The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 249 , Issue 3
November
Showing 1-11 articles out of 11 articles from the selected issue
Regular Contribution
  • Ken Inoue, Sadayuki Hashioka, Haruo Takeshita, Masanori Kamura, Yasuyu ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 143-146
    Published: 2019
    Released: November 02, 2019
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    Problematic smartphone use among adolescents has become a social concern and is associated with poor sleep quality. The relationship between life habits, such as smartphone use and sleep duration, and levels of immunological and neuroendocrine biomarkers, including the stress hormone cortisol, in adolescents seems to be important to objectively comprehend their health and well-being in school life. However, such a relationship has not been well documented. We therefore studied rural junior high school students in Japan to elucidate the relationship between serum cortisol (SC) levels and their life habits. A total of 155 students in the seventh grade in 2016 were recruited as subjects. Of them, 140 students with eligible responses and blood samples (12-13 years; 80 boys, 60 girls) were finally included in the study (response rate 90.3%). A questionnaire survey concerning wake-up time, sleep duration, and the length of time using a smartphone per day was conducted. Blood samples were collected from peripheral veins of participants under fasting conditions between 8:30 and 11:00 a.m. The Spearman rank correlation coefficients were as follows: between SC and wake-up time, 0.199 (p = 0.018); between SC and sleep duration, 0.185 (p = 0.029); and between SC and time spent on smartphones, 0.172 (p = 0.042). The multiple regression analysis showed that high SC levels were significantly associated with late wake-up time and with short sleep duration. We therefore propose that measuring SC levels is useful for early detection of the change in the well-regulated daily life among junior high school students.

  • Toshihiro Kanda, Naoto Endo, Naoki Kondo
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 147-154
    Published: 2019
    Released: November 08, 2019
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    Osteoporosis is characterized by bone loss and skeletal fragility and is likely to occur in postmenopausal women. Distal radius fracture is a type of fragility fractures associated with osteoporosis. Bone mineral density (BMD) refers to the amount of mineral in bone tissue and is an indicator of osteoporosis. This study aimed to investigate the relationship between the severity of distal radius comminution and the BMD of the healthy contralateral forearm and femur in postmenopausal women. Of 165 women who sustained low-energy trauma from falls on flat ground, forearm and femoral neck BMDs were measured in 155 and 163 participants, respectively. Evaluation of distal radius comminution was performed by computed tomography, and the severity is classified based on the degree of articular surface comminution and on the presence of metaphyseal comminution. We thus evaluated 165 cases of articular surface comminution (extra-articular, 43 cases; intra-articular simple, 91 cases; and intra-articular multifragment, 31 cases) and metaphysis comminution (metaphyseal simple, 58 cases; metaphyseal monocortical comminution on either the palmar or dorsal side, 82 cases; and metaphyseal bicortical comminution on the palmar and dorsal sides, 25 cases). There was no significant association between intra-articular comminution and BMD of the forearm and femur. By contrast, the participants with metaphyseal bicortical comminution showed lower BMD of the forearm and femur compared with other types of metaphysis comminution (p < 0.05). In conclusion, postmenopausal women who developed bicortical comminuted fractures of the distal radius tend to have lower femoral BMD, which may predispose them to future hip fractures.

  • Maiko Kaga, Masatoshi Sanjo, Tomoki Sato, Yuichiro Miura, Toshikazu On ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 155-161
    Published: 2019
    Released: November 09, 2019
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    Patent ductus arteriosus (PDA) is a common problem among preterm infants. The standard of care for PDA has been to attempt to close the PDA by pharmacological treatment or surgical ligation. Recently, conservative approach for PDA (i.e., infants receive no treatment for PDA unless it is necessary for rescue) is gaining interest. However, when PDA is persisted under the conservative approach, there is a concern about the neurodevelopmental problems caused by decreased cerebral oxygenation. Our objective was to examine the risk of neurodevelopmental impairment in preterm infants, when PDA remained persistently open under conservative approach for PDA. We retrospectively analyzed data from the medical charts in 72 included infants (gestational age < 29 weeks, birth weight < 1,250 g). Under our conservative approach for PDA, we divided infants by their ductal patency: a closed ductus group (ductus closure within 14 days after birth, n = 52) and a persistent patent ductus arteriosus group (ductus closure after 14 days, n = 20). We compared the clinical parameters and neurodevelopmental outcomes assessed with the Kaufman Assessment Battery for Children (K-ABC) at 5 years of corrected age in two groups. Among the children who completed the K-ABC test, there were no significant differences in neurodevelopmental scores between a closed ductus group (n = 44) and a persistent patent ductus arteriosus group (n = 17). A conservative approach for PDA, even in the case of prolonged PDA, does not increase the risk of neurodevelopmental impairment at 5 years of corrected age in preterm infants.

  • Junichi Yokota, Yoshiko Ogawa, Yoshimi Takahashi, Nobuhiro Yamaguchi, ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 163-171
    Published: 2019
    Released: November 14, 2019
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    Dysphagia, defined as a dysfunction in any stage or process of eating, is common among heart failure (HF) patients. In some diseases state, dysphagia hinders patients from being discharged to home. However, it remains unclear whether dysphagia affects discharge disposition of HF patients. This study aimed to identify the impact of dysphagia on discharge disposition of HF patients. A total of 323 patients, hospitalized with acute exacerbation of HF, were eligible for the study (excluding patients who lived at nursing care facilities before admission). Following the withdrawal of 37 patients, a total of 286 patients were analyzed. Dysphagia was determined using the functional oral intake scale (FOIS), which evaluates a patient’s ability to swallow. The FOIS is a 7-point scale, with a level of ≤ 5 indicating dysphagia. Of the 286 patients analyzed, 231 (80.8%) were discharged to home, and 55 were discharged to nursing care facilities or rehabilitation hospitals (non-home). FOIS level was significantly lower, and dysphagia incidence was significantly higher among patients discharged to non-home than among those discharged to home. Multivariate analysis showed that FOIS level was an independent predictor of discharge disposition. Additionally, after propensity score matching, which was performed to adjust for baseline characteristics, FOIS level remained significantly lower in patients discharged to non-home than in those discharged to home. In conclusion, dysphagia hinders patients hospitalized with HF from being discharged to home. We conclude that evaluating dysphagia and its severity on admission is useful for predicting discharge disposition in patients hospitalized with HF.

  • Mónica Alejandra Rosales-Reynoso, Anilú Margarita Saucedo-Sariñana, Ka ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 173-183
    Published: 2019
    Released: November 14, 2019
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    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named “destruction complex” has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

  • Daisuke Yamamoto, Hiroyuki Koizumi, Daisuke Ishima, Hiroki Kuroda, Ich ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 185-192
    Published: 2019
    Released: November 23, 2019
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    Knowledge of branching patterns of external carotid artery (ECA) is essential for planning and execution of head and neck surgeries. Digital subtraction angiography (DSA) images of 532 ECAs from 302 consecutive patients were retrospectively evaluated. We classify the branch variants of ECA into three types, simply based on the number of branches arising close together. Type A, Type B, and Type C variants are defined as two, three, and four or more branches of ECAs arising at a common point from the proximal ECA, respectively. In this classification, the distal ECA was counted as one branch. Of 532 ECAs, Type A was found in 344 ECAs (64.6%) of 237 patients (78.5%), Type B in 134 ECAs (25.2%) of 110 patients (36.4%), and Type C in 54 ECAs (10.2%) of 49 patients (16.2%). The distance from the common carotid artery (CCA) bifurcation to the first branch of ECA with Type C was 14.7 ± 6.6 mm; its distance is shorter compared with Type A (21.8 ± 15.6 mm) and Type B (20.6 ± 8.9 mm) (P < 0.05). The position of CCA bifurcation with Type C was detected at the third-fourth junction cervical vertebral level or higher in 52 of 54 ECAs (96.3%), significantly higher than those of the other types (P < 0.05). In conclusion, Type C ECA has aggregated vessels with short distance from CCA and high position of CCA bifurcation. Type C ECA is not uncommon; thus, special consideration should be paid to avoid complications during surgeries.

  • Arisa Sato, Yoshinori Ohtsuka, Yujiro Yamanaka
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 193-201
    Published: 2019
    Released: November 23, 2019
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    Postprandial glucose concentration is dependent on the time of day and its concentration in the morning is lower than in the evening. However, whether it is dependent on mastication at different times of the day has not been studied before. We hypothesized that mastication affects insulin-mediated glucose metabolism differently in the morning and evening in healthy individuals. Firstly, nine healthy male volunteers (22.0 ± 0.7 SEM years, body mass index 22.0 ± 1.0 kg/m2) performed a 75-g oral glucose tolerance test (OGTT). One week after the OGTT, they participated in a high-carbohydrate food (rice) consumption test with 10 or 40 chews per mouthful. Each experiment was conducted in the morning (0800 h) and evening (2000 h) on the same day. Blood samples were collected before and at 30-min intervals for 120 min after glucose or rice consumption. The incremental area under the curve (iAUC) for glucose in the OGTT was significantly lower in the morning than in the evening, whereas the iAUC for insulin was similar at both times. In participants who chewed 40 times, the iAUC for glucose after rice consumption was significantly lower in the morning than in the evening but was similar at both times in individuals who chewed 10 times. Chewing 40 times in the morning (but not the evening) significantly increased insulin secretion at 30 min. This suggests that morning mastication improves early-phase insulin secretion after rice consumption. This novel finding may aid in reducing the incidence of obesity and type 2 diabetes mellitus.

  • Tomoyuki Kato, Yuji Takeda, Hiromi Ito, Yuta Kurota, Atsushi Yamagishi ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 203-212
    Published: 2019
    Released: November 26, 2019
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    Myeloid-derived suppressor cells (MDSCs), which include neutrophilic MDSCs and monocytic MDSCs, exhibit high immunosuppressive activity. Glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) is selectively expressed on mature neutrophils in healthy individuals. Increased GPI-80 expression on monocytes and variations in GPI-80 expression on neutrophils indicate the appearance of MDSCs in the peripheral blood of cancer patients. However, it is still unclear whether GPI-80 expression on myeloid cells, neutrophilic MDSCs and monocytic MDSCs, is correlated with the clinical outcomes of patients with cancer. In this study, we investigated the characteristics of myeloid cells expressing GPI-80 and the implication of GPI-80 expression in the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), in which primary renal cell carcinoma spreads from the kidney to other organs. The study included 20 patients with mRCC (a mean age of 66.0 years) and 16 healthy volunteers (a mean age of 47.8 years). To determine the heterogeneity of myeloid cells in peripheral blood samples, we performed the three-dimensional principal component analysis using the combination of GPI-80, CD16, and latency-associated peptide-1 (LAP), derived from the N-terminal region of transforming growth factor-β1 precursor. The results showed that myeloid cells in mRCC patients were widely distributed and clearly distinguishable from those in the healthy volunteers. The survival analysis revealed that GPI-80 expression on neutrophils and monocytes was correlated with poor prognostic outcomes of patients with mRCC. In conclusion, the expression of GPI-80 on myeloid cells, a useful index for the heterogeneity of MDSCs, serves as a potential prognostic biomarker for mRCC.

  • Chian-Feng Chen, Kate Hua, Lin-Chung Woung, Chin-Hui Lin, Chueh-Tan Ch ...
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 213-221
    Published: 2019
    Released: November 26, 2019
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    Myopia is the most common refractive disorder in Eastern Asia. The development of myopia is associated with the cooperation of various ocular tissues. Exosomes in the aqueous humor (AH) have been implicated to modulate intracellular communications by transferring exosomal miRNAs and proteins between cells. These exosomal miRNAs and proteins are likely involved in the pathogenesis of various eye diseases. In this study, we aimed to explore human exosomal miRNA profiles and their roles in myopia development. AH samples were collected from 16 patients (8 myopia and 8 control) undergoing routine cataract surgeries. Exosomes were isolated from AH of each individual using the ExoQuick solution. The numbers and sizes of exosomes were not significantly different between the myopia and control groups. The individual exosomes of the same group were pooled to purify RNA. Unexpectedly, the myopia group contained 2.78-fold total RNA amount than that in the control group. Thereafter, miRNA profiles were analyzed using the OpenArray system. We thus found 15 myopia-specific miRNAs and four myopia-absent miRNAs. By using bioinformatics analysis, we identified six well-known myopia-associated genes that are potential targets of five myopia-specific miRNAs (has-miR-582-3p, has-miR-17-5p, has-miR-885-3p, has-miR-19b-3p, and has-miR-450b-5p). These genes are cholinergic receptor muscarinic 2 (CHRM2), cyclic nucleotide-gated channel beta 3 (CNGB3), vascular endothelial growth factor A (VEGFA), adenosine A2a receptor (ADORA2A), insulin-like growth factor 1 (IGF1), and lumican (LUM). Moreover, CHRM2 may be a target of myopia-absent miRNA (has-miR-378a-5p). In conclusion, we show the expression profiles of AH-derived exosomal miRNAs and their potential roles in myopia development.

Case Report
  • Masahiro Nezu, Masataka Kudo, Yoshikiyo Ono, Yuta Tezuka, Ryo Morimoto ...
    Type: Case Report
    2019 Volume 249 Issue 3 Pages 223-229
    Published: 2019
    Released: November 27, 2019
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    Hypothalamic obesity is a clinical syndrome characterized by severe and refractory obesity that is caused by hypothalamic function impairment. Recently, bariatric surgery has been attempted for patients with hypothalamic obesity after craniopharyngioma, but experiences have not yet been accumulated in other hypothalamic disorders. Here, we report the case of a 39-year-old male patient with panhypopituitarism who received laparoscopic sleeve gastrectomy (LSG) after intracranial germinoma treatment. The patient was diagnosed with intracranial germinoma at age 15 and achieved complete remission after radiotherapy (total 50 Gy). He was obese during diagnosis [body mass index (BMI), 29.2 kg/m2], and his obesity gradually worsened after the intracranial germinoma treatment, and LSG was considered when his BMI was 48.6 kg/m2. After 1 month of hospitalized diet-exercise program, LSG was performed. After LSG, his BMI gradually decreased and reached 38.8 kg/m2 on the day of discharge (6 weeks after the surgery). Five months after LSG, his insulin resistance improved, but insulin hypersecretion remained. Fifteen months after the surgery, his BMI was 31.2 kg/m2, with marked decrease in visceral and subcutaneous fat areas (from 393.8 cm2 and 168.2 cm2 before the surgery to 111.5 cm2 and 56.3 cm2, respectively.). To our knowledge, this is the first case of LSG for hypothalamic obesity after intracranial germinoma treatment. Although the pathophysiology of hypothalamic obesity is different from that of primary obesity, LSG could be a successful therapeutic choice for patients with hypothalamic obesity after the intracranial germinoma treatment.

Regular Contribution
  • Junko Ushijima, Seishi Furukawa, Hiroshi Sameshima
    Type: Regular Contribution
    2019 Volume 249 Issue 3 Pages 231-236
    Published: 2019
    Released: November 28, 2019
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    Thyroid dysfunction (TD) is caused by thyroid peroxidase (TPO) antibody, as seen in Hashimoto’s disease. TD is a common problem of reproductive age and may impair fetal development. Here, we determined the effect of TPO antibody on perinatal outcomes in Japanese women with TD before conception. A retrospective study involving cases of maternal TD with term singleton birth was conducted. The subjects with TD were divided into two groups according to the presence (n = 22) or absence (n = 20) of TPO antibody. The control groups matched for age, parity, and gestational weeks were selected for TPO antibody-positive (n = 44) and -negative TD subjects (n = 40), respectively. Using the standard curve of Japanese placental weight, the frequency of placental weight less than the 50th percentile (small placenta) was examined. Placental weight was lower among TPO antibody-positive TD subjects, compared with TPO antibody-negative TD subjects (p < 0.01). However, other outcomes were similar between the groups. Importantly, compared with control mothers, placental weight was significantly lower (p < 0.01), birth weight tended to be lower (p = 0.07), and the incidence of gestational diabetes mellitus was higher (p = 0.02) among TPO antibody-positive subjects. There was no significant difference in placental weight between TPO antibody-negative subjects and controls. The frequency of small placenta was significantly higher in TPO antibody-positive subjects (odds ratio: 16.7) even when considering diabetes and pregnancy induced hypertension. Thus, the presence of TPO antibody is associated with lower placental weight among Japanese women having TD.

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