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Biomedical subjects

J Nakanishi

Publications and source records attributed to J Nakanishi.

At least 19 recordsLinked to original sources

Polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls in livers of birds from Japan.

Concentrations of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non- and mono-ortho-chlorine-substituted polychlorinated biphenyls (dioxin-like PCBs) were measured in livers of 17 species of birds collected from Japan. Birds were grouped according to their feeding habits as granivores, piscivores, omnivores, and predators for discussions. Livers of granivores contained relatively low concentrations of PCDD/DFs (80-660 pg/g) followed in increasing order by omnivores (2,300-8,000 pg/g), piscivores (61-12,000 pg/g) and predators (480-490,000 pg/g on a fat weight basis). Especially, one species of predatory bird (mountain hawk eagle) contained elevated concentrations of PCDDs, PCDFs, and dioxin-like PCBs, and the measured concentration is one of the highest reported to date. Homolog and congener patterns of PCDDs and PCDFs varied among species; hence, the results suggested that feeding habits, specific elimination, and metabolism influence contamination pattern. Concentrations of dioxin-like PCBs were in the order of granivores (32-83 ng/g) < predators [excluding mountain hawk eagle] (32-2,500 ng/g) < piscivore (61-12,000 ng/g) < omnivores (1,800-67,000 ng/g on a fat weight basis). Mountain hawk eagle contained the highest concentration of dioxin-like PCBs (55,000 ng/g fat weight). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQs) ranged from 53-450,000 pg/g fat weight. 23478-PeCDF, 2378-TCDD/TCDF, and PCB congeners IUPAC 126 and 77 were major contributors to TEQs in birds. To our knowledge, this is the first study of PCDD/DFs and dioxin-like PCBs in livers of several species of Japanese birds.

Animals↗

Polychlorinated dibenzo-p-dioxins, dibenzofurans, and polychlorinated biphenyls in human tissues, meat, fish, and wildlife samples from India.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non- and mono-ortho-substituted polychlorinated biphenyls (dioxin-like PCBs) were measured in tissues of humans, fishes, chicken, lamb, goat, predatory birds, and Ganges River dolphins collected from various locations in India. PCDDs/DFs were found in most of the samples analyzed with the liver of spotted owlet containing the highest concentration of 3,300 pg/g, fat wt. 2,3,7,8-Substituted PCDDs and PCDFs were found in human fattissues at concentrations ranging from 170 to 1,300 pg/g, fat wt. Concentrations of PCDDs were generally greaterthan those of PCDFs in human tissues, fishes, animal fat, and dolphin. Among fishes, meat, and wildlife samples analyzed, concentrations of PCDDs/DFs were found in the following order: country chicken < goat/lamb fat < fishes < river dolphins < predatory birds. Hepta-CDDs and OCDD were the major PCDD homologues found in humans, fishes, meat products, and dolphins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin equivalents of PCDDs/DFs were greater than those of PCBs in selected fish, dolphin, and human samples. To our knowledge, this is the first report of PCDDs and PCDFs in human tissues, fishes, meat, and wildlife collected from India.

Adult↗

Cost effectiveness of reducing dioxin emissions from municipal solid waste incinerators in Japan.

The main sources of dioxin emissions are municipal solid waste incinerators. The Japanese national government has set an emission standard for dioxins to reduce dioxin exposure levels. In this study, cost-effectiveness analyses are carried out regarding countermeasures that were recently taken and are being taken at municipal solid waste incinerators in Japan. Annual costs were estimated by telephone survey and model calculations. Annual decrease in the incidence of cancer was estimated in three steps. First, the annual decrease in the volume of dioxin emissions was estimated. Next, using a mathematical model, the annual decrease in human exposure was estimated. Finally, the annual decrease in the incidence of cancer was estimated by applying the cancer slope factor. When annual costs are divided by the annual number of life-years saved, cost per life-year saved (CPLYS) was obtained. CPLYS was estimated to be 7.9 million yen for emergency countermeasures and 150 million yen for long-term countermeasures. However, it must be noted that these obtained CPLYSs are highly dependent on the cancer slope factor and should be considered as an upper limit since there may be a cancer effect threshold.

Air Pollution↗

Imaging of conformational changes of proteins with a new environment-sensitive fluorescent probe designed for site-specific labeling of recombinant proteins in live cells.

We demonstrate herein a new method for imaging conformational changes of proteins in live cells using a new synthetic environment-sensitive fluorescent probe, 9-amino-6,8-bis(1,3,2-dithioarsolan-2-yl)-5H-benzo[a]phenoxazin-5-one. This fluorescent probe can be attached to recombinant proteins containing four cysteine residues at the i, i + 1, i + 4, and i + 5 positions of an alpha-helix. The specific binding of the fluorescent probe to this 4Cys motif enables fluorescent labeling inside cells by its extracellular administration. The high sensitivity of the fluorophore to its environment enables monitoring of the conformational changes of the proteins in live cells as changes in its fluorescence intensity. The present method was applied to calmodulin (CaM), a Ca2+-binding protein that was well-known to expose hydrophobic domains, depending on the Ca2+ concentration. A recombinant CaM fused at its C-terminal with a helical peptide containing a 4Cys motif was labeled with the fluorescent probe inside live cells. The fluorescence intensity changed reversibly depending on the intracellular Ca2+ concentration, which reflected the conformational change of the recombinant CaM in the live cells.

Amino Acid Sequence↗

Identifying sources and mass balance of dioxin pollution in Lake Shinji Basin, Japan.

On the basis of congener-specific analysis of dioxins in a dated sediment core, the sources and behavior of dioxins in Lake Shinji Basin, Japan, were estimated. The dioxins in the core showed that their deposition in the lake increased rapidly during the 1960s, peaked in the early 1970s, and then decreased gradually. Principal component analysis of the congener-specific data showed that three major sources existed: pentachlorophenol (PCP), chloronitrophen (CNP), and combustion. PCP and CNP are paddy field herbicides used extensively in the basin. The time trends of source contributions were estimated by multiple regression analysis using the source profiles. The results revealed that dioxin emission from PCP and CNP herbicides was high in the 1960s and the early 1970s, respectively. The contributions from PCP, CNP, and combustion in recent surface sediment were about 68, 16, and 16% in terms of total amount of dioxins. From the decreasing trend of dioxin deposition in the lake after extensive herbicide use, the amount of dioxins that accumulated in the agricultural soil in the basin was estimated to have decreased by about 2%/yr or a half-life of about 35 yr, indicating that dioxin runoff from agricultural fields would continue for a long time.

Agriculture↗

Effect of linear alkylbenzene sulfonate on population growth of Daphnia galeata: a life table evaluation.

The chronic effect of linear alkylbenzene sulfonate (LAS12) on a daphnid species (Daphnia galeata) was examined by the life table experiment. The estimated responses in the intrinsic rate of population growth r were analyzed with two alternate concentration-response functions, i.e., the power function and the quadratic function. Based on the best-fit power function model with biases corrected by the jackknife procedure, the population-level EC50, which is defined as the concentration of chemicals that reduces the population growth rate (the intrinsic rate of natural increase) by 50%, was estimated as 2.5 mg/L. The 48-h acute immobility test yielded EC50 of 4.6 mg/L. The population-level effect of LAS12 on this test species is considerably more sensitive than the acute lethal effects to neonates.

Age Factors↗

Dioxin and dioxin-like PCB impurities in some Japanese agrochemical formulations.

The profile and amount of dioxin impurity in agrochemicals were studied through detailed analysis of historic Japanese formulations. The chemicals analyzed include pentachlorophenol (PCP), 2,4,6-trichlorophenyl-4'-nitrophenyl ether (chloronitrofen, CNP), 2,4-dichlorophenyl-4'-nitrophenyl ether (nitrofen, NIP), tetrachloro-iso-phthalonitrile (chlorothalonil, TPN), 2-methyl-4-chloro-phenoxyacetic acid (MCP) and 2,4-dichlorophenoxyacetic acid (2,4-D). Among the six, two herbicides, PCP and CNP, produced during the 1960s and 1970s, contained very high concentrations of PCDD/DFs and TEQ. Others contained relatively low concentrations of PCDD/DFs. Dioxin-like PCB concentrations in all chemicals studied were low and their contributions to TEQ were negligible. The total dioxin emissions from the use of agrochemicals in Japan during the past 40 years (1955-1995) were estimated to be about a few hundred thousand kg of PCDD/DFs and 250 kg of WHO-TEQ from PCP and 190 x 10(3) kg of PCDD/DFs and 440 kg of WHO-TEQ from CNP. The major dioxin congeners present in PCP formulations were highly chlorinated PCDD/DFs that can be formed by the coupling of PCP and/or 2,3,4,6-tetrachlorophenol, and those in the CNP formulations were tetra- to hexa-chlorinated PCDD/DFs that can be formed from 2,4,6-trichlorophenol and/or 2,3,4,6-tetrachlorophenol.

Agriculture↗

Atmospheric deposition of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls in the Kanto Region, Japan.

The atmospheric bulk (dry and wet) deposition of dioxins was investigated at four locations (Tokyo, Yokohama, Tsukuba, and Tanzawa) in the Kanto region (in Japan) over one year using a stainless-steel pot. Annual average polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/PCDF) deposition fluxes were estimated to be from 450 to 1300 ng/m2/yr, and the annual average TEQ fluxes from 5.7 to 17 ng-TEQ/m2/yr at the four locations. The PCDD/PCDF deposition flux was higher in winter than in summer. The deposition flux could be related to ambient temperature, particularly for less chlorinated PCDDs/PCDFs, while the deposition flux is not necessarily related to the amount of precipitation. The PCDD/PCDF deposition flux increased as the particle deposition flux increased, for the winter samples. Based on the ratio of the PCDD/PCDF deposition fluxes to the particle deposition fluxes, the contribution of the reentrainment of soil particles to the TEQ of PCDD/PCDF deposition was considered to be negligible in this region. Based on the air concentrations monitored near our deposition sampling points by the municipalities, the ratio of the annual deposition flux to the annual average air concentration was roughly estimated to be 0.082 cm/s. The range of deposition flux in the Kanto region was estimated to be from 1.5 to 31 (median: 9.8) ng-TEQ/m2/yr based on the range of air concentration data measured by the municipalities. The total annual deposition flux in the entire Kanto region was estimated to range from 50 to 900 g-TEQ/yr (median 320 g-TEQ/yr). This estimated flux was of the same order as the sum of estimated emissions from municipal solid waste incinerators and industrial waste incinerators in the Kanto region. The contributions of dioxin-like PCBs in Yokohama, Tsukuba, and Tanzawa depositions were less than 10% of the total TEQ; however, in Tokyo it was almost equal to or more than 50%.

Air Pollutants↗

Congener-specific characterization of PCDDs/PCDFs in atmospheric deposition: comparison of profiles among deposition, source, and environmental sink.

In order to examine the input of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) from various airborne sources to environmental sinks, the atmospheric deposition of congener-specific PCDDs/PCDFs was investigated. Homologue and congener profiles of atmospheric depositions were compared with those of sources and environmental sinks to identify the relationship among atmospheric depositions, sources, and environmental sinks. Moreover, factor analysis was used to detect similarities, differences, and relationships of the variations in deposition fluxes among congeners within the same and different homologues. The results showed that the congener profiles of the atmospheric depositions were primarily determined by those of combustion emissions. Several congeners in some specific samples showed higher proportions within each homologue compared with representative depositions. This result can be partly explained by the influence of impurities in herbicides, 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP) and pentachlorophenol (PCP). The congener profiles of combustion emissions, representative depositions, and urban soils were very similar although their homologue profiles varied. This implied that PCDDs/PCDFs in the urban soils originate from the deposition of combustion emissions and that all congeners within each homologue behave identically in air and soil. Although the congener profiles of the representative depositions were different from those of the sediments in Tokyo Bay and the soil of a paddy field, the combination of congener profiles of the representative depositions and of the impurities in herbicides. CNP and PCP, can explain the congener profiles of the sediments and the paddy field. This study showed that congener-specific data are useful for source identification.

Agriculture↗

Validation of modeling approach to evaluate congener-specific concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans in air and soil near a solid waste incinerator.

A concise modeling approach using long-term averaged meteorological data was developed to estimate site-specific concentrations of congeners of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) near a solid waste incinerator. This approach consists of calculation of atmospheric dispersion, dry and wet deposition of gaseous and particle-bound congeners, and non-steady-state concentrations in soil. The predictability of this approach was evaluated by comparison of calculated concentrations of congeners in soil with those measured at eight locations near a municipal solid waste incinerator (MSWI). The variation of these concentrations due to variability of meteorological parameters is small. A considerable number of mean values show good agreement with measured concentrations within a factor of three. The reasonable agreement between calculated and measured concentrations indicates that algorithms for the calculation of vapor-phase deposition and non-steady-state concentrations in soil must be included in the modeling approach for an accurate estimation of the concentrations of congeners of PCDD/Fs emitted from MSWIs to the atmosphere. For a detailed estimation of site-specific concentrations, it is important to specify the bulk density of soil in the evaluated area, together with meteorological parameters.

Air Movements↗

Mercury pollution in the Tapajos River basin, Amazon: mercury level of head hair and health effects.

There is increasing concern about the potential neurotoxic effects of exposure to methylmercury for the 6 million people living in the Amazon, even in regions situated far away from the gold mines (garimpos), considered to be the major source of mercury pollution. In November 1998, a spot investigation on mercury contamination was conducted in three fishing villages (Barreiras, Rainha, and Sao Luiz do Tapajos) on the Tapajos River, an effluent of the Amazon, situated several hundred kilometers downstream from the gold-mining areas. A total of 132 fishermen and their families volunteered for the current study. As was anticipated, the total mercury levels in the head hair collected from the fishing villages were relatively high (14.1-20.8 ppm on the average) and the number of subjects with a high total mercury level over 10 ppm (the least upper bound of a normal value) was 103 (78.0%) in total, along with various symptoms, thereby suggesting wide mercury contamination in the Tapajos River basin. Moreover, in view of the absence of other diseases (e.g., alcoholism or malaria), a high intake of fish containing a methylmercury level, and high hair mercury levels in addition to the various symptoms such as sensory disturbance (especially glove-and-stocking type, which is characteristic of Minamata disease), tremor, failure in two-point discrimination, and slight balancing failure, several subjects examined were diagnosed with mild Minamata disease. The findings obtained suggest, thus, that the mercury pollution in the Amazon should be crucially observed for head hair mercury level and health in a much broader region.

Adolescent↗

Model selection and parameterization of the concentration-response functions for population-level effects.

As concentration response functions for chronic population-level effects of pollutant chemicals, three mathematical models were presented and examined for goodness of fit to published toxicological data that estimated the population-level effects of chemicals in terms of the intrinsic rate of population growth (r). Among the examined concentration-r functions, the power function model, that is, r(x) = r(0)[1 - (x/alpha)beta], in which x is the exposure concentration and alpha and beta are parameters, performed with the best fit to each data set. The power function model is characterized by two parameters representing the absolute value of toxicity, alpha, and the curvature of responses, beta. The bootstrap simulation, conducted on the entire data set consisting of all published data that we collected, indicated that the observed variance of beta among actual data sets could be mostly explained by the random error variation generated from the bootstrap resamplings. The generic beta value, determined from the entire data set and expected to denote the best estimate of beta if the variability of beta was completely due to random sampling error, was estimated as 1.84. It was implied that the response of the intrinsic rate of natural increase (r) to chemical exposure was nearly quadratic in many cases.

Animals↗

Polychlorinated naphthalenes, biphenyls, dibenzo-p-dioxins, and dibenzofurans as well as polycyclic aromatic hydrocarbons and alkylphenols in sediment from the Detroit and Rouge Rivers, Michigan, USA.

Sediment from the upper Detroit and lower Rouge Rivers in southeastern Michigan, USA, were analyzed to examine the distribution of polychlorinated naphthalenes (PCNs), biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) as well as polycyclic aromatic hydrocarbons (PAHs) and alkylphenolic compounds such as butylphenol, octylphenol, and nonylphenol (NP). Sediments from a non-point source location in Lake Michigan were also analyzed for target compounds. Concentrations of target compounds in the upper Detroit and lower Rouge Rivers varied considerably among locations, and notable spatial variation existed. Concentrations of PCNs and PCDDs/PCDFs in sediments from the upper Detroit and lower Rouge Rivers ranged from 0.08 to 187 ng/g and 69 to 1420 pg/g dry weight, respectively. Total PCBs, PAHs, and NP concentrations ranged from 8 to 25,000, 17 to 44,000, and < 10 to 60,000 ng/g dry weight, respectively. Concentrations of all target compounds except PCNs were significantly correlated with total organic carbon content of sediments. Similarly, concentrations of PCBs, PCDDs, and PCDFs were significantly correlated with each other. The distribution of organic contaminants in the upper reaches of the Detroit River and lower Rouge River suggested the presence of localized, but multiple, sources of contamination for each compound class. Conners Creek combined sewer overflow has been identified as one of the potential sources for the upper Detroit River, where the highest concentrations PCBs and PCDDs/PCDFs were found. Polycyclic aromatic hydrocarbon and NP concentrations were consistently high in sediment from the lower Rouge River. Analysis of data from selected locations suggested that PCNs contributed a greater proportion of the dioxin-like activity than PCBs and PCDDs/PCDFs contributed.

Benzofurans↗

Characterization of dioxin-like activity of sediments from a Czech river basin.

Synthetic organic chemicals are present in environmental compartments as complex mixtures and therefore their potential effects are difficult to predict. In this study, in vitro bioassays using wild-type fish and rat hepatoma cell lines and their corresponding recombinant cell systems were used to evaluate 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activity in extracts of sediments collected from rivers of the Czech Republic. All the sediment extracts elicited statistically significant responses in all the cell lines tested. For most sediment extracts, a complete dose-response relationship was obtained. The maximal efficacy of the samples was between 57 and 143% of the maximal induction elicited by TCDD. Greater responsiveness, sensitivity, and reproducibility were observed for recombinant than wild-type cells. Cell line-specific differences in the sensitivity to compounds present in the complex sediment extracts were observed. The TCDD equivalents (TCDD-EQs) determined from the different cell bioassays were correlated. Greater concentrations of TCDD-EQs were obtained with fish cell lines. The TCDD-EQs calculated from the results of chemical analysis of toxic equivalents (TEQs) were in good agreement with those determined by bioassays; the arly hydrocaron receptor (AhR)-effects of the identified chemicals appear to be generally additive. This indicates that most of the TCDD-like activity was accounted for by the compounds identified and quantified by instrumental analysis. Fractionation along with mass-balance calculations allowed identification of the active fractions and classes of compounds. Polycyclic aromatic hydrocarbons (PAHs) were found to be responsible for most of the AhR-mediated activity in sediments.

Animals↗

Comparing risk factors for population extinction.

Extinction risk of natural populations of animals and plants is enhanced by many different processes, including habitat size reduction and toxic chemical exposure. We develop a method to evaluate different risk factors in terms of the decrease in the mean extinction time. We choose a population model with logistic growth, environmental and demographic stochasticities with three parameters (intrinsic growth rate r, carrying capacity K, and environmental noise sigma(2)(e)). The reduction in the habitat size decreases carrying capacity K only, whilst toxic chemical exposure decreases survivorship (or fertility) and in effect reduces both r and K. We derived a formula for the reduction in habitat size that decrease the mean extinction time by the same magnitude as a given level of toxic chemical exposure. In a large population (large K) or in a slowly growing population (small r), a small decrease in survivorship can cause the extinction risk increase corresponding to a significant reduction in the habitat size. This conclusion depends also on the nonlinearity of dose-effect relationship. To illustrate the method, we analyse a freshwater fish, Japanese crucian carp (Carassius auratus subsp.) in Lake Biwa.

Animals↗

Assessment of human health risk of dioxins in Japan.

The human health risk of dioxins was evaluated for four Japanese receptor groups: the general population, local residents living near a municipal solid waste incinerator, heavy fish consumers, and their infants and fetuses. In describing the risk for these groups, four endpoints, namely, cancer, reproductive dysfunction, endometriosis and neurobehavioral effect, were considered, and the incremental cancer risk and margin of exposure (MOE) corresponding to these endpoints were calculated, based on three measures of dosimetry; average daily intake, area under the curve, and body burden. The uncertainties of these risk descriptors were also evaluated by probabilistic analysis. Although the estimated risk of cancer and reproductive dysfunction were not exceptionally high in the three adult receptor groups, the MOE values for endometriosis were not sufficiently high to guarantee safety against this endpoint. Furthermore, the MOE values for neurobehavioral effects on infants and fetuses suggest that dioxins may cause a considerable risk to those of local residents and heavy fish consumers.

Adult↗

Polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment, soil, fish, shellfish and crab samples from Tokyo Bay area, Japan.

Concentrations of tetra- to octa-chlorinated dibenzo-p-dioxins and dibenzofurans in samples collected in or near Tokyo Bay, Japan, with a densely inhabited catchment area, were congener-specifically determined and discussed. Analyzed in this study were samples of surface sediment covering the whole bay area, reference soil representing atmospheric impact, and fish, shellfish and crab commonly consumed as food. The range of concentrations were comparable to or higher than those in other parts of Japan. The origins of these compounds in the catchment area of the bay were investigated in terms of homolog and isomeric compositions in the sediment samples. Biota-sediment accumulation factors for benthic species declined as the degree of chlorination increased.

Animals↗

A method for evaluating chemical selectivity of agonists for glutamate receptor channels incorporated in liposomes based on an agonist-induced ion flux measured by ion-selective electrodes.

A new method for evaluating chemical selectivity of agonists for the NMDA subtype of glutamate receptor (GluR) channels is described. The method is based on the magnitude of Ca2+ release from GluR-incorporated liposomes, which is measured by a Ca2+ ion-selective electrode with a thin-layer mode. The partially purified GluRs from rat whole brain were reconstituted into Ca2+-loaded liposomes. Small aliquots (each 50 microl) of the proteoliposomes, in the presence of an antagonist DNQX for blocking non-NMDA subtype, were subjected to potentiometric measurements of Ca2+ release under stimulation by three kinds of agonists, i.e. NMDA, L-glutamate and L-CCG-IV. The amount of the Ca2+ ion flux through the GluR channel induced by the agonists was found to increase in the order of NMDA < L-glutamate < L-CCG-IV, which was consistent with that of binding affinity of the agonists toward the NMDA subtype. However, the range of selectivity of the relevant agonists was much smaller compared with results based on binding affinities. The present method provides physiologically more relevant values for the agonist selectivity of GluRs as compared to that of the conventional binding assay in the sense that the selectivity is based on the very magnitude of Ca2+ flux through the NMDA receptor, i.e. the extent of signal transduction by a given agonist. The evaluation of agonist selectivity based on Na+ release was also investigated by using a Na+ ion-selective electrode, but agonist-induced Na+ release was not detected, because of low permeability of Na+ through the NMDA subtype.

Amino Acids, Dicarboxylic↗