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Biomedical subjects

M Tokunaga

Publications and source records attributed to M Tokunaga.

At least 163 records · Page 9Linked to original sources

[Electronmicroscopic study on the vitreous membrane of the Stickler syndrome].

The vitreous membrane obtained from a patient with Stickler syndrome, an 8 year-old female, was investigated electronmicroscopically. The cells found in the membrane had cilia, microvilli and cytoplasmic filaments. Gap junctions and basement membrane-like structures were also found. Several of the cells had phagosomes containing crystalline materials. Thus, these cells seemed to be glial cells.

Abnormalities, Multiple↗

Cancer incidence in atomic bomb survivors. Part I: Use of the tumor registries in Hiroshima and Nagasaki for incidence studies.

More than 30 years ago, population-based tumor registries were established in Hiroshima and Nagasaki. This report, the first of a series of papers on cancer incidence, describes methodological aspects of the tumor registries and discusses issues of data quality in the context of the Life Span Study (LSS) cohort, the major atomic bomb survivor population. The tumor registries in Hiroshima and Nagasaki are characterized by active case ascertainment based on abstraction of medical records at area hospitals, augmented by tissue registries operational in the area and a number of clinical and pathological programs undertaken over the years among the atomic bomb survivors. Using conventional measures of quality, the Hiroshima and Nagasaki tumor registries have a death certificate-only (DCO) rate of less than 9%, a mortality/incidence (M/I) ratio of about 50%, and a histological verification (HV) rate in excess of 70%, which place these registries among the best in Japan and comparable to many established registries worldwide. All tumor registry data pertaining to the LSS population were assembled, reviewed and handled with special attention given to the quality and uniformity of data based on standardized procedures. Special studies and monitoring programs were also introduced to evaluate the quality of the tumor incidence data in the LSS. Analyses were performed to examine the quality of incidence data overall and across various substrata used for risk assessment such as age, time and radiation dose groups. No significant associations were found between radiation dose and data quality as measured by various indices. These findings warrant the use of the present tumor registry-based data for studies of cancer incidence in the atomic bomb survivors.

Adolescent↗

Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.

This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon (ERR1SV = 0.72), lung (ERR1SV = 0.95), breast (ERR1SV = 1.59), ovary (ERR1SV = 0.99), urinary bladder (ERR1SV = 1.02) and thyroid (ERR1SV = 1.15), significant radiation associations were observed. There was some indication of an increase in tumors of the neural tissue (excluding the brain) among persons exposed to the bombs before age 20. For the first time, radiation has been associated with liver (ERR1SV = 0.49) and nonmelanoma skin (ERR1SV = 1.0) cancer incidence in the LSS cohort. The present analysis also strengthened earlier findings, based on a smaller number of cases, of an effect of A-bomb radiation on salivary gland cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Successful treatment of chemotherapy-resistant adult T cell leukemia/lymphoma by irinotecan hydrochloride (CPT-11)].

A 62-year-old man was hospitalized in March 1990 due to upper abdominal discomfort and anorexia. The chest X-ray revealed an upper anterior mediastinal tumor, and abdominal ultrasound showed lymphadenopathy. Endoscopic examination of the stomach revealed a large, irregular ulcer, which was histologically confirmed to be malignant lymphoma by biopsy. Serum anti-HTLV-1 antibody was positive. A diagnosis of ATLL (lymphoma type) was made. The usual therapy for this disease, including the LSG4 and RCM protocols, was only transiently effective. Therefore, the patient was treated with CPT-11 (40 mg/m2) by intravenous infusion on 3 consecutive days with weekly repetition in November 1990. Complete remission was obtained after 2 weeks of treatment, and was maintained for 5 months. This case suggests that CPT-11 may be effective for the treatment of ATL.

Aged↗

Incidence of female breast cancer among atomic bomb survivors, 1950-1985.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

Adult↗

Differentiation between cutaneous form of adult T cell leukemia/lymphoma and cutaneous T cell lymphoma by in situ hybridization using a human T cell leukemia virus-1 DNA probe.

Adult T cell leukemia/lymphoma (ATLL) shares overlapping clinicopathological features with cutaneous T cell lymphoma (CTCL), requiring detection of monoclonal integration of proviral DNA of type 1 human T cell leukemia virus for its differential diagnosis from the latter. We applied in situ hybridization (ISH) and polymerase chain reaction (PCR) to paraffin sections from 63 Japanese autopsy cases that had been diagnosed as CTCL in earlier years when ATLL was still not widely known. Eleven and two cases with confirmed diagnoses of ATLL and CTCL served as positive and negative controls, respectively. It was found that ISH was positive in 7 of 63 test cases and 10 of 11 positive controls, whereas PCR was positive in none of the test cases and eight of the positive control cases. Two negative controls were negative for both ISH and PCR. We conclude that ISH is superior to PCR for detecting type 1 human T cell leukemia virus proviral DNA on paraffin sections and that the ISH method is useful for differentiating CTCL from the cutaneous form of ATLL.

Base Sequence↗

Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue.

BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.

Adolescent↗

Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Using in situ hybridization, we studied muscle biopsy specimens from 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Three of the 4 patients with MELAS had a mutation at position 3243 of mitochondrial DNA (mtDNA) in the transfer RNALeu(UUR) gene, and the other patient had a mutation at position 3271 in the same transfer RNALeu(UUR) gene. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) were extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase-reactive blood vessels) and ragged-red fibers. Cytochrome c oxidase activity in most of these reactive blood vessels and ragged-red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome c oxidase is not a primarily defective enzyme. The pattern of expression of genes for mtDNA-encoded ribosomal RNA and the protein-coding region cytochrome c oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.

Blood Vessels↗

Secretion of mouse alpha-amylase from fission yeast Schizosaccharomyces pombe: presence of chymostatin-sensitive protease activity in the culture medium.

We have constructed two secretion vectors for Schizosaccharomyces pombe using an SV40 promoter and the secretion signals of the pGKL killer toxin complex derived from Kluyveromyces lactis. Although indigenous secretory glycoproteins tend to accumulate in the periplasmic space of S. pombe, we have succeeded in the secretion of mouse alpha-amylase into the culture medium. The efficiency of secretion, processing pattern, stability and culture conditions for mouse alpha-amylase were studied in S. pombe. The 128 kDa killer secretion signal was more effective in directing secretion of mouse alpha-amylase than the 28 kDa killer secretion signal. We detected a chymostatin-sensitive protease activity in the culture medium of S. pombe, which digests mouse alpha-amylase secreted into the culture medium. The addition of 5 micrograms/ml chymostatin was shown to protect mouse alpha-amylases from this degradation.

Amino Acid Sequence↗

EBER-1 expression in thymic carcinoma.

The Epstein-Barr virus-encoded small nuclear RNA, EBER-1, has been shown to be a suitable target for the in situ hybridization detection of EBV in routinely processed tissue specimens. We evaluated the presence of EBV in thymic carcinoma and invasive thymoma using EBER-1 in situ hybridization on formalin-fixed paraffin-embedded tissue sections. EBER-1 expression was demonstrated in a case of lymphoepithelioma-like thymic carcinoma, but was not detectable in other thymic carcinomas including six squamous cell carcinomas, a clear cell carcinoma and seven invasive thymomas. As reported in three previous cases of EBV-associated thymic carcinoma, lymphoepithelioma-like thymic carcinoma was shown to be closely associated with EBV in our series.

Adolescent↗

Epstein-Barr virus related gastric cancer in Japan: a molecular patho-epidemiological study.

Epstein-Barr virus (EBV) involvement in gastric carcinoma has been demonstrated by the presence of EBV genomes and EBV-encoded small RNA (EBER) in the carcinoma cells, monoclonal proliferation of EBV-infected carcinoma cells and elevated antibody titers. The present study was conducted to investigate the prevalence of EBV involvement among gastric carcinomas observed in nine Japanese cities with varying gastric cancer rates. In situ hybridization of EBER-1 was applied to paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement was detected based on uniform hybridization in carcinoma cells. Epstein-Barr virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV involvement did not vary significantly for each city and there was no correlation with underlying gastric cancer mortality rates. Thus, geographic variation of gastric cancer rates within Japan cannot be explained in terms of EBV involvement. Epstein-Barr virus-related gastric carcinoma is one of the most common EBV-related tumors in Japan. The involvement of EBV was significantly more frequent among males than among females, mainly for cancers occurring in the upper and middle part of the stomach, and exhibited more variation by cell type among males. These observations suggest that other factors yet to be discovered may modulate the causal role of EBV in gastric carcinogenesis.

Adolescent↗

Primary carcinoma of the choroid plexus in Li-Fraumeni syndrome: case report.

An 8-month-old female infant with a primary carcinoma of the choroid plexus developed a rhabdomyosarcoma in the anterior chest wall at the age of 1 year and 2 months. Her mother had developed a liposarcoma in her left thigh at the age of 17 years. One of the patient's siblings had a rhabdomyosarcoma of the epipharynx at the age of 1 year. This is the fourth reported case of a choroid plexus carcinoma occurring in Li-Fraumeni syndrome.

Carcinoma, Papillary↗

[A study of birth weight of the Republic of Central Africa].

It is known that the rate of low birth weight in African developing countries is very high. A birth weight analysis based on their delivery charts is made in this paper for the babies born from 1988 to 1990 at two maternity hospitals, Castor and Boy-Rabe, in Bangui, the capital of the Republic of Central Africa. The total number of births amounted to 27,188 for Castor and 7,667 for Boy-Rabe, excluding multiple births. As a result, it was found that the youngest mother's age was twelve and the oldest fifty three, with the average age at the first delivery seventeen, followed by the another delivery every two years. Mean birth weight (MBW) values were significantly higher in Castor (males 3,134 +/- 527.5, females 3,018 +/- 511.6 grams) than in Boy-Rabe (males 3,017 +/- 542.6, females 2,909 +/- 507.1 grams). The total rate of low birth weight (LBW) under 2,500 grams was 10.9 percent. That of Castor maternity was 9.8 percent, while it was 14.7 percent for Boy-Rabe, which is significantly higher than the former. In addition, the rate of LBW is the highest in the first delivery for mothers younger than 16, while it is the lowest in the sixth delivery of the group of mothers group aged 25-29. Looking at the seasonal variation of LBW, we noticed that it became higher in July and August every year, the busiest period for farming, with harvesting followed by planting. These findings suggest that low birth weight infants are due to the age of delivery being younger than sixteen and also to the mother's heavy labor.

Adolescent↗

Increased human T lymphotropic virus type-1 (HTLV-1) proviral DNA in peripheral blood mononuclear cells and bronchoalveolar lavage cells from Japanese patients with HTLV-1-associated myelopathy.

Human T lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is endemic in tropical areas and in southwestern Japan, and has now been identified among risk groups in the United States and some European countries. Patients with HAM/TSP may also have T lymphocyte alveolitis related to the HTLV-1 infection. To quantify proportions of HTLV-1-infected cells, a fragment of HTLV-1 proviral DNA was amplified from peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells obtained from patients with HAM/TSP, non-HAM/TSP HTLV-1 carriers with chronic pulmonary inflammation, and asymptomatic HTLV-1 carriers. The proportion of HTLV-1-infected cells in PBMC from patients with HAM/TSP was much higher (3-30%) than that from asymptomatic HTLV-1 carriers (mostly < 1%), based on findings with the quantitative polymerase chain reaction. In non-HAM/TSP carriers with chronic pulmonary inflammation, HTLV-1-infected cells in PBMC were also increased, but not as markedly as that seen in patients with HAM/TSP. Integration of HTLV-1 was also noted in BAL cells from patients with HAM/TSP or non-HAM/TSP carriers with chronic pulmonary inflammation. However, in patients with HAM/TSP, there was a marked increase in HTLV-1-infected cells in the lung (7.5-30% of BAL cells), as compared with findings in non-HAM/TSP carriers (< 5%). These results suggest that increased HTLV-1 proviral DNA loading may play an important role in the development of T lymphocyte alveolitis and myelopathy in patients with HAM/TSP.

Adolescent↗