist on chromosome 6p. Therefore, one might consider chromosomal analyses in children with FSGS who have mental retardation.
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  • He-Zuo Lü, An-You Zhu, Yong Chen, Jie Tang, Bai-Qing Li
    2011 Volume 223 Issue 3 Pages 193-198
    Published: 2011
    Released on J-STAGE: March 02, 2011
    JOURNAL FREE ACCESS
    Lipid rafts are plasma membrane microdomains that are implicated in diverse signaling pathways in immune cells. Based on the distinct types of T-cell receptors, two T-cell subpopulations have been identified: αβ and γδ T cells. In humans, γδ T cells represent a relatively rare T lymphocyte population but play a critical role in the immune response to infection by Mycobacterium tuberculosis. It has been demonstrated that Mycobacterium tuberculosis antigens (Mtb-Ag) preferentially activate γδ T cells. Thus, we investigated whether lipid rafts are involved in the Mtb-Ag-mediated activation of γδ T cells. Human peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-Ag, and expression of a lipid raft marker ganglioside GM1 (GM1) was determined by flow cytometry. The aggregation of lipid rafts was evaluated by laser confocal microscopy. Non-stimulated fresh PBMCs minimally expressed GM1 (6.55 ± 2.01%) and had no aggregated rafts in γδ T cells. Mtb-Ag stimulation gradually increased the expression of GM1 in a time-dependent manner. At 72 h, the majority of γδ T cells expressed GM1 (88.69 ± 7.55%). Furthermore, accompanied with the increased expression of GM1, aggregation of lipid rafts became gradually visible in γδ T cells. The aggregated rafts, however, were not evenly distributed and only occurred over a small portion of GM1-positive cells. Pretreatment with methyl-β-cyclodextrin, a cholesterol-depleting reagent, completely inhibited the Mtb-Ag-mediated aggregation of lipid rafts. These results demonstrate that lipid raft aggregation occurs in Mtb-Ag-activated γδ T cells, suggesting that lipid rafts are involved in activation of γδ T cells.
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  • Jae Woo Jung, Jong Wook Shin, Jae Yeol Kim, In Won Park, Byoung Whui C ...
    2011 Volume 223 Issue 3 Pages 199-204
    Published: 2011
    Released on J-STAGE: March 02, 2011
    JOURNAL FREE ACCESS
    Paradoxical response (PR) is the unusual expansion or new formation of a tuberculous lesion during anti-tuberculosis (TB) treatment. Pleural TB is the second most common form of extrapulmonary TB and has clinical importance because it occurs in a restricted space. Limited information is available for PR in HIV-negative patients with pleural TB. The aim of this study was to evaluate the clinical characteristics and risk factors of PR in HIV-negative patients with pleural TB. Patients diagnosed with pleural TB between 2003 and 2008 at Chung-Ang University Hospital and Yong-San Hospital, Seoul, South Korea were included. We evaluated the incidence and treatment outcome of PR in pleural TB, and compared baseline clinical characteristics and laboratory findings between TB patients with PR and those without PR. PR was present in 32 (23%) of 139 patients after mean 51.1 days following initiation of treatment. Out of 32 patients, 18 patients needed additional treatment for symptom control. PR patients had a high incidence of adverse drug reaction such as drug skin reaction or liver function abnormality (P < 0.05). The risk factors for PR are younger age, high serum albumin level, low proportion of lymphocyte, and high proportion of PMN in pleural fluid (P < 0.05). PR is not an uncommon problem in HIV-negative pleural TB and half of these patients need additional treatment. Therefore, physicians must pay more attention for PR during the management of pleural TB in the expected patients to develop PR.
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  • Toru Okamura, Mitsugi Nagashima, Yukiko Yamada, Takeshi Hiramatsu, Ken ...
    2011 Volume 223 Issue 3 Pages 205-209
    Published: 2011
    Released on J-STAGE: March 02, 2011
    JOURNAL FREE ACCESS
    Congenital coronary artery fistula (CAF) is a rare anomaly involving communication between the coronary artery and any cardiac chamber. We retrospectively studied 23 patients with CAF who were surgically treated at 2 institutes over the past 38 years. All patients had continuous murmur and were diagnosed using echocardiography and cardiac catheterization. Eighteen patients had no other heart anomalies, and 5 had an associated anomaly. Fifteen patients were treated using cardiopulmonary bypass via differential surgical approaches (6 patients, CAF orifice closure through cardiac chamber; 6, coronary arteriotomy for CAF orifice closure; and 3, CAF ligation). Eight patients underwent CAF ligation without cardiopulmonary bypass. CAF originated from the right coronary artery in 11 patients; the left coronary artery in 10, and both arteries in 2. Drainage occurred at the following sites: the right ventricle (10 patients), right atrium (6), left ventricle (4), left atrium (2), and pulmonary artery (1). All surgeries were performed through a median sternotomy. There were no mortalities during or after the hospital stay. Aortic root replacement was performed in 1 patient 30 years after the CAF surgery. Three of the 6 patients who underwent coronary arteriotomy for CAF orifice closure showed coronary artery occlusion at the distal coronary arteriotomy site with long-term collateral formation. Surgical management of CAF was thus effective, resulting in 100% long-term survival and closure rates. Dilated CAF-associated vessels have been normalized for the long term. CAF should be therefore considered even in asymptomatic patients because of the risk of future complications.
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  • Yuko Shimizu, Kazuo Fujihara, Sachiko Kubo, Toshiyuki Takahashi, Tatsu ...
    2011 Volume 223 Issue 3 Pages 211-214
    Published: 2011
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    Optic neuritis and myelitis are manifestations in both multiple sclerosis (MS) and neuromyelitis optica (NMO). But unlike MS, NMO is characterized by severe optic neuritis, longitudinally extensive and transverse myelitis, and the presence of aquaporin-4 antibody. Since patients with optic neuritis and myelitis have often been diagnosed with “optic-spinal MS (OSMS)” in Asia, it was obscure whether “OSMS” is synonymous with NMO or includes both NMO and MS. Interferon β (IFNβ)-1a and -1b are used as the first-line disease-modifying therapy for MS. However, some neurologists have been reluctant to use IFNβ to treat patients with optic-spinal symptoms, because IFNβ therapy is not efficacious in NMO. To evaluate the therapeutic effect of IFNβ in patients with “genuine” OSMS, we retrospectively evaluated Japanese MS patients who fulfilled the following six criteria: 1) Relapsing-remitting MS with optic-spinal presentation alone (no brain symptoms), 2) With or without asymptomatic brain MRI lesions, 3) Oligoclonal IgG band-positive, 4) aquaporin-4 antibody seronegativity, 5) No myelitis extending longitudinally over ≥ 3 vertebral segments, and 6) Duration of IFNβ-1b therapy ≥ 2 years. Among 157 patients with MS, six (four women and two men, age 43.8 ± 8.5 years old) met all the criteria. Their Expanded Disability Status Scale scores were lowered (4.1 ± 2.4 → 3.1 ± 2.8) (P = 0.033) and annualized relapse rate was decreased (0.59 ± 0.34 → 0.13 ± 0.15) (P = 0.027) after IFNβ-1b therapy. These results suggest that IFNβ is therapeutically effective in inhibiting functional worsening and reducing relapse rate in “genuine” OSMS.
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  • Takuya Ito, Kaori Hoshiai, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, ...
    2011 Volume 223 Issue 3 Pages 215-222
    Published: 2011
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.
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  • Zhanhui Ou, Qing Li, Weiqiang Liu, Xiaofang Sun
    2011 Volume 223 Issue 3 Pages 223-226
    Published: 2011
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    β-thalassemia is one of the most prevalent inherited hemoglobin disorders. Compound heterozygotes or homozygous mutations of the β-globin chain gene account for severe cases of β-thalassemia that require lifelong transfusion, and make it necessary to identify β-thalassemia carries for prenatal diagnosis. The increase in hemoglobin A2 (HbA2) level is the most significant parameter in the identification of β-thalassemia carriers. HbA2, composing of two α chains and two δ chains, is a minor component of the hemoglobin present in normal adult red blood cells, accounting for about 2.5% of the total hemoglobin in healthy individuals. However, HbA2 level is also elevated in some pregnant women. This study aimed to evaluate the value of HbA2 level in the screening of pregnant women with β-thalassemia trait. Pregnant and non-pregnant women were randomly recruited who attended the prenatal care or diagnosis at our hospital located in Guangdong, a province in South China. Hemoglobin capillary electrophoresis was performed on high performance liquid chromatography to measure HbA2 levels in blood. The β-globin gene mutations were detected by the PCR-reverse dot-blot assay, and some were verified by direct sequencing. Pregnant women (n = 96) and non-pregnant women (n = 114) with normal HbA2 level (< 3.5%) had no β-thalassemia mutation. In contrast, pregnant women (n = 55) and non-pregnant women (n = 85) with elevated HbA2 level (≥ 3.5%) are β-thalassemia carriers. In conclusion, HbA2 level is a good marker for screening β-thalassemia trait in pregnant women in South China population.
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  • Hack-Lyoung Kim, Goh Eun Chung, In Young Park, Jin Man Choi, Se-Min Hw ...
    2011 Volume 223 Issue 3 Pages 227-233
    Published: 2011
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    An elevated white blood cell (WBC) count is associated with nonalcoholic fatty liver disease (NAFLD); however, a leukocyte subtype that is involved in the pathogenesis of NAFLD is not known. This study was conducted to investigate the association between NAFLD and WBC subtype fractions (%) among healthy elderly Koreans. A total of 794 subjects who underwent a health check-up were investigated. After excluding excessive alcohol intake and other liver diseases, NAFLD was diagnosed based on sonographic findings: hyperechogenecity of liver tissue, difference of echogenicity between liver and kidney, and visibility of vascular structures. The prevalence of NAFLD among entire cohort was 39.0% (310/794). The presence of NAFLD was significantly associated with higher blood WBC counts (5,485 ± 1073 vs. 5,230 ± 995 per mm3, p = 0.001) and monocyte fraction (6.08 ± 2.40% vs. 5.12 ± 1.31%, p < 0.001). The multiple logistic regression analysis, after controlling confounders, including age, gender, body mass index, systolic and diastolic blood pressure, fasting blood glucose, alanine aminotransferase, triglyceride, and high-density lipoprotein cholesterol, showed that the prevalence risk of NAFLD was increased significantly according to the monocyte fraction quartiles: odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.00, 2.75 (1.63-4.62), 2.84 (1.67-4.84) and 5.17 (3.03-8.83), respectively. There were no significant associations between NAFLD and the total WBC count quartiles in this model. These results indicate that the elevated peripheral blood monocyte fraction is associated with NAFLD. The monocyte fraction might be a useful marker for NAFLD.
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