The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 215, Issue 1
May
Displaying 1-13 of 13 articles from this issue
Regular Contributions
  • Takaharu Ishibashi, Tomoko Miwa, Ikumi Shinkawa, Naoki Nishizawa, Miho ...
    2008 Volume 215 Issue 1 Pages 1-11
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Nitrite (NO2-) is assumed to play an important role in regulation of vascular tone as a reservoir of nitric oxide (NO). To examine its physiological contribution, however, a sensitive method is required for determination of the true level of NO2- in biological samples. To this end, practical consideration to avoid NO2- contamination through the quantification procedure is important. We present here a highly sensitive and accurate method for determining NO2- in plasma by improving the HPLC-Griess system with minimal NO2- contamination in the samples. The system achieved high sensitivity (detection limit of 2 nM and sensitivity to 1 nM) and complete separation of the NO2- signal peak by modifying the system setup and mobile phase. Using this method, we achieved acceptable quantification of low NO2- levels in plasma. Deproteinization by ultrafiltration and exposure to atmosphere before measurement were identified as the major sources of NO2- contamination during sample processing. We addressed these issues by the use of methanol for deproteinization and gas-tight caps. These countermeasures allowed us to detect small arterio-venous NO2- differences in rabbit plasma that may indicate kinetic difference of NO2- in a small number of samples (n = 6). This difference became prominent when NO2- or a NO releasing agent, NOR1, was intravenously applied. Our results indicate that application of a sensitive method with careful handling is important for accurate determination of NO2- and that our method is applicable for further examination of the kinetic features of NO2- in vivo.
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  • Nobuhiro Yamaguchi, Koji Kumagai, Koji Fukuda, Yuji Wakayama, Yoshinao ...
    2008 Volume 215 Issue 1 Pages 13-22
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Common-type atrial flutter (AFL) is a type of atrial tachyarrhythmia with counterclockwise rotation around the tricuspid annulus within the right atrium (RA). It was recently reported that the electrogram voltage reduction observed in the RA was involved in the development of AFL. However, the relationship between the low voltage areas and conduction velocity during AFL has not been fully described. In this study, patients with AFL (n = 17) and without AFL (n = 4) were examined using an electro-anatomical mapping system. The patients with AFL were divided into 2 groups; AFL group (n = 8) and coronary sinus ostium (CSO) group (n = 9). The AFL group was defined as exhibiting the maintenance of AFL and the CSO group sinus rhythm before the catheter ablation. The electrogram voltages of each area in the RA (septum, and posterior and lateral walls), conduction velocity during AFL and transverse and longitudinal conduction velocities were evaluated. In the septum, the mean electrogram voltage was significantly lower in the AFL and CSO groups than in the group without AFL. Moreover, the conduction velocity during AFL was significantly slower in the septum, and both the septal transverse and longitudinal conduction velocities were significantly slower in the AFL and CSO groups than in the group without AFL. In conclusion, these findings suggest that both the slower conduction velocities and lower voltage in the RA septum may be involved in the development of AFL. Thus, ablation of the RA septum may represent a therapeutic approach of AFL.
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  • Atsuko Omori, Kenji Takahashi, Masaharu Hazawa, Naoko Misaki, Hisateru ...
    2008 Volume 215 Issue 1 Pages 23-32
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Placental/umbilical cord blood (CB) contains nucleated cells and hematopoietic stem/progenitor cells (CD34+ cells). However it is difficult to predict the number of nucleated/CD34+ cells in each CB before cell processing. Despite many previous studies from institutes affiliated with CB banks in metropolitan areas, little information is available regarding the characteristics of CB units from other medical facilities. The purpose of the present study was to analyze the maternal/neonatal factors on the yield of cells in CB units. A total of 176 CB units were obtained from single-birth and normal vaginal deliveries. Mononuclear low-density (LD) cells were separated using Ficoll-Paque within 24 hrs after CB collection and then processed for the purification of CD34+ cells. A multiple linear regression analysis was performed to assess the correlations between the yield of cells and maternal/neonatal factors including maternal age, gravid status, duration of labor, gestational age, neonatal height and weight, cord length, and meconium in the amniotic fluid. The total LD cells per CB unit had a weak positive correlation with the maternal age of primigravidae. The total LD cells per CB unit from the primigravidae aged ≥ 25 were significantly higher than those from the primigravidae aged ≤ 24. The total CD34+ cells per CB unit from the 1-gravidae were significantly higher than those from the 2-gravidae and 3-gravidae, respectively among all donors. These results indicate that the CB units from the primigravidae aged ≥ 25 are more likely to contain higher yield of LD/CD34+ cells.
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  • Junichiro Nakamura, Kenshi Terajima, Yutaka Aoyagi, Kouhei Akazawa
    2008 Volume 215 Issue 1 Pages 33-42
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and − 749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.
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  • Huayan Liu, Jun Wang, Atsuo Sekiyama, Takeshi Tabira
    2008 Volume 215 Issue 1 Pages 43-54
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Microglia are the main resident immunocompetent and phagocytic cells in the central nervous system (CNS). Activated microglia could play phagocytic roles as well as mediate inflammatory processes in the CNS. Involvement of activated microglia in the pathogenesis has been demonstrated in several neurological diseases including Alzheimer's disease (AD). Juzen-taiho-to (JTT), a traditional herbal medicine, has been reported to have effects on activating immune responses and phagocytosis. So far, little is known about the effects of this Kampo formulation JTT on microglia and in AD. In this report, we studied the effects of JTT on the activation and phagocytic functions of mouse microglia and bone marrow-derived macrophages (BMM). JTT could activate microglia, which was confirmed by the prominent morphological change and increased surface expression of an activation marker CD11b. In addition, JTT was revealed to induce microglial proliferation, and enhance microglial phagocytosis of, without eliciting an excessive production of nitric oxide. Furthermore, when mice were administrated with JTT in vivo, their BMM showed more effective phagocytosis of fibrillar Aβ1-42. These findings implicate the therapeutic potential of JTT in AD and other neurological diseases accompanied by microglial activation.
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  • Rina Takano, Tatsuro Misu, Toshiyuki Takahashi, Masahiro Izumiyama, Ka ...
    2008 Volume 215 Issue 1 Pages 55-59
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Neuromyelitis optica (NMO) is a neurologic disease characterized by severe optic neuritis, longitudinally extended, transverse myelitis and serum aquaporin-4 (AQP4) antibody. Our recent neuropathological study revealed the extensive loss of AQP4 and glial fibrillary acidic protein (GFAP), an astrocyte-specific protein, in NMO lesions, but not in MS lesions, suggesting that severe astrocytic damage or dysfunction may be related to the pathogenesis of NMO. Here we report a patient of NMO, in which the cerebrospinal fluid (CSF) levels of GFAP were measured both during relapse of myelitis and after high-dose intravenous methylprednisolone (HIMP). The patient was a 34-year old woman with two previous episodes of optic neuritis. She developed myelitis longitudinally extending from C3 to T12 with contrast enhancement, and was AQP4 antibody-positive. In the acute phase, the GFAP level in the cerebrospinal fluid (CSF) was prominently elevated (18,966.7 ng/ml) as compared with controls (0.6 ± 0.33 ng/ml). However, following HIMP, the clinical and MRI findings improved, and the CSF-GFAP level was near-normal (2.1 ng/ml). The CSF of myelin basic protein was also elevated in relapse (1,016.0 pg/ml), and became lower but still remained high (158.7 pg/ml) after HIMP compared with controls (3.36 ± 3.83 pg/ml). The prominent elevation of the CSF-GFAP level in relapse of NMO, followed by its sharp decline after therapy, suggests severe astrocytic damage with a temporal profile distinct from that of the demyelinating process in NMO. CSF-GFAP may be useful as a biomarker of NMO.
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  • Mingxue Zhou, Hao Xu, Lin Pan, Jianyan Wen, Yanru Guo, Keji Chen
    2008 Volume 215 Issue 1 Pages 61-69
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Increasing evidence indicated that plaque stabilization is attributed to the composition of the atherosclerotic plaque, and inflammation plays an important role in the formation and progress of vulnerable atherosclerotic plaque (VAP), which is prone to rupture. Emodin, an important component of traditional Chinese herb rhubarb, has obvious anti-inflammatory effect, although its effect on atherosclerotic plaque stabilization is unknown. Apolipoprotein E (ApoE) is an important component of plasma lipoprotein with anti-atherosclerosis function, and the plaque in the aorta of ApoE-deficient mice has been demonstrated with characteristics of VAP. Therefore, this study was designed to determine whether emodin can stabilize the VAP in the ApoE-deficient mice and explain the possible mechanism. After fat-fed for 13 weeks, mice were randomized into three groups (11 animals/group) and intragastrically administrated with emodin, simvastatin or distilled water for 13 weeks, respectively. The plaque stability was evaluated by the morphology and composition of atherosclerotic plaques. Additionally, the expression of peroxisomal proliferator-activated receptor-γ (PPAR-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase 9 (MMP-9) in plaques was determined by the immunohistochemistry method. We showed that emodin could decrease the lipid core area and the ratio of lipid to collagen content in plaques. In addition, emodin significantly inhibited the expression of GM-CSF and MMP-9, whereas it induced the expression of PPAR-γ in plaques. In conclusion, these results suggest that emodin can stabilize the VAP in the aortic root of ApoE-knockout mice, which is probably due to its anti-inflammatory effect.
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  • Hiroe Matsuzuki, Takashi Muto, Yasuo Haruyama
    2008 Volume 215 Issue 1 Pages 71-77
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Salt intake in childhood is a risk factor for developing hypertension later in life. As health education for children to decrease salt intake, it is important for them to know the relationship between salty taste preference and salt intake. The objective of this study was to investigate the relationship between children's salty taste preference and their salt intake. We employed a cross-sectional study design, and the subjects were 199 elementary school children (5th or 6th grade) and their mothers. The amount of salt intake was estimated by the amount of urinary sodium excretion. Children's salty taste preference was assessed 1) by asking children about their own salty taste preference as well as measuring their threshold level of salty taste, and 2) by their mothers' observation of their salt intake behavior using a questionnaire. The salt intake and salt taste threshold of children who liked a salty taste were similar to those in children who disliked it. No association was found between the threshold level of salty taste and sodium intake. Regarding the relationship between children's salt intake and their salt intake behavior score, assessed by their mothers using a questionnaire, the high score group had a higher estimated salt intake than the low score group. In conclusion, children's salt intake may be accurately assessed by their mother's observation rather than children's own salty taste preference. This study suggests the importance of a mother's role in salt restriction education for children.
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  • Furong Wan, Nan Lu, Xiong Zou, Yi Zhang, Ningning Shan, Xiaojing Yang, ...
    2008 Volume 215 Issue 1 Pages 79-87
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Early prediction of acute rejection (AR) is important in clinical practice of organ and tissue transplantation. The aims of this study were to investigate the expression of major histocompatibility complex (MHC)-I and MHC-II genes in peripheral blood lymphocytes (PBLs) following skin grafting and whether their expression can be used as early markers for AR. Skin-grafted mice were selected as an animal model and PBL samples were collected daily for up to 2 weeks post-transplant. Full-thickness skin from the backs of C57BL/6 mice (H-2b) was transplanted onto that of BALB/c mice (H-2d) in allograft group (H-2b to H-2d) and in syngeneic graft group (H-2d to H-2d). The expression levels of MHC-I (H-2K, H-2D) and MHC-II (H-2Ia, H-2Ie) mRNAs were examined using real-time PCR. The histopathological changes of graft biopsies were also analyzed with hematoxylin-eosin staining. The real-time PCR analysis showed that MHC-I and MHC-II mRNA levels were increased in a bimodal distribution pattern during AR in allograft group, whereas no significant changes were detected in syngeneic graft group. The level of H-2K mRNA was significantly increased at day 5 post-transplants compared with those pre-transplant controls (p < 0.01). This increase was detected 5-6 days earlier before graft rejection observed macroscopically. H-2K mRNA level was increased significantly in 93.8% of mice (61/65) in allograft group. These results indicate that the expression of MHC-I and MHC-II mRNAs is up-regulated in PBLs during AR. Especially, the expression of H-2K mRNA can be used as an early marker for AR.
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  • Besir Erdogmus, Ali Tamer, Ramazan Buyukkaya, Burhan Yazici, Ayla Buyu ...
    2008 Volume 215 Issue 1 Pages 89-93
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Paralleling the rise in the incidence of obesity and diabetes worldwide, nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as one of the major causes of chronic liver disease. Doppler sonography is used as a diagnostic method in the non-invasive assessment of the hemodynamics of hepatic vascular flow in liver diseases. We investigated the effects of fatty infiltration in the liver on the Doppler flow hemodynamics of the portal vein. Doppler sonography of the liver and portal vein was performed in 60 subjects with NAFLD and 20 healthy volunteers (control). The patients were grouped into mild (grade 1), moderate (grade 2), and severe (grade 3) according to sonographic appearance of hepatosteatosis (n = 20 for each group). The vein pulsatility index (VPI), mean flow velocity (MFV), peak maximum velocity (Vmax), and peak minimum velocity (Vmin) of the portal vein were significantly lower in patients with NAFLD than those of the controls (p < 0.001). The VPI was 0.20 in the patients and 0.31 in the control. The MFV was 12.3 cm/sec in the patients and 16.5 cm/sec in the control group. The portal vein flow was found to be decreased as the grade of fatty infiltration increased for VPI (r = −0.946, p < 0.001), MFV (r = −0.951, p < 0.001). The alteration in Doppler waveform pattern of portal vein with fatty liver population suggests reduced vascular compliance in the liver.
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  • Hideki Hayashi, Chihiro Fujimaki, Seiji Tsuboi, Taiji Matsuyama, Takas ...
    2008 Volume 215 Issue 1 Pages 95-101
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Rheumatoid arthritis (RA) is a chronic disease characterized by the painful joints, inflammation, uncontrolled proliferation of synovial tissue and multisystem comorbidities. Weekly low-dose methotrexate (MTX) has been established as effective treatment in RA patients. MTX is converted to γ-glutamyl polyglutamates, an active form of MTX, through the action of folylpolyglutamate synthetase in the cells. MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) may be useful as a therapeutic marker of RA. However, the previously reported methods for the quantification of MTX and MTX-PGs in RBCs are impractical for clinical use due to time-consuming, laborious and high cost. We attempted to apply a method with the commercially available fluorescence polarization immunoassay (FPIA) kit. We found that anti-MTX monoclonal antibody showed the reactivity to 4-amino-10-methylpteroylheptaglutamic acid (MTX-PG7) as equal to MTX. Good agreement was observed in the concentration-response curves between MTX and MTX-PG7 spiked samples. Accordingly, the anti-MTX monoclonal antibody for FPIA appeared to show the equal reactivity to MTX and MTX-PGs. The recoveries of MTX and MTX-PG7 from RBCs were 99.0% and 94.1%, respectively. Furthermore, we determined total MTX-PGs concentrations in RBCs of 71 patients with RA treated with weekly pulse MTX. Total MTX-PGs concentrations in 70% of the patients were found to be more than 50 nM that is the lower limit of MTX-PGs concentration in RBCs for expected therapeutic outcome. The routine measurement of total MTX-PGs concentration in RBCs might be useful for prediction about therapeutic outcome of MTX in RA patients.
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  • Hana Svacinová, Marie Nováková, Zdenek Placheta, ...
    2008 Volume 215 Issue 1 Pages 103-111
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Favorable effects of exercise training on cardiovascular prognosis have been reported repeatedly in patients with diabetes mellitus type 2 (DM2). However, little is known about the cardiovascular rehabilitation effects in diabetic patients with coronary artery disease (CAD). This study has evaluated the benefits of combined aerobic-resistance training in two groups of patients - diabetics and non-diabetics - after percutaneous coronary intervention (PCI). Changes in exercise capacity parameters, resting cardiovascular and anthropometrical parameters were evaluated in 77 patients who completed 12-weeks of combined aerobic-resistance training: 32 patients with DM2 (DM) and 45 patients without DM2 (NDM). Significant improvements in exercise capacity (total peak workload [Wpeak], peak workload per kg of body weight [Wpeak/kg], total peak oxygen uptake [VO2peak], peak oxygen uptake per kg of body weight [VO2peak/kg]) were found in both DM and NDM (p < 0.01 and p < 0.001, respectively). The decrease in resting heart rate (HRrest), resting systolic (SBPrest) resting diastolic (DBPrest) blood pressures, body weight (BW) and BMI in the DM group was not statistically significant. However, there was a statistically significant decrease in SBPrest, BW and BMI in the NDM group. In conclusion, this study demonstrated similar beneficial effects of combined cardiovascular training on exercise capacity in patients with or without type 2 diabetes mellitus. Our results suggest that the combined cardiac training is well tolerated and useful in secondary prevention in patients with DM2 and CAD.
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  • Ejder Kardesoglu, Mustafa Aparci, Gunalp Uzun, Selami Suleymanoglu, Om ...
    2008 Volume 215 Issue 1 Pages 113-117
    Published: 2008
    Released on J-STAGE: May 29, 2008
    JOURNAL FREE ACCESS
    Diabetes mellitus is frequently associated with the malignant ventricular arrhythmias and sudden death. The QT dispersion is the difference between the longest and shortest QT interval calculated from the standard 12-lead electrocardiogram. The QT dispersion is suggested as an index of myocardial electrical activity. An increase in QT dispersion is associated with the malignant ventricular arrhythmias and sudden cardiac death. Diabetic patients receive hyperbaric oxygen (HBO) therapy for non-healing lower extremity ulcers. The aim of this study was to determine the effect of HBO therapy on QT dispersion in diabetic patients. Thirty diabetic patients (18 male and 12 female, 59.9 ± 10 years), who were planning to undergo ten sessions of HBO therapy in two weeks for non-healing lower extremity ulcers, were consecutively enrolled into the study. The 12-lead resting electrocardiography recordings were taken before the first HBO therapy and after the 10th HBO-therapy session. QT intervals were measured on electrocardiogram. QT intervals were corrected for heart rate by using Bazett's formula (corrected QT [QTc] = QT/√R − R [seconds]). QTc dispersion was significantly decreased from 59.8 ± 17.4 msec to 52.2 ± 15.5 msec after ten sessions of HBO therapy (p < 0.05). However, maximum QTc, minimum QTc and mean QTc did not change significantly after HBO therapy. We have concluded that HBO therapy may reduce the risk of malignant ventricular arrhythmia and sudden cardiac death in diabetic patients when applied repetitively.
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