The purpose of this cohort study was to identify the predictors of lifestyle-related disorders, such as dyslipidemia, hyperuricemia, and liver dysfunction in Japanese young male workers. As candidates for the predictors, we chose obesity at entry and weight gain. The study subjects were 166 Japanese male workers aged 28 to 35 years at two printing plants in Tokyo who showed no blood abnormalities on 6 chemistry items, i.e., total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT); the subjects completed a self-administered questionnaire survey in 1993, and underwent blood examinations in 2000. Covariates we included in the models were age, drinking habit, smoking habit and regular exercise. Linear regression models revealed that weight gain was consistently associated with the above 6 blood chemistry items at endpoint, whereas obesity was not a better predictive variable than weight gain except for UA. Logistic regression models showed that the odds ratios (ORs) of each 5% weight gain were 1.47 [95% confidence interval (CI): 0.94-2.28] for high TC, 1.27 (0.88-1.84) for high UA, 2.61 (1.32-5.18) for high ALT, and 1.88 (1.14-3.11) for high GGT. The ORs of obesity were 3.05 (0.98-9.50) for high TC, 3.88 (1.40-10.8) for high UA, 4.94 (1.05-23.22) for high ALT, and 1.78 (0.43-7.31) for GGT. In conclusion, for a period during which workers do not undergo blood tests, weight gain, in combination with obesity, may be used as a predictor of the later occurrence of blood abnormalities.

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Objective: The literature documents and supports the fact that many art supplies contain toxic substances which are considered harmful to the health of artists, teachers, and students. The goal of this study is to investigate printmaking students awareness of hazardous printmaking materials. Methods: A questionnaire consists of seven questions was mailed to a 130 students from non-toxic printmaking programs, and 130 students from traditional printmaking programs in 10 liberal arts colleges and universities in the United States and Canada (5 universities for the safe printmaking program, and 5 for the traditional program). A total of 189 printmaking students responded to the survey instrument. The questionnaire sought information on demographic characteristics of respondents, and the awareness of students of the hazardous nature of printmaking materials. Information collected from the questionnaire was coded for the purpose of entering it into a computer for statistical analysis (SPSS Program). Results: It was found that printmaking students in both programs were moderately aware of the toxic nature of printmaking materials, but the t-test analysis showed non-toxic printmaking students were more aware than traditional printmaking students. Conclusion: This study pointed to the importance of increasing awareness of students to art materials in the traditional program.

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Exposure experiments in medaka and photodecomposition tests were performed using a metabolite of bisphenol A [4-methyl-2,4-bis(p-hydroxyphenyl)-pent-1-ene; MBP], the solubility limit of which is 42 mg/l of water. Three adult medaka were kept in a 2 l glass beaker at 25 ± 1°C for 4 days. The LC₅₀ for 96 hr was > 1000 ppb. The measured average MBP concentration in the breeding water (nominal concentration of 100 ppb) was 49.2 ppb. The average concentration in the whole bodies of medaka after 4 days was 1.92 mg/g-wet body, and the bioconcentration factor (BCF) of MBP was calculated to be 39.0. MBP in water and acetone was decomposed very easily, with about 98% of the MBP being decomposed after several hours under sunlight. MBP was also decomposed after 48 hr of illumination under a white fluorescent lamp.

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The estrogenic effect of chemicals, including 1-chloro-2,4-dinitrobenzene (CDNB), in the combination with 17β-estradiol (E₂) was screened by a reporter gene assay using breast cancer cells (MCF-7). It was found that CDNB stimulated E₂-induced transcriptional activity of estrogen receptor (ER) and down-regulated both ER protein and mRNA. However, CDNB alone and CDNB metabolite(s) showed no estrogenic activity and no binding activity to ER, suggesting an indirect pathway other than ER. CDNB gave no transcriptional activity for an aryl hydrocarbon receptor (AhR), suggesting no possibility of a pathway through cross-talk between AhR and ER. On the other hand, CDNB enhanced the mitogen activated protein kinase (MAPK) pathway, suggesting estrogenic action via MAPK. These results indicated that CDNB possessed estrogen-like activity in the transcription and regulation of ER though a different pathway from E₂.

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The adsorption properties of bisphenol A (BPA), suspected as endocrine disrupting chemicals (EDCs), and β-estradiol (E2) were examined in this study. Based on the adsorption isotherm results, the adsorption amount of BPA increased as the carbonization temperature increased. The adsorption effect of a porous carbon carbonized at 400°C was minimal, while the adsorption effect of a porous carbon carbonized at 1000°C was significant. Although the adsorption effect of the activated carbon was also significant, that of activated carbon was lower than that of the 1000°C porous carbon in the low concentration range, while that of the activated carbon was higher than that of the 1000°C porous carbon in the high concentration range. The adsorption amount of E2 increased as the carbonization temperature increased. The adsorption effect of the activated carbon was midway between 700 and 1000°C. Porous carbon carbonized at 1000°C with a low surface polarity was more effective for the removal of EDCs from environmental water than activated carbon with a large pore volume. It is expected that the 1000°C porous carbon can be used with activated carbon, which has already been used in waste water treatment, in purification plants, etc.

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The peroxidase-like activity of the Fe³⁺ complex of thiacalix[4]arenetetrasulfonate on a modified anion-exchanger (Fe³⁺-TCAS[4]_A-500) has been applied to the spectrofluorometric determination of uric acid and glucose in connection with uricase and glucoseoxidase (GOD), respectively. Uric acid and glucose were spectrofluorometrically determined by measuring the amounts of H₂O₂ produced through each catalytic reaction by uricase and GOD for uric acid and glucose in a sample solution, respectively. The calibration curves obtained by the Uricase-Fe³⁺-TCAS[4]_A-500 and the GOD-Fe³⁺-TCAS[4]_A-500 methods were linear from 0.5 to 5.0 μg of uric acid in a 1.0 ml sample solution and from 0.5 to 6.0 μg of glucose in a 0.5 ml sample solution, respectively. The methods using Fe³⁺-TCAS[4]_A-500 were applied to the determination of uric acid and glucose in control sera.

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The cultivation or trafficking of “Magic mushrooms,” containing hallucinogenic psilocin and psilocybin, has been prohibited by the Narcotics and Psychotropics Control Law in Japan since 2002. To identify these mushrooms, we attempted to prepare the monoclonal antibody (mAb) reactive to these hallucinogens. As an antigen inducing an anti-psilocin mAb, N-{4-[3-(2-dimethylaminoethyl)indol-4-yl-oxy]butyl}succinamic acid was synthesized by modifying the 4-hydroxyl moiety of psilocin and coupled to a carrier protein of keyhole limpet hemocyanin. BALB/c mice were immunized five times with the antigen emulsified with an adjuvant, and their spleen cells were fused with mouse myeloma cells. We obtained several hybridoma cells producing mAbs reactive to psilocin, from which four clones, BA631, CA231, KA422, and MA332 with a higher production of anti-psilocin mAb were selected by limiting dilution. Isotype of CA231 and KA422 mAbs were IgG2a and that of BA631 and MA332 mAbs were IgG1. Enzyme immunoassay (EIA) using BA631 mAb, revealed that BA631 cross-reacted with psilocin and dimethyltryptamine, but not with the other indole derivatives such as psilocybin, 4-hydroxyindole, tryptamine, and tryptophan. Therefore, these antibodies could be used for the identification of magic mushrooms.

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Arthrobacter sp. strain PY1, a bacterium having the ability to degrade 1,3-dichlotopropanol (1,3-DCP), was isolated from a soil sample of a chemical plant. Strain PY1 degraded 1000 mg/l (7.75 mM) of 1,3-DCP completely within 7 days, and the ability was elevated by acclimatization up to 4000 mg/l/week. Addition of nutrients such as peptone, glucose or glycerol showed no or slight effect on the degrading activity. These results suggest that strain PY1 is a useful organism in a biological control system for 1,3-DCP pollution. The ability to degrade 1,3-DCP was induced by addition of 1,3-DCP to the culture of strain PY1. A 1,3-DCP-degrading enzyme (Deh-PY1) was purified from the cytoplasmic fraction of strain PY1 by fractionation with ammonium sulfate, hydrophobic chromatography and anion exchange chromatography. Purified Deh-PY1 is a tetramer of a homogeneous subunit having a molecular weight of 20 kDa. Analysis of the N-terminal amino acid sequence of Deh-PY1 showed that the 31 residues were quite similar to those of known 1,3-DCP-dehalogenases of other organisms, Arthrobacter sp. strain AD2 and Corynebacterium sp. strain N-1074, although some differences in composition or enzymatic characteristics were observed. The Km value and Vmax of Deh-PY1 were 2.67 mM and 7.81 μmol/min/mg, respectively, and the optimum reaction temperature and pH were 40-50°C and 9.5-10.5.

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The effect of residual chlorine on the growth of Selenastrum capricornutum was investigated by an algal growth test to evaluate toxicity. Significant reductions in growth due to monochloramine were observed in the green alga, Selenastrum capricornutum; however, algal growth was not inhibited in the medium containing rice bran because of the disappearance of monochloramine. The removal of monochloramine by rice bran was attributed to the chemical's decomposition by direct reaction with the rice bran. In contrast, no significant reduction in growth was observed in the medium containing free chlorine. The decomposition rate of monochloramine was slower than that of free chlorine in the medium.

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A change in circulating biochemical markers of bone metabolism in normal individuals with the intake of juice prepared from Satsuma mandarin (Citrus unshiu MARC.) containing β-crypthoxanthin was investigated. Twenty-one volunteers (ten males and eleven females) were divided into two groups of ten volunteers (five males and five females) and eleven volunteers (five males and six females), and each group was given sequentially juice (192 ml) containing two different contents of β-crypthoxanthin once a day for 28 or 56 days as follows: either regular juice with naturally occurring 802 μg β-cryptoxanthin/100 ml or a reinforced juice containing 1500 μg β-cryptoxanthin/100 ml. As serum bone markers, bone-specific alkaline phosphatase, γ-carboxylated osteocalcin, bone tartrate-resistant acid phosphatase (TRAP), and N-telopeptide of type I collagen were assayed. The intake of regular juice for 28 or 56 days caused a significant increase in γ-carboxylated osteocalcin, a marker of bone formation, and the intake for 56 days produced a significant decrease in serum bone TRAP activity. Moreover, intake of the β-cryptoxanthin reinforced juice for 28 or 56 days caused a significant increase in serum β-carboxylated osteocalcin concentration and a corresponding decrease in serum bone TRAP activity and N-telopeptide of type I collagen, a marker of bone resorption. This study suggests that the intake of β-cryptoxanthin reinforced juice has a stimulatory effect on bone formation and an inhibitory effect on bone resorption in normal individuals.

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Mutagenic 1-chloro-3-nitropyrene (1,3-CNP), 1,6-CNP and 1,8-CNP were detected in surface soil collected in Kyoto, Japan. First, 1,3-, 1,6- and 1,8-CNPs were synthesized by chlorination of 1-nitropyrene. Mutagenic activities obtained by Ames assay using Salmonella typhimurium strain TA98 under conditions without S9 mix were 1.22 revertants per nmol for 1,3-CNP, 1.14 for 1,6-CNP and 0.83 for 1,8-CNP. Miller's aryl hydrocarbon receptor (AhR) yeast reporter gene assay showed that the three CNPs had no AhR ligand activity. Surface soil was collected in Kyoto, Japan and analyzed for 1,3-, 1,6- and 1,8-CNPs by two-dimensional high-performance liquid chromatography with fluorescence detection and a zinc on-line catalytic column. 1,3-CNP, 1,6-CNP and 1,8-CNP were detected in the ranges 9.2-13.8, 3.4-4.6 and 4.3-5.0 pg per gram of soil (n = 2), respectively.

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The marine alga Sargassum horneri (S. horneri) has an anabolic effect on bone metabolism (J. Health Sci., 47, 533-538, 2001). The effect of the fractionated extracts obtained from S. horneri on bone calcium content and osteoclast-like cell formation in vitro was investigated. S. horneri was gathered from various coasts (Shimoda, Iwate, or China). Rat femoral-diaphyseal and -metaphyseal tissues were cultured for 24 hr in a medium containing either vehicle or a water-solubilized extract (25 μg/ml of medium) obtained from S. horneri. Diaphyseal and metaphyseal calcium contents were significantly increased in the presence of S. horneri extract from Shimoda, Iwate, or China. The active component of S. horneri extract in increasing calcium content in diaphyseal tissues was seen in the nearby fraction molecular weight (MW) of 1000. This effect completely disappeared upon heat treatment with 80°C for 30 min. Mouse marrow cells were cultured for 7 days in a medium containing 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] (10^-7 M) in the presence or absence of S. horneri extract (1.0 μg/ml of medium). The 1,25(OH)₂D₃-induced increase in osteoclast-like cell formation was markedly suppressed in the presence of the crude extract or a fraction more than MW 50000 of S. horneri extracts obtained from Iwate or China. This effect was also seen by heat treatment. The present study suggests that the active components of S. horneri extract in stimulating bone formation or suppressing osteoclastic bone resorption are different.

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Many intestinal hormones are also distributed throughout the central nervous system (CNS). However, the existence of secretin, a typical intestinal hormone, has not been clearly shown in the brain. There have been conflicting data concerning the expression of secretin in the CNS. The aim of this study was to confirm the existence of secretin in the CNS immunochemically and histochemically. Proforms of secretin were detected in porcine cortex extracts by gel filtration chromatography and reverse-phase HPLC with a radioimmunoassay using different specific antibodies raised against secretin and prosecretin (1-41), indicating the production and processing of secretin precursor in the CNS. An immunocytochemical search in several regions of the rat CNS with the two antibodies revealed that secretin-positive neurons were concentrated in a limited area ranging from the corner of the dentate gyrus to the molecular layer in the hippocampus. In situ hybridization also supported this finding. The limited location of secretin-positive cells shown here caused difficulty in detecting secretin in the CNS. The hippocampus is thought to contribute to aging, and secretinergic neurons in this region might play an important role. This study suggests that secretin is produced in the CNS and may act as a neurotransmitter or neuromodulator in the hippocampus.

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Acute exposure of mice to potassium bromate (KBrO₃), which is a major disinfection by-product of ozonation and/or chlorination of bromide-containing raw waters, causes serious kidney failure and neuropathological disorders. We observed significant elevations of serum uric acid levels and xanthine oxidase activity by KBrO₃ administration (1.2 mmol/kg) with elevating relative kidney weight, serum creatinine levels and renal oxidative stress. Therefore, allopurinol was administered to KBrO₃-treated mice to examine if the elevation of blood uric acid levels causes acute kidney damage and renal oxidative stress. These KBrO₃-induced elevations were significantly prevented by intraperitoneal administration of allopurinol (10 or 50 mg/kg) and significant correlation between kidney damage and uric acid levels was observed. Reduction of catalase activity in the kidney of KBrO₃-treated mice, which results in the accumulation of hydrogen peroxide, was also restored by allopurinol. There were significant correlations between catalase activity and uric acid levels or kidney damage. Furthermore, in in vitro experiment, catalase activity was reduced in the presence of physiological concentration of uric acid (approximately 0.3 mM or more). These results suggest that the reduction of catalase activity by the elevation of blood uric acid levels is a major cause of KBrO₃-induced acute kidney damage. Allopurinol also suppressed KBrO₃-induced increases of renal thiobarbituric acid reactive substances levels and renal protein carbonyl levels of mice. Furthermore, significant correlation between oxidative stress and blood uric acid levels was observed. Therefore, KBrO₃ seems to cause hyperuricemic status which in turn brings about acute kidney damage and oxidative stress with reducing catalase activity.

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Our previous study suggested that sodium spirulan (Na-SP) stimulated the release of proteoglycans from cultured vascular endothelial cell layers. In the present study, we characterized the stimulatory effect of Na-SP on endothelial proteoglycan release from the viewpoint of the Na-SP structure. The following results were obtained: Na-SP is a potent stimulator of endothelial proteoglycan release. The stimulatory effect of Na-SP disappears with desulfation or removal of sodium ion. Depolymerized Na-SPs (M_r ∼14700 or greater) also exhibits stimulatory effects as does Na-SP (M_r ∼220000). The stimulation occurs more potently in endothelial cells than in vascular smooth muscle cells. Therefore it is suggested that the stimulatory effect of Na-SP on proteoglycan release requires both the sulfate group and sodium ion, and the effect is achieved by an active structure in the molecule which interacts particularly with the endothelial cell extracellular matrix.

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Heparan sulfate (HS) chains bind and activate fibroblast growth factor-2 (FGF-2) depending on their microstructure. The glycosaminoglycan chains present particularly as a large HS proteoglycan perlecan in vascular endothelial cells. A heavy metal lead induces a lower response to FGF-2 by inhibition of perlecan synthesis and inhibits the proliferation of the cells. The present study was undertaken to address the question whether lead influences the formation of HS chains in vascular endothelial cells. The data indicate that lead decreases the amount of disaccharide units including hexuronic acid-N-acetylglucosamine, hexuronic acid-N-sulfated glucosamine and 2-O-sulfated hexuronic acid-N-sulfated glucosamine in HS chains accumulated in the cell layer and the conditioned medium. However, no percentage of any disaccharide unit was affected by the metal. The percentage of disaccharide units in chondroitin/dermatan sulfate was also unaffected by lead. The present data support the hypothesis that lead-induced lower response of vascular endothelial cells to endogenous FGF-2 mainly results from a decrease in perlecan molecules of extracellular matrix as a result of selective inhibition of perlecan core protein synthesis rather than a change in the HS structure.

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Biochemical changes that occurred in the blood of myocardial infarction patients were investigated. Two hundred and fifty two patient, 180 males and 72 females were involved in this study. The mean age was 49.3 ± 9.25 years. Biochemical parameters including serum total protein, albumin, total bilirubin, and total cholesterol to albumin ratio were analyzed. Biochemical parameters showed that the increased level of triglyceride and total bilirubin were associated with myocardial infarction. Triglyceride and total bilirubin levels in myocardial infarction patients were 2.3 ± 1.4 mmol/l and 12.3 ± 3.2 μmol/l respectively, whereas those of healthy controls were 1.7 ± 1.2 mmol/l for triglyceride and 9.7 ± 3.7 μmol/l for bilirubin. On the other hand, serum total protein and albumin concentrations were lower in myocardial infarction patients compared with those of controls. Total protein level was 65.5 ± 3.1 g/l in myocardial infarction patients and 76.2 ± 5.3 g/l in healthy controls. Albumin levels in both patients and controls were 40.2 ± 3.2 g/l and 45.4 ± 4.5 g/l correspondingly. Interestingly, serum total cholesterol level was not significantly different in myocardial infarction patients compared with controls. Patients cholesterol level was 5.8 ± 1.3 mmol/l and that of controls was 5.2 ± 1.2 mmol/l. In addition, cholesterol/albumin ratio in infarction patients (0.14 ± 0.04) found to be significantly higher than that in healthy controls (0.11 ± 0.03).

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Tofuyo is a fermented soybean curd that has angiotensin I-converting enzyme (ACE) inhibitory activity in vitro. The aim of this study was to examine the antihypertensive and hypocholesterolemic effects of tofuyo in vivo. Spontaneously hypertensive male rats at 8 weeks of age were fed a diet containing lyophilized tofuyo for 6 weeks. At 13 weeks of age, the systolic blood pressure of rats in the tofuyo group was significantly lower than that in the control group. After feeding the experimental diets, the ACE activity of kidney was significantly lower in the tofuyo group than that in the control group. Total cholesterol in serum in the tofuyo group was significantly lower while the ratio of high density lipoprotein (HDL) to total cholesterol in the tofuyo group tended to be higher than that in the control group.

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To investigate whether long-term ingestion of guava juice has anti-diabetes and/or anti-obese actions, we employed spontaneous non-insulin-dependent diabetes mellitus Otsuka Long-Evans Tokushima Fatty (OLETF) rats and its control strain Long-Evans Tokushima Otsuka (LETO) rats. Thirty rats of each strain were divided into three groups consisting of glucose, vitamin E, and guava juice ingestion groups. Ingestion of these test solutions was continued from 9 to 32 weeks old. Serum lipid parameters including total cholesterol, triglyceride, free fatty acid, and high-density lipoprotein (HDL)-cholesterol were measured. Oral glucose tolerance test (OGTT) was performed at 32 weeks old rats and at 42 weeks old rats (10 weeks after discontinue of ingestion of guava juice), and then blood glucose levels and plasma insulin concentrations were measured. There were no significant differences in body weight, the amount of food intake and the volume of drink among the groups in OLETF rats. Although the blood glucose level in the guava juice group was not changed as compared with the glucose group, the amount of initial insulin secretion was significantly increased in OLETF rats and was restored by discontinue of ingestion of guava juice. Therefore, the long-term ingestion of guava juice may increase plasma insulin concentration in OLETF rats.

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A four-period crossover study was conducted to evaluate the dose-related response of daily cocoa intake on the oxidative susceptibility of low-density lipoprotein (LDL) in healthy human volunteers. Each supplementation phase consisted of a 14-day feeding period followed by a 28-day washout period. During the period, healthy male volunteers (n = 8) ingested 18, 24 or 36 g of cocoa powder per day (1.3, 1.74 or 2.61 g of polyphenols per day). During the control period, these subjects ingested sugar. LDL oxidative susceptibility was measured as the lag time of conjugated diene formation that started with the addition of a radical initiator, 2,2′-azobis (4-methoxy-2,4-dimethylvaleronitrile). Samples were analyzed at pre-, one week, and two weeks post-supplementation. In the 24 and 36 g cocoa powder ingestion period, significant lag time prolongation was observed. We conclude that the ingestion of more than 24 g of cocoa powder per day (1.74 g of polyphenols) clearly protects LDL from oxidation.

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The in vitro binding assay seems to be a useful first screening method for endocrine disrupting chemicals. Various methods have been developed and applied to the testing of chemicals. Since these assays should be applied to estrogen receptors (ER) of not only humans but also wildlife, we previously developed a standardized in vitro binding assay system for human, quail, Japanese medaka, and Xenopus laevis ERs using a competitive enzyme immunoassay. Since that was a first report on an in vitro binding assay system for Xenopus ERα, and the capacities of chemicals to bind Xenopus ERα were not tested yet, we here evaluated the ability of 20 test chemicals, which were selected by the Ministry of the Environment of Japan, to bind Xenopus ERα. Of these, 4-nonylphenol, p-octylphenol and bisphenol A had relatively high binding capacity, and these results are similar to those obtained previously in quail ERα.

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Hydroxysteroid sulfotransferase (HS-ST) is thought to be a key enzyme in the synthesis of neurosteroid sulfates, which are known to act as potent regulators of neuronal activity within the brain. In rat liver, three isoforms of HS-ST (ST2A1, ST2A2 and ST2A5) have now been identified and to further elucidate the precise contribution of each of these variants in neurosteroid sulfation in rat brain, we analyzed the expression of their transcripts in different brain regions using isoform-specific RT-PCR. The expression of ST2A1 was found exclusively in the olfactory bulb and ST2A2 expression levels were most abundant in the hippocampus, but no ST2A5 expression was detectable in any brain region. We then measured the HS-ST activity in these same regions and detected low but significant activity levels in the olfactory bulb and hippocampus, but less activity in the cortex. These activity levels were found to correlate with the mRNA levels of the HS-ST isoforms. Our findings will further our understanding of the physiological role of HS-ST enzymes within the brain, particularly how they affect neurosteroid metabolism and modulate neuronal activity.

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