The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
237 巻, 3 号
November
選択された号の論文の11件中1~11を表示しています
Regular Contribution
  • Kosho Yamanouchi, Naomi Hayashida, Sayaka Kuba, Chika Sakimura, Tamots ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 157-162
    発行日: 2015年
    公開日: 2015/10/14
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    Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p < 0.01) and these did not return to the baseline level one hour after the operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p < 0.01) during the operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.
  • Laixi Bi, Zhijie Yu, Jianbo Wu, Kang Yu, Guangliang Hong, Zhongqiu Lu, ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 163-172
    発行日: 2015年
    公開日: 2015/10/14
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    Constitutive and inducible activation of signal transducer and activator of transcription 3 (STAT3) signaling facilitates the carcinogenesis in most human cancers including acute myeloid leukemia (AML). Negative regulators, such as protein tyrosine phosphatases SHP1, inhibit the activated STAT3 signaling. In this study, we investigated the effect of honokiol (HNK), a constituent of Magnolia officinalis, on the STAT3 signaling. STAT3 signaling and SHP1 expression were measured by quantitative real-time PCR and western blotting in leukemic cell lines and primary AML blasts treated with HNK. HNK decreased the phosphorylated STAT3 but not the total STAT3 through increasing the expression of SHP1. In addition, HNK inhibited transcription activity of STAT3, reduced nuclear translocation of STAT3, and decreased the expression of STAT3 target genes. Knockdown of SHP1 by small hairpin RNA (shRNA) or treatment with vanadate, a protein tyrosine phosphatases inhibitor, abolished HNK-induced STAT3 inhibition, suggesting that SHP1 plays an important role in the inhibition of STAT3 signaling by HNK. Further, HNK increased the expression of transcript factor PU.1, which had been reported to activate the expression of SHP1 via binding SHP1 promoter region. Knockdown of PU.1 reversed HNK-induced upregulation of SHP1 and inactivation of STAT3 signaling. Finally, HNK increased the expression of PU.1 and SHP1 in hematopoietic progenitors isolated from patients with AML. In conclusion, our data have shown a regulatory mechanism underlying the inhibition of STAT3 signaling by HNK. Therefore, as a relative non-toxic compound, HNK may offer a therapeutic advantage in the clinical treatment for AML.
  • Miki Shimada, Hoshimi Okawa, Yasuteru Kondo, Takahiro Maejima, Yuta Ka ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 173-182
    発行日: 2015年
    公開日: 2015/10/16
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    Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUCsorafenib and AUCN-oxide, respectively). Inter-group comparison revealed that AUCN-oxide and AUC ratio (AUCN-oxide /AUCsorafenib) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUCN-oxide and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUCN-oxide: 2.0 μg∙day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUCN-oxide ≤ 2.0 μg∙day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.
  • Yingjie Zhong, Ye Wang, Jun Guo, Haifeng Chu, Yong Gao, Limin Pang
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 183-191
    発行日: 2015年
    公開日: 2015/10/17
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    Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.
  • Gordana Bogdanovic, Ljudmila Stojanovich, Aleksandra Djokovic, Natasa ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 193-199
    発行日: 2015年
    公開日: 2015/10/20
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    Given the crucial events in systemic lupus erythematosus (SLE) such as joint and muscle pain, fatigue, depression, obesity and osteoporosis, the very thought of exercising can be challenging. This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women performed isotonic exercises (to stretch and lengthen muscles and improve the range of motion) for 30 minutes, 3 times per week during the same period. Fatigue Severity Scale (FSS), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. At baseline FSS score was 53.8 ± 5.7 and after the physical activity FSS score was 29.1 ± 7.8 (FSS ≥ 36; fatigue is present). The largest number of patients (66.7%) was in a moderate depressed state at the baseline, while after physical activities 61.7% of patients, had a mild mood disturbance. There were significant differences (p < 0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. The type of physical activity had no influence in FSS and BDI values. Continuous physical activity, regardless of its type, significantly improved quality of life of SLE patients. We recommend regular physical activity as an integral part of modern therapeutic approach in this patient population.
  • Hiroyuki Yamamoto, Kyoko Yamamoto, Katsumi Yoshida, Chiyohiko Shindoh, ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 201-207
    発行日: 2015年
    公開日: 2015/10/24
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    Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen’s kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.
  • Masayuki Omoto, Hiroo Matsuse, Ryuki Hashida, Yoshio Takano, Shin Yama ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 209-217
    発行日: 2015年
    公開日: 2015/10/31
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    Performing aerobics and resistance exercise at exactly the same time has not been available although combining both types of exercise in one training program has been attempted. The hybrid training system (HTS) is a resistance exercise that combines voluntary concentric muscle contractions with electrically stimulated eccentric muscle contractions. We devised an exercise technique using HTS on a cycle ergometer (HCE). Growth hormone (GH) and lactate are indicators of adequate training intensity. Interleukin-6 (IL-6) reflects enhancing lipid metabolism. The purpose of this study was to show that HCE provides sufficient exercise to stimulate the secretion of GH, lactate and IL-6. We compared an HCE test with cycle ergometer alone (CE). Ten healthy male subjects performed HCE and CE tests for 30 minutes each. The workload of both tests was set the same at 40% of each subject’s peak oxygen uptake. For HCE, 2-minute HTS and 1-minute rest intervals were repeated. GH, lactate, and IL-6 were evaluated before and immediately after exercise, and at 15, 30 and 60 minutes. GH and lactate increased immediately after HCE. Moreover, the degree of the increases in GH after HCE (0 and 15 minutes) was higher than that after CE. IL-6 increased after HCE at 30 min, and the rate of change was higher than for CE. These results showed that HCE was more efficient in stimulating acute increases in GH, lactate and IL-6 than CE at the same workload. We may be able to combine electrically stimulated resistance exercise with aerobic exercise using HCE.
  • Jerrold Petrofsky, Haneul Lee
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 219-226
    発行日: 2015年
    公開日: 2015/11/03
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    One of the sexual hormones, estrogen, increases elasticity of human connective tissue such as the anterior cruciate ligament during the menstrual cycle in women. In the present investigation, the plantar fascia was investigated to see if there is a difference in elasticity with the menstrual cycle. Fifteen young healthy females in the age range of 18-35 years old with a regular menstrual cycle were tested twice throughout one full menstrual cycle; once during the early follicular phases and once at ovulation. Foot length, while standing on both feet and one foot were used to assess plantar fascia elasticity, ultrasound measured plantar fascia thickness while lying and standing, and posture sway and tremor using a balance platform during 8 different balance tests were assessed to see the impact of elasticity changes. Foot length increased significantly at ovulation compared to menstruation when standing on two feet (p = 0.03) and standing on one foot (p < 0.001). There was also a significant increase in plantar fascia in thinning per kilogram weight applied to the foot at ovulation compared to menstruation (p = 0.014). Associated with this increase in elasticity at ovulation, there was a reduction in balance in the most difficult balance tasks and an increase in tremor during ovulation (p < 0.05). Plantar fascia elasticity change during the menstrual cycle might have effects on posture sway and tremor, which could have a potential risk of falling. Therefore, healthy professionals working with young female adults should recognize these physiological effects.
  • Suli Huang, Ziquan Lv, Qifei Deng, Lu Li, Binyao Yang, Jing Feng, Tang ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 227-233
    発行日: 2015年
    公開日: 2015/11/05
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    MicroRNAs (miRNAs) can contribute to the development of cardiovascular diseases, and single nucleotide polymorphisms (SNPs) in miRNA genes may influence disease susceptibility by altering mature miRNA expression levels. However, the effect of SNPs located in miR-146a and miR-196a2 genes on risk of acute coronary syndrome (ACS) has not been reported in the Chinese population. Two miRNA polymorphisms located in miRNA genes (miR-146a rs2910164 C>G and miR-196a2 rs11614913 T>C) were genotyped in 722 ACS patients and 721 control subjects. The CG genotype of rs2910164 was significantly associated with decreased risk of ACS [CG vs. CC, odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.55-0.95, P = 0.020; dominant model, OR = 0.77, 95% CI: 0.60-0.99, P = 0.044]. We did not find any association of rs11614913 with the risk of ACS. Stratification analysis showed that the rs2910164 CG genotype was associated with decreased risk of ACS (dominant model) in males, subjects with body mass index more than 24 kg/m2, and in hypertensive subjects. Significant combined effects were also observed between rs2910164 and blood lipids or C-reactive protein levels. In summary, this study provides the first evidence that the CG genotype of miR-146a rs2910164 is associated with a significantly decreased risk of ACS in a Chinese population. Moreover, rs2910164 and blood lipids or an inflammatory marker may have a combined effect on the onset of ACS. These findings indicate that miR-146a rs2910164 may act as a novel molecular marker for ACS susceptibility.
  • Sayaka Kato, Yoko Nakajima, Risa Awaya, Ikue Hata, Yosuke Shigematsu, ...
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 235-239
    発行日: 2015年
    公開日: 2015/11/06
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    Fructose-1,6-bisphosphatase (FBPase), an enzyme involved in gluconeogenesis, catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. FBPase deficiency is an autosomal recessive inherited disorder, characterized by episodic attacks of hypoglycemia, ketosis, and lactic acidosis during fasting. In general, urinary organic acid analysis using gas chromatography-mass spectrometry (GC/MS) is very useful for the diagnosis of FBPase deficiency, because the appearance of glycerol or glycerol-3-phosphate in the urine is characteristic of this disease. Here, we report a case of FBPase deficiency in a girl with a history of several severe lactic acidosis events, both as a neonate and after the age of 12 months. The patient was identified as a compound heterozygote with two mutations in the FBPase 1 gene: c.841G>A (p.Glu281Lys) and c.960_961insG (p.Ser321fs). The c.841G>A is a newly identified pathogenic mutation. An abnormal level of glycerol-3-phosphate was not detected in the conventional urinary organic acid analysis using GC/MS after solvent extraction. This method, which is a widely used diagnostic standard, could not detect increased levels of glycerol or glycerol-3-phosphate in the patient’s urine, which was sampled during the episode. However, glycerol and glycerol-3-phosphate were detected in the same sample, when it was analyzed using GC/MS with the urease pretreatment non-extraction method. Patients with FBPase deficiency have good glycemic control after correct treatment. Therefore, accurate and early diagnosis is essential for a good prognosis. Accordingly, when a patient presents with hypoglycemia and lactic acidosis, it is important to select the appropriate method of urinalysis for organic acids by GC/MS.
  • Aiko Kohara, ChangWan Han, HaeJin Kwon, Masahiro Kohzuki
    原稿種別: Regular Contribution
    2015 年 237 巻 3 号 p. 241-248
    発行日: 2015年
    公開日: 2015/11/07
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    The improvement of the quality of life (QOL) of children with disabilities has been considered important. Therefore, the Special Needs Education Assessment Tool (SNEAT) was developed based on the concept of QOL to objectively evaluate the educational outcome of children with disabilities. SNEAT consists of 11 items in three domains: physical functioning, mental health, and social functioning. This study aimed to verify the reliability and construct validity of SNEAT using 93 children collected from the classes on independent activities of daily living for children with disabilities in Okinawa Prefecture between October and November 2014. Survey data were collected in a longitudinal prospective cohort study. The reliability of SNEAT was verified via the internal consistency method and the test-pretest method; both the coefficient of Cronbach’s α and the intra-class correlation coefficient were over 0.7. The validity of SNEAT was also verified via one-way repeated-measures ANOVA and the latent growth curve model. The scores of all the items and domains and the total scores obtained from one-way repeated-measures ANOVA were the same as the predicted scores. SNEAT is valid based on its goodness-of-fit values obtained using the latent growth curve model, where the values of comparative fit index (0.983) and root mean square error of approximation (0.062) were within the goodness-of-fit range. These results indicate that SNEAT has high reliability and construct validity and may contribute to improve QOL of children with disabilities in the classes on independent activities of daily living for children with disabilities.
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