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1,3,5-Trichloro-2-(4-nitrophenoxy)benzene in fish, shellfish, and seawater in Tokyo Bay, 1977-1979.

Concentrations of 1,3,5-trichloro-2-(4-nitrophenoxy)benzene (CNP) were measured in goby-fish, sea bass, shellfish, and seawater samples collected in the coastal waters of Tokyo Bay. The concentrations of CNP found in goby-fish were in the range of 2.6 to 91,400 ppb in liver, 0.1 to 360 ppb in muscle, trace to 2,900 ppb in short-necked clam, and not detectable to 1.9 ppb in seawater. Although the concentrations in the samples varied with time and place of sampling, the maximum levels were found in the samples obtained in May or June of 1977, 1978, and 1979.

Animals↗

Polychlorinated biphenyl residues in maternal and cord blood in Tokyo metropolitan area.

PCB levels were determined with maternal and cord blood sampled at the time of delivery. All of the twentyfour mothers selected for this experiment are residents to Tokyo Metropolitan area. Gaschromatographic patterns of PCBs in cord blood closely resembled those of mothers. The cord blood in general showed lower PCB levels on both whole and fat basis than those in the maternal blood. No correlation was noticeable on statistical basis as regards the concentrations of PCBs between the cord blood and maternal blood. Our data suggests that the passage of PCBs through the placenta follows general patterns observed in other organochlorine insecticides.

Adipose Tissue↗

Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area.

We examined 613 Toranomon Hospital patients with HCV RNA-positive chronic liver disease to elucidate the viral genotype in the Tokyo metropolitan area. An epidemiological and clinical study was conducted in the 565 patients whose HCV genotype could be determined. The HCV genotypes found were type II, in 414 patients (67.5%); type III, in 103 (16.8%); type IV, in 37 (6.0%); type V, in 4 (0.7%); mixed genotype II and III, in 5 (0.8%); and mixed genotype II and IV, in 2 (0.3%). The HCV genotype could not be determined in 48 patients. Type II was most prevalent. The HCV genotype I was not found at all. There were no significant differences between genotypes in relation to sex, age, history of blood transfusion, or the progression of the disease. It was uncommon to find a history of blood transfusion in the patients with mixed genotypes; however, a high incidence of hepatic disorders was noted among the family members of these patients. Ninety-two percent of the patients with HCV genotype II tested positive for C100-3, while 70.9% of those with type III, and 43.2% of those with type IV tested positive for this antibody. HCV genotype II was most prevalent, and the positivity rate for anti C100-3 in patients with this HCV genotype was significantly higher (P < 0.00001) than that in patients with the other genotypes.

Adolescent↗

Thyroid lesions and dioxin accumulation in the livers of jungle crows (Corvus macrorhynchos) in urban and suburban Tokyo.

Wild jungle crows (Corvus macrorhynchos) captured from three different areas of Tokyo were examined to evaluate environmental contamination of dioxins. In addition to the pathologic examination of their whole body, accumulation of dioxins, mRNA expression of the aryl hydrocarbon receptor (AhR), and pentoxyresorufin-O-depenthylase (PROD) activity in the liver were determined. Marked histopathologic changes were observed in the thyroid glands, especially in the crows from the urban downtown area. Levels of dioxins and their toxic equivalents (TEQs) and AhR mRNA expression in the livers of the crows from the urban area were higher than those from the suburban area. There was a high correlation between the levels of TEQs and PROD activity. The results of the present study demonstrated that jungle crows possess AhR-mediated toxicologic pathways similar to those of mammals and suggest the possibility that the thyroidal changes observed in the adult crows from the urban areas are one of the toxic manifestations resulting from exposure to dioxins and other environmental chemicals.

Age Factors↗

Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack.

Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

Acute Disease↗

Incidence of von Hippel-Lindau disease in hemangioblastoma patients: the University of Tokyo Hospital experience from 1954-1998.

BACKGROUND: Incidence of von Hippel-Lindau disease among hemangioblastomas is important clinical information affecting the management of hemangioblastomas. Studies from Western countries reported 36-40% for the incidence, but no report has been made on the Japanese population. METHOD: To investigate the incidence in Japan, we retrospectively analyzed all hemangioblastoma patients treated at The University of Tokyo Hospital from 1954 to 1998. By reviewing medical records and imaging studies, von Hippel-Lindau disease was diagnosed clinically following the currently suggested diagnostic criteria. FINDINGS: There were 82 hemangioblastoma patients recorded during the period, and 14 cases (17%) were compatible with von Hippel-Lindau disease. However, when the incidence was calculated for each of the three 15-year periods, which are 1954-1968 (first), 1969-1984 (second), and 1985-1998 (third), the number increased dramatically in the later periods: 2 of 33 (6%) during the first, 4 of 26 (15%) during the second, and 8 of 22 (36%) during the third period. Such increase occurred after the introduction of whole body CT to our institution in 1981, suggesting that improvement of imaging techniques contributed to the sensitivity of diagnosis. In addition, one recent patient with multiple hemangioblastomas was found to harbor germline mutation of the VHL, thereby being diagnosed as von Hippel-Lindau disease on the basis of molecular genetics. INTERPRETATION: The 40% incidence of von Hippel-Lindau disease in hemangioblastomas suggests that extensive screening for von Hippel-Lindau disease associated neoplasms, and probably molecular genetic examination, is indicated for all patients with hemangioblastomas, which should aim for earlier diagnosis and better management of this devastating hereditary disease.

Adolescent↗

Frequency of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in 19 clinical isolates of Neisseria gonorrhoeae in Tokyo in 2002.

The frequency of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in 19 clinical isolates of Neisseria gonorrhoeae obtained in Tokyo in 2002 was studied. The frequencies of GyrA and ParC mutations in these 19 isolates were 100% (19 of 19) and 84.2% (16 of 19), respectively, and these results were 1.48-fold (100%/67.6%) and 3.58-fold (84.2%/23.5%) higher, respectively, than the frequencies reported in 1998 in 68 isolates obtained in Fukuoka during the period from 1992 to 1996. Isolates with increasing numbers of mutations were more resistant not only to levofloxacin but also to other antibiotics. The 50% and 90% minimum inhibitory concentrations (MICs) to levofloxacin during the period from 1995 to 1996 were 0.063 and 1 micro g/ml, and they increased to 4 and 8 micro g/ml, respectively, in the present study. All 19 cases of gonoccocal urethritis in the present study were cured with a single intramuscular injection of 2 g spectinomycin.

Anti-Bacterial Agents↗

Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies.

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], > or =16 microg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 microg/ml (MIC90 32 microg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 microg/ml (MIC90, 64 microg/ml). Meropenem (MIC range, < or =0.25 to 16 microg/ml) was more active than panipenem (MIC range, 2 to 64 microg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Anti-Bacterial Agents↗

Incidence of hydatidiform mole in a Tokyo hospital: a 5-year (1989 to 1993) prospective, morphological, and flow cytometric study.

This prospective study reports the incidence of hydatidiform mole (HM) in a population of 13,510 pregnancies in a Tokyo hospital over a 5-year period between 1989 and 1993. During this period all "products of conception" from first- and second-trimester abortions were histologically reviewed, and 76 hydropic placentas were retrieved and analyzed by flow cytometry (FCM). Of 23 specimens originally diagnosed as complete hydatidiform mole (CM), 21 were diploid, and two were aneuploid (nontriploid/tetraploid). Of 22 partial hydatidiform moles (PMs), 20 were triploid, and two were diploid. Of 31 hydropic abortions (HAs), 20 were diploid, nine were triploid, one was tetraploid, and one was aneuploid. As to the correlation between morphology and data of FCM, two PMs were reclassified as HA, and eight HAs as PM, giving a ratio of 1 CM to 1.22 PM (23:28 cases). The incidence of HM was 1:265 pregnancies, (CM, 1:587; PM, 1:483). Only one case (3.6%) of PM was suspected clinically. One specimen of persistent disease occurred following a diploid CM. In our retrospective histological and FCM study in which 172 cases diagnosed as HM were retrieved from surgical pathology files between 1981 and 1991, there were 129 CMs and 43 PMs (CMs:PMs = 3:1). These findings indicate that PM is a common but underdiagnosed condition. Almost all studies in the literature may have severely underreported the incidence of PM. It is suggested that during routine delivery and pathology examination only the most florid PMs are recognized, whereas most with subtler changes go undiagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in street dust from the Tokyo Metropolitan area.

Molecular distributions of polycyclic aromatic hydrocarbons (PAHs) in street dust samples collected from the Tokyo Metropolitan area were determined by capillary gas chromatography following HPLC fractionation. Three- to six-ring PAHs and sulfur-heterocyclics were detected. PAHs in the dusts were dominated by three and four unsubstituted ring systems with significant amounts of their alkyl homologues. PAHs were widely distributed in the streets, with concentrations (sigma COMB) of a few microgram/g dust. Automobile exhaust, asphalt, gasoline fuel, diesel fuel, tyre particles, automobile crankcase oils, and atmospheric fallout were also analysed. The PAH profile, especially the relative abundance of alkyl-PAHs and sulfur-containing heterocyclics, indicated that PAHs in the street dusts from roads carrying heavy traffic are mainly derived from automobile exhausts; dusts from residential areas have a more significant contribution from atmospheric fallout.

Chromatography, High Pressure Liquid↗

Mutagenicities of Bangkok and Tokyo river waters.

Samples of water from the Chao Phraya river and some connected canals in Bangkok, Thailand, and from the Sumida and Ara rivers in Tokyo, Japan, were tested for mutagenicity using blue rayon to adsorb the mutagens. The samples from the Chao Phraya river and connected canals at sites located 50-150 km from the river mouth taken in May 1993 showed a mutagenicity of 87-1213 revertants per 0.05 g blue rayon extract towards S. typhimurium YG1024 in the presence of S9 mix. Samples from most sites taken in December 1993, which follows the rainy season, showed a lower mutagenicity than those taken in May, possibly due to dilution by the larger volume of water in the river and canals in December. Water samples from the Sumida river were collected in July 1993 and February 1994, and those from the Ara river in January 1994. Mutagenicity of samples from all sites of the Sumida and Ara rivers, which were located 2-30 and 2-20 km, respectively, from the river mouth was also clearly detected in the presence of S9 mix and did not differ much, being 155-748 revertants of YG1024 per 0.05 g blue rayon extract. These results demonstrated that the water in all three rivers contained some frameshift mutagens.

Frameshift Mutation↗

Health and its determining factors in the Tokyo megacity.

This study was designed to (i) analyze community health in post-industrial, densely populated Tokyo, and (ii) find a statistical-based prediction model for the health level of the communities from the environment. For this purpose, we compiled health-level indicators for each city-ward, and indicators for demography, infrastructure, land-use, amenities, education, working conditions, economics, and medical and welfare services. The health factors and the environmental factors were obtained by using weighted principal factor analysis; their relation was examined by weighted correlation analysis and weighted linear regression analysis. One to six environmental factors correlating significantly to health were found for each health-level indicator or factor. The prediction model explained up to 0.98 of the variance of the health-level factors and indicators. This analysis elicited health-determinant factors in various fields. The community health level was well reproduced by the present method; the model will be conducive to decision making pertaining to health policies.

Aged↗

Incidence of congenital malformations in Tokyo Metropolitan Hospitals, 1979-1993.

Congenital malformations in all babies delivered at 11 Tokyo Metropolitan Hospitals (TMH) (8 hospitals since July 1989) for 15 years, January 1979 to December 1993, were monitored. Congenital malformations found within 7 days after birth were observed in 2085 babies (1.5%) of 138,544 births including stillbirths after 16 weeks gestation. The prevalence rates of selected malformations were calculated and compared in the 5-year periods of 1979-1983, 1984-1988 and 1989-1993. There was no typical secular trend in prevalence rates of malformations except for the heart and circulatory system, which showed an increase because of the recent progress in prenatal diagnosis of these malformations. The specificity of the TMH Monitoring System is also discussed.

Congenital Abnormalities↗

Dioxin concentration in human milk in Hebei province in China and Tokyo, Japan: potential dietary risk factors and determination of possible sources.

Very limited information is available on body burdens and environmental levels of dioxins and dioxin-like PCBs (dl-PCBs) in mainland China. In the current studies, human milk samples were collected from 30 breastfeeding mothers in Shijiazhuang city (industrialized) and 11 in the Tanshan countryside (agricultural) of Hebei Province in northern China. An additional 20 samples were obtained from mothers in Tokyo, Japan. PCDDs, PCDFs, and dl-PCBs in human milk were analyzed by high-resolution gas chromatography/high-resolution mass spectrometry. Our results show that arithmetic means for body burdens of PCDDs/Fs and dl-PCBs in Hebei were 3.6 and 1.9 pg TEQg(-1) fat, respectively, which were only about one fourth of the levels in Japan. In addition, no difference was found in the chemical levels except dl-PCBs between the urban and rural areas. Based on the results of an in-person interview of the Chinese mothers using a 59-item questionnaire, freshwater fish consumption was found to correlate with the body burden of dioxins. Principal component analysis of dioxin congeners revealed that the patterns of dioxins in the Hebei urban and rural areas are quite similar; however, they are clearly different from those in Japan. Collectively, our results suggest that the lower body burdens of dioxin in Hebei may be due in part to the relatively slow industrialization and a lower consumption of marine foods. Finally, the results indicate that comprehensive monitoring of dioxins and dl-PCBs in humans as well as in the environment and foods is necessary in China.

Adult↗

The input-output balance of cadmium in a paddy field of Tokyo.

Field monitoring was practiced from 2001 to 2003 to evaluate the input (irrigation, atmospheric deposition, and fertilizer application) and the output (uptake and accumulation into the above-ground biomass of rice plants and leaching) of cadmium (Cd) in a contaminated paddy field in Tokyo. The cadmium concentrations of irrigated water, open-bulk precipitation, soil solution (leaching water), rice plants collected at the harvesting stage and the chemical fertilizer and the cow manure compost applied were determined. The Cd flux of each factor was calculated by multiplying the Cd concentration by the volume or mass of the media. The annual input-output balance of Cd in the paddy field in 2001 and 2002 was estimated to be -5.44 [corrected] g ha(-1) and -2.01 [corrected] g ha(-1), respectively, indicating the loss of Cd from the paddy field, although the losses accounted for only 0.24% [corrected] and 0.089% [corrected] of the total amount of Cd in the ploughed layer soil in 2001 and 2002, respectively. Among the factors involved, the input from fertilizers (including manure compost) and the output due to the uptake by rice plants played a major role in the balance. The former largely depended on the types and amounts of fertilizers applied, and the latter on the water management practices in the paddy field, such as flooding and drainage of the surface water.

Animals↗

The relationship between obesity and seasonal variation in body weight among elementary school children in Tokyo.

Typical patterns of seasonal variation in body weight among Japanese children involve increases during the fall and/or winter and decreases during the summer. However, atypical variations, namely, increases in weight during the summer, have been reported for obese children. The present study examines whether weight gain during the summer (i.e., July through September) is a possible cause of obesity. We examined seasonal changes in weight for 446 elementary school children in Tokyo in six waves between 1972 and 2004. Weight was measured monthly for 6 years in each child and was evaluated by means of time-series analysis. Overall, significant seasonal variations in weight were found in 86% of the children, most of which were typical (i.e., decreases during the summer and increases during the fall, winter, and/or early spring). On the other hand, weight gain in the summer was observed exclusively among obese children. Children whose weight increased during the summer holiday spent most of their time comfortably indoors because of air conditioners, which became popular in 1970s. A possible explanation of the observed weight gain during the summer seems to be changes in life style associated with the use of air conditioning, concomitant with insufficient physical exercise and excessive consumption of food and drink, which could disturb the rhythms of seasonal weight changes and lead to obesity.

Child↗

Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo sarin disaster 3 years after the event.

We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway sarin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and N,N-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls.

Adult↗

Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment.

We measured six acidic analgesics or anti-inflammatories (aspirin, ibuprofen, naproxen, ketoprofen, fenoprofen, mefenamic acid), two phenolic antiseptics (thymol, triclosan), four amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide), three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol, bisphenol A), and three natural estrogens (17beta-estradiol, estrone, estriol) in 24-h composite samples of influents and secondary effluents collected seasonally from five municipal sewage treatment plants in Tokyo. Aspirin was most abundant in the influent, with an average concentration of 7300 ng/L (n = 16), followed by crotamiton (921 ng/L), ibuprofen (669 ng/L), triclosan (511 ng/L), and diethyltoluamide (503 ng/L). These concentrations were 1 order of magnitude lower than those reported in the USA and Europe. This can be ascribed to lower consumption of the pharmaceuticals in Japan. Aspirin, ibuprofen, and thymol were removed efficiently during primary + secondary treatment (> 90% efficiency). On the other hand, amide-type pharmaceuticals, ketoprofen, and naproxen showed poor removal (< 50% efficiency), which is probably due to their lower hydrophobicity (logKow < 3). Because of the persistence of crotamiton during secondary treatment, crotamiton was most abundant among the target pharmaceuticals in the effluent. This is the first paper to report ubiquitous occurrence of crotamiton, a scabicide, in sewage. Because crotamiton is used worldwide and it is persistent during secondary treatment, it is a promising molecular marker of sewage and secondary effluent.

Endocrine Disruptors↗