First insight into accumulation of characteristics and tissue distribution of PCBs, PBDEs, and other BFRs in the living Indonesian coelacanth (Latimeria menadoensis).

Persistent organic pollutants, including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and other brominated flame retardants, were detected in the liver, muscle, and ovary tissues of the Indonesian coelacanth (Latimeria menadoensis) incidentally caught around Gangga Island, North Sulawesi Province, Indonesia, on November 5, 2014. Concentrations of total PCBs (209 congeners, 300-2600 ng g-1 lipid weight) in all tissues showed higher than those of PBDEs (41 congeners, 3.9-6.3 ng g-1 lw) and BTBPE (1.1-3.6 ng g-1 lw). The tissue-specific PCB and PBDE profiles were likely due to differences in the lipid composition. Toxic equivalent (TEQ) values of dioxin-like PCBs in coelacanth tissues were lower than the benchmark values for early-life fish. However, compared with the data reported for deep-sea fishes in the Pacific and Indian Oceans, the relatively high concentrations of PCBs detected in this study raise concerns regarding Indonesian coelacanth conservation and habitat conditions.

Effect of dietary energy and polymorphisms in BRAP and GHRL on obesity and metabolic traits.

OBJECTIVE: Obesity, a risk factor for all-cause and cardiovascular mortality, is a major health concerns among middle-aged men. The aim of this study was to investigate a possible association of dietary habits and obesity related single nucleotide polymorphisms (SNPs) with obesity and metabolic abnormalities. METHODS: We conducted a retrospective cohort study using annual health examination data of 5112 male workers, obtained between 2007 and 2011. Average dietary energy was estimated using electronically collected meal purchase data from cafeteria. We examined 8 SNPs related to obesity: GHRL rs696217, PPARG rs1175544, ADIPOQ rs2241766, ADIPOQ rs1501299, PPARD rs2016520, APOA5 rs662799, BRAP rs3782886, and ITGB2 rs235326. We also examined whether SNPs that were shown to associate with obesity affect other metabolic abnormalities such as blood pressure (BP), glucose, and lipid profile. RESULTS: Average dietary energy significantly associated with increased abdominal circumference (AC) and body mass index (BMI). The odds ratios (ORs) of overweight and obesity also increased. The major allele of rs696217 significantly increased BMI and an increased OR with obesity, while the minor allele of rs3782886 was associated with significantly decreased AC and the decreased ORs with overweight and obesity. The minor allele of rs3782886 was also associated with significantly decreased systolic BP (SBP), triglyceride (TG), high-density lipoprotein (HDL), and fasting blood sugar (FBS), while rs696217 was not associated with other metabolic abnormalities. CONCLUSIONS: Average dietary energy in lunch, rs3782886, and rs696217 were associated with obesity, and rs3782886 was associated with other metabolic abnormalities.

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers.

BACKGROUND: Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. METHODS: We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. RESULTS: In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). CONCLUSIONS: After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers.

BACKGROUND: Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). METHODS: This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. RESULTS: BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). CONCLUSION: The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

The pectoral fin muscles of the coelacanth Latimeria chalumnae: Functional and evolutionary implications for the fin-to-limb transition and subsequent evolution of tetrapods.

To investigate the morphology and evolutionary origin of muscles in vertebrate limbs, we conducted anatomical dissections, computed tomography and kinematic analyses on the pectoral fin of the African coelacanth, Latimeria chalumnae. We discovered nine antagonistic pairs of pronators and supinators that are anatomically and functionally distinct from the abductor and adductor superficiales and profundi. In particular, the first pronator and supinator pair represents mono- and biarticular muscles; a portion of the muscle fibers is attached to ridges on the humerus and is separated into two monoarticular muscles, whereas, as a biarticular muscle, the main body is inserted into the radius by crossing two joints from the shoulder girdle. This pair, consisting of a pronator and supinator, constitutes a muscle arrangement equivalent to two human antagonistic pairs of monoarticular muscles and one antagonistic pair of biarticular muscles in the stylopod between the shoulder and elbow joints. Our recent kinesiological and biomechanical engineering studies on human limbs have demonstrated that two antagonistic pairs of monoarticular muscles and one antagonistic pair of biarticular muscles in the stylopod (1) coordinately control output force and force direction at the wrist and ankle and (2) achieve a contact task to carry out weight-bearing motion and maintain stable posture. Therefore, along with dissections of the pectoral fins in two lungfish species, Neoceratodus forsteri and Protopterus aethiopicus, we discuss the functional and evolutionary implications for the fin-to-limb transition and subsequent evolution of tetrapods. Anat Rec, 299:1203-1223, 2016. © 2016 Wiley Periodicals, Inc.

Identification of an interaction between VWF rs7965413 and platelet count as a novel risk marker for metabolic syndrome: an extensive search of candidate polymorphisms in a case-control study.

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP-SNP interaction, SNP-environment interaction, and SNP-clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS.

Coelacanth genomes reveal signatures for evolutionary transition from water to land.

Coelacanths are known as "living fossils," as they show remarkable morphological resemblance to the fossil record and belong to the most primitive lineage of living Sarcopterygii (lobe-finned fishes and tetrapods). Coelacanths may be key to elucidating the tempo and mode of evolution from fish to tetrapods. Here, we report the genome sequences of five coelacanths, including four Latimeria chalumnae individuals (three specimens from Tanzania and one from Comoros) and one L. menadoensis individual from Indonesia. These sequences cover two African breeding populations and two known extant coelacanth species. The genome is ∼2.74 Gbp and contains a high proportion (∼60%) of repetitive elements. The genetic diversity among the individuals was extremely low, suggesting a small population size and/or a slow rate of evolution. We found a substantial number of genes that encode olfactory and pheromone receptors with features characteristic of tetrapod receptors for the detection of airborne ligands. We also found that limb enhancers of bmp7 and gli3, both of which are essential for limb formation, are conserved between coelacanth and tetrapods, but not ray-finned fishes. We expect that some tetrapod-like genes may have existed early in the evolution of primitive Sarcopterygii and were later co-opted to adapt to terrestrial environments. These coelacanth genomes will provide a cornerstone for studies to elucidate how ancestral aquatic vertebrates evolved into terrestrial animals.

Genetically distinct coelacanth population off the northern Tanzanian coast.

Since the sensational discovery of a living coelacanth off the east coast of South Africa, the geographic distribution of viable coelacanth populations has been a subject of debate. In the past, the coelacanths off the African mainland were thought to be strays from the Comoros because most coelacanths captured were caught in the waters surrounding the Comoros archipelagos. However, in recent years, a large number of coelacanths were captured off the coast of Tanzania, including nine living specimens observed in a remotely operated vehicles survey. Thus, it is possible that there is a reproducing population inhabiting waters off the Tanzania coast. We have sequenced the complete mitochondrial genomes of 21 Tanzanian and 2 Comoran coelacanths and analyzed these sequences together with two additional full mitochondrial genomes and 47 d-loop sequences from the literature. We found that the coelacanth population off the northern Tanzanian coast is genetically differentiated from those of the southern Tanzania coast and the Comoros, whereas no significant genetic differentiation occurs between the latter two localities. The differentiation between the northern and southern Tanzanian coast populations is consistent with the hypothesis that the existence of northward-flowing ocean current along the Tanzanian coast may reduce or prevent gene flow from the northern to the southern population. Finally, we estimated that the population localized to the southern Tanzanian coast and the Comoros diverged from other coelacanths at least 200,000 y ago. These results indicate that the coelacanths off the northern Tanzania coast are not strays but a genetically distinct group. Our study provides important information for the conservation of this threatened "living fossil."

[Characteristics of the stages of change in physical behavior of male workers suffering from impaired glucose tolerance].

OBJECTIVE: The purpose of this study was to describe the characteristics of the stages of change in physical behavior of workers with diabetes and impaired glucose tolerance according to their dietary behavior, BMI, FBS, and HbA1c. SUBJECT AND METHODS: The annual health checkup records of 15,317 male employees of an automobile corporation were examined. The stages of change in physical behavior were assessed through a self-reported questionnaire about "regular exercise" related to the five transformation stages and the date were used to analyze analyzes its relationship to dietary behavior, BMI, FBS, and HbA1c. RESULTS AND DISCUSSION: The older age groups reported that the time spent on the "Action" and the "Maintenance" stages increased gradually over time. From the results we deduced that activity in the 30-39-year-old age group is low, which may be due lifestyle influence. The groups with advanced HbA1c levels reported that the time spent on the "Action" and the "Maintenance" stages increased. This may reflect the effects of present health management and continued research on its effects is needed. Significant correlations between the stages of change for physical and dietary behavior were observed in every age group and in every HbA1c level group. Developing regular exercise habits was closely related to developing adequate dietary habits in every age group and in every HbA1c level group. The correlation between exercise and dietary habits is so strong that future research into the causes inhibiting individuals from developing regular exercise habits is needed for workers with diabetes and impaired glucose tolerance. Developing regular exercise habits did not have a significant relation to FBS disorders in the 30-39 yr old age group or obesity in any age group. The results suggest that the effect and the limit of the physical behavior can be appropriately guided, and the offer of that encourages and supports the maintenance of the education physical behavior established is important. CONCLUSION: Health management systems for the prevention of diabetes mellitus should include independent education programs for encouraging regular exercise habits combined with diet programs in consideration of characteristics of the stages of change in physical behavior of working populations.

Relationship between prostate-specific antigen and obesity in prostate cancer screening: analysis of a large cohort in Japan.

Previous studies have shown that lower prostate-specific antigen (PSA) levels in obese men might decrease the sensitivity of prostate cancer screening, leading to delayed diagnosis and unfavorable prognosis. We examined whether the effect of obesity is important in prostate cancer screening of Japanese men, who have a low prevalence of obesity. We analyzed 19,294 male subjects from a large cohort of Toyota Motor Corporation (TMC) employees (aged > 50 years, serum PSA level ≤ 4.0 ng/mL) who underwent physical examinations from August 2006 to December 2009. The relationship between PSA level and obesity-related factors was analyzed by simple and multiple regression analysis. The relationships between six body mass index (BMI) categories, and PSA level and PSA mass (PSA concentration × plasma volume) were analyzed. PSA level decreased significantly with increasing BMI, but the coefficient of determination was very low. Mean PSA values decreased from 1.02 to 0.85 ng/mL as BMI increased from underweight (BMI <18.5) to morbidly obese (BMI >35). However, PSA mass peaked in the overweight category and was slightly reduced with increasing BMI. On multiple regression analysis, PSA level was influenced by age, diastolic blood pressure and high-density lipoprotein as well as BMI. We found an inverse but weak relationship between PSA level and BMI. Obesity seems to have very limited influence on prostate cancer screening in this population. Nonetheless, when considering indications for prostatic biopsy in obese men, we should be aware that the hemodilution effect might reduce PSA levels.

A pilot study on inducement of smoking cessation by a simple 5A (asking, advice, assess, assist, and arrange) approach at outpatient clinics.

Asking smokers about their smoking status, followed by advice to quit smoking, assessing the intention to quit, assistance with cessation, and arrange of follow-up (5A) is recommended for induction of smoking cessation. To obtain preliminary data on effects of "5A" , we investigated the smoking cessation rate with two modes in the phase I: 1) self-administered questionnaire and 2) doctor's interview at respiratory disease clinics of three general hospitals in Japan, and another mode in phase II: 3) doctor's interview with an additional pamphlet at one of the three hospitals. The interviews for smokers were conducted by doctors in charge of treatment. Subject smoking habits were followed up by postal surveys three months after the enrollment. In phase I, 359 outpatients were recruited and 189 smokers responded, among whom 27 patients (7.5% of 359 outpatients) had quit smoking at the three months after the enrollment. The cessation rate of the self-administered questionnaire group (8.4% of 238 smokers) did not differ significantly from that of doctors' interview group (5.8% of 121 smokers). Age and intention to quit at enrollment were found to be independent predictors of smoking cessation. Patients aged 50 years or older (odds ratio=5.05, 95% confidence interval 1.89-13.54), and participants with an intention to quit (odds ratio=6.78, 95% confidence interval 2.66-17.30) were more likely to be successful in quitting. In phase II, another 212 smokers of one hospital were interviewed by doctors in charge and provided with an additional pamphlet describing how to practice to dislike smoking. No significant difference in the cessation rate was observed between phase I and phase II (5.8% vs. 8.0%). In conclusion, there were no differences among the three modes of "5A", but 7.7% of the 571 outpatients visiting respiratory divisions quit smoking with this simple "5A". The findings may indicate that this simple practice at clinics is useful for smoking cessation strategy, although randomized trials are now required.

[In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002].

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

[Moderately differentiated adenocarcinoma of the lung presenting as multiple pulmonary metastases with thin-walled cavities].

A 63-year-old woman was admitted because of diabetes mellitus and abnormal chest radiographic findings. Computed tomographic scan showed a large mass in the S1 region of the right lung and many pulmonary nodules with thin-walled cavities in both lung fields. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. The patient could not receive systemic chemotherapy because of her poor physical status, and died of respiratory failure due to advanced pulmonary metastases. Histopathological examination of an autopsy specimen confirmed the diagnosis of primary bronchial adenocarcinoma with multiple cavitary metastases. The cavity wall consisted of moderately differentiated adenocarcinoma cells, and central necrosis with neutrophil infiltration and fibrin precipitation were recognized. These findings suggest that the mechanism of cavity formation in this case may depend on the ischemic tumor necrosis or colliquative tumor necrosis associated with neutrophil infiltration into the central portion of metastatic lesion.

[Chemoradiation using 5-fluorouracil (5-FU) and nedaplatin (NDP) for gynecological malignancy--the relation between hemotoxicity and sequence of 5-FU and NDP].

We compared sequence-dependent schedules of 5-fluorouracil (5-FU) and nedaplatin (NDP) for hemotoxicity in genecological malignancy (GM). The safety of schedules using 5-FU before/after NDP combined radiotherapy in 8 patients with GM was evaluated. They received either 5-FU 700 mg/m2 i.v. continuous infusion on days (D) 1-4 + NDP 100 mg/m2 i.v. bolus on D1 (group A: 5 pts), or NDP on D4, 5-FU on D1-4 (group B: pts). In group A, 4 patients received a reduced dose of NDP because of less than 60 ml/min of creatinine clearance. In group A, WBC (2 pts), hemoglobin (3 pts), and platelet (1 pts) were grade 3 or higher. In group B, grade 3 or higher in hemotoxicity was not seen. A higher percentage of hemotoxicity was seen in group A compared with group B.