[Show abstract][Hide abstract] ABSTRACT: Conflicting findings have been reported regarding the role of adiponectin in asthma. The aim of this study was to evaluate the association of adiponectin with pulmonary functions and asthma in the Japanese population. First, among a general population that participated in a previous study (group 1), we selected 329 subjects after excluding those with asthma, chronic obstructive pulmonary disease, and a smoking history and examined the associations of the serum total adiponectin levels with pulmonary functions. In a second cohort (group 2) consisting of 61 asthmatic patients and 175 control non-asthmatic subjects, we examined the associations between asthma and the levels of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms as well as the ratio of each isoform to total adiponectin level. Although the total adiponectin levels were not significantly different between the asthmatic and control subjects in group 2, the levels were significantly and positively associated with the forced expiratory volume in 1 s after adjustments for confounding factors (P < 0.05) in women in group 1. In group 2, the LMW adiponectin level was significantly higher and the MMW/total adiponectin ratio was significantly lower among the asthmatic subjects than among the control subjects after adjustments for confounding factors in both sexes (P < 0.05). The present study showed that a low total adiponectin level may lead to airway narrowing compatible with asthmatic airways in women, and higher LMW adiponectin levels and lower MMW/total adiponectin ratio are significantly associated with current asthma in both sexes.
[Show abstract][Hide abstract] ABSTRACT: Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment.
Molecular and Clinical Oncology 05/2015; 3(4). DOI:10.3892/mco.2015.568
[Show abstract][Hide abstract] ABSTRACT: We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and 7 susceptibility loci originally identified by European genome-wide association study (GWAS) in 2012: ZMIZ1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, and BCAR1. We also examined the association of 3 additional loci: CCND2 and GIPR, identified in sex-differentiated analyses, and LAMA1, which was shown to be associated with non-obese European type 2 diabetes.
We genotyped 6,972 Japanese participants (4,280 type 2 diabetes patients and 2,692 controls) for each of the 10 single nucleotide polymorphisms (SNPs): rs12571751 in ZMIZ1, rs10842994 near KLHDC5, rs2796441 near TLE1, rs459193 near ANKRD55, rs10401969 in CILP2, rs12970134 near MC4R, rs7202877 near BCAR1, rs11063069 near CCND2, rs8108269 near GIPR, and rs8090011 in LAMA1 using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using a logistic regression analysis.
All SNPs examined in this study had the same direction of effect (odds ratio > 1.0, p = 9.77 × 10-4, binomial test), as in the original reports. Among them, rs12571751 in ZMIZ1 was significantly associated with type 2 diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037-1.215, adjusted for sex, age and body mass index (BMI)], but we did not observe significant association of the remaining 9 SNP loci with type 2 diabetes in the present Japanese population (p ≥ 0.005). A genetic risk score, constructed from the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses in the European GWAS meta-analysis were associated with type 2 diabetes in the present Japanese population (p = 2.3 × 10-4, adjusted for sex, age and BMI).
ZMIZ1 locus has a significant effect on conferring susceptibility to type 2 diabetes also in the Japanese population.
PLoS ONE 05/2015; 10(5):e0126363. DOI:10.1371/journal.pone.0126363 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim/hypothesis Lowering the body weight set point is a prerequisite for the maintenance of reduced body weight. In this context, obesity is known to be strongly linked to leptin resistance, and it remains to be clarified whether recovery from leptin resistance might lower the body weight set point to allow sustained body weight loss. Methods Obese IRS-2 knockout (IRS-2 −/−) mice were subjected to calorie restriction (CR) or β3-adrenergic receptor (AR) agonist treatment. The physiological effects of leptin, hypothalamic leptin signaling, and alterations of the body weight set point were evaluated. Results In the CR mice, recovery from acquired leptin resistance was observed, as shown by the restoration of the suppressive effects of leptin on food intake and weight gain, as well as the recovery of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Nevertheless, the body weight quickly rebounded to the original body weight after cessation of the CR, suggesting that CR failed to overcome the primary defect in IRS-2/phosphatidylinositol 3-kinase (PI3K) signaling. On the other hand, after 2 weeks β3-AR agonist treatment, the mice began to lose body weight, indicating that the treatment was able to overcome the primary defect in IRS-2/PI3K signaling and lower the body weight set point. Conclusions/interpretation Recovery of acquired leptin resistance does not lead to a resetting of the body weight set point in obese IRS-2/PI3K-defective mice. β3-AR agonist treatment may act on some pathways distal to or independent of PI3K and/or STAT3, inducing resetting of the body weight set point.
[Show abstract][Hide abstract] ABSTRACT: Background: Few medical education programs provide hands-on classes using electronic medical charts for a large number of students.
Methods: To simulate medical interview, the third- and sixth-year medical students viewed the electronic medical chart samples on screen, created by FileMaker and discussed the management of them. Following this, they underwent a questionnaire survey.
Results: A total of 63.1 and 76.3% of the third- and sixth-year students responded to the questionnaire, and 87.1 and 78.9% of the responders became interested in the class, respectively, because it focused on hands-on, practical training. A total of 5.6% third-year students stated that the class was difficult to master but they hoped to continue learning.
Discussion: The adoption of hands-on class using electronic medical charts interested even junior medical students.
[Show abstract][Hide abstract] ABSTRACT: Aims To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 % confidence interval = 0.33-0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.
[Show abstract][Hide abstract] ABSTRACT: Chronic inflammation is a pathophysiology of insulin resistance in metabolic diseases, such as obesity and type 2 diabetes. Adipose tissue macrophages (ATMs) play important roles in this inflammatory process. SIRT1 is implicated in the regulation of glucose metabolism in some metabolic tissues, such as liver or skeletal muscle. This study was performed to investigate whether SIRT1 in macrophages played any roles in the regulation of inflammation and glucose metabolism. Myeloid cell-specific SIRT1-knockout mice were originally generated and analyzed under chow-fed and high-fat-fed conditions. Myeloid cell-specific SIRT1 deletion impaired insulin sensitivity and glucose tolerance assessed by the glucose- or insulin-tolerance test, which was associated with the enhanced expression of inflammation-related genes in epididymal adipose tissue of high-fat-fed mice. Interestingly, the M1 ATMs from the SIRT1-knockout mice showed more hypoxic and inflammatory phenotypes than those from control mice. The expressions of some inflammatory genes, such as Il1b and Nos2, which were induced by in vitro hypoxia treatment, were further enhanced by SIRT1 deletion along with the increased acetylation of HIF-1α in cultured macrophages. These results suggest that deletion of SIRT1 in myeloid cells impairs glucose metabolism by enhancing the hypoxia and inflammatory responses in ATMs, thereby possibly representing a novel therapeutic target for metabolic diseases, such as type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Cortisol plays an important role in the physical status of patients with end-stage lung cancer, but the association of urine cortisol levels with TNM stage/performance status (PS) is unclear in patients with advanced lung cancer receiving chemotherapy. The objective of this study was to examine this association.
In this single-center, retrospective, observational study, cortisol concentrations in 24-h pooled urine from 22 patients with advanced lung cancer were measured over 2 days. The mean concentration in each patient was compared with PS, TNM stage, and serum sodium and potassium ion levels.
The 24-h urine cortisol levels were higher in PS2 or PS3 cases compared to PS1 (p < 0.05) and increased proportionally with PS. Urine cortisol also increased in N2 or N3 cases compared to N1 (p < 0.01) and also increased in M1 cases (p < 0.05). Urine cortisol levels were negatively correlated with serum sodium (R = -0.49, p < 0.05) and had a tendency for a positive correlation with serum potassium (R = 0.40, p = 0.06).
The 24-h urine cortisol level increased in patients with advanced lung cancer undergoing chemotherapy. Low serum levels of potassium and high levels of sodium may indicate relative adrenal insufficiency.
Supportive Care Cancer 12/2014; 23(7). DOI:10.1007/s00520-014-2585-5 · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although phenotypically polarized macrophages are now generally classified into two major subtypes termed proinflammatory M1 and anti-inflammatory M2 macrophages, a contributory role of lung M2 macrophages in the pathophysiological features of acute lung injury is not fully understood. Herein, we show in an endotoxemic murine model that M2 macrophages serve as key anti-inflammatory cells that play a regulatory role in the severity of lung injury. To study whether M2 macrophages can modify inflammation, we depleted M2 macrophages from lungs of CD206-diphtheria toxin (DT) receptor transgenic (Tg) mice during challenge with lipopolysaccharide. The i.p. administration of DT depleted CD206-positive cells in bronchoalveolar lavage fluid. The use of M2 macrophage markers Ym1 and arginase-1 identified pulmonary CD206-positive cells as M2 macrophages. A striking increase in neutrophils in bronchoalveolar lavage fluid cell contents was found in DT-treated CD206-DT receptor Tg mice. In CD206-DT receptor Tg mice given DT, endotoxin challenge exaggerated lung inflammation, including up-regulation of proinflammatory cytokines and increased histological lung damage, but the endotoxemia-induced increase in NF-κB activity was significantly reduced, suggesting that M2 phenotype-dependent counteraction of inflammatory insult cannot be attributed to the inhibition of the NF-κB pathway. Our results indicate a critical role of CD206-positive pulmonary macrophages in triggering inflammatory cascade during endotoxemic lung inflammation.
American Journal Of Pathology 10/2014; 185(1). DOI:10.1016/j.ajpath.2014.09.005 · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The usefulness of the Palliative Prognostic Index (PPI) has been successfully validated in a variety of clinical settings. However, while lung cancer is the leading cause of death worldwide, patients with lung cancer accounted for only 6.9-25.8 % of the study populations in these previous studies. We conducted a retrospective study to evaluate the usefulness of the PPI for survival prediction in patients with lung cancer. Patients with lung cancer who were admitted to our hospital between 2009 and 2013 to receive palliative care were enrolled. The association between the Palliative Prognostic Index, determined based on the data recorded in the clinical charts at the last admission to our hospital, and survival was evaluated. The patient group with a PPI of >6 showed a significantly shorter survival time than the patient group with a PPI of ≤6 (P < 0.0001, log-rank test). The sensitivity and specificity of the PPI determined using the cutoff value of 6 for predicting less than 3 weeks of survival were 61.3 and 86.8 %, respectively. However, the sensitivity decreased to 50.0 % when the assessment was carried out in only patients with small cell lung carcinoma. Our findings suggest the existence of a close association between the PPI and survival in patients with lung cancer receiving palliative care. However, the sensitivity of the index for predicting less than 3 weeks of survival was relatively low in patients with small cell lung carcinoma.
Medical Oncology 09/2014; 31(9):154. DOI:10.1007/s12032-014-0154-x · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims and background. It is reported that about 20% of patients with small cell lung cancer (SCLC) receive third-line chemotherapy. We conducted a retrospective study to investigate the outcome and prognostic factors of patients with SCLC who receive third-line chemotherapy. Methods and study design. The medical records of patients with SCLC who received third-line chemotherapy at our institution were reviewed. Overall survival (OS) from the initiation of third-line chemotherapy was evaluated, and the association between OS and patient characteristics was assessed by the log-rank test. Results. A total of 73 patients with SCLC were treated with cytotoxic drugs between 2004 and 2012, and 19 patients received third-line chemotherapy. Median OS from initiation of third-line chemotherapy was 8.5 months. Patients with higher body mass index (BMI) (P = 0.0071), lower levels of lactate dehydrogenase (LDH) (P = 0.0036), higher levels of hemoglobin (P = 0.048), longer time to progression (TTP) from the initiation of second-line treatment (P = 0.0036), and better response to second-line treatment (P = 0.029) had longer duration of OS. Conclusions. It is suggested that TTP and tumor response in second-line chemotherapy, serum levels of LDH and hemoglobin, and BMI at initiation of third-line chemotherapy could be possible prognostic factors.
[Show abstract][Hide abstract] ABSTRACT: A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemotherapy or thymoma surgical resection in the management of autoimmune hemolytic anemia with thymoma.
Case Reports in Oncology 09/2014; 7(3):764-8. DOI:10.1159/000369491
[Show abstract][Hide abstract] ABSTRACT: Central venous catheterization at the femoral site is associated with higher complication rates of infections and thrombosis than at the jugular or subclavian sites. However, the procedure of insertion at the femoral site is considered safer. We present a unique but dangerous positioning of a left femoral central venous catheter into the iliolumbar vein. We were aware of this accidental cannulation by chance when our patient underwent bone scintigraphy. Although a few cases were reported about accidental cannulation into the ascending lumbar vein, this is the first case where a femoral central venous catheter was misplaced into the iliolumbar vein.
Clinical Nuclear Medicine 08/2014; 40(2). DOI:10.1097/RLU.0000000000000551 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in previously untreated elderly patients with non-small cell lung cancer has been reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to docetaxel, a standard therapeutic option, in patients with previously treated non-small cell lung cancer and in those with a lower incidence of toxicity such as febrile neutropenia.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2014; 41(7):849-52.