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Persistent organic pollutants, including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and other brominated flame retardants, were determined in the liver, muscle, and ovary tissue of 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 (9 congeners, 3.9–6.1 ng g− 1 lw) and BTBPE (1.1–3.6 ng g− 1 lw). Tissue-specific PCBs and PBDEs profiles are likely because of differences in the lipid composition. Toxic equivalent (TEQ) values of dioxin-like PCBs in the coelacanth tissues were lower than benchmark values for early life fish. However, compared with the data reported in deep-sea fishes in the Pacific and Indian Ocean, relatively high concentrations of PCBs detected in this study raise concerns about Indonesian coelacanth's conservation and habitat condition.

Summary 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.

Here, we report the results of our preliminary study on deep sea eDNA at fishing ground to approach the fisheries resources abundance at Sulawesi sea by using deep-sea water sampling collected from 10 sites ranging from 110m-200m in depth at front side of the International Coelacanth Research Center and Museum Base at Lolak Waters and Manado Bay North of Sulawesi using Nansen Bottle Sampler (1500 cc). The collected waters were filtered using Power Water Sterivex DNA Isolation Kits and preserved with the DNAiso Reagent then transported to Center for Strategy Research Project, University of the Ryukyus, Okinawa Japan where eDNA analyses were conducted. Our results revealed that the concentrations of eDNA has a good quality were measured with a NanoDrop Lite spectrophotometer, indicating eDNA was successfully extracted. Therefore, by using universal primers for eDNA, MiFish-U-F/R for the 1st-PCR (mt-12S amplification) and 2nd-PCR (tag-indexing) for library preparation to accommodate sequence variations and show that intense signal of MiFish eDNA amplification. Using a high-throughput Illumina MiSeq platform for sequencing analyses, we detected eDNA from 40 fish's species with dominantly by Caranx sexfasciatus, Encrasicholina punctifer., 論文

1) DNA was extracted from blood samples at DNA Chip Research Inc. 2) SNP genotyping: using the DigiTag2 assay.

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). 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. 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). The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

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 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.

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.

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.

Kondisi perairan laut pada kedalaman tertentu sangatlah tidak mudah dipahami secara menyeluruh jika hanya mengandalkan kemampuan manusia tanpa didukung oleh fasilitas pendukung seperti ketersediaan peralatan dan teknologi yang memadai, seperti Remotely Operated Vehicle (ROV). ROV merupakan robot bawah air yang dikontrol oleh orang yang telah professional untuk mengendalikan alat tersebut. Dalam bidang kelautan dan perikanan penelitian dengan menggunakan ROV dapat mempermudah proses penelitian organisme-organisme laut dalam. ROV diklasifikasikan berdasarkan ukuran, berat dan kekuatannya yang dikategorikan sebagai berikut: Micro ROV, Mini ROV, General ROV, Light Workclass, Heavy Workclass dan Trenching/Burial. Penelitian ini menggunakan General ROV dengan panjang 1076 mm, lebar 640 mm dan tinggi 515 mm. Penelitian dilaksanakan di dua tempat yakni di perairan Sulawesi Utara dan Biak Provinsi Papua.

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. Language: en

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 (aged50 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 (BMI18.5) to morbidly obese (BMI35). 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.

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.

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.

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.

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.

Penelitian ini bertujuan untuk mendeskripsikan sebaran suhu dan salinitas di Teluk Manado, Sulawesi Utara. Pengukuran suhu dan salinitas secara vertikal dilakukan di delapan tempat di teluk. Profil vertikal suhu dan salinitas memperlihatkan keberadaan pelapisan kolom air. Secara horizontal, kontur suhu dan salinitas di permukaan memiliki dua “kolam” massa air, yakni kolam yang bersuhu tinggi tapi bersalinitas rendah di bagian timur teluk dan kolam yang bersuhu rendah tapi bersalinitas tinggi di bagian barat teluk. Pada lapisan dalam, kontur suhu dan salinitas cenderung sejajar dengan garis pantai bagian timur. Kata kunci: suhu, salinitas, air sungai, Teluk Manado. The objective of this research is to describe temperature and salinity distribution in Manado Bay, North Sulawesi. The vertical measurements of temperature and salinity were done at eight locations in the bay. The vertical profiles of temperature and salinity shows the existence of water column stratification. Horizontally, temperature and salinity contours of the surface layer have two pools, i.e. a pool of high temperature but low salinity in the eastern part of the bay and a pool of low temperature but high salinity in the western part of bay. In a deeper layer, the contours of temperature and salinity tend to be parallel to eastern coastline. Keywords: temperature, salinity, river discharge, Manado Bay.

Pengukuran salinitas dan suhu perairan dilakukan pada hari-hari hujan dan tidak hujan di dua tempat di perairan Teluk Manado, yang memiliki lima sungai utama di pinggirannya, untuk menyelidiki profil vertikal dari salinitas dan suhu, serta ketebalan air tawar. Profil salinitas dan suhu perairan pada hari yang sama di kedua tempat adalah mirip. Pada hari-hari hujan, salinitas rata-rata lapisan permukaan perairan adalah 33,9 lebih rendah 0,3 dibandingkan pada hari-hari tidak hujan. Salinitas permukaan ini setara dengan ketebalan lapisan air tawar sebesar 0,45 m. di lapisan permukaan, profil suhu cukup mirip. Akan tetapi, pada lapisan yang lebih dalam, suhu berosilasi pada fase yang berbeda dengan bertambahnya kedalaman. Kata kunci: ketebalan lapisan air tawar, termoklin, Bunaken. Salinity and temperature measurements were carried out on rainy days and non rainy days in two locations in Manado Bay, which is the outlet of fresh water masses from five main rivers, to investigate vertical profiles of salinity and temperature, and the thickness of the fresh water layer. Same day salinity and temperature profiles in both places is similar. On rainy days, the average salinity in the surface layer was 33.9, 0.3 lower than that of non rainy days. The surface salinity is equivalent to the thickness of the freshwater layer thickness of 0.45 m. In the surface layer, the temperature profile is quite similar. However, in the deeper layers, the temperature oscillates at different phases according to the increasing depths. Keywords: freshwater thickness, thermocline, Bunaken.

n-Hexane is one of the solvents widely used in industry and well known to be neurotoxic. Recently it was clearly revealed that n-hexane is metabolized in vivo and its metabolites are excreted in the urine. However, the relationship between the exposed dose of n-hexane and the metabolites in the urine has not yet been substantially determined. Therefore, in this investigation we intended to clarify the above relationship in order to establish its usefulness for biological monitoring of n-hexane exposure. The exposed dose was measured by means of a personal monitoring badge worn by workers in seven factories manufacturing vinyl sandals. The time-weighted average (TWA) concentration of n-hexane was 0.2-47.4 ppm. The n-hexane metabolites in the urine of 22 workers were measured with modified Perbellini's method [12] in the early morning (6:00-7:00 hrs) and at 17:00 hrs. 2,5-Dimethylfuran, 2,5-hexanedione and gamma-valerolactone were identified by gas chromatography and mass spectrometory. At 17:00 hrs the means +/- SD of the metabolites were 0.21 +/- 0.11 mg/l for 2,5-dimethylfuran, 1.13 +/- 0.71 mg/l for 2,5-hexanedione, and 2.04 +/- 2.31 mg/l for gamma-valerolactone. The metabolites were also found in the urine in the early morning. 2-Hexanol was not detected in the urine of any worker examined. A strong correlation between TWA concentration of n-hexane and 2,5-hexanedione in the urine was found at 17:00 hrs (r = 0.895, P less than 0.001). The results suggest that the urinary metabolites of n-hexane, especially 2,5-hexanedione, could be useful indicators for biological monitoring of n-hexane exposure. Furthermore the present study offers the advantage of a better estimate of n-hexane TWA.

A total of 1,179 organic solvent products used as thinners, paint, degreasers, inks, adhesive and others, were collected nationwide from factories of various sizes and kinds in Japan, and analyzed by gas chromatography. Solvent components per sample, frequency of each solvent component, and contents of each component were analyzed and classified by use. Paints, inks, and adhesives which contained nonvolatile substances were analyzed by head space techniques. Seventy-seven percent of all samples, 93% of paints, 85% of thinners, 73% of adhesives, and 52% of degreasers contained mixed organic solvents. The average numbers of solvent components per sample were 4.14 (max. 13) in thinner, 3.29 (max. 7) in paint, 2.23 (max. 5) ink, 2.19 (max. 6) in adhesive, 1.71 (max. 6) in degreaser, when gasoline was excluded. Toluene, xylene, methylalcohol, isopropylalcohol, ethylacetate, methylethylketone, industrial gasoline were widely used in the above-mentioned products. Toluene was the most popular component in the solvent products, excluding degreasers. Many kinds of solvent components were used in thinner and paint. However, toluene, xylene and industrial gasoline were their main components and contents per sample were very high. Acetates, alcohols, ketones and glycols were frequently detected in solvent products, but their contents per sample were relatively low, because these solvent components were usually used as subordinate solvents. The chlorinated hydrocarbons such as trichloroethylene, tetrachloroethylene and 1,1,1-trichloroethane, and industrial gasoline were the most popular components in degreasers. 1,4-dioxane was detected in a relatively large number of the samples, but its content per sample was very low, because it is usually used as an additive to 1,1,1-trichloroethane. Toluene was the most popular component in ink solvents, too. In addition, isopropylacohol, methylalcohol, methylethylketone were frequently detected in inks. Toluene was also the most popular component in adhesives, and n-hexane was also frequently detected in them. In order to prevent poisoning by industrial solvents, special attention should be paid to toluene and xylene, which are frequently and largely used for wide purposes, trichloroethylene which is largely used as a degreaser and has a severe toxicity, n-hexane which is frequently used in adhesives and has a high volatility and severe neurotoxicity, and other popular and toxic solvents. The severely toxic solvents such as benzene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane and carbon disulfide were detected in few samples.(ABSTRACT TRUNCATED AT 250 WORDS)

The association between asbestos fibers in human lung tissues and those in other extrapulmonary organs was studied by analysing three autopsied cases, one of whom had a high pulmonary asbestos burden, one an intermediate burden, and one a low burden. The amount, types and sizes of asbestos fibers in the tissues of lung, liver, spleen, pancreas, kidney, and gastrointestinal tract were identified and measured by transmission electron microscopy equipped with an energy dispersive X-ray analyser. The following results were obtained: 1) The concentrations of asbestos fibers in extrapulmonary organs tended to increase with that in lung tissues. 2) The types of fibers identified in lungs were approximately consistent with those in other organs. 3) A relatively large range of fiber length was observed in both lungs and other organs. The findings extend and support previous light microscopic studies comparing asbestos bodies in various organs, and may imply that persons with high levels of asbestos in their lungs are also likely to have the same types and high levels of asbestos in their other tissues.

Chlordane has been widely used to protect soil and house foundations against termite infestation. Pest control operators (PCOs) are occupationally exposed to chlordane. The relationship between chlordane and its metabolites in blood of PCOs and spraying conditions were investigated. Chlordane and its metabolites were detected in the blood of some chlordane-exposed PCOs, but not in that of the controls. Trans-nonachlor and the metabolites oxychlordane and heptachlor epoxide were detected in the blood of PCOs. Total concentration of chlordane and its metabolites in blood (trans-nonachlor + oxychlordane + heptachlor epoxide) was less than 5.6 ppb (mean: 0.89 ppb). The concentration of chlordane and its metabolites in blood of chlordane-exposed PCOs was significantly correlated with the number of spraying days and the amount of chlordane sprayed, particularly with a large correlation coefficient (r = 0.81, P less than 0.001) with the spraying days in the three months prior to the medical examination. The concentration of chlordane and its metabolites in blood is considered to be a useful indicator of biological monitoring for chlordane exposed workers (PCOs).

Organic solvent products used in the various factories were collected nationwide in Japan, and analyzed by gas chromatogarphy. Of the 1179 samples collected, 522 samples were homogeneous (including 321 thinners, 145 degreasers and 56 reagents and others), and were analyzed by means of direct injection into a FID-gas chromatograph with two FSWCOT (OV 101 and PEG 6000) capillary columns. In thinners (n=248), the average number of solvent components per sample was 4.14 when the thinners containing gasoline were excluded. Toluene was the most popular component in thinners (present in 56%) followed by ethyl acetate, methanol, xylenes, ethylbenzene, isobutyl alcohol, ethyleneglycol mono-ethylether acetate, butyl acetate and methyl isobutyl ketone. Gasoline was also detected in 23%. In degreasers (n=123), the average number of solvent components per sample was 1.64 when the degreasers containing gasoline were not taken into account. Trichloroethylene was present in 21% of degreasers followed by tetrachloroethylene, 1, 1, 1-trichloroethane, toluene, acetone, xylenes and ethyl-benzene. Gasoline was found in 14%. A small amount of 1, 4-dioxane was detected as an additive in every 1, 1, 1, -trichloroethane products. With regard to reagents and others (n=53), the avarage number of components per sample was 1.40 if samples containig gasoline were excluded, and most (73%) of reagents and others (n=41) consisted of a single component. The potent toxic solvents such as benzene, chloroform, carbon tetrachloride, 1, 2-dichloroethane, 1, 1, 2-trichloro-ethane, 1, 1, 2, 2-tetrachloroethane and carbon disulfide were only rarely found in the present homogeneous products.

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and γ-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm. The maximum concentration of the excreted metabolites in urine was delayed when the concentration of n-hexane increased. These findings may indicate that the capacity of hydroxylation in rat liver microsomes was saturated when exposed to high concentrations of n-hexane. Free (not conjugated) metabolites were also excreted in the urine in all concentrations during exposure and 16 h after exposure. In the second experiment, four separate groups of five rats each were exposed to 1000 ppm of n-hexane, 1000 ppm of n-hexane plus 1000 ppm of toluene, 1000 ppm of n-hexane plus 1000 ppm of MEK, or fresh air. The analyzing procedure was the same as that in the first experiment. Distributions of n-hexane metabolites in the mixed exposure group were almost similar to that of the n-hexane-alone group. The amount of metabolites decreased to about one-sixth of that in the n-hexane group by co-exposure with toluene and to about one-fourth by co-exposure with MEK. From these results, it can be considered that toluene decreases the neurotoxicity of n-hexane by the inhibition of n-hexane metabolism. However, the reason the neurotoxicity of n-hexane is increased by co-exposure with MEK cannot be clearly explained.

Petroleum benzine is one of the mixtures of organic solvents containing n-hexane. The occurrence of polyneuropathy in the workers using petroleum benzines is attributed mainly to n-hexane, though other hydrocarbons present are also suspected of having some neurotoxicity or some potential which could modify the neurotoxicity of n-hexane. The present experiment was performed in order to clarify the toxicity of petroleum benzine to the peripheral nerve and compare it with that of n-hexane. Forty rats were randomly divided into five groups. The groups were exposed to 200 ppm n-hexane, 500 ppm n-hexane, and petroleum benzine vapor containing 200 ppm n-hexane or 500 ppm n-hexane, together with aliphatic and aromatic hydrocarbons for 12 h a day for 24 weeks. The body weight, motor nerve conduction velocity, motor distal latency, and mixed nerve conduction velocities were measured before exposure and every 4 weeks of exposure. A rat from each exposed group was histopathologically examined after 24 weeks' exposure. The function of the peripheral nerve was conspicuously impaired by 500 ppm n-hexane, slightly impaired by 200 ppm n-hexane and petroleum benzine containing 500 ppm n-hexane, and even less impaired by petroleum benzine containing 200 ppm n-hexane. Degenerations of the myelin sheaths and axons were demonstrated in all exposed groups upon examination of the revealed tail nerves. Thus, the experiment revealed that petroleum benzine could impair the peripheral nerves, while some components of petroleum benzine were considered to inhibit the neurotoxicity of n-hexane.

It is well known that the neurotoxicity of n-hexane may be modified upon co-exposure with other organic solvents. In order to elucidate this mechanism further, rats were exposed to 500ppm n-hexane, 500ppm n-hexane plus 500ppm methyl ethyl ketone (MEK), 500ppm n-hexane plus 500ppm toluene, or air only for 8h per day for 33 weeks. The body weight, motor nerve conduction velocity (MCV) and distal latency (DL) were determined before exposure and after 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. From each group one rat was histologically examined after 33 weeks of exposure. To establish a relationship between the n-hexane neurotoxicity and changes in biotransformation, urinary metabolites (2-hexanol, methyl n-butyl ketone (MBK), 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone) were measured by gas chromatography on the first exposure day, and after 1, 2, 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. The total amounts of metabolites of n-hexane in the urine significantly decreased upon co-exposure of n-hexane, with MEK as well as with toluene, in comparison with those of animals exposed to n-hexane alone. 2,5-Hexanedione, which is considered the ultimate neurotoxic metabolite of n-hexane, also decreased. Electrophysiological and histological studies did not reveal statistically significant differences between any two groups among the four groups. It is considered that the present results might explain the combined effects of n-hexane and toluene which decrease n-hexane neurotoxicity, but do not explain those of n-hexane and MEK. Therefore, other mechanisms of the combined effects of n-hexane and MEK should be studied.