The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 242 , Issue 3
July
Showing 1-11 articles out of 11 articles from the selected issue
Editorial
Regular Contribution
  • Seishi Furukawa, Kazuko Miyakawa, Joichi Shibata, Mitsutoshi Iwashita
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 167-172
    Published: 2017
    Released: July 07, 2017
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    Maternal subclinical hypothyroidism may be associated with adverse pregnancy outcomes, although not consistently across regions. Here, we sought to determine the effect of elevated thyroid-stimulating hormone (TSH) on pregnancy outcomes in Japanese women without known medical complications. TSH was determined by dried blood spots at 8-20 weeks of gestation, and 3.0-10.0 μU/mL of TSH was considered as elevated TSH (eTSH). A retrospective study involving 167 cases of eTSH was conducted. Five hundred and seventy eight of controls with normal TSH and without thyroid antibodies were selected. We compared a composite adverse maternal outcome comprised of spontaneous abortion, premature delivery, gestational diabetes mellitus (GDM), placental abruption, and pregnancy-induced hypertension, as well as composite adverse neonatal outcome including stillbirths, heavy for date, light for date, and a low Apgar score (< 7) at 5 minutes between two groups. The incidence of GDM was significantly higher in eTSH (p < 0.01); however, composite adverse maternal and neonatal outcome did not differ between groups (p = 0.19 and p = 0.50, respectively). Although 27 out of 167 cases in eTSH have antibodies, composite adverse outcome did not differ between eTSH with antibodies and controls (p = 0.64 and p = 0.50, respectively). Additionally, composite adverse maternal and neonatal outcome did not differ between the group larger than the median of TSH in eTSH (n = 81) and controls (p = 0.43 and p = 0.98, respectively). Thus, elevated TSH is not associated with overall adverse pregnancy outcomes in women without known medical complications.

  • Xiaoyan Guo, Mingrui Lin, Tengfei Shi, Wei Yan, Wenxu Chen
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 173-181
    Published: 2017
    Released: July 07, 2017
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    Multiple osteochondromas (MO) is one of the most common benign bone tumors in humans with an autosomal dominant hereditary mode. MO is a genetic heterogeneity disease with variable number and size of osteochondromas, as well as changeable number and location of diseased bones. Mutations in Exostosin-1/Exostosin-2 (EXT1/EXT2) genes are the main molecular basis of MO. EXT1 and EXT2 genes encode exostosin 1 and exostosin 2, respectively, both of which are transmembrane glycosyltransferases that elongate the chains of heparin sulfate (HS) at HS proteoglycans (HSPGs). HSPGs are considered to be involved in regulating the proliferation and differentiation of chondrocytes. Owing to large size of EXT1/EXT2 genes and lack of mutation hotspots, molecular diagnosis of MO is challenging. Here, we applied targeted next-generation sequencing (t-NGS) in mutation screening of EXT1/EXT2 genes for 10 MO patients. The results were compared and validated with Sanger sequencing. Overall, nine mutations identified by t-NGS were confirmed with Sanger sequencing, excluding two variants of false positive, suggesting the reliability of mutation screening by t-NGS. The nine mutations identified by t-NGS include two missense mutations (EXT1: c.1088G>A and c.2120C>T), one splicing mutation (EXT2: c.744-1G>T), and six nonsense mutations (EXT1: c.351C>G, c.1121G>A, and c.1843_1846dup; EXT2: c.67C>T, c.561delG, and c.575T>A). In summary, our paper provides the primary data of the application of t-NGS in MO molecular diagnosis, including six newly identified mutations (EXT1: c.1843_1846dup, c.1088G>A, c.351C>G, and c.2120C>T and EXT2: c.744-1G>T and c.575T>A), which further enrich the mutation database of MO from the Chinese population.

  • Akihito Usui, Yusuke Kawasumi, Kiyotaka Usui, Yuya Ishizuka, Kaito Tak ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 183-192
    Published: 2017
    Released: July 07, 2017
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    Traditional autopsy has changed little in the past century. In Japan, the rate of forensic autopsy in cases of unusual death is very low. Therefore, multi-slice computed tomography (CT) has been used to obtain imaging data instead of or in addition to autopsy in suspicious forensic cases. In our institute, postmortem multi-slice CT has been performed since 2009, and by 2014 there were over 1,000 cases. Our extensive experience with postmortem CT shows that in many cases of death by drug overdose, stomach contents exhibit high X-ray absorption. This article reviews the relationship between CT findings of stomach contents and toxicological analysis results in 23 cases of death by drug overdose. All cases (12 females and 11 males, aged 44 ± 11 years) known to have orally ingested drugs were included in this study. We assessed the slices of all stomach areas on consecutive axial CT images. Twenty cases (87%) showed high X-ray absorption in the stomach, while the other three did not demonstrate radio-dense stomach contents even though drug analysis detected lethal concentrations of drugs in the blood. In conclusion, drugs were frequently, but not always, visualized as contents with high X-ray absorption in the stomach. Postmortem gastric CT images can provide useful information in cases of oral drug intoxication if there are empty drug packages or a suicide note at the death scene. However, precise determination of the cause of death requires full autopsy in cases where there is no indication of suicide at the death scene.

  • Yoshihiro Hagiwara, Takuya Sekiguchi, Yumi Sugawara, Yutaka Yabe, Masa ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 193-201
    Published: 2017
    Released: July 11, 2017
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    The Great East Japan Earthquake (GEJE) and Tsunami devastated the northeastern coast of Japan on March 11, 2011. This study attempted to determine whether socio-psychological factors such as sleep disturbance and psychological distress influenced new-onset subjective shoulder pain in survivors, during the post disaster phase of the GEJE. From November 2012 to February 2013 (2 years after the GEJE) and November 2014 to January 2015 (4 years after the GEJE), survivors (18 years old or over) answered self-reported questionnaires. In total, 1,454 survivors responded to the questionnaires and were thus included in this study. New-onset subjective shoulder pain was defined as shoulder pain by encircled response absent at 2 years, and present at 4 years after the GEJE. Two years after the GEJE, ≥ 10/24 points on the Kessler Psychological Distress Scale-6, and ≥ 6/24 points on the Athens Insomnia Scale defined the presence of psychological distress and sleep disturbance, respectively. Multiple logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of the association between new-onset subjective shoulder pain, and psychological distress or sleep disturbance. Amongst participants, 7.2% (105/1,454) reported new-onset subjective shoulder pain. Sleep disturbance was significantly associated with new-onset subjective shoulder pain (OR = 1.92, 95% CI = 1.24-2.98, P = 0.004); however, psychological distress was not (OR = 0.78, 95% CI = 0.42-1.42, P = 0.41). In conclusion, this is the first study indicating an association between sleep disturbance and new-onset subjective shoulder pain amongst the survivors of the GEJE.

  • Junko Okuyama, Shunichi Funakoshi, Hiroaki Tomita, Takuhiro Yamaguchi, ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 203-213
    Published: 2017
    Released: July 19, 2017
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    How natural disasters affect the psychological state of adolescents has not been well studied. Thus, we examined the effect of a natural disaster on high-school-aged youth and considered the most effective forms of support following such a disaster. We examined students from two high schools that were near the epicenter of the 9.0-magnitude Great East Japan Earthquake, which struck the Tohoku coastal area on March 11, 2011, causing severe damage to the region. The questionnaires measuring depression, anxiety, and post-traumatic stress reaction (PTSR) was administered to the students 3 times between July 2012 and August 2014; students who scored above the cut-off values of these measures were considered high-risk students. School teachers, nurses, and counselors provided a school-based intervention for all high-risk students identified in the survey. Data were analyzed using the Kruskal-Wallis H-test. Survey data revealed that 860 of the 1,432 (55.9%) high school students were at high risk of psychological trauma in 2012. This rate did not change substantially in the following 2 years, reaching 1,059 of 1,488 (69.1%) in 2013, and 949 of 1,430 (62.7%) in 2014. Depression and PTSR scores were significantly lower after the intervention (for 2nd and 3rd grade students in 2013 and 2014) compared to before (for the initial 2012 survey). However, there were no significant differences between the 1st grade students for all three years. Thus, school-based interventions involving psychological testing and interviews might reduce the rates of depression and PTSR in high school students.

  • Tamao Takahashi, Satoru Ebihara, Masahiro Kohzuki
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 215-221
    Published: 2017
    Released: July 19, 2017
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    Obesity is a major risk factor of cardiovascular, osteoarthritis, metabolic and pulmonary disorders, and exercise is an efficient method for treating obesity. However, obese patients often complain of dyspnea on exertion, which makes it difficult to continue exercise program. Obesity is also known to have an adverse effect on pulmonary function. The purpose of this study was to examine the effects of a comprehensive obesity rehabilitation (COR) program on pulmonary function in Japanese patients with morbid obesity. We enrolled 29 Japanese obese patients (14 males and 15 females) with BMI > 29 and an average age of 42.2 ± 11.7 years, who underwent the COR program for 1-3 months. Our COR program included a calorie-restricted diet, nutritional counseling, exercise training, and health education. We focused on the changes in pulmonary function, anticipating that changes in ventilation volume may contribute to improving exercise tolerance. After the intervention, all the subjects had lost weight, with a mean value of 12.0 kg (P < 0.001). We found that the lung volume compartment was significantly increased after our COR program, and that there is a strong positive correlation between a change in expiratory reserve volume and the weight loss (r = 0.74, P < 0.01). Through the COR program, body fat mass was significantly reduced, while the skeletal muscle mass remained more or less unchanged, which is advantageous for improvement in exercise tolerance. In conclusion, our COR program is helpful to improve the pulmonary function of patients with obesity.

  • Tomowaki Nakagawa, Ko Hashimoto, Takumi Tsubakino, Takeshi Hoshikawa, ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 223-228
    Published: 2017
    Released: July 15, 2017
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    Human lumbar spine usually consists of five vertebrae; however, some individuals have vertebral anomalies with four or six lumbar vertebrae because of sacralized fifth lumbar vertebra (L5 sacralization) or lumbarized first sacral vertebra (S1 lumbarization), respectively. These vertebral anomalies are called lumbosacral transitional vertebra (LSTV). Although LSTV is an asymptomatic anomaly, it is known to cause misconception in spinal counts and in spinal level at lumbar spinal surgery. The purpose of this study is to evaluate how LSTV affects the diagnosis and surgeries in lumbar spine disorders. In 550 consecutive patients who underwent lumbar spinal surgeries, a whole-spine X-ray was taken on admission to assess the true number of lumbar vertebrae. We assessed the coherence between the neurological level diagnosis and the level of spinal canal stenosis on imaging studies before and after the recognition of LSTV to clarify how recognition of LSTV affected pre-operative surgical planning. Out of 550 patients, LSTV was found in 71 (12.9%) patients: 37 cases with L5 sacralization and 34 cases with S1 lumbarization. The number of vertebrae was miscounted at the outpatient department (OPD) in 38 cases (54%): 10 L5-sacralization cases and 28 S1-lumbarization cases. Moreover, surgical spinal levels were altered from the original surgical plans at OPD in 11 cases (15%; 3 L5-sacralization and 8 S1-lumbarization cases), after recognizing the true spinal counts by the whole spine X-ray. To avoid errors in spinal level diagnosis, we should recognize the possibility of LSTV that could be assessed by a whole spine X-ray.

  • Takero Nakajima, Yang Yang, Yu Lu, Yuji Kamijo, Yosuke Yamada, Kozo Na ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 229-239
    Published: 2017
    Released: July 19, 2017
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    Insufficient intake of polyunsaturated fatty acids (PUFA) causes fatty liver. The mechanism responsible is primarily related to increased lipogenesis and decreased FA degradation based on rodent studies. However, these studies were limited by the fact that the typical PUFA-deficient diets contained insufficient amounts of long-chain FA, the PUFA-containing diets were primarily composed of n-3 PUFA-enriched oil, and the intake of PUFA was excessive compared with the physiological requirement. To address these issues, mice were fed a PUFA-deficient diet containing long-chain FA at a standard fed level and then were orally fed a n-3/n-6-balanced PUFA-containing oil [PUFA (+)] or a PUFA-deficient oil [PUFA (−)] at physiological relevant levels (0.1 mL/mouse/2d). We compared these groups and examined whether fatty liver in PUFA deficiency was attributable to both the effects of increased lipogenesis and decreased FA catabolism. Compared with the PUFA (+) group, the PUFA (−) group showed increases in liver triglyceride and serum FA content. Hepatic gene expression of several mitochondrial β-oxidation enzymes, the serum 3-hydroxybutyrate level, and DNA-binding ability of peroxisome proliferator-activated receptor α (PPARα) were increased in the PUFA (+) group, whereas these adaptive responses were significantly attenuated in the PUFA (−) group. The hepatic expression of typical lipogenesis genes did not differ between the groups. Therefore, fatty liver in PUFA deficiency is attributable to suppression of the FA-degrading system probably from decreased PPARα adaptive responsiveness, and PUFA may be an essential factor for PPARα functioning. This finding is helpful for managing clinical situations having a risk of PUFA deficiency.

  • Yukio Nakamura, Shigeharu Uchiyama, Mikio Kamimura, Shota Ikegami, Mas ...
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 241-246
    Published: 2017
    Released: July 22, 2017
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    Osteoporosis is characterized by the systemic impairment of bone mass, strength, and microarchitecture, leading to an increased risk of fragility fracture. Bisphosphonates (BPs) are the first-line drugs for osteoporosis. Vitamin D is considered to be essential for osteoporotic treatment. However, long-term effects of BPs on the serum levels of 25-hydroxyvitamin D3 (25(OH)D3) are unknown. Accordingly, in this retrospective study, we collected clinical data of 41 post-menopausal Japanese women with osteoporosis treated with BP for over 3 years, without vitamin D supplementation. We measured lumbar and femoral neck bone mineral density (BMD) and serum levels of bone specific alkaline phosphatase (BAP) as a bone formation marker, and tartrate-resistant acid phosphatase (TRACP)-5b as a bone resorption marker, before and after the 3-year treatment. Serum 25(OH)D3, 1,25(OH)2D3, and whole parathyroid hormone (PTH) were also measured. Notably, no fracture occurred during the treatment. Compared with baseline values, 25(OH)D3 levels were significantly increased from 21.6 to 26.4 ng/mL (P = 0.006), despite no vitamin D supplementation. 1,25(OH)2D3 and whole PTH levels tended to be decreased from 62.6 to 57.8 pg/mL and 27.3 to 25.1 pg/mL, respectively. Both bone formation and resorption markers were significantly suppressed (P < 0.01). Both lumbar BMD (7.3% increase) and femoral neck BMD (4.1% increase) were significantly improved (P < 0.0001) after 3 years of the treatment. Thus, even without vitamin D supplementation, serum 25(OH)D3 levels were significantly increased after 3-year BP therapy. These results suggest that vitamin D supplementation might not be required in the long-term BP therapy for osteoporosis.

  • Hitoshi Kuroda, Kazuo Inoue, Shin Takayama, Tadashi Ishii
    Type: Regular Contribution
    2017 Volume 242 Issue 3 Pages 247-249
    Published: 2017
    Released: July 22, 2017
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    On March 11, 2011, a magnitude 9.0 earthquake and huge tsunami occurred near the Pacific coast of northeast Japan, in which more than 18,000 people died or went missing and more than 120,000 buildings were destroyed. In Taro district, one of the areas struck hardest by the tsunami, a middle-aged woman was found deceased in the rubble. Generally, a family physician can recognize victims based on their appearance; the place where they were found; their home or work address; their belongings; the identifying marks on their clothes; their dental charts; and their living biological parents, children, or multiple siblings through DNA analysis. However, in this case, the middle-aged woman remained the area’s sole unidentified person for months, because her appearance was different, her body was slightly swollen, and she was missing some teeth. The district’s medical and dental facilities were destroyed and almost all medical records and dental charts lost. Fortunately, a family physician who had worked in the district for many years survived the disaster, and was available to provide background information about the victim, her family, and their relationship. He recalled the existence of tissue samples of her mother who had died several years earlier. Subsequently, the individual was identified through the DNA analysis of her blood and mother’s tissue samples. As demonstrated in the case, appropriately managed medical information and samples from previously deceased relatives can aid disaster victim identification. The destruction caused by the Great East Japan Earthquake forms our investigation’s background.

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