The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 244, Issue 4
April
Displaying 1-9 of 9 articles from this issue
Regular Contribution
  • Takakuni Tanaka, Guang Hong, Kanako Tominami, Tada-aki Kudo
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 249-261
    Published: 2018
    Released on J-STAGE: March 24, 2018
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    Oral fat sensitivity (OFS), the ability to taste fat, is associated with eating habits in humans, including daily fatty food consumption; namely, proper OFS is important for health. In addition, lifestyle factors, such as stress and sleep, may affect fat intake. However, correlations between OFS, stress management, and sleep are largely unknown. Thus, we investigated the associations of OFS with lifestyle factors regarding stress management and daytime sleepiness in healthy young adult men. We measured OFS, sensitivities for three prototypical tastes (sweet, salty, and sour), and BMI in 22 subjects (27.2 ± 6.0 years), who also completed a self-reported questionnaire on health, including lifestyle-related questions. The correlations of taste sensitivities with stress management and daytime sleepiness were analyzed. We thus found that the number of mentors for personal concerns (a question regarding stress management, social support) was positively associated with OFS (P = 0.041), but not the other taste sensitivities. In contrast, other lifestyle factors related to stress management (frequency of relaxation, frequency of eating when irritated or worried, and degree of satisfaction with one’s sleep) and daytime sleepiness were not significantly associated with OFS, similar to that observed for other tested taste sensitivities. These results characterize the unique association of OFS with the degree of social support in healthy young men and provide novel insights into the nature of individual OFS differences. Thus, measuring the degree of social support may be helpful for the evaluation of OFS impairment, thereby contributing to the prevention of stress-induced overeating.

  • Di He, Min Liu, Bo Liu
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 263-270
    Published: 2018
    Released on J-STAGE: March 23, 2018
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    Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a wide range of clinical presentations. Lupus nephritis (LN) is the most serious manifestation of SLE. Interleukin-35 (IL-35), a member of the interleukin-12 family, has been identified as a novel anti-inflammatory cytokine. In the past ten years, the role of IL-35 in inflammatory and autoimmune diseases has been studied extensively. Serum IL-35 levels, however, have not been studied in LN patients. The aim of the study was to determine serum IL-35 levels in SLE patients with and without nephritis, and their clinical values. The study was carried out on 120 SLE patients, which comprised 80 LN patients and 40 SLE patients without nephritis. SLE disease activity was measured according to Systemic Lupus Erythematosus Disease Activity Index-2 k (SLEDAI-2 k). Statistical evaluation was based on Mann-Whitney U-test, t-test, chi-square test, Spearman rank correlation test and Pearson’s correlation test. The result showed that active SLE patients (n = 65) have lower serum IL-35 levels, compared to inactive SLE patients (n = 55, P < 0.001). Furthermore, serum IL-35 levels were significantly lower in LN patients (n = 80) than SLE patients without nephritis (n = 40, P = 0.013). Serum IL-35 levels had significant correlations with SLEDAI-2k (r = –0.626, P < 0.001) in SLE patients and estimated glomerular filtration rate (eGFR) (r = 0.348, P = 0.002) in LN patients. These results indicate that IL-35 is a potential biomarker of renal involvement in LN patients.

  • Emilija Nikolić, Tijana Brandmajer, Vesna Bokan, Maria Ulyashova, Maya ...
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 271-277
    Published: 2018
    Released on J-STAGE: April 05, 2018
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    Urinary tract infection (UTI), which is typically caused by Escherichia coli (E. coli), is an insufficiently recognized co-morbidity among patients with chronic obstructive pulmonary disease (COPD). Adequate treatment can be complicated by resistance of the causative pathogen to beta-lactam antibiotics, which often produce beta-lactamase enzymes that destroy the antibiotic. The beta-lactamase family of enzymes is extremely diverse, including different types of enzyme and mutant forms. In this study, we analyzed 580 patients with COPD (236 females and 344 males) and thus found 218 patients with co-morbid UTIs, including 58 patients with UTI caused by E. coli (38 females and 20 males). We also investigated cases of uncomplicated symptomatic and asymptomatic UTI caused by E. coli and the presence of resistance to beta-lactam antibiotics among those patients. The E. coli strains resistant to beta-lactam antibiotics were selected for their ability to grow on selective media, before DNA microarrays were applied for specific identification of three beta-lactamase gene types (i.e., TEM, SHV and CTX-M). Overall, 83% of E. coli strains responsible for UTIs in COPD patients carried extended-spectrum beta-lactamase genes. The most prevalent were those producing CTX-M, with CTX-M-15 being predominant. The rare CTX-M-27 and TEM-15 genes were also detected in two samples. Three samples contained several extended-spectrum beta-lactamase genes simultaneously (CTX-M-15 or CTX-M-14 plus SHV-5 or TEM-15). This high prevalence of resistant E. coli strains necessitates rational antibiotic selection when treating UTI to prevent COPD exacerbations. Additionally, antibiotic therapy should be aligned with and adapted to existing and potential COPD co-morbidities.

Case
  • Kimitaka Nakazaki, Erika Ogawa, Mika Ishige, Nobuyuki Ishige, Tatsuo F ...
    Article type: Case
    2018 Volume 244 Issue 4 Pages 279-282
    Published: 2018
    Released on J-STAGE: April 06, 2018
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    Carnitine is a water-soluble amino acid derivative required for β-oxidation of long-chain fatty acids. In carnitine cycle abnormalities and low carnitine states, fatty acid β-oxidation is inhibited during fasting, resulting in hypoglycemia. Pivalic acid is a substance used in prodrugs to increase absorption of parent drugs, and antibiotics containing pivalic acid are frequently used as wide spectrum antibiotics for pediatric patients in Japan. Pivalic acid released after absorption is conjugated with free carnitine to form pivaloylcarnitine, which is then excreted in urine. As a consequence, long-term administration of pivalic acid containing antibiotics has been associated with depletion of free carnitine, inhibition of energy production and subsequent hypoglycemia. Here we report a case of a 23-month-old boy treated with an antibiotic containing pivalic acid for 3 days for upper respiratory tract infection. Laboratory data at referral indicated hypoglycemia, decreased free carnitine and elevated five-carbon acylcarnitine. Isomer separation confirmed the major component of increased five-carbon acylcarnitine to be pivaloylcarnitine, thereby excluding the possibility of a genetic metabolic disorder detected with similar acylcarnitine profile. The level of carnitine was normal when the antibiotic was not administered. Our case shows that the use of antibiotics containing pivalic acid in young children requires consideration of hypocarnitinemia, even with short-term administration.

Regular Contribution
  • Xing-Jie Bao, Shu-Qi Mao, Tian-Lun Gu, Shu-Ying Zheng, Jin-Shun Zhao, ...
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 283-290
    Published: 2018
    Released on J-STAGE: April 10, 2018
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    Essential hypertension (EH) is a multifactorial disease. Interferon-γ (IFN-γ) plays an important role in the onset of EH through cytokine-mediated systemic inflammatory responses. We aimed to determine whether the methylation status of the IFN-γ gene (IFNG) promoter is involved in the pathogenesis of EH. Six copies of CpG dinucleotides are distributed between 3,203 bp and 3,121 bp upstream from the transcription initiation site of IFNG, termed CpG1 to CpG6 in the 5′-to-3′ direction. We recruited 96 patients with EH and 96 sex- and age-matched healthy subjects as controls. Using bisulfate pyrosequencing datasets, we analyzed the methylation status of the six CpG sites and thus found that CpG5 was consistently methylated in all of the 96 EH patients and 96 control subjects. Among the remaining five CpG sites, there was no significant difference in the methylation levels of CpG4 and CpG6 between the two groups. By contrast, CpG1 (P = 0.003) and CpG3 (P = 5.87 × 10−7) were highly methylated among the EH subjects compared with the controls, whereas CpG2 (P = 1.24 × 1012) was significantly less methylated in among EH subjects. The methylation levels of CpG2 were still lower after adjustment with logistic regression (adjusted P = 0.032). The CpG2 methylation level was an effective marker of EH (area under curve = 0.384; P = 1.40 × 10−15). The present study shows that hypomethylation of the IFNG promoter is significantly related to the risk of EH, providing new insights into the pathogenesis of EH.

  • Qin Meng, Pengjing Duan, Lin Li, Yongmei Miao
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 291-296
    Published: 2018
    Released on J-STAGE: April 10, 2018
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    Ovarian cancer is the fourth leading cause of cancer death in women and the most fatal gynecologic malignancy. Placenta growth factor (PGF), a member of the vascular endothelial growth factor, plays an important role in angiogenesis. The overexpression of PGF was observed in several types of cancers, but the clinical significance of PGF in epithelial ovarian cancer (EOC) is still unknown. To explore the prognostic value of PGF among patients with serous EOC, we analyzed the expression of PGF in 89 EOC specimens by immunohistochemistry. The scoring system of immunohistochemistry was based on the staining intensity and the percentage of PGF-positive cells in each EOC tissue. According to the immunohistochemical score, 34 patients with score ≥ 6 were defined as high PGF expression, and other 55 patients were the group with low PGF expression. The prognostic significance of PGF expression was analyzed. EOC patients with higher IHC scores of PGF expression are significantly associated with positive lymphatic invasion and poorer response to chemotherapy. Patients with higher IHC scores of PGF expression had poorer response to chemotherapy and lower overall survival rate. Additionally, the positive lymph node metastasis, advanced TNM stage, and poorer response to chemotherapy were all remarkably correlated to poorer prognosis. In conclusion, patients with higher PGF in EOC tissues were more predisposed to positive lymphatic invasion, poorer response to chemotherapy and unfavorable prognosis of patients with serous EOC. We propose that PGF expression may be predictive of chemoresistance and poor prognosis of serous EOC.

  • Yutaka Yabe, Yoshihiro Hagiwara, Takuya Sekiguchi, Haruki Momma, Masah ...
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 297-304
    Published: 2018
    Released on J-STAGE: April 10, 2018
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    Verbal or physical abuse from coaches has a negative impact on young athletes. To prevent abuse against young athletes, it is important to know the characteristics of abusive coaches. This study aimed to elucidate the characteristics of coaches who commit verbal or physical abuse in youth sports teams. A cross-sectional study was conducted with coaches of youth sport teams in Miyagi prefecture, Japan (n = 1,283), using a self-reported questionnaire (response rate was 24.0%). Multivariate logistic regression models were used for analyses. The prevalence of verbal and physical abuse towards young athletes was 64.7% (n = 830) and 6.2% (n = 79), respectively. Verbal abuse was significantly associated with lower educational attainment (odds ratio (OR): 1.32, 95% confidence interval (95% CI): 1.03-1.69), experiences of verbal abuse by own coaches (OR: 1.85, 95% CI: 1.37-2.50), acceptability for verbal or physical abuse (OR: 2.53, 95% CI: 1.82-3.52), and dissatisfaction with athletes’ attitude (OR: 1.62, 95% CI: 1.26-2.07). Physical abuse was significantly associated with experiences of physical abuse by respondents’ coaches (OR: 2.71, 95% CI: 1.50-4.92), acceptability for verbal or physical abuse (OR: 3.89, 95% CI: 2.39-6.33), and longer experience of coaching in years (OR: 2.45, 95% CI: 1.20-4.98). The results of this study show that coaches who commit verbal or physical abuse had typically experienced abuse from their former coaches, and adopted a similar style. Breaking the negative cycle of verbal and physical abuse is necessary to eliminate the abuse of young athletes.

  • Hiroki Isono, Tetsuhiro Maeno, Shigeyuki Watanabe
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 305-315
    Published: 2018
    Released on J-STAGE: April 13, 2018
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    ST-elevation myocardial infarction (STEMI) is a fatal condition. Prompt primary percutaneous coronary intervention is associated with lower mortality. However, community hospitals in Japan lack human and medical resources, and implementation of the same strategies as those used in the USA, such as an on-call cardiologist at the hospital, to achieve a door-to-balloon time of ≤ 90 min appears particularly challenging. Therefore, we used Training for Effective and Efficient Action in Medical Service-Better Process (TEAMS-BP) to develop a new process and assessed its effectiveness in reducing door-to-balloon time. TEAMS-BP can optimize the process by making the best use of available materials, machines, facilities and manpower. All processes conducted by physicians, nurses, electrocardiogram technicians, radiological technologists, and clerical staff in the emergency room were reviewed, documented, and standardized using the four steps of TEAMS-BP. The following processes were implemented: setting time goals, calling an electrocardiogram technician beforehand, minimizing tasks before calling a cardiologist, confirming the checklist, and providing data feedback. Forty-four STEMI patients who were treated after TEAMS-BP implementation were compared with 58 who were treated before implementation. Median door-to-balloon, door-to-electrocardiogram and door-to-laboratory times were significantly reduced after TEAMS-BP implementation, decreasing from 106 to 82 min, 14 to 6 min, and 67 to 45 min, respectively. In conclusion, implementation of TEAMS-BP improved the door-to-balloon time of STEMI cases without additional resources or costs incurred by the hospital. TEAMS-BP can be implemented by any hospital wishing to develop a new process that accommodates local working conditions.

  • Hideki Okata, Waku Hatta, Katsunori Iijima, Kiyotaka Asanuma, Atsuki T ...
    Article type: Regular Contribution
    2018 Volume 244 Issue 4 Pages 317-325
    Published: 2018
    Released on J-STAGE: April 20, 2018
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    Ethanol is oxidized by alcohol dehydrogenase to acetaldehyde, a recognized carcinogen for the esophagus. However, no previous study has measured the acetaldehyde levels in the esophageal tissue. L-cysteine has been shown to reduce the acetaldehyde levels in the saliva; however, it is unknown whether L-cysteine intake affects the acetaldehyde concentration in the esophageal tissue. The aim of this study was to measure the acetaldehyde concentration in the esophageal tissue after ethanol drinking and evaluate the effect of L-cysteine intake on the acetaldehyde levels in the esophagus. We enrolled 10 male subjects with active acetaldehyde dehydrogenase-2*1/*1 (ALDH2*1/*1) genotype and 10 male subjects with the inactive acetaldehyde dehydrogenase-2*1/*2 (ALDH2*1/*2) genotype, the mean ages of whom were 25.6 and 27.9 years, respectively. In this prospective, single-blind, placebo-controlled study using L-cysteine and placebo lozenges (first and second examination), saliva and blood were collected before and after ethanol drinking. Esophageal tissue was obtained by endoscopic biopsy at 60 minutes after drinking, and the acetaldehyde and ethanol concentrations were measured. The acetaldehyde concentration of the saliva was significantly lower in those taking L-cysteine than in those taking the placebo. Acetaldehyde in the esophageal tissue was detected only in those taking L-cysteine lozenges. There were no correlations between the acetaldehyde concentrations in the esophageal tissue and saliva or blood. In conclusion, we detected acetaldehyde in the human esophageal tissue after ethanol drinking. Unexpectedly, intake of L-cysteine lozenges appears to contribute to detection of acetaldehyde in the esophageal tissue.

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