The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 212, Issue 2
June
Displaying 1-12 of 12 articles from this issue
Regular Contributions
  • Toshihide Oizumi, Makoto Daimon, Yumi Jimbu, Wataru Kameda, Nobuko Ara ...
    2007 Volume 212 Issue 2 Pages 91-99
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Palatinose is a disaccharide present in honey, which has the characteristics of delayed digestion and absorption. We developed a palatinose-based balanced formula (PBF) and reported its beneficial effects on metabolic syndrome-related parameters in rats. To examine the effects of PBF in humans, we here conducted a crossover study using twenty-three subjects with impaired glucose tolerance. The subjects were divided into two groups: intervention to control (I/C) and control to intervention (C/I) groups. The I/C group consumed PBF (250 kcal) together with foods that were 250 kcal less than their usual breakfast (intervention meal) for the first 12 weeks, followed by their usual breakfast (control meal) for the last 12 weeks. The protocol for the C/I group was opposite in order: the control meal for the first 12 weeks, followed by the intervention meal for the last 12 weeks. In the first 12-week period, the intervention meal decreased 2-hr plasma glucose levels after 75-g oral glucose tolerance test (−15.7 ± 20.1% change), while the control meal did not (0.8 ± 31.6% change). The difference between these changes was significant (p = 0.038). The similar results were obtained from the comparison of the changes between the first and the last 12-week periods in the two groups combined (intervention vs control: −11.8 ± 22.5 vs 11.2 ± 30.2% change, p = 0.024). PBF also had the beneficial effects on serum free fatty acids levels and visceral fat area. In conclusion, PBF consumption has beneficial effects on metabolic syndrome-related parameters in humans.
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  • Eleni Albanidou-Farmaki, Anastasios K. Markopoulos, Filanthi Kalogerak ...
    2007 Volume 212 Issue 2 Pages 101-105
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    One of the factors involved in the pathogenesis of recurrent aphthous stomatitis (RAS) is a cell-mediated immune response in which several cytokines seem to play a major role. The aim of this study was to detect, enumerate and characterize T helper cells which are secreting type 1 cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) and type 2 cytokines (IL-4, IL-5, IL-6, and IL-10) in the peripheral blood of patients with RAS. Thirty-two patients in the active phase of RAS (14 men and 18 women) and 40 healthy individuals participated in the study. T helper (T) cells were detected and characterized using Elispot assay. T cells secreting IL-2, IL-12 or IFN-γ were increased in patients with RAS compared with the controls (p < 0.05, p < 0.001 and p < 0.001, respectively). T cells secreting TNF-α in RAS patients and controls were not statistically different (p > 0.05). T cells secreting IL-10 were increased in patients with RAS compared with the controls (p < 0.05). T cells secreting IL-4 were decreased in patients with RAS compared with the controls (p < 0.001), No statistical difference was observed between T cells secreting IL-5 or IL-6 in patients with RAS and controls. Our findings suggest that the increased numbers of T cells secreting type 1 cytokines may influence the immune response against RAS. Whether this action is of etiological importance or epigenetic phenomenon is a question that needs to be answered.
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  • Kyoko Nomura, Toshikazu Yamanouchi, Gwang U Kim, Kazuhiro Ohwaki, Eiji ...
    2007 Volume 212 Issue 2 Pages 107-113
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Metabolic syndrome has the unique concept that the common occurrence of individual disease components increases the risk of coronary artery disease (CAD). However, some studies suggest that the burden of different CAD risk factors is not equal, and focusing on the whole set of risk factors might neglect the impact of individual factors that could be useful targets for prophylactic therapies. The purpose of this study was to investigate the effect of glucose intolerance on CAD using multislice computed tomography (MSCT). Ninety-eight consecutive patients with at least one traditional CAD risk factor who visited a municipal hospital were enrolled in this study. The risk factors were impaired glucose tolerance (fasting glucose ≥ 110 mg/dl or patients with diabetes), low high-density lipoprotein cholesterol (HDL-C, < 40 mg/dl for men and ≤ 50 mg/dl for women), hypertriglycemia (triglyceride ≥ 150 mg/dl), hypertension (blood pressure ≥ 130/85 mmHg), and obesity (body mass index, > 25 kg/m2 for men and > 23 kg/m2 for women). CAD was determined by the presence of either stenoses, non-calcified plaques or calcified lesions. The following risk factors were significantly related in univariate logistic models: glucose intolerance and coronary calcified lesions (p = 0.001), and hypertriglycemia and non-calcified plaque lesions (p = 0.048). Multivariate models showed that glucose intolerance was significantly associated with calcified lesions, even after adjustment for gender, age, low HDL-C, hypertriglycemia, hypertension, and obesity (p = 0.018). Our results suggest that glucose intolerance might be closely related to the presence of coronary calcified lesions among traditional CAD risk factors.
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  • Takuji Miyasaka, Akira Naito, Masaomi Shindo, Shinji Kobayashi, Masahi ...
    2007 Volume 212 Issue 2 Pages 115-131
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Group I fibers from muscle spindles and Golgi tendon organs modulate motoneuron excitabilities to coordinate smooth movements. In this study, to elucidate the effects of group I fibers of the median nerve (MN) on the excitabilities of the brachioradialis (BR), we evaluated the changes in the firing probability of a BR motor unit after electrical conditioning stimulation (CS) to MN with a post-stimulus time-histogram technique in six healthy human subjects. We tested 171 motor units: in 72 of them CS to MN at the elbow with the intensity just below the threshold of alpha motor fibers (MT) produced a facilitatory effect (facilitation), while in 43 of them it produced inhibitory one (inhibition). The facilitation and inhibition were not produced by electrical stimulation of the skin overlaying MN. The central synaptic delays of the facilitation and inhibition were on average -0.13 and 0.13 msec, respectively, longer than those of the homonymous facilitation mediated by a monosynaptic path. The thresholds of the facilitation and inhibition were less than 0.7-0.8 and 0.7-0.9 times MT, respectively. CS to MN of hand muscles produced facilitatory effects and that of the pronator teres, palmaris longus, and flexor carpi radialis inhibitory effects. The facilitatory and inhibitory effects were compatible, for latency, with the facilitation and inhibition. These findings suggest that BR motoneurons receive monosynaptic facilitation and oligosynaptic inhibition from MN in humans. Group I fibers of the hand and forearm muscles should mediate the facilitation and inhibition, respectively, to coordinate movements of the hand, forearm, and elbow.
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  • Ahmet Isik, Suleyman Serdar Koca, Bilal Ustundag, Sahabettin Selek
    2007 Volume 212 Issue 2 Pages 133-141
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Behcet's disease (BD) is a chronic systemic inflammatory disease. Inflammatory reactions trigger the oxidative stress and oxidants decrease the level of antioxidants. In the present study, we aimed to determine serum oxidative/antioxidative status in patients with BD. Serum antioxidative status was evaluated by measuring total antioxidant capacity (TAC), paraoxonase 1, arylesterase, sulfhydryl groups and ceruloplasmin in patients with BD and in healthy controls. Serum oxidative status was evaluated by measuring total peroxide (TP), lipid hydroperoxides and oxidative stress index (OSI). OSI was calculated by percent ratio of TP to TAC. Serum levels of TAC, sulfhydryl groups and activities of paraoxonase 1, arylesterase, and ceruloplasmin were significantly lower in patients than in controls (p < 0.001 for all). In contrast, TP, lipid hydroperoxides and OSI values were significantly higher in patients than in controls (p < 0.001 for all). Further, the level of TAC was negatively correlated with the levels of TP, lipid hydroperoxides and OSI both in the BD (r = −0.578, p < 0.01; r = −0.559, p < 0.01 and r = −0.552, p < 0.01, respectively) and the control groups (r = −0.469, p < 0.05; r = −0.351, p < 0.05 and r = −0.391, p < 0.05, respectively). These results indicate that the oxidant parameters increased and antioxidant parameters decreased in patients with BD; therefore, these patients might have been exposed to oxidative stress. We suggest that impaired oxidant/antioxidant balance should be taken into consideration in the follow-up of patients with BD.
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  • Kohsei Kudo, Yoshinao Abe, Dong-Liang Hu, Hiroshi Kijima, Akio Nakane
    2007 Volume 212 Issue 2 Pages 143-150
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Radiation-induced intestinal injury is a common complication in radiotherapy for the cancer located in abdomen or pelvis. However, there is no effective treatment for radiation-induced intestinal injury now. It is therefore important to develop new treatments for radiation-induced intestinal injury. In this study, we investigated whether embryonic stem (ES) cells could be transplanted directly into the radiation-damaged intestine and could colonize and differentiate into the intestinal epithelial cells. The intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy, and were immediately transplanted with male 129/Sv-derived ES cells into the wall of the irradiated intestine by direct injection. The intestine was removed on days 13 to 27 after transplantation. The Y-chromosome DNA of transplanted ES cells in the irradiated intestine was determined by polymerase chain reaction. Colonization and differentiation of transplanted ES cells in the irradiated intestine were analyzed by histological and immunohistochemical methods with antibodies against stage-specific embryonic antigen-1, α-smooth muscle actin and cytokeratin AE1/AE3. The cells of donor origin were identified in the intestine of irradiated mice, and intestinal crypt-like structures were observed on day 13 after transplantation. Importantly, we observed that ES cells could differentiate into epithelial cells in the submucosa of irradiated intestine on day 13 and 27 after transplantation. These results suggest that transplanted ES cells could colonize and differentiate in the intestinal intestine. Such a new approach for damaged intestine with transplanted stem cells would be promising.
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  • Kensuke Orito, Nanae Gotanda, Masaru Murakami, Tomoaki Ikeda, Nobuaki ...
    2007 Volume 212 Issue 2 Pages 151-157
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Polychlorinated biphenyls (PCBs) are environmental contaminants that have adverse effects on the endocrine and nervous systems. As they are still detected in breast milk and adipose tissue in humans, the accumulated PCBs may transfer from mothers to children and damage central nervous system. It is revealed from epidemiological studies that cognitive and motor functions were damaged in children born to mothers who ingested PCBs-contaminated foods. However, it remains unclear whether prenatal exposure to PCBs affects emotionality. In the present study, we therefore examined the effect of prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126) on emotionality in rats by focusing on anxiogenic behavior and response of the hypothalamus-pituitary-adrenal axis to stress. Pregnant rats were treated orally with PCB126 at a dose of 30 μg/kg or corn oil, its vehicle, on gestational day 15, and their male offspring were subjected to the following experiments at 4-5 weeks old. In an open field test, rats with prenatal exposure to PCB126 showed anxiogenic behavioral responses, including decrease in time spent in the center of an open field and the number of rearings and extension of grooming duration. Interactive behavior, which is an index of anxiety level, was shortened in the social interaction test. The increase in the serum corticosterone level induced by forced swim stress was facilitated by prenatal exposure to PCB126. This evidence suggests that PCB126 may exert anxiogenicity on the offspring of exposed dams, and dysfunction of the hypothalamus-pituitary-adrenal axis may at least in part contribute to this abnormality.
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  • Ali K. Adiloglu, Mehmet Isler, Ibrahim Goren, Ozden Candir, Altug Seno ...
    2007 Volume 212 Issue 2 Pages 159-167
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    The Helicobacter pylori (H. pylori) load in both stomach and stool and the resulting severity of gastritis are important criteria in validating the status of H. pylori infection. We aimed to assess the reliability of the H. pylori stool antigen (HpSA) test for the primary diagnosis of H. pylori infection by calculating the best cut-off value to obtain the highest sensitivity and specificity in dyspeptic patients. We also investigated the correlation of HpSA test with the severity of gastritis and H. pylori load. The H. pylori statuses of 95 patients were evaluated by the positivity of both rapid urease test and microscopic detection of H. pylori in biopsy specimens, 88 subjects of whom were H. pylori positive. The sensitivity and specificity of the HpSA test were 51.1% (45/88) and 100% (7/7), respectively, according to the manufacturer's recommended cut-off value of 0.16. However, with the best cut-off value of 0.048, calculated by receiver operator characteristics analysis, the sensitivity of the test increased to 92.0% (81/88) with the same specificity. High values of the HpSA test were correlated with high scores of corpus H. pylori load and the severity of antrum and corpus inflammation (p < 0.05). With the best cut-off value of the HpSA test, the primary diagnosis of H. pylori infection can be made with higher sensitivity and specificity. The HpSA test is a helpful tool that evaluates the severity of H. pylori infection and the degree of gastric inflammatory activity and gastric H. pylori load.
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  • Mutlu Vural, Ömer Satiroglu, Berfu Akbas, Isin Göksel, Ö ...
    2007 Volume 212 Issue 2 Pages 169-175
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Psychological variables, such as depression and anxiety, are known as independent risk factors for coronary artery disease (CAD), suggesting the interaction of psychological and physiological factors in the development of CAD. In the present study, we analyzed the possible association between depressive and anxiety symptoms and major atherosclerotic risk factors in patients with chest pain warranting coronary angiography. The patients without CAD (n = 159) and those with CAD (n = 155) were evaluated for the severity of depression and anxiety by the symptom scales; high scores indicate severe symptoms. Age, male/female ratio, prevalence of diabetes mellitus (DM), and depression level were significantly higher in the CAD group. Among a total of 314 patients with chest pain, the mean depression score was higher in patients with DM (16.01 ± 8.12 vs 13.01 ± 9.6, p = 0.01) and those with hypercholesterolemia (15.43 ± 9.61 vs 12.53 ± 9.61, p = 0.02). The mean anxiety score was also higher in patients with DM (20.81 ± 12.85 vs 16.51 ± 12.09, p = 0.008), hypercholesterolemia (20.67 ± 13.11 vs 15.29 ± 11.36, p = 0.002), or hypertension (20.74 ± 12.94 vs 14.1 ± 10.8, p = 0.001). Thus, DM and hypercholesterolemia are associated with depression and anxiety, while hypertension is only related to anxiety. In contrast, smoking and family history of atherosclerosis are not related to depression and anxiety scores. These results suggest depression and anxiety symptoms may contribute to the development and progression of CAD, especially in patients with DM or hypercholesterolemia.
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  • Tomohiko Ishii, Kazuyoshi Kohu, Shigeyuki Yamada, Shigeto Ishidoya, Sa ...
    2007 Volume 212 Issue 2 Pages 177-190
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    From a developmental point of view, human testicular germ cell tumor (TGCT) can be traced back to the primordial germ cells in the embryo, which, upon tranformation, become either seminoma or non-seminoma. Thus, TGCT provides a useful model system for the study of gene regulation involved in oncogenesis as well as development. In this study, we focused and analyzed the expression and epigenetic alteration of DNA-methyltransferase (DNMT) genes in TGCT tissues. The examined genes included DNMT1, DNMT3A and DNMT3B that function to maintain or generate a methylation status of genomic DNA. Using semi-quantitative reverse transcription-polymerase chain reaction, we found that the expression of DNMT3A, but not DNMT1 or DNMT3B, was up-regulated markedly in TGCT specimens compared to non-tumor testicular tissues. To explore mechanisms involved in the up-regulation of DNMT3A, we examined the methylation status of CpGs in the gene. The distal and proximal promoter regions of DNMT3A were non-methylated in both TGCT and non-tumor tissues. In contrast, non-tumor testicular tissues exhibited a mixture of methylated and non-methylated CpGs in intron 25 of DNMT3A, whereas most CpGs in intron 25 were demethylated in TGCT specimens. This difference in the degree of methylation was confirmed by Southern blot analysis, in which an EcoRI site in intron 25 could be digested only when the CpG was non-methylated. Thus, epigenetic alteration of intron 25 toward de-methylation is associated with increased expression of DNMT3A in TGCT. The intron 25 may represent a differentially-methylated region in DNMT3A that is modulated during development and/or tumorigenesis of germ cells.
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  • Osamu Yamanoshita, Shu Ichihara, Hidetoshi Hama, Gaku Ichihara, Momoko ...
    2007 Volume 212 Issue 2 Pages 191-198
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Breast cancer is one of the major cancers in women, and dietary intake must be controlled to prevent it. Selenium (Se), especially Se compound in vegetables, is thought to be a promising chemopreventive dietary ingredient for preventing breast cancer. In this study, we developed Se-enriched Japanese radish sprout using a special Se-additional fertilizer, and identified the Se chemical forms. The newly developed Se-enriched sprout is produced within a week by the tank forming method, and the major chemical form was identified as Se-methylselenocysteine (MeSeCys) (80%). Then, the chemopreventive effects of the Se-enriched sprout were investigated using Sprague-Dawley female rats with mammary cancer, induced by a single oral dose of 10 mg or 14 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). Mammary tumors were found in 11, 16 and 2 rats treated with DMBA and thereafter fed the basal (n = 34), sprout-added basal (n = 30) and Se-enriched sprout-added test diets (n = 30), respectively. The incidence of mammary tumors was significantly lower in the Se-enriched sprout-added test diet group (7%) than in the basal diet group (32%) or sprout-added basal diet group (53%). In contrast, no significant difference was detected in the numbers and incidence of the tumor between the basal diet group and Se-enriched sprout-added test diet group before DMBA-dosing. These results suggest that the diet supplement of Se-enriched sprout after DMBA-dosing provides a significant chemoprevention against chemical-induced mammary cancer. Thus, Se-enriched sprout may be a useful dietary ingredient for preventing breast cancer.
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Case Report
  • Shigeki Gorai, Tsutomu Numata, Sawako Kawada, Masayuki Nakano, Jun-ich ...
    2007 Volume 212 Issue 2 Pages 199-205
    Published: 2007
    Released on J-STAGE: June 05, 2007
    JOURNAL FREE ACCESS
    Warthin's tumor (WT), so-called adenolymphoma, is a benign salivary gland tumor with both epithelial and lymphoid histological characteristics, so the histogenesis remains unclear. Treatment consists primarily of tumor removal or conservative follow up. Here we present a rare case of malignant lymphoma arising from heterotopic (ectopic) WT. A 102-year-old man presented with a mass in the left side of the neck which was painless but gradually enlarged over 1 month. The mass was 2-3 cm in diameter, and freely moveable below the angle of the mandible. The mass was totally removed. The histological diagnosis was malignant lymphoma, diffuse large B-cell type, arising from heterotopic WT. Postoperative staging examination including chest radiography, bone scan, and computed tomography of the abdomen and pelvis revealed no evidence of dissemination of malignant lymphoma. Malignant transformation within WT is rarer in the lymphoid component than in the epithelial component. Only 16 cases of malignant transformation arising from WT have been reported, including only three cases of non-Hodgkin lymphoma apparently arising from heterotopic WT. Tumor removal or careful follow up is recommended in patients with WT because of the potential risk posed by such malignant transformation.
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