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Objective: Resistin is secreted by monocytes/macrophages and is associated with insulin resistance, inflammation and cardiovascular diseases. In the Japanese cohort, serum resistin is tightly associated with a single-nucleotide polymorphism (SNP) at -420 (rs1862513) in the promoter region of the human resistin gene. However, interactions between SNP-420 and environmental factors remain to be elucidated. The aim of this study was to investigate the association between serum resistin levels and nutrient intake, and the effect of SNP-420 on this association., Design, Participants and Measurements: The Toon Genome Study is a cohort study of Japanese community-dwelling subjects. A total of 1981 participants were cross-sectionally analysed. Each nutrient intake was assessed using the semiquantitative food frequency questionnaire and categorized into the quartiles (Q1-Q4). Serum resistin was measured by ELISA., Results: Serum resistin tended to be inversely associated with fish intake and positively associated with meat intake after adjustment for age, sex, BMI and energy intake. Serum resistin was inversely associated with n-3 polyunsaturated fatty acids (PUFA) intake after adjustment for age, sex, BMI and energy intake (Q1 12.5, Q2 12.5, Q3 12.2, Q4 11.5 ng/mL; P for trend = .007). This inverse association was strongest in the G/G genotype of SNP-420, followed by C/G and C/C (G/G, Q1 18.9, Q2 19.5, Q3 18.4, Q4 14.5 ng/mL, P = .001; C/G, 14.4, 13.3, 13.1, 12.9, P = .015; C/C, 9.5, 9.5, 9.2, 8.8, P = .020; P for interaction = .004)., Conclusions: The inverse association between serum resistin and n-3 PUFA intake was strongest in SNP-420 G/G genotype in the Japanese cohort., (© 2017 John Wiley & Sons Ltd.)

Context: We previously reported that single nucleotide polymorphism (SNP)-420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of cytosine-phosphate-guanine dinucleotides., Objective: To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420., Design and Methods: Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion., Results: Methylation at SNP-420 was highest in the C/C genotype (36.9 ± 5.7%), followed by C/G (21.4 ± 3.5%) and G/G (2.9 ± 1.4%; P < 0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in the C/C (β = -0.134, P < 0.001) or C/G (β = -0.227, P < 0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC, decreased the methylation at SNP-420 and increased RETN messenger RNA. SNP+1263 (rs3745369), located in the 3' untranslated region of RETN, was also associated with methylation at SNP-420. In addition, highly sensitive C-reactive protein was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body mass index was positively associated., Conclusions: Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic effects on plasma resistin., (Copyright © 2017 by the Endocrine Society)

We have investigated 4-μm-band SO 3 absorption lines for in situSO 3 detection using a mid-infrared laser source based on difference frequency generation in a quasi-phase-matched LiNbO 3 waveguide. In the wavelength range of 4.09400-4.10600 μm, there were strong SO 3 absorption lines. The maximum absorption coefficient at a concentration of 170 ppmv was estimated to be about 3.2×10 -5   cm -1 at a gas temperature of 190°C. In coexistence with H 2 O, the reduction of the SO 3 absorption peak height was observed, which was caused by sulfuric acid formation. We discuss a method of using an SO 3 equilibrium curve to derive the total SO 3 molecule concentration.

Clinical examinations are also influenced by medical globalization. Samples from patients for some special tests, including genetic analyses, are transported across the world. International standardization should be applied to clinical examinations as a part of medical care. The quality of techniques and management in clini- cal laboratories are evaluated by organizations for ISO 15189 authorization. This process helps detect issues overlooked on a daily basis and establish a system to maintain the high quality of laboratory examinations. In Ehime University Hospital Clinical Laboratory, we went through examinations from ISO 15189 authorization acquisition to the 3rd periodical surveillance. When the incongruent rate was assessed in each in- spection process under the quality management system (QMS), that of the process before the inspection ac- counted for 47% of the total. Therefore, the management of early processes including sample extraction, inspection, reception, and processing appears to be particularly important. [Review].

Objective: Lower heart rate variability (HRV) is associated with the inflammation that is linked with the progression of atherosclerosis. We examined this association, taking insulin sensitivity into consideration, as it is related to both HRV and inflammation., Methods: Subjects were 1728 individuals ages 30-79 years who did not smoke between 2009 and 2012. C-reactive protein (CRP) concentrations and white blood cell (WBC) counts were assessed as markers of inflammation. The homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt's insulin sensitivity index (ISI) were calculated based on fasting and 2h-post-load glucose and insulin concentrations in a 75-g oral glucose tolerance test. Pulse was recorded for 5 min, and time-domain HRV indices of standard deviation of NN intervals (SDNN) and root mean square of successive differences (RMSSD) were calculated. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power and LF/HF., Results: Sex and age-adjusted logistic models presented quartiles of SDNN, RMSSD, LF, and HF significantly associated with the highest quartile of CRP or WBC. After adjustment for body mass index and ISI, the associations were attenuated for WBC; however, even after further adjustment for several variables, SDNN, RMSSD, LF, and HF remained significantly associated with elevated CRP concentrations. When results were stratified by weight, the associations appeared more evident among non-overweight individuals., Conclusion: Lowered HRV, primarily due to parasympathetic dysfunction, was associated with elevated inflammation, independent of weight, insulin sensitivity, and other related factors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We examined staphylococcal coagulase types and homologous analysis using the DiversiLab repetitive-sequence-based PCR system in exfoliative toxin (ET)-producing Staphylococcus aureus. Twenty-two isolates (17 methicillin-sensitive Staphylococcus aureus (MSSA) and 5 methicillin-resistant Staphylococcus aureus (MRSA) isolates) obtained in our hospital from January 2012 and December 2013 were used. Three groups were classified according to the coagulase types and serotypes of ET. The first group (4 MSSA) showed coagulase type I and ET-A, and the second group (3 MSSA and 2 MRSA) showed coagulase type I and ET-B. The third group (10 MSSA and 3 MRSA) showed coagulase type V and ET-B. An analysis by DiversiLab demonstrated that homology was high in both the first and second groups. The homogenousness was high among the third group isolates except for the ocular isolates. In our hospital, three important groups were present according to a coagulase type and an ET type, and the homology of ocular isolates could be different from other materials isolates.

Bacteriological examinations were conducted for seven Arcanobacterium haemolyticum strains isolated from elderly patients with skin and soft-tissue infections, such as cellulitis and skin ulcers. Streptococcus dysgalactiae or Gram-positive cocci were isolated together with A. haemolyticum from all patients. The strains were identified as A. haemolyticum based on their being catalase negative, reverse Christie, Atkins and Munch-Petersen (CAMP) positive and phospholipase D gene positive in respective tests. Moreover, API Coryne and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry confirmed the identification of A. haemolyticum. All strains showed good susceptibility to minocycline, vancomycin and β-lactam antibiotics, but several strains were resistant to gentamicin and levofloxacin., (© 2015 The Authors.)

Identification method positive blood culture bottles with MALDI Biotyper is the most important test on precisely and rapidly, for detamination the bacterial name in sepsis and bacteremia is very significant for decision a cure. This time, we devised a new method "blend" to identify the mixture hypostasis that were come into being by centrifuging blood culture broths and 70% formic acid with MALDI Biotyper (Bruker). This time, we identified 65 samples rapidly with MALDI biotyper by "on plate" and "blend," and verified their effectivity. As a result of six ways (on plate, blend-3, blend-6, blend-9, blend-12, blend-15), the highest detection rate was Gram negative rods: blend-15 (74.1%), Gram positive cocci: blend-9 (56.3%), total: blend-9 (55.4%). Moreover, we confirmed that the detection rate raised to 85.2% (GNR), 71.0% (GPC) and 77.6% (total), and the usefully was suggested. Our invented method is more excellently than recommended on Gram negative rods, especially Enterobacteriaceae, Staphylococcus aureus, and Enterococcus spp.

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

Background: A considerable number of patients with atrial fibrillation (AF) develop cardioembolic stroke (CE) despite low CHADS2 score. We examined the possibility that use of the atrial electromechanical interval (AEMI) improves prediction of CE in patients with paroxysmal AF (PAF), particularly those with low CHADS2 score., Methods: We consecutively enrolled 108 patients with nonvalvular PAF and 52 healthy subjects as controls. The PAF patients were divided into 2 groups depending on presence (n = 36) or absence (n = 72) of the history of CE. Left atrial (LA) volume index (LAVI), peak myocardial velocity during late diastole (a'), and AEMI as time from onset of P-wave to onset of lateral a' were measured., Results: Patients with PAF had significantly larger LAVI, longer AEMI, and lower lateral a' than those in controls. Area under the curves for LAVI, lateral a', and AEMI for identifying patients with PAF were 0.70, 0.69, and 0.88, respectively. Multivariate logistic regression analysis indicated that age, use of antiarrhythmic drugs, and AEMI, but not LAVI or a', were independently associated with history of CE in patients with PAF. PAF patients were categorized into low risk by CHADS2 score (i.e. CHADS2 score = 0 or 1, n = 60), those with prolonged AEMI (>82 msec) had significantly higher rates of CE than those with ≤ 82 msec (48% vs. 15%, P < 0.05)., Conclusion: As compared with echocardiographic parameters of LA size and LA function, AEMI appears to be more useful for identifying PAF patients. AEMI may enable to detect high risk PAF patients, especially those categorized into low risk by CHADS2 score., (© 2013, Wiley Periodicals, Inc.)

Resistin is an adipokine secreted from adipocytes in mice. We previously reported that a single nucleotide polymorphism (SNP) -420 (rs1862513) in the human resistin gene (RETN), is correlated with plasma resistin. Decorin is a multifunctional proteoglycan, and its isoform, lacking 14 amino acids from the N terminal region of mature core decorin, recently was identified as a resistin receptor in mice. To examine whether SNPs in the vicinity of the human decorin gene (DCN) are associated with plasma resistin, we cross-sectionally analyzed six tag SNPs selected around DCN in the same linkage disequilibrium block in 2,078 community-dwelling Japanese subjects. Plasma resistin was associated with the rs7139228, rs7956537, rs516115, and rs3138167 genotypes in DCN. A multiple regression analysis revealed that the genotype of rs7308752 (G/G) or rs516115 (C/C) was associated with decreased plasma resistin after adjusted for age, sex, BMI, and the RETN SNP rs1862513. The effect of rs7139228 and rs1862513 seemed to be additive without synergistic interaction. Therefore, plasma resistin was associated with some tag SNPs around DCN in the general Japanese population. The possibility that human decorin is a human resistin receptor should be pursued.

Reports of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have recently increased in Japan. To determine the status of MRSA infections in our hospital, we investigated their Staphylococcal cassette chromosome mec (SCCmec) types and prevalence of Panton-Valentine leukocidin (PVL). In addition, we investigated the relation between their SCCmec and antimicrobial susceptibility. The 191 strains were isolated from January to July in 2011 and were classified as SCCmec type I (2, 1.0％), type II (136, 71.2％), type IV (36, 18.8％), type V (4, 2.1％) and type VIII (2, 1.0％). Eleven isolates (5.8％) were designated as nontypable. No isolates were PVL-positive in this study. The SCCmec type IV strains were more susceptible to imipenem (MIC90, 0.25 μg/ml) than SCCmec type II strains (MIC90, >16 μg/ml). This difference was also observed between SCCmec type IV and SCCmec type II in susceptibility levels to clarithromycin, clindamycin, minocycline, and levofloxacin, but not to gentamicin. In particular, SCCmec type IV strains were susceptible to imipenem and minocycline. The result indicates these susceptibility is useful to discriminate CA-MRSA from Hospital-associated MRSA (HA-MRSA).

We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min]=0.825xGFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (-3.45 to -1.38) of the difference in each value of the mean absolute error (-2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

A 69-year-old man was referred to our hospital due to acute myocardial infarction. Systolic heart murmur was first noted on the 23rd day after the onset, but no cardiac shunt flow was detected by echocardiography at that time. Six days later, cardiac function deteriorated rapidly, followed by oliguria and shock. Re-do echocardiography showed ventricular septal perforation. Emergency operation was performed, and septal perforation was seen on the anterior portion of the septum. In addition to infarct-exclusion-technique (Komeda-David method) with the equine pericardial patch, direct closure of the septal defect was performed (double closure technique). Fibrin glue was applied between the ventricular septum and the patch. After surgery, he suffered from Candida mediastinitis and received omentum plombage. Furthermore tracheotomy was performed for pneumonia. He recovered gradually, and was discharged about 3 months after surgery. Echocardiography showed no residual shunt.

We validated Heart Risk View (HRV) software for estimating cardiac event probability in patients with suspected ischemic heart disease. This software is based on the results of the J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT). The HRV software can calculate stress summed scores (SSS), summed rest scores (SRS), and summed difference scores automatically using the 5 point, 20 or 17 segment model of myocardial SPECT images. It can also calculate the probability of cardiac events occurring in patients within 3 years using SSS and parameters obtained from the results of gated SPECT. Changing the threshold of % uptake for determining SPECT scores elevated the agreement of SSS (kappa = 0.269 to 0.657). Cardiac event probability calculated from Perfusion and Function Assessment for Myocardial SPECT (p-FAST) using end systolic volume (ESV), tended to be higher than that calculated from Quantitative Gated SPECT software (QGS). In contrast, cardiac event probability calculated from QGS and p-FAST using left ventricle ejection fraction (LVEF) closely agreed.

Objective: Some formulas using the serum cystatin C level to estimate the GFR have recently been reported. However, there has been no report of a serum cystatin C-based formula for adjusting the dosage of the drugs cleared by the kidney. In this study, we compared the predictive performance of the serum vancomycin trough concentration predicted using serum cystatin C-based formulas., Method: The data were collected from 158 hospitalized patients. Five formulas have been published to predict the GFR using serum cystatin C. The cystatin C-based formulas were divided into two groups, formulas with or without anthropometric data. We predicted the serum vancomycin trough concentrations using VCM-TDM S&#95;edition ver. 1.00 software., Results: In formulas with anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38, the MAE using Grubb's 1 formula was 4.13, the MAE using Sjöström's formula was 2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42. On the other hand, in formulas without an anthropometric data group, the MAE using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63., Conclusion: These results suggested that Hoek's formula is the most useful formula for determining the initial dosage settings for vancomycin.

In recent years, it has been suggested that the glomerular filtration rate (GFR) can be predicted on the basis of serum cystatin C concentrations and that this measurement is more sensitive than serum creatinine concentration as a marker of renal function. In this study, to investigate the clinical utility of the initial dose setting of vancomycin by the population mean method with use of serum cystatin C as a marker of renal function, we compared the correlations between measured vancomycin concentrations and predicted vancomycin concentrations based on serum cystatin C or serum creatinine concentrations in elderly (>/=65 years old) and nonelderly (<65 years old) patients. An analysis of prediction accuracy (bias) and precision was evaluated by calculating the mean prediction error (ME), the mean absolute error (MAE), and the root mean squared prediction error (RMSE). For nonelderly patients (n = 50), there was no significant difference in the MAE based on the use of serum creatinine or serum cystatin C concentration. However, for elderly patients (n = 105), the MAE based on serum cystatin C concentration was significantly better than that based on serum creatinine level. These results suggest that serum cystatin C is a good marker of renal function in comparison with serum creatinine for dose setting of vancomycin, especially in an elderly population.

Defects in insulin receptor function have been associated with insulin resistant states such as obesity and type 2 diabetes mellitus. Several types of mutations in the insulin receptor gene have been identified in patients with genetic syndromes of extreme insulin resistance. We have studied a 10-year-old Japanese girl with type A insulin resistance with hirsutism and hyperinsulinemia but without the dysmorphic features characteristic of leprechaunism or Rabson-Mendenhall syndrome. Despite the presence of severe insulin resistance, the patient did not develop overt diabetes mellitus at the time of investigation. Using direct sequencing, we identified a nonsense mutation causing premature termination after amino acid 345 in the alpha subunit of the insulin receptor.