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Estimation of 1999-2004 dietary daily intake of PCDDs, PCDFs and dioxin-like PCBs by a total diet study in metropolitan Tokyo, Japan.

A study of the dietary intake of dioxins, consisting of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) through foods retailed in the metropolitan Tokyo area from 1999 to 2004 was carried out by the total diet-market basket method on the basis of food classification (14 groups) and the data on food consumption in the Tokyo region obtained from the Japan Nutrition Survey. The daily intake of dioxins per kg of body weight for a 50 kg average adult body was 2.18 pg TEQ/kg/day in 1999, 1.87 pg TEQ/kg/day in 2000, 1.25 pg TEQ/kg/day in 2001, 1.60 pg TEQ/kg/day in 2002 and 2003 and 1.55 pg TEQ/kg/day in 2004, respectively. These amounts were less than the tolerable daily intake (TDI) of 4 pg TEQ/kg/day for dioxins established in Japan. The dioxins taken daily through fish and shellfish (group 10) accounted for more than 50% of sum WHO-TEQs. In addition, more than 90% of the daily intake of dioxins was taken through fish and shellfish (group 10), meat and eggs (group 11), milk and dairy products (group 12). Also, this study clearly showed that the ratio of dioxin-like PCBs in the daily intake of dioxins was increasing yearly because the reduction rate of dioxin-like PCBs was lower than that of PCDDs and PCDFs in foods.

Benzofurans↗

Horizontal distribution of steroid estrogens in surface sediments in Tokyo Bay.

A monitoring survey was conducted to investigate the distribution of steroid estrogens and their conjugates in surface sediments of Tokyo Bay for the first time, which is known as one of the most heavily polluted marine embayments in the world. The surface sediment samples were collected at 20 locations covering the whole area of Tokyo Bay and analyzed for steroid estrogens and their conjugates using liquid chromatography-tandem mass spectrometry. The concentrations of 17beta-estradiol (beta-E2) and estrone (E1) ranged from ND (below the detection limit; <0.07) to 0.59 and from 0.05 to 3.60 ng g-1 dry, respectively. Those concentrations were higher in the northern part of the bay, which is directly receiving huge quantities of pollutants from adjacent rivers containing a large amount of municipal and industrial wastewater. 17alpha-Estradiol (alpha-E2) and estrone-3-sulfate (E1-3S) were detected in some of the samples, whereas neither of the other conjugates, estriol (E3) or 17alpha-ethynylestradiol (EE2), was found.

Chromatography, Liquid↗

Prehospital management of sarin nerve gas terrorism in urban settings: 10 years of progress after the Tokyo subway sarin attack.

Chemical agents have been used previously in wartime on numerous occasions, from World War I to the Gulf War. In 1994 and 1995, sarin nerve gas was used first in peacetime as a weapon of terrorism in Japan. The Tokyo subway sarin attack was the first large-scale disaster caused by nerve gas. A religious cult released sarin gas into subway commuter trains during morning rush hour. Twelve passengers died and about 5500 people were harmed. Sarin is a highly toxic nerve agent that can be fatal within minutes to hours. It causes the clinical syndrome of cholinergic hyperstimulation by inhibition of the crucial enzyme acetylcholinesterase. Therapy of nerve agent toxicity is divided into three categories, decontamination, respiratory support, and antidotes. All of these therapies may be given simultaneously. This article reviews toxicology and management of this acute chemical emergency. To help minimize the possible catastrophic impact on the public, we make several recommendations based on analysis of the Tokyo subway sarin attack and systematically review the current scientific literature.

Antidotes↗

Source and behavior analyses of dioxins based on congener-specific information and their application to Tokyo Bay basin.

Identification of pollution sources and estimation of their contribution to dioxin pollution are important for taking better countermeasures against such sources. The information based on seventeen 2,3,7,8-chlorine-substituted congeners and 10 homologues is usually not sufficient for source identification. The usefulness of detailed congener-specific information of tetra- to octachlorinated polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans was examined by principal component analysis and compared with conventional dioxin information. It was revealed that congener-specific information was far more effective for source identification than conventional information. For source apportioning, it was shown that multiple regression analysis with detailed source congener profiles could be carried out successfully when calculations were performed for individual homologues. This was because of the large variation in homologue composition in source dioxin profiles in addition to the difference in environmental behavior among the homologues. The newly proposed methods for statistical analysis were applied to the estimation of dioxin mass balance in Tokyo Bay basin. It was found that Tokyo Bay sediment core contained dioxins from three major sources: combustion, pentachlorophenol (PCP), and chloronitrophen (CNP). PCP and CNP contained large amounts of dioxin as impurity and were used extensively as paddy field herbicides in Japan in the past. The total dioxin load from the two herbicides to the basin during the past 45 years (1951-1995) was estimated to be five times larger than that from combustion source in terms of toxic equivalents (WHO-TEQ). However, in the surface sediment of the bay, the contribution from the herbicides was nearly equal to that from combustion. The herbicide contribution peaked during the 1960s and 1970s and gradually decreased thereafter.

Agriculture↗

Dynamics of PCDDs/DFs and coplanar-PCBs in an aquatic food chain of Tokyo Bay.

Concentrations and accumulation profiles of PCDDs/DFs and coplanar-PCBs (co-PCBs) in aquatic biota (e.g., plankton, shellfish, benthic invertebrate, and fish) and sediment from Tokyo Bay were examined to elucidate the relationship between bioaccumulation and trophic level in the food web as determined by the stable nitrogen isotope analysis. Bioaccumulation patterns of PCDDs/DFs and co-PCBs varied greatly among congeners. Accumulation patterns of PCDDs/DFs and co-PCBs are not solely explained by their physicochemical properties. Biota-sediment accumulation factors (BSAFs) for co-PCBs in biota from Tokyo Bay were significantly greater than those of PCDDs/DFs. Furthermore, the slopes of the plots of delta15N and BSAF values and water solubility of 2,3,7,8-substituted PCDDs/DFs and co-PCBs were highly correlated. The results of our study would provide the valuable information to understand the accumulation properties of PCDDs/DFs and co-PCBs that can be used as a scientific basis to determine the sediment quality criteria of PCDDs/DFs and co-PCBs.

Animals↗

Present state of hepatitis E virus epidemiology in Tokyo, Japan.

Recently studies have reported the possibility that an indigenous hepatitis E virus (HEV) exists in Japan, but the epidemiological features of HEV in Japan are inadequate to make a judgment. In order to search the present state of HEV infection in Japan, we used ELISA to test 1033 sera from residents living in Tokyo and the Tokyo suburbs, for the presence of the antibody against HEV. The positive rate of anti-HEV IgG was 15.4% in all liver disease patients (68 of 440), 3% (6/200) in healthy individuals and 0.4% in infants (1/246), respectively (P<0.01). Anti-HEV IgG was seen in 17.6% (35/199) of liver disease patients of unknown etiology; 29.4% (5/17) of fulminant hepatitis, 17% of acute hepatitis (15/88) and 16% of chronic hepatitis (15/94). Anti-HEV IgG co-existed with hepatitis B virus and hepatitis C virus in 23.6% (21/89) and 7.9% (12/152), respectively. Furthermore, the prevalence of anti-HEV IgG was significantly higher in hemodialysis patients (18/60: 30%) and hospital workers (8/87: 9.2%) than in the healthy population (P<0.01). Anti-HEV IgM was detected in 0.1% of all samples tested (1/1033). The prevalence of anti-HEV IgG increased with age. No individuals with HEV antibody had a recent history of visiting countries where hepatitis E is endemic. These results indicate that generally 15.4% of Japanese patients with liver diseases had a history of HEV infection in the past. The routes of transmission of HEV require clarification in Japan.

Journal Article↗

Molecular defect in factor IX Tokyo: substitution of valine-182 by alanine at position P2' in the second cleavage site by factor XIa resulting in impaired activation.

Utilizing polymerase chain reaction and directly sequencing the amplified exon 6 of the factor IX gene derived from a mild hemophilia Bm patient, we have identified a T to C mutation at nucleotide 20,525. This point mutation predicted a Val182 to Ala substitution in the abnormal factor IX molecule, designated as factor IX Tokyo. The patient manifested a low factor IX activity and a moderately prolonged ox-brain prothrombin time but a normal factor IX antigen level in plasma. Immunopurified factor IX derived from the patient was found to have a normal molecular weight but a reduced specific activity (23% of normal). Limited proteolysis by activated factor XI or by a snake venom-derived factor X-activating enzyme was considerably delayed, indicating the presence of structural alteration(s) most probably at or near the second enzyme-cleavage site. Once activated, however, factor IXa Tokyo was able to activate factor X normally and was inactivated by antithrombin III also in a normal fashion. The structural model of factor IXa and a docking model of factor IX and activated factor VII (factor VIIa) suggested that the Val182 to Ala substitution would not affect the local conformation of the catalytic domain. This mutation would rather loosen the fitness of the molecule into the substrate-binding pocket of factor VIIa due to a shorter side chain of the Ala substitution at the P2' position of the second cleavage site.

Adolescent↗

The Pennsylvania Green Fluorophore: a hybrid of Oregon Green and Tokyo Green for the construction of hydrophobic and pH-insensitive molecular probes.

[structure: see text] Fluorescent small molecules are powerful tools for exploring cellular biology. As a more hydrophobic, photostable, and less pH-sensitive alternative to fluorescein, we synthesized Pennsylvania Green, a bright, monoanionic fluorophore related to Oregon Green and Tokyo Green. Comparison of membrane probes comprising N-alkyl-3beta-cholesterylamine linked to 4-carboxy-Tokyo Green (pK(a) approximately 6.2) and 4-carboxy-Pennsylvania Green (pK(a) approximately 4.8) revealed that only Pennsylvania Green was highly fluorescent in acidic early and recycling endosomes within living mammalian cells.

Fluoresceins↗

Dioxin-like compounds in pine needles around Tokyo Bay, Japan in 1999.

Pine needle samples collected at ten spatially distant sites around Tokyo Bay in 1999 indicated a widespread lower troposphere pollution with ultra-trace dioxin-like compounds such as chlorodibenzo-p-dioxins (PCDDs), -furans (PCDFs), non-ortho- and mono-ortho-chlorobiphenyls (pPCBs), and -naphthalenes (PCNs). Elevated concentration of planar PCBs and the total PCNs were found at the sites which are located innermost to the Bay, suggesting the regional importance of the evaporative nature of the source of pollution by those compounds over this vast area. The concentrations and profiles for PCDDs and PCDFs remained largely uniform. An exception was the site near the town of Tateyama in the Chiba Prefecture, which is the southernmost but also relatively separate from the inner Bay. The site near Tateyama showed somehow background contamination with all compound groups and highly different profiles of PCNs. The principal component analysis (PCA) of the data matrix has revealed that around the Tokyo Bay, apart from the evaporative emission sources for PCNs and PCBs, combustion related processes also play an important role as sources of the ambient air contamination not only with PCDDs/Fs but also with chloronaphthalenes and planar chlorobiphenyls.

Benzofurans↗

The reliability and validity of the Tokyo Autistic Behaviour Scale.

The Tokyo Autistic Behavior Scale (TABS) consisting of 39 items provisionally grouped in four areas--interpersonal-social relationship, language-communication, habit-mannerism and others--is an instrument used by a child's caretaker to rate the child's autistic behaviors on a 3-point scale. Test-retest reliability was satisfactory (i.e., an r for a total score was .94). Among six DSM-III diagnostic groups, infantile autism showed a significantly higher total TABS score than the other five groups, and a taxonomic validity coefficient was .54. An r between total scores of the TABS and the Childhood Autism Rating Scale--Tokyo Version was .59. The area scores showed a lower validity than the total score. The TABS appears to be a useful instrument to assess autistic behavior.

Autistic Disorder↗

Changes in the awareness of oral health among new students newly enrolled at the University of Tokyo over the past 15 years.

OBJECTIVE: The aim of this study was to examine changes in awareness of oral health among Japanese university students. METHODS: Between 1990 and 2004, a total of 51,650 students newly enrolled at the University of Tokyo responded to an annual written questionnaire on oral health. RESULTS: (i) Approximately 60% of the students brushed their teeth twice a day. Female students brushed more frequently than male students. (ii) The percentage of students who brushed for 2-3 min per time decreased, while the percentage who brushed four or more minutes increased. (iii) The number of students who had learned how to brush properly increased. This trend was particularly clear-cut among male students, although the proportion of female students who had learned to brush properly remained higher than that of male students. (iv) The percentage of female students who sought treatment for malocclusion was higher than that of male students. The percentage of students who underwent orthodontic treatment increased from 11.6 to 19.7%. The percentage of female students who received orthodontic treatment was approximately twofold that of male students. (v) The percentage of students who had temporomandibular disorders was 0.7% in males and 1.5% in females. (vi) More than 40% of the students had periodontal diseases, with a higher prevalence among male students than female students. (vii) Approximately 20% of the students wanted to consult our service centre. CONCLUSIONS: The awareness of oral health among new undergraduates at the University of Tokyo has improved over the past 15 years.

Adult↗

Earthquake source fault beneath Tokyo.

Devastating earthquakes occur on a megathrust fault that underlies the Tokyo metropolitan region. We identify this fault with use of deep seismic reflection profiling to be the upper surface of the Philippine Sea plate. The depth to the top of this plate, 4 to 26 kilometers, is much shallower than previous estimates based on the distribution of seismicity. This shallower plate geometry changes the location of maximum finite slip of the 1923 Kanto earthquake and will affect estimations of strong ground motion for seismic hazards analysis within the Tokyo region.

Journal Article↗

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.

Adult↗

Skull morphology and mitochondrial DNA sequence analysis in the lesser Japanese mole (Mogera imaizumii) from the Imperial Palace (Tokyo, Japan).

Since about 1630, the Imperial Palace has been biologically isolated from other habitats by the development and urbanization of Tokyo. We morphologically examined the skulls of the lesser Japanese mole (Mogera imaizumii) from the Imperial Palace and compared them with those from Kanto District, while the sequences of the cytochrome b and 12S rRNA genes were also analyzed to clarify the genetic status of this isolated population. The skulls from the Imperial Palace were much larger than those from Kanto District in the length items. We suggest that the Imperial Palace skulls morphologically may compose a cluster as a large body-sized type in Kanto District within the dots of Mogera imaizumii in charts of principal component analysis. The mitochondrial DNA sequences of the Imperial Palace population were highly homologous to those of other Tokyo population at the level of 98.5% in cytochrome b and 98.7% in 12S rRNA genes.

Animals↗

Clinical and laboratory features of in-patients with multiple sclerosis in a University Hospital in Tokyo from 1988-2002.

OBJECTIVE: The aim of this study was to analyze the clinical and laboratory features of each subtype of multiple sclerosis (MS) (relapsing-remitting, primary progressive, and secondary progressive) in the Tokyo metropolitan area. METHODS AND PATIENTS: We retrospectively analyzed the medical records of 104 consecutive patients with a diagnosis of MS, who had been admitted to our university hospital from 1988 to 2002. They all met criteria for definite MS, by clinical or laboratory standards. RESULTS: Eighty-four (80.8%) patients were classified as having relapsing-remitting MS, while 8 patients (7.7%) and 12 patients (11.5%) were classified as having primary progressive MS and secondary progressive MS, respectively. A significant female predominance existed in the relapse-remitting MS (female : male=2.4 : 1) cohort, but this ratio was 1 : 1 in both primary progressive and secondary progressive MS. The age at onset was older in the primary progressive MS (36.6+/-17.1 years of old) population than in either the relapsing-remitting MS (27.9+/-11.1) or the secondary progressive MS (27.8+/-11.5) subjects. Although the duration of illness was similar among the three types of MS, the number of exacerbations in the secondary progressive (5.9+/-4.6) cohort was significantly higher than that in the relapsing-remitting MS subjects (3.2+/-2.6). Patients with primary progressive MS showed a significantly higher rate of gait disturbance (87.5%) as the initial symptom than those with relapsing-remitting MS (23.8%), and this was thought to be due to the higher incidence of brainstem and spinal cord lesions. Visual disturbance as the initial symptom was frequently noted in those with secondary progressive MS (50.0%), while it was noted only in 29.8% and 12.5% in the relapsing-remitting and primary progressive patients, respectively. Primary progressive MS subjects had a higher propensity to be wheelchair-bound (75.0%) than those suffering from relapsing-remitting MS (1.2%). Increased total protein in the cerebrospinal fluid (CSF) of the secondary progressive cohort was statistically significant compared to the relapsing-remitting cohort. The frequency of oligoclonal IgG bands was rather low in each type of MS (17.1-33.3%). Gadolinium enhancement of plaques on MRI was more frequently present in secondary progressive MS (66.7%) than in either relapsing-remitting MS (32.1%) or primary progressive MS (50.0%). Of note, the opticospinal form was found in only 16.3% of the total MS patients, a proportion less than that in previous reports from southern Japan. CONCLUSION: The present study confirms that while the clinical and laboratory features of the MS patients in the Tokyo metropolitan area are similar to those in Western countries in most regards, features such as proportionally fewer primary and secondary progressive MS patients as well as less oligoclonal IgG bands on CSF analysis are different from those in Western countries.

Adult↗

[Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group].

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

Effective isolation of MPB64 from a large volume of culture filtrate of Mycobacterium bovis BCG Tokyo.

MPB64, a secretory protein of Mycobacterium bovis BCG Tokyo, was isolated from a culture filtrate of the bacteria in Sauton synthetic medium harvested on day 8. The protein was isolated by five steps; (i) concentration of the culture filtrate by cutting the molecules smaller than 5 kDa with the Millipore Pellicon Cassette system, (ii) affinity separation by a Phenyl Sepharose CL-4B column, (iii) separation with a DEAE-Sepharose CL-6B column with 3 M urea, (iv) separation with a Sephacryl S200HR column, and (v) separation with a DEAE-Sepharose column without urea. MPB64 in each fraction was determined by comparing the band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with that of standard MPB64. The specificity of isolated MPB64 was tested by immunoblotting with anti-MPB64 antibody. The potency of isolated MPB64 in eliciting skin reaction in the BCG-sensitized guinea pigs was the same to that of standard MPB64. The method described herein is an improved one for isolating MPB64 from a large volume of culture filtrate of M. bovis BCG Tokyo. The technique should be applicable to isolation of other mycobacterial secretory proteins.

Antigens, Bacterial↗

[Textbook of surgery by W. Schultze, used at the Tokyo Medical Academy in the early Meiji era].

Wilhelm Schultze, Professor of Surgery of the Tokyo Medical Academy, wrote "Vortraege der Allgemeine Chirurgie" for the benefit of his students in about 1880. The author examined this book and concluded that it was based upon "Lehrbuch der Chirurgie und Operationslehre" by Prof. Adolf Bardeleben, his teacher at the Charité in Berlin. Schultze's textbook was translated into Japanese and published by G. Yamazaki and U. Ishiguro, his students at the Tokyo Medical Academy, in 1884. This version was widely used as a textbook in many medical schools at that time, as well as S. Sato's translation of "Die Allgemeine Chirurgische Pathologie und Therapie" written by Prof. Theodor Billroth. The author found and introduced two different Japanese versions of Schultze's textbook printed without permission.

General Surgery↗