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Identification of polychlorinated dibenzo-p-dioxin, dibenzofuran, and coplanar polychlorinated biphenyl sources in Tokyo Bay, Japan.

A dated sediment core collected from Tokyo Bay, Japan, was used to assess the historical inputs of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) from multiple sources. The levels, patterns, and profiles of these compounds in the core were congener-specifically investigated, and the results show that the PCDD and PCDF (PCDD/F) and the Co-PCB inputs increased abruptly from the late 1950s and peaked during the period 1967 to 1972. From 1972 to 1981, the inputs decreased continuously and then generally leveled off. Using principal component analysis, two herbicides widely used in the past, pentachlorophenol (PCP) and chloronitrofen (CNP), as well as combustion processes were identified as the major dioxin sources in Tokyo Bay. The PCB formulations and combustion processes were estimated to be the major sources of Co-PCBs. Furthermore, multiple regression analysis was performed for dioxin-source apportioning, and it was found that the herbicides PCP and CNP have mainly contributed to the PCDD/F burdens since the late 1950s. This study suggests that herbicide-derived PCDD/Fs remaining in agricultural land will continue to run off and pollute the aquatic environment in Japan for a long time.

Agriculture↗

Explaining the recent migration trends of the Tokyo metropolitan area.

Recent migration trends affecting the Tokyo metropolitan area (TMA) in Japan are analyzed. The focus is on the factors affecting the change in migration patterns which resulted in a net outflow of migrants from the area in 1994, the first time this has occurred. "The results from a set of time-series analyses lead the authors to conclude that, as far as the study period (1979-92) as a whole is concerned, the changing migration pattern of the TMA arose from factors closely related to Tokyo's transformation into a world city (specifically in terms of industrial restructuring and changes in residential land prices) and from cycles of economic boom and bust. However, it was found that the change to world city was more important than the economic cycle. Such findings suggest that the Japanese migration system experienced structural change during the 1980s and entered a new phase in the 1990s."

Agriculture↗

[Isolation of MPB63 in the culture fluid of Mycobacterium bovis BCG Tokyo: genetical and immunological characterization].

MPT63 is a secretory protein first isolated from a culture fluid of M. tuberculosis H37Rv by Nagai et al. In this study, this protein was isolated from an 8-day-culture fluid (Sauton synthetic medium) of M. bovis BCG Tokyo 172 according to Nagai's method. It was shown that M. bovis BCG Tokyo 172 secreted this protein in the medium. The mpt63 gene was detected only in the species of M. tuberculosis complex by polymerase chain reaction (PCR) among 40 different mycobacterial species. Therefore, it is appropriate to designate this protein as MPB63 or MPB/T63 from M. bovis BCG, in similar way as other major secretory proteins of Mycobacteria, such as MPB59 and MPB64. Comparison of the nucleotide sequences of the genes encoding MPB63 protein of M. bovis BCG and MPT63 protein of M. tuberculosis showed only single nucleotide difference at the position 474 where thymine (T) in the former was replaced by adenine (A) in the latter. Amino acid sequences of both proteins were completely identical. MPB63 didn't show delayed-type hypersensitivity (DTH) skin reaction in the sensitized guinea pigs with live or heat-killed M. bovis BCG or heat-killed M. tuberculosis. However, the measurements of serum IgG antibody titers of active tuberculosis patients by enzyme-linked immunosorbent assay (ELISA) showed 74% sensitivity and 96% specificity compared to healthy subjects. Therefore, MPB63 seems to be a promising candidate as an antigen for serodiagnosis of active tuberculosis.

Animals↗

[An outbreak of epidemic louse-borne typhus in Tokyo 1914: a study on the prevention of epidemics].

In 1914, the third year of the Taisho era, a period of democracy and prosperity of Japan, Tokyo was attached by an outbreak of epidemic louse-borne typhus. The number of patients was 4,119 and number of deaths was 778 (mortality rate of 18.9%) in Tokyo and 7,309 patients had been suffering from typhus fever that year in Japan. Many possible causes of the outbreak were suspected by the Health Authority of the Home Office, but these were not confirmed. One of the most likely reasons is the poor and congested living conditions of seasonal construction workers. Laborers had moved from the northwest region of Japan where typhus fever had developed occasionally in those days. Some of the laborers probably brought pathogenic germs with lice. The main preventive method for epidemic louse-borne typhus was isolation of patients and disinfecting of the areas. Kitasato Shibasaburou proposed the improvement of residential conditions of workers to prevent the prevalence of disease, but the proposal was not accepted because of financial reasons of the government. Recurrence of the outbreak did not occur in the following years. However, a huge outbreak of typhus fever with 32,366 patients and 3,351 deaths, was documented in 1946, amidst the disordered conditions of Japan after World War II.

Communicable Disease Control↗

MCC-555 (Mitsubishi-Tokyo Pharmaceuticals).

Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing MCC-555, a thiazolidinedione peroxisome proliferation activated receptor (PPAR)-gamma agonist, as a potential treatment for type 2 diabetes [204644]. Johnson and Johnson is developing the compound outside of Japan [304271,322655]. As of March 2000, MCC-555 was in phase II trials as an insulin sensitizer, both in Japan and abroad [371091]. Phase I trials have been completed by Mitsubishi-Tokyo in the UK and Japan [304271]. Johnson and Johnson trials have shown that the drug is 3-fold more potent than rosiglitazone in the diabetic mouse model, KK-Ay. MCC-555 activates the PPARgamma target gene, aP2, with greater maximal efficacy than other agonists of this target [322655]. MCC-555 binds PPARgamma transcriptional activity which is highly context-specific, such that it can function as a full or partial agonist, or an antagonist, depending on the cell type or DNA binding site. These transcriptional properties are partially explained by unique partial agonism of coactivator recruitment to PPARgamma. This context-specific activity may contribute to its enhanced hypoglycemic potency in vivo despite reduced affinity for PPARgamma [335218]. In February 1999, ING Barings reported that Mitsubishi Chemical expected peak potential sales of yen100 billion for MCC-555, although analysts regarded this prediction as being excessively high at the time [405416].

Journal Article↗

Current situation of web-based chemical registration system in the University of Tokyo.

The web-based University of Tokyo Chemical Registration Information System with computational support has been introduced in all areas using chemicals owing to the unified management of the university and the management of chemicals in conformity with legal controls. This system enables chemical users to manage chemicals easily and reduces the burden inflicted by such management. In this report, we introduce the style of chemical management in the University of Tokyo, the functions of the web-based chemical registration system, the current situation of the system and future plans.

Chemical Phenomena↗

Radical surgery for cervical carcinoma: experience with "the Tokyo method".

Thirty patients of cervical carcinoma were treated by radical abdominal hysterectomy and pelvic and lower paraaortic lymphadenectomy between November 1986 and October 1988 by the 'Tokyo method.' Blood loss in the majority of the patients (80%) was less than 1000 ml. The incidence of intra and postoperative complications was found to be low. None of the patients developed urinary fistula and the incidence of bladder dysfunction was also low (3.3%). Follow up of the patients for nine to 32 months revealed local recurrent tumour in only one case. We feel that the "Tokyo method" of radical hysterectomy offers several advantages over other methods.

Adult↗

Lactation and reproductive histories of breast cancer patients in Tokyo, Japan.

Epidemiological characteristics of breast cancer have been studied in Tokyo, an area of relatively low breast cancer rates, as part of an international collaborative study. Breast feeding of infants is customary for Japanese women, but even very prolonged lactation did not appear to be associated with a reduction in breast cancer risk. Late age at menarche and early age at first pregnancy were both associated with reduced breast cancer risk. The protective effect of early pregnancy seems much greater than has previously been recognized, and may indeed be greater in Japan than in other areas. However, the average age at first pregnancy is not lower in Tokyo than in areas than in areas where breast cancer rates are high.

Adult↗

Two new glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: GD(-) Tokushima and GD(-) Tokyo.

Two new variants of glucose 6-phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan. Gd(-) Tokushima was found in a 17-years-old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km NADP five-to sixfold higher than normal; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(-) Tokyo was characterized from a 15-year-old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris-hydrochloride buffer system and a tris-EDTA-borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km NADP; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(-) Heian and Gd(-) Kyoto. The mothers of both Gd(-) Tokushima and Gd(-) Tokoyo were found to be heterozygote by an ascorbate-cyanide test.

Adolescent↗

Detection of group C rotaviruses in Tokyo.

Four human group C rotaviruses were detected in Tokyo in 1987 and 1988 during a survey over 7 years. Among the four rotaviruses, two electrophoretic patterns were indicated by polyacrylamide gel electrophoretic (PAGE) analyses. Clinical symptoms, signs, family history, and patients' ages varied. Group C rotaviruses were found also in other parts of Japan in 1988. It was suspected that group C rotaviruses would continue to spread throughout Japan within the near future.

Blotting, Western↗

Serotyping of human rotaviruses in the Tokyo area (1990-1993) by enzyme immunoassay with monoclonal antibodies and by reverse transcription and polymerase chain reaction amplification.

Serotyping of human rotavirus in the Tokyo area was conducted from 1990 to 1993 by enzyme immunoassay with monoclonal antibodies (EIA-MAbs) against VP7 and by reverse transcription and polymerase chain reaction (RT-PCR) amplification of the VP4 and VP7 genes. The results by EIA-MAbs were very similar to those obtained by RT-PCR. Evidence of intraserotypic variations was suggested because strains of undetermined serotypes were detected by either EIA-MAb or RT-PCR. This kind of study is required for vaccine development.

Antibodies, Monoclonal↗

Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: long-term outcome of the children with AML treated on two consecutive trials of Tokyo Children's Cancer Study Group.

BACKGROUND: Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase. PROCEDURE: A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm. RESULTS: The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years. CONCLUSIONS: These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.

Acute Disease↗

Improvement in treatment results of gastric cancer with surgery and chemotherapy: experience of 9,700 cases in the Cancer Institute Hospital, Tokyo.

Treatment results of 9,741 cases of gastric cancer treated at the Cancer Institute Hospital, Tokyo during the past 42 years were retrospectively analyzed. Resectability was 89.6% (94.1% for 1960-1988) and operative mortality was 1.9% (1.5% for 1960-1988). Five-year survival rate was 48.5% (54.9% for 1960-1988) for all cases, 68.8% (73.1% for 1960-1988) for patients with curative surgery, and 4.7% (4.9% for 1960-1988) for those with noncurative surgery. Curative rate was improved twofold among patients with curative gastrectomy. Postoperative adjuvant chemotherapy had a marginal benefit for stage II and III disease. Improvement could be attributed mainly to the relative increase in early gastric cancer, and partly to the extended surgeries for stage III and IV cases, such as systemic lymphadenectomy and combined resection of involved adjacent organs. Multimodality therapy is expected to control the relapse of peritoneal dissemination (14.2%) and hematogenous metastasis (8.9%).

Antineoplastic Combined Chemotherapy Protocols↗

Particulate matter and particle-attached polycyclic aromatic hydrocarbons in the indoor and outdoor air of Tokyo measured with personal monitors.

Using two types of personal monitors for suspended particulate matter of diameter under 10 microm (PM-10) and for particles of diameter under 1 microm with attached polycyclic aromatic hydrocarbons (PPAH), we measured the PM-10 and PPAH concentrations in the indoor and outdoor air in various locations in the Tokyo area. The major findings were as follows. (1) The PPAH concentrations in a clean living room increased rapidly within several minutes after one cigarette was smoked. (2) Using the average indoor concentrations of PM-10 and PPAH in a department store as control concentrations, respectively, where the average indoor PM-10 concentration was closest to an annual average outdoor concentration in Japan, the mean value for indoor air concentrations of PM-10 by location ranged from 2.2 to 6.2 times the control concentration, and the mean value for indoor air concentrations of PPAH by location ranged from 1.0 to 32.2 times the control concentration. (3) Using the same control concentrations, the mean value of outdoor concentrations of PM-10 by location ranged from 1.6 to 8.5 times the control concentration, while the mean value of outdoor concentrations of PPAH by location were up to 353.7 times the control concentration. The major polluted places were main traffic roads, highways, and street tunnels. (4) The correlation coefficient between the PM and the PPAH concentrations in the total monitoring time was 0.014, which was not significant (P>0.05).

Air Pollutants↗

Definitive evidence for the acute sarin poisoning diagnosis in the Tokyo subway.

A new method was developed to detect sarin hydrolysis products from erythrocytes of four victims of sarin (isopropylmethylphosphonofluoridate) poisoning resulting from the terrorist attack on the Tokyo subway. Sarin-bound acetylcholinesterase (AChE) was solubilized from erythrocyte membranes of sarin victims, digested with trypsin, the sarin hydrolysis products bound to AChE were released by alkaline phosphatase digestion, and the digested sarin hydrolysis products were subjected to trimethylsilyl derivatization and detected by gas chromatography-mass spectrometry. Isopropylmethylphosphonic acid, which is a sarin hydrolysis product, was detected in all sarin poisoning, victims we examined and methylphosphonic acid, which is a sarin and soman hydrolysis product, was determined in all victims. Postmortem examinations revealed no macroscopic and microscopic findings specific to sarin poisoning and sarin and its hydrolysis products were almost undetectable in their blood. We think that the procedure described below will be useful for the forensic diagnosis of acute sarin poisoning.

Acetylcholinesterase↗

Research and development on total artificial heart in University of Tokyo.

The research and development on the total artificial heart (TAH) in the University of Tokyo can be divided chronologically into the three stages, i.e., the first stage (1959-1970); trial and error stage to find appropriate hardwares, the second stage (1970-1985); software stage to find how to control pneumatic TAH and to manage the animals, and the third stage (1985- ); final goal to develop implantable TAH for animal and human. This paper reviews the process of research and development in each stage.

Animals↗

Incidence of 47,XYY karyotype in a consecutive series of newborn males in Tokyo.

A series of 3545 newborn males, born consecutively at a maternity hospital in the western suburbs of Tokyo and with no detectable physical abnormalities, were studied for fluorescent Y-chromatin. Buccal cell smears from each infant were screened. Cases with ambiguous results were subjected to a second test by blood smears, which were found to be more reliable. After the second test, chromosomal analysis was carried out in five infants: three had a 47,XYY karyotype; one, the karyotype 46,XY-D,t(D:Y) (Iijima et al., in preparation); and one, a normal male karyotype. The XYY karyotype occurred in 0.11% of newborn males in this series.

Cheek↗

Epidemiological study of patients with systemic sclerosis in Tokyo.

We conducted an epidemiological study of systemic sclerosis in the city of Tokyo using the records of patients who had been registered to receive free medical service for intractable diseases. A total of 636 patients were registered as having systemic sclerosis in 1987, and we sent questionnaires to the doctor of each patient. The contents of the questionnaires included the patient's name, sex, age, occupation, major symptoms, therapy and laboratory findings. We received 357 completed replies, and were able to analyse them. Our study estimated that at 1 January 1988 the prevalence rate in Japan was between 2.1 and 5.3 per 100,000. The male/female ratio was 14:1. The ages of the patients when surveyed ranged from 17 to 82 years, with a mean age of 51 years, peaking with the most numerous group being 50-59 years. The characteristic signs of systemic sclerosis were as follows: proximal scleroderma, 75%; sclerodactyly, 91%; pitting scars, 49%; short sublingual frenulum, 49%; pulmonary fibrosis, 45%; diffuse pigmentation, 45%; and phalangeal contracture, 35%. Raynaud's phenomenon was present in 93% of patients, and was the initial symptom in 59% of cases. With respect to specific antinuclear antibodies, anticentromere antibody was present in 19% and antitopoisomerase I antibody was present in 27%.

Adolescent↗