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PubMed2000

Total Synthesis of (+)-Eurylene and (+)-14-Deacetyleurylene We thank K. Ujihara (Sumitomo Chemical Co.) for generously supplying an authentic sample and a copy of the (1)H NMR spectrum of synthetic eurylene. We are grateful to Prof. H. Iio and Dr. Y. Usuki (Osaka City University) for the HPLC purification. T.I. thanks the Japan Society for the Promotion of Science for providing a JSPS Research Fellowship for Young Scientists. This research was supported by the Naito Foundation, the Fujisawa Pharmaceutical Award in Synthetic Organic Chemistry, Japan, the SUNBOR GRANT from the Suntory Institute for Bioorganic Research, and a Grant-in Aid for Encouragement of JSPS Research Fellows from the Japan Society for the Promotion of Science.

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Journal Article↗
PubMed2006

Clinical characteristics and outcome of Wilms tumors with a favorable histology in Japan: a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

BACKGROUND/PURPOSE: Since 1996, the standard treatment of Wilms tumors in Japan has been based on the regimen of the Japanese Wilms Tumor Study. However, in Japan, there have been no reports about Wilms tumors that analyzed the clinical features and patient outcome in a large series until now. This study aims to assess the clinical characteristics of patients with Wilms tumor with a favorable histology from a retrospective standpoint in the Kyushu area in Japan and, furthermore, to analyze the historical changes of clinical features and outcome from the 1980s to the 1990s. METHODS: Between 1982 and 1996, 90 cases of Wilms tumors with a favorable histology were registered in the Kyushu area. Regarding the clinical feature and outcome, they were divided into 2 groups (group A, 1982-1989, n = 50; group B, 1990-1996, n = 40). The outcome was analyzed based on the 5-year overall survival rate. RESULTS: The clinical features (age, sex, initial symptom, location, stage) demonstrated no definite differences between group A and group B. Regarding the operation, the rate of an initial complete resection in the early stages was significantly higher in group B than in group A. All stage V cases in group B undewent a bilateral tumor biopsy instead of a radical nephrectomy as the initial operation. The 5-year overall survival rate throughout the whole period was 87.8%, whereas the rates were 84.0% for group A and 90.0% for group B (P = NS), respectively. Of particular note, the outcome of patients with stage I and stage V in group B substantially improved in comparison to that in group A. However, in advanced cases, no significant improvement in the outcome was noted. CONCLUSIONS: This is the first report about the clinical features and outcome for Wilms tumors with a favorable histology in Japan from the 1980s to the 1990s. The present study suggested that in the early-stage cases, an initially complete resection followed by standard postoperative chemotherapy substantially improved the outcome of the patients in group B. In the stage V cases, the performance of renal salvage surgery may have positively contributed to the improvement in the outcome in group B. However, in the advanced stage cases, no definite improvement was noted. In the future, an improved efficacy of the treatments for Wilms tumors based on the standard protocol established by the Japanese Wilms Tumor Study in 1996 is expected in Japan.

Child, Preschool↗
PubMed2000

Survey of the current state of pediatric drug use in Japan (1994-6). Drug Therapy Committee of the Japan Pediatric Society.

BACKGROUND: A survey of the current state of pediatric drug therapy in Japan was conducted using a questionnaire completed by committee members and the former president of the Drug Therapy Committee of the Japan Pediatric Society. METHODS: Questionnaires were mailed to the members of the Drug Committee, who represent the various specialties of the Japan Pediatric Society, and to its former chairperson. Questionnaires contained eight items. RESULTS: This survey demonstrated that, although use of drug therapy in adults is clearly defined, pediatric drug therapy in Japan is extremely imprecise, with the potential to lead to undesirable consequences. CONCLUSION: The Japan Pediatric Society demands that the standardization of drug information labels and dosages specifically for children, including premature and full-term neonates, should be included under all aspects of National Health Insurance.

Child↗
PubMed1987

A statistical study of brain tumors in Japan: general features. The Committee of the Brain Tumor Registry in Japan.

A total of 20,192 brain tumors, registered in Japan between 1969 and 1978 have been studied. Differences in frequency between Japan and other countries, and also between children and adults were discussed in relation to tumor distribution, by site in the brain, and the frequencies of various types tumor were classified pathologically and by age and sex. Glioma frequency in Japan was a little lower (38.1%) than in western countries and China (43-49%). Germinomas occurred in 435 patients in all age groups (2.7% of primary tumors), of whom 184 were children (7.8% of primary pediatric brain tumors), these percentages being also much larger than those found outside Japan. The frequencies of craniopharyngiomas were also high in Japan, having totals of 914 cases, or 5.8%, from all primary tumors, and 295 cases, or 12.5%, from all primary pediatric brain tumors. Teratomas occurred mostly in children (67% of the total) and at a relatively high frequency in infants, but, in contrast, dermoid and epidermoid cysts appeared frequently in people between 30 and 55 years of age.

Adenoma↗
PubMed1993

[Clinical Oncology Groups in Japan: experience of the Japan Adult Leukemia Study Group (JALSG)].

Although Grants-in-Aid of the Ministry of Health and Welfare support a considerable number of clinical cancer studies in Japan, there is no established clinical oncology group in Japan which is supported by the government or public grants. The Japan Adult Leukemia Study Group is a voluntary clinical oncology group, established in 1987; it started with 14 institutions and had 45 institutions as of 1993. Operating funds are donated from each participating institution with some help from a Grant-in-Aid of the Ministry of Health and Welfare of Japan. Establishment of government-supported nation-wide clinical oncology groups is urgently needed for further development of high quality clinical cancer studies in Japan.

Acute Disease↗
PubMed2006

[Requirement of standardizing anti-HBs assay methods in Japan for HBV infection-preventing strategy--discrepancy of anti-HBs measurements among three different kits widely used in Japan].

The strategy to eliminate hepatitis B virus (HBV) infection by administrating an HB vaccine is changing worldwide; however, this is not the case in Japan. An important concern about the HBV infection-preventing strategy in Japan may be that the assay methods for the antibody to hepatitis B surface antigen (anti-HBs) are not standardized. The minimum protective anti-HBs titer against HBV infection has been established as 10 mIU/ml by World Health Organization (WHO) -standardized assay methods worldwide, but that is still determined as a "positive" test result by the passive hemagglutination (PHA) method in Japan. We compared anti-HBs measurements in given samples among PHA(Mycell II, Institute of Immunology), chemiluminescent enzyme immunoassay (CLEIA) (Lumipulse, Fujirebio), and chemiluminescent immunoassay (CLIA) (Architect, Abbott), all of which are currently in wide use in Japan. First, anti-HBs measurements in serum from individuals who received a yeast-derived recombinant HB vaccine composed of the major surface protein of either subtype adr or subtype ayw were compared. The results clearly showed that in subtype adr-vaccinees CLIA underestimated the anti-HBs amount compared with CLEIA and PHA, but in ayw-vaccinees, the discordance in the measurements among the three kits was not prominent. Second, anti-HBs measurements in standard or calibration solutions of each assay kit were compared. Surprisingly, CLEIA showed higher measurements in all three kit-associated standard or calibration solutions than CLIA. Thus, the anti-HBs titer of 10 mIU/ml is difficult to introduce in Japan as the minimum protective level against HBV infection. Efforts to standardize anti-HBs assay methods are expected to share international evidence about the HBV infection-preventing strategy.

Clinical Laboratory Techniques↗
PubMed1984

Follow-up study of a nation-wide neonatal metabolic screening program in Japan. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan.

A nationwide neonatal screening program for phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria, histidinemia and galactosemia was started in Japan in 1977. The total number of infants screened had reached 6,311,754 by March, 1982. A follow-up study revealed the incidence of the disease in Japan: 1/108,823 for PKU; 1/450,840 for hyperphenylalaninemia (HPA); 1/1,577,939 for biopterin deficiency; 1/525,980 for MSUD; 1/1,051,959 for homocystinuria; 1/8,371 for histidinemia, and 1/788,969 for galactosemia type 1. The incidences of PKU, HPA, homocystinuria, and galactosemia (type 1) were found to be markedly low in Japan as compared with those in Caucasian countries. There was no great difference in the incidence of MSUD between both. On the other hand, the incidence of histidinemia was higher in Japan. It was found that most of the patients with PKU, HPA, MSUD, homocystinuria, or galactosemia are developing normally due to the early initiation of dietary treatment. These results clearly indicate that the neonatal mass screening program plays a great role in preventing the occurrence of handicapped children.

Biopterins↗
PubMed1998

Clinical trials for advanced gastrointestinal cancers in Japan. Japan Clinical Oncology Group Gastrointestinal Oncology Study Group.

No standard chemotherapy regimen for the treatment of advanced gastrointestinal cancer exists. However, 5-fluorouracil (5-FU) is being used more frequently as a key component of combination therapy regimens for this disease, and including cisplatin (CDDP) in combination therapy regimens produces significant tumor shrinkage. Although oral formulations of 5-FU are widely used in Japan, their clinical activity and toxicity have not been thoroughly evaluated. In 1992, the Japan Clinical Oncology Group initiated a phase III study in which the survival rates of patients treated with 5-FU 800 mg/m2/day for 5 days by continuous infusion (5-FUci), 5-FUci with CDDP 20 mg/ m2/day for 5 days by infusion, or oral uracil/Ftorafur 375 mg/m2/day with weekly MMC 5 mg/m2 i.v. were compared. This study was closed with 280 patients accrued in 1997, and final analysis was made in early 1998. Irinotecan and paclitaxel are new drugs with activity against gastric cancer. Combination chemotherapy consisting of irinotecan with CDDP has also been evaluated. For treatment of metastatic colorectal cancer, the only active drug previously available in Japan was 5-FU, although 5-FU + leucovorin is the international standard regimen. Irinotecan is now approved in Japan, Europe, and the USA and is the most effective drug for 5-FU-refractory patients. The optimal irinotecan and 5-FU combination regimen is being extensively examined but further trials aimed at accumulating basic data are warranted.

Antineoplastic Agents↗
PubMed1999

Chronic granulomatous disease in Japan: incidence and natural history. The Study Group of Phagocyte Disorders of Japan.

PURPOSE: To analyze the incidence and causes of fatality of patients with chronic granulomatous disease (CGD) in Japan and to provide an opportunity for comparison with reports from other countries. METHODS: The Study Group of Phagocytic Disorders in Japan conducted a questionnaire survey on CGD patients in Japan, results of which formed the basis of the study. RESULTS: Clinical details of 221 patients were analyzed: 194 male and 27 female (ratio: 7.2/1), 152 living, 51 dead and 18 unknown. The prevalence of CGD was estimated to be 1/287,709 live births. The fatality rate was 23.1%. The mean age of the surviving patients increased from 8 years 4 months in 1985 to 16 years 0 months in 1998. Although the mean age of death was advanced by 4 years 11 months during the same period of time, the fatality rate has remained practically unchanged during the past 13 years. The number of living adult patients has tended to increase (32.1%). At the time of study, approximately 90% of patients had been placed on sulfamethoxazole-trimethoprim prophylactically or therapeutically, either singly or in combination with other modalities, including interferon-gamma, antifungal agents and various antibiotics. Pulmonary infections were responsible for 58.3% of fatalities. CONCLUSIONS: With early diagnosis and prompt institution of appropriate therapy, the mean age of CGD patients in Japan has been increasing, but the fatality rate has remained practically unchanged during the last 13 years, mostly due to the fungal infections.

Adolescent↗
PubMed1998

Cancer incidence in Japan, 1985-89: re-estimation based on data from eight population-based cancer registries. The Research Group for Population-based Cancer Registration in Japan.

The Research Group for Population-based Cancer Registration in Japan has been conducting a cooperative study to estimate cancer incidence in Japan since 1975. Estimated incidence data calculated annually were accumulated in 1996 for 18 years. The Group has separately provided another re-calculated incidence estimate series which were prepared for 1975-79, 1980-84 and 1985-89. The former two results, each of five years were previously published elsewhere. These recalculated estimate series made more reliable observations of time trends in incidence feasible by using the same eligible registries' data throughout each 5-year period. This report presents results of the latter 5 years between 1985 and 1989; age-specific, crude and age-standardized incidence rates, as well as the number of incidence according to site and gender, under the cooperation of eight eligible population-based cancer registries in Japan: Miyagi, Yamagata, Kanagawa, Fukui, Osaka, Tottori, Hiroshima City and Nagasaki City. Incidence in Japan was estimated at 187,200 and 150,700 for all cancer sites among males and among females, respectively, in 1985 and 216,700 and 166,900, respectively, in 1989. The leading site was the stomach among both males and females from 1985 to 1989. Among males the second leading site was the lung, followed by the liver, colon and rectum. Among females, it was the breast, followed by the colon, uterus and lung in 1989. The proportion of the cases registered by a death certificate only for all sites was 14.0-15.7 and 13.7-15.3% and the ratio of incidence to mortality was 1.69-1.73 and 1.95-2.01 among males and females, respectively, during the period.

Breast Neoplasms↗
PubMed1986

Incidence of congenital rubella syndrome in Japan (1965-1985). A nationwide survey of the number of deaf children with history of maternal rubella attending special schools for the deaf in Japan.

Accurate congenital rubella syndrome surveillance in Japan is of great interest because of the hypothesis that the Japanese rubella virus was less virulent than the strains prevalent in Europe and the Americas 20 years ago. A nationwide survey of deaf children with a history of maternal rubella in special schools for the deaf in Japan yielded a total of 365 deaf school children with congenital rubella syndrome born between 1963 and 1982. The overall average prevalence was 0.31 case per 100,000 population, and the incidence was 0.1-6.1 cases per 100,000 annual live births in Japan. If one considers the decrease in the number of deaf children attending special schools for the deaf because of the recent adoption of the policy of integrating deaf children into ordinary schools, the number of cases of congenital rubella syndrome might actually be much greater than that revealed by this survey and much greater than the 88 cases previously reported in Japan. Among the 365 cases who had deafness, 8.2% were found to have cataract (with and without congenital heart disease), and 11.0% were found to be complicated by congenital heart disease (but without cataract).

Cataract↗
PubMed1993

Accidental poisoning of children in Japan: a report from the Japan Poison Information Center.

The Japan Poison Information Center (JPIC) was founded only 6 years ago as a result of co-operation between the Ministry of Health and Welfare, the Japanese Association for Acute Medicine, the Japan Pediatric Society and other related medical organizations. The JPIC is the only poison information center admitted by the Ministry of Health and Welfare to provide toxicological information to medical personnel and the general public, and has two offices on duty in alternating 24 h shifts. Every year, JPIC receives about 30,000 inquiries. About 82% of these inquiries are from the general public and 84% of the patients are children 5 years and younger. We contrasted the data in the fiscal year 1991 with the data of the American Association of Poison Control Centers (AAPCC). Child poison exposure in Japan is characterized by a high exposure rate of children under 1 year of age to (mostly) household products. The JPIC also analyzed the cause of tobacco ingestion. It is considered that the Japanese lifestyle causes differences from those reported by AAPCC. We report the accidental poisoning of children in Japan.

Accidents↗
PubMed2002

Epstein-Barr virus (EBV) subtype in EBV related oral squamous cell carcinoma in Okinawa, a subtropical island in southern Japan, compared with Kitakyushu and Kumamoto in mainland Japan.

AIM: In Okinawa, a subtropical island located between the East China Sea and Pacific Ocean, 2000 km south of mainland Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that seen in mainland Japan, and a large number of these patients have been reported to be infected with the Epstein-Barr virus (EBV). This study aimed to gain a better understanding of the pathogenesis of this malignancy in this area by carrying out genomic analysis of EBV. METHODS: Fifty four patients with oral squamous cell carcinoma reported from 1997 to 1999 in Okinawa were compared with 21 and 20 patients from Kitakyushu and Kumamoto in Kyushu, mainland Japan, respectively. Diagnosis was confirmed by conventional histological examination of paraffin wax sections. EBV was detected by non-isotopic in situ hybridisation (NISH) and the polymerase chain reaction (PCR) (Bam HI-F, EBV nuclear antigen 2 (EBNA2), and latent membrane protein 1 (LMP-1) regions). Sequence analysis of the PCR products was also carried out. RESULTS: In Okinawa, 25 patients were found to be infected with EBV type A by analysing the 3' sequence divergence of the EBNA2 genes. Six patients were positive for EBV type B, and eight for both type A and B. Therefore, type A virus infection was demonstrated in 33 of 54 patients, and type B in 14 of 54. In total, 39 of 54 patients were infected with EBV. However, the "f" variant was shown in only one patient, who was also infected with type A virus. In contrast, 97.0% of EBV type A infected patients showed a 30 bp deletion of the LMP-1 gene, but those infected with EBV type B did not. Sequence analysis of the type A virus EBNA2 gene revealed slight variations of the sequence (mutations)-(48991)G-->T and (48998)C-->A-in 18 of 33 cases compared with the B95-8 strain, and in 14 cases, in addition to these, a further mutation of (48917)T-->C was demonstrated; in the single remaining case, only one mutation at (49137)A-->G was detected. The mutations at 48991 (G-->T), and 49137 (A-->G) are associated with amino acid changes Arg-->Met and Thr-->Ala, respectively. In contrast, no mutation was seen in the EBNA2 DNA from the 14 cases of type B virus when compared with that of the Jijoye strain. In Kitakyushu and Kumamoto, only 10 of 41 patients (six in Kitakyushu and four in Kumamoto) were infected with EBV. Among them, nine patients were infected with type A virus, and only one patient from Kitakyushu was infected with type B virus. The (48991)G-->T and (48998)C-->A mutations of the EBNA2 region were demonstrated in type A virus, but the (48917)T-->C and (49137)A-->G mutations were not when compared with the B95-8 strain. In the case of type B virus no mutation was noted. A 30 bp deletion was found in these nine cases of type A, but not in type B. The sequence analysis of EBV type A in Okinawa, Kitakyushu, and Kumamoto showed slight variations when compared with B95-8, but EBV type B LMP-1 did not when compared with the Jijoye strains. CONCLUSION: In Okinawa, EBV infection was frequently demonstrated in oral squamous cell carcinoma (p < 0.001). However, in mainland Japan there was no significant correlation between EBV and oral squamous cell carcinoma. In Okinawa, EBV type B infection is approximately 10 times more common than in the mainland. However, in these areas-Okinawa, Kitakyushu, and Kumamoto-the frequency of the "f " variant was very low, whereas a high incidence of a 30 bp deletion of LMP-1 was noted. The number of EBV (including type A and/or B) infected oral squamous cell carcinomas in Okinawa was about three times higher than that seen in the mainland, although the frequency of oral squamous carcinoma was only 1.5 times higher than that seen in the mainland. A high prevalence of type B virus infection and slight differences in the EBNA2 gene sequence in the type A virus might influence the frequency of this carcinoma in Okinawa.

Adult↗
PubMed2001

Familial predisposition of type 1 diabetes mellitus in Japan, a country with low incidence. Japan Diabetes Society Data Committee for Childhood Diabetes.

The study group of the Japan Diabetes Society (JDS) carried out nationwide hospital-based and population-based surveys of childhood type 1 diabetes mellitus (DM) in Japan. According to the nationwide population-based survey, the incidence of childhood type 1 DM in Japan was 1.5 (1.4-1.6)/10(5), which did not differ for the 5 years from 1986-1990. Predisposition for DM and autoimmunity were studied in the first-degree relatives of the patients, including older and later cohorts. The prevalence of type 1 DM was 3.3% (12/369) among siblings and 2.2% (8/369) among parents, while the prevalence of type 2 DM was 0% among siblings and 4.3% (16/369) among parents. The risk of type 1 DM among siblings of the patients was 330 times higher than that among the general population in the Japanese population. The rate of positivity for autoantibodies, including ICA, IAA, GAD and IA-2, was 1.4-2.9% in parents (n=140) and 2.0-3.9% in siblings (n=203). The genetic susceptibility for type 1 DM is far lower in Japanese children than in Caucasian children, but predisposition to the disease and positive autoimmunity are almost the same in Japanese families of patients as in Caucasian families. The quality of life of Japanese parents of children with type 1 DM was less satisfactory that that of the Caucasian parents previously reported, which might be a result of the low incidence of type 1 DM in Japan.

Child↗