The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 246 , Issue 2
October
Showing 1-9 articles out of 9 articles from the selected issue
Regular Contribution
  • Motohiko Suzuki, Meiho Nakayama, Kayoko Bhardwaj Ando, Sachie Arima, ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 65-71
    Published: 2018
    Released: October 02, 2018
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    Actigraphy is an easy and noninvasive method used to monitor human ultradian cycles. However, to our knowledge, it has been not applied to experiments with rodents. Therefore, using actigraphy, we assessed the ultradian cycles and behavior of rats. Rats with or without allergic rhinitis wore an actigraphy device, and triaxial acceleration was recorded. The counts that represent physical activity were lower from 8:00 to 20:00 than those from 20:00 to 8:00 in control rats, suggesting that their sleep phase was from 8:00 to 20:00 and their awake phase from 20:00 to 8:00. The counts from 8:00 to 10:00 were significantly higher in allergic rhinitis rats than in control rats (p < 0.01), suggesting the presence of difficulty with sleep induction in rats with allergic rhinitis. The counts from 18:00 to 20:00 were also significantly higher in allergic rhinitis rats than in control rats (p < 0.05), suggesting the presence of early awakening in rats with allergic rhinitis. Moreover, the counts were significantly higher in allergic rhinitis rats than in control rats from 20:00 to 8:00. These results suggest that rats with allergic rhinitis experienced hyperactivity disorder during the daytime. Additionally, hyperreactivity and difficulty with sleep induction were observed in 6-hydroxydopamine-lesioned rats, an animal model of attention-deficit hyperactivity disorder. This study shows for the first time that actigraphy can be successfully used for behavioral analysis in rodents. These rat models could be useful for analyzing the mechanisms involved in sleep disturbances and hyperactivity disorder.

  • Yoshifumi Shoho, Takao Kimura, Yoshimaro Yanagawa, Ai Saito, Toshiya I ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 73-79
    Published: 2018
    Released: October 03, 2018
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    In 2014, for the protection of medical workers against measles and rubella infection, the Japanese Society for Infection Prevention and Control (JSIPC) recommended either maintaining antibody titers of seroprotective range or two-dose vaccination. JSIPC defined antibody titers into 3 ranges: seroprotective as expected prevention of infection, seronegative as under detection levels, and seropositive as antibody titers ranged between seronegative and seroprotective. This study aimed to explore the association between the number of vaccine doses received and the antibody titers against measles and rubella among Japanese college students majoring in childcare. A total of 841 female students with no history of measles or rubella were serologically screened at the time of college admission between 2015 and 2018. All 841 students had been vaccinated against measles; 738 (87.8%) received two doses of the measles vaccine and 103 (12.2%) received one dose. Likewise, 839 students, except for two, had been vaccinated against rubella; 719 (85.7%) received two doses of the rubella vaccine and 120 (14.3%) received one dose. We thus found that 107 students (12.7%) were seropositive for measles-specific IgG and 731 (86.9%) attained seroprotective titers. By contrast, in case of rubella-specific IgG, only 462 students (55.1%) attained seroprotective titers, and 371 students (44.1%) were seropositive. The two students without receiving rubella vaccination were classified as seronegative. In conclusion, despite that > 85% of students surveyed had received two doses of measles and rubella vaccines, a substantial number of students remain susceptible to measles and especially rubella at the time of college admission.

  • Jung-Min Kim, Jun-Seon Choi, Yoon-Hyeong Choi, Hee-Eun Kim
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 81-86
    Published: 2018
    Released: October 17, 2018
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    Dental caries assessment needs to be targeted at specific age groups, as many risk factors are related to patient age. Pre-teen and teenage patients, who are still at risk of occurrence of new carious lesions, need more individualized caries management strategies. Therefore, this study aimed to identify caries-related risk factors and develop a simplified risk prediction model for dental caries. Risk factors for caries were assessed in 171 participants aged 10-18 years, based on a questionnaire survey, previous history of caries, oral hygiene, microorganism colonization, saliva secretion, saliva buffer capacity examinations, and the acidogenicity of dental biofilms. These risk factors were entered into a computer-based risk assessment program (the Cariogram), and correlations between these factors and Cariogram scores were investigated. Significant risk predictors were used to develop a simplified risk prediction model. The performance of this model in predicting dental caries incidence was evaluated using receiver operating characteristic analysis, to determine its applicability to the management of caries. Our simplified prediction model included three predictors that were significantly associated with caries incidence: use of fluoride-containing toothpaste, the acidogenicity of dental biofilms, and saliva secretion (p < 0.001). The resulting model had a sensitivity and specificity of 60.5 and 85.0%, respectively, with a cut-off value of 69.41 as the threshold. The area under the curve of this model was 0.782 (95% confidence interval = 0.681-0.884, p < 0.001). Our new caries risk prediction model is expected to allow clinicians to accurately and easily predict patients’ risk of occurrence of new caries.

  • Zhe-Wei Zhang, Ming Wang, Jun-Jie Hu, Gang Xu, Yong Zhang, Nan Zhang
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 87-96
    Published: 2018
    Released: October 17, 2018
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    MicroRNAs (miRNAs) are small noncoding RNA molecules that participate in normal B cell lineage development through posttranscriptional gene regulation. Antibody-mediated renal allograft rejection (ABMR) is emerging as one of the most common serious threats to renal transplant patients. In this study, we explored the role of miRNAs in the pathogenesis of ABMR. The differentially expressed miRNAs were identified by Affymetrix miRNA microarray analysis using B lymphocytes from 5 recipients and 5 volunteers. Based on quantitative RT-PCR, the expression levels of miR-107 were lower in the B lymphocytes from recipients than in those from volunteers. Computational analysis predicted that 3′-untranslated region of the autophagy-related protein 12 (ATG12) mRNA was targeted by miR-107, and we identified ATG12 as a target of miR-107 by Luciferase assay. Importantly, the expression levels of ATG12 in B lymphocytes of recipients were higher than those in the volunteer group, and miR-107 mimic significantly decreased ATG12 expression and formation of autolysosomes in B lymphocytes of recipients. Furthermore, we observed that levels of autophagy in B lymphocytes of transplant recipients were higher than those in B cells from volunteers. These findings suggest that miR-107 may contribute to the regulation of autophagy via targeting ATG12. Lastly, treatment with an miR-107 mimic caused the decrease in the secretion of IgG and IgM antibodies from B lymphocytes of transplant recipients, indicating that deregulated miR-107 could be involved in the pathogenesis of ABMR. Taken together, we propose that decreased miR-107 expression is associated with autophagy activation in B lymphocytes from patients with ABMR.

  • Mami Ishikuro, Taku Obara, Tamae Osanai, Chizuru Yamanaka, Yuki Sato, ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 97-105
    Published: 2018
    Released: October 18, 2018
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    Involvement of family members, especially grandparents, in genome epidemiological research is important to investigate both genetic and environmental factors of common diseases. The aim of the present study was to establish strategies to obtain enough number of family recruitment, especially focusing on grandparents, for the Tohoku Medical Megabank Birth and Three-Generation Cohort Study. Our main strategies are summarized below. 1) We standardized informed consent process with reference materials to help people understand the consent form, 2) we created an invitation letter to contact family members, and 3) we recruited family members in several settings. To obtain informed consent, we were careful of explaining clearly the complex reasons as well as drawing people’s attention. By the end of March 2017, the number of invitation letters distributed to family members through the pregnant women was 23,806, including 18,702 grandparents. Among the grandparents who received invitation letters, 2,935 (15.7%) responded to us. Furthermore, some grandparents were asked to provide informed consent with other family members by staff at maternal clinics or Community Support Centers, and others directly booked Community Support Centers without responding to the invitation letter. Grandparents joined the study anytime during mother’s maternal check-ups or delivery. Overall, 8,054 grandparents participated in our birth cohort study. The setting in which most grandparents were recruited was our own facilities. Importantly, both paternal and maternal grandparents more frequently participated in the study if the father also participated. In conclusion, we are able to recruit not only pregnant women but also fathers and grandparents.

  • María Cristina Negrete-Garcia, Sandra Lizbeth Ramírez-Rodriguez, Claud ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 107-120
    Published: 2018
    Released: October 24, 2018
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    Cancer-associated fibroblasts (CAFs) are the main component of the tumor stroma and promote tumor progression through several mechanisms. Recent evidence indicates that small noncoding RNAs, microRNAs (miRNAs), play key roles in CAF tumor-promoting properties; however, the role of miRNAs in lung cancer-associated fibroblasts remains poorly defined. We characterized the differential miRNA expression profile of fibroblasts isolated from matched tumor front (F-CAFs), inner tumor (In-CAFs), and normal adjacent (NFs) tissues from four lung adenocarcinoma patients (ADs) using microarray analysis. Proliferation and invasion assays of A549 human lung cancer cells in the presence of conditioned medium from F-CAFs, In-CAFs or NFs were performed to assess tumorigenic properties. Ten identified candidate miRNAs in F-CAFs, In-CAFs and NFs from 12 ADs were then validated by RT-PCR. Both F-CAFs and In-CAFs enhanced the proliferation and invasion of A549 cells compared with NFs; moreover, F-CAFs showed a significantly stronger effect than In-CAFs. RT-PCR validation demonstrated three downregulated miRNAs in F-CAFs compared with NFs (miR-145-3p, miR-299-3p, and miR-505-3p), two in F-CAFs compared with In-CAFs (miR-410-3p and miR-485-5p), but no differentially expressed miRNAs between In-CAFs and NFs. Further target-gene prediction and pathway enrichment analysis indicated that deregulated miRNAs in F-CAFs showed significant associations with “pathways in cancer” (miR-145-3p, miR-299-3p and miR-410-3p), “Wnt signaling pathway” (miR-410-3p and miR-505-3p), and “TGF-beta signaling pathway” (miR-410-3p). Importantly, a tumor-promoting growth factor targeted by those miRNAs, VEGFA, was upregulated in F-CAFs compared with NFs, as judged by RT-PCR. In conclusion, deregulated miRNAs in F-CAFs are potentially associated with CAF tumor-promoting properties.

  • Chitaru Tokutake, Akiko Haga, Kesami Sakaguchi, Atsuko Samejima, Miki ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 121-130
    Published: 2018
    Released: October 24, 2018
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    Co-sleeping and breastfeeding in the side-lying position have recently been pointed out as risk factors for suffocation in sleeping infants; however, there is no actual report on an “incident.” “Incident” is defined as a tense or sobering experience without a consequential fatal suffocation accident. It is important to understand infant suffocation incidents to prevent accidents during co-sleeping and breastfeeding in the side-lying position. We investigated factors and frequency of infant suffocation incidents associated with co-sleeping and breastfeeding in the side-lying position using a self-administered questionnaire survey of 895 mothers during their infant’s 1-, 4-, or 10-month health checkups. Co-sleeping and breastfeeding in the side-lying position were practiced by 28.3% and 56.0% of mothers, respectively; thus, 84.3% of the mothers surveyed were practicing either co-sleeping or breastfeeding in the side-lying position. Of those who received guidance from a medical professional, 36.1% practiced only co-sleeping while 60.1% practiced only side-lying breastfeeding. In the co-sleeping group, 10.6% had faced infant suffocation incidents, while 13.2% in the breastfeeding in the side-lying position group had faced similar incidents. Regarding factors associated with suffocation incidents while co-sleeping, the frequency of occurrence was significantly more in mothers of 1-month and 4-month-old infants compared with those of 10-month-old infants. Of mothers who faced suffocation incidents while breastfeeding in the side-lying position, 45% also had faced similar incidents while co-sleeping. These results demonstrate the importance of thoroughly educating mothers about the risks associated with co-sleeping and breastfeeding in the side-lying position for preventing infant suffocation.

  • Shigeto Koizumi, Satoru Motoyama, Noboru Watanabe, Tamotsu Matsuhashi, ...
    Type: Regular Contribution
    2018 Volume 246 Issue 2 Pages 131-140
    Published: 2018
    Released: October 27, 2018
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    With the decreasing global trend in the Helicobacter pylori infection rate, compositional changes in the gastric cancer subsites have occurred worldwide. However, the compositional changes in Asian countries, including Japan, remain to be clarified. The aim of this study is to investigate the latest chronological changes in the gastric cancer subsite using a hospital-based registration system in Akita prefecture in Japan. From 2007-2015, subsites of gastric cancers were coded according to the International Classification of Diseases for Oncology (ICD-03). The nine-year registration period was divided into the three 3-year periods: 2007-2009, 2010-2012, and 2013-2015. A total of 10,804 cases of gastric cancer were registered. The proportion of cardiac cancer among total gastric cancer slightly but significantly declined from 12.1% in 2007-2009 to 9.2% in 2013-2015 (P < 0.01). Among non-cardia cancer, the proportion of corpus cancer significantly increased from 41.3% to 50.2% during the study period (P < 0.01), while that of antropylorus cancer significantly decreased from 37.6% to 34.3% (P < 0.05). Such compositional changes in the gastric cancer subsite were observed largely in men, regardless of the histologic subtype of cancer. With the decreasing H. pylori infection rate, compositional changes in the gastric cancer subsite are occurring in Japan. While the proportion of cardia and antropylorus cancer is declining, that of corpus cancer is increasing, indicating diverse etiology of gastric carcinogenesis depending on the subsites. Identifying the most common sites of occurrence, may help to improve the efficiency of screening for gastric cancer.

Case
  • Jun Suzuki, Yoriko Harazaki, Shinkichi Morita, Yoshiko Kaga, Kazuhiro ...
    Type: Case
    2018 Volume 246 Issue 2 Pages 141-146
    Published: 2018
    Released: October 27, 2018
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    Myeloid sarcoma (MS) is an uncommon extramedullary malignant tumor, and often represents a subgroup of acute myeloid leukemia (AML). MS of paranasal sinus origin is extremely rare. We report an uncommon case of sinonasal MS associated with AML, who was successfully treated with hematopoietic stem-cell transplantation. A 39-year-old male was admitted with complaints of left nasal obstruction and proptosis. Computed tomography and magnetic resonance imaging identified a left ethmoidal mass involving the maxillary sinus, the orbit, and the skull base. Nasal endoscopic examination detected a whitish homogeneous mass occupying the left nasal cavity. Although accumulation of atypical lymphocytes was suspected based on initial pathological inspection, immunohistochemical analysis showed myeloperoxidase-positive myeloid cells. Together with concomitant leukocytosis (149,000/µL) composed of myeloid blast cells and excess of myeloblasts in the bone marrow, the patient was diagnosed as sinonasal MS with AML with maturation (French-American-British Classification M2). The patient was treated by chemotherapy (remission induction therapy with daunorubicin and cytarabine; salvage chemotherapy with high-dose cytarabine), radiotherapy (30 Gy in 10 fractions) and allogeneic hematopoietic stem-cell transplantation, and followed up for 12 months with no recurrence. Early diagnosis is critical for the best improvement of MS. MS of the paranasal sinuses may easily be misdiagnosed as malignant lymphoma or poorly differentiated carcinoma. Prompt hematological and immunohistological investigations with suspicion of MS are essential for correct diagnosis. Furthermore, we concisely review nine previously reported patients with MS and indicate the importance of hematopoietic stem-cell transplantation for good prognosis.

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