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Biomedical subjects

K Yokoro

Publications and source records attributed to K Yokoro.

At least 37 records · Page 2Linked to original sources
PubMed1991

Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer.

We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E2 without progesterone stimulates alveolar colony formation in the presence of cortisol and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E2, cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure.

Animals↗
PubMed1991

Analysis of transforming genes in indirectly induced radiogenic thymomas in mice.

The expression of oncogenes was studied in 12 types of 178 mouse tumors induced by radiations and chemicals. DNA was analyzed in tumors in which the overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not in sarcomas induced by radiation. Activation of oncogenes by small mutations and the inactivation of tumor suppressor genes has to be taken in account in the radiation induction of mouse tumors. We therefore made further analyses of radiogenic thymomas. Loss of heterozygocity was revealed in directly induced thymomas by the deletions of allele specific minisatellite bands. Analysis of a hypervariable minisatellite locus also revealed that these thymoma cells suffered high recombinogenic activity during tumorigenesis. In addition, transfection of cellular DNA to normal Golden hamster cells identified the activated K-ras oncogene in the directly induced radiogenic thymomas. Indirectly induced radiogenic thymomas were tested similarly. Transformed cells from secondary transfection experiment were positive for the mouse-specific repetitious sequences, but devoid of mouse ras oncogenes. Indirectly induced radiogenic thymomas originate from unirradiated normal thymus cells transplanted in irradiated hosts. The spontaneous activation of oncogenes yet to be identified may therefore be involved in the development of this tumor.

Animals↗
PubMed1991

Parathyroid tumors in atomic bomb survivors in Hiroshima: a review.

Parathyroid tumors in A-bomb survivors in Hiroshima have been studied. Thirteen cases of parathyroid tumor were confirmed from 4,136 autopsy cases between 1961 to 1977, and an elevated incidence of tumor with increase of dose (T65D) was demonstrated (P less than 0.01). A high proportion of 42.9%, 6 out of 14 parathyroid tumors extirpated at Hiroshima University Hospital between 1956 and 1988, were atomic bomb survivors exposed within 4.1 km from the hypocenter. From an epidemiological study using 23 parathyroid tumor cases detected in Hiroshima Prefecture between 1974 and 1987, an elevated incidence of parathyroid tumors with increase of dose (proximally exposed, other exposed and control nonexposed) was demonstrated (P less than 0.001).

Humans↗
PubMed1991

Studies of radioactivity produced by the Hiroshima atomic bomb: 1. Neutron-induced radioactivity measurements for dose evaluation.

This review summarizes measurements made of 152Eu and 60Co radioactivity induced by neutron radiation from the Hiroshima atomic bomb (A-bomb) with the goal of estimating the neutron dose released by the bomb. Prior to these measurements, A-bomb-irradiated specimens such as rocks and pieces of concrete, which had not been shielded were collected. The specific radioactivity obtained (in bequerels per gram of Eu or Co) were compared with those calculated from DS86 neutrons. Findings of usefulness of 152Eu data within 700 m ground range are reported and systematic differences between measured activities and calculations are discussed. The 152Eu data were also useful for the discussion of circular asymmetry, and there was no asymmetry within the experimental errors. This review also covers the similar difference found in 32P data, which were measured immediately after the A-bomb, along with the other 152Eu and 60Co data. The need for more measurements of 152Eu activity in samples farther away from the hypocenter in order to verify the DS86 calculations is also discussed.

Humans↗
PubMed1991

Studies of radioactivity produced by the Hiroshima atomic bomb: 2. Measurements of fallout radioactivity.

Three studies of fallout measurements were reviewed for the discussion of possible radioactivity intake from the Hiroshima atomic bomb. The first study discussed correlations between enriched 234U and 137Cs specific activities from the measurement of soil samples collected in the "black rain" area. The second study measured 137Cs activity on the rock and roof tile samples collected in the hypocenter area immediately after the explosion. Some of the rock and roof tile samples collected near the hypocenter had a small but detectable amount of 137Cs activity. However, it has been determined that 137Cs exposure, for example, was negligible compared with DS86 dose estimates, since these activity levels were low. The third study detected 90Sr activity in some of the specimens of human bones exhumed on Ninoshima Island. This study compared the difference in activity between the bone head and shaft, with higher activities obtained in the bone head. This fact suggests a short intake period for this activity, however, the levels of 90Sr contamination were too low to allow a discussion of the exposure risks.

Humans↗
PubMed1991

Parathyroid tumors in atomic bomb survivors in Hiroshima: first report of surgical cases, 1956-1988.

Seventeen patients with parathyroid gland tumors underwent surgical resection at the Hiroshima University Hospital between 1956 and 1988. Three of them where born after the atomic bomb explosion, and 6 of the remaining 14 patients (42.9% of the total- a high proportion) were atomic bomb survivors. Because parathyroid gland tumors and hyperparathyroidism are assumed to develop in patients who have been exposed to radiation after a long latent period, it is necessary to anticipate the possible occurrence of these diseases in atomic bomb survivors. The present paper is the first to report surgically extirpated parathyroid gland tumors in atomic bomb survivors.

Adolescent↗
PubMed1990

Characterization of the negative regulatory element of the 5' noncoding region of Moloney murine leukemia virus in mouse embryonal carcinoma cells.

An intragenic untranslated region of Moloney murine leukemia virus suppressed gene expression from a long terminal repeat about 30-fold in F9 cells, an embryonal carcinoma (EC) cell line. In another EC line, PCC4 cells and their subline, EA2 cells, and in a fibroblast line, NIH3T3 cells, the suppression by this region was about 4- and 3-fold, respectively. Deletion analysis indicated that the upstream of the previously defined region is required for the suppression. Although not as efficient, this region exhibited suppressive activity even when placed upstream of the transcriptional start site of the long terminal repeat. These results suggest that the suppression is cell type specific and operates partly at the level of the initiation of transcription.

Animals↗
PubMed1990

HTO oral administration in mice. I: Threshold dose rate for haematopoietic death.

Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. These data allowed absorbed organ doses to be estimated. Within a range of 1.48 x 10(11) to 5.92 x 10(11) Bq/dm3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10(10) Bq/dm3 and 1.48 x 10(11) Bq/dm3. At concentrations lower than 9.25 x 10(9) Bq/dm3, mice no longer died from haematopoietic failure. We conclude, therefore, that there should be a threshold dose rate for haematopoietic death.

Animals↗
PubMed1990

Analysis of clonal evolution in a tumor consisting of pSV2neo-transfected mouse fibrosarcoma clones.

The process of clonal evolution was analyzed in a line of methylcholanthrene-induced mouse fibrosarcomas. The tumor cells were transfected with pSV2neo gene and 22 clones were randomly isolated. Genetically tagged clones were mixed and inoculated into syngeneic mice. Southern blot analysis revealed that one of the clones, no. 11, dominated both in tumors in situ and in lung metastatic nodules. No. 11 clone and other clones were similar in growth rates in vitro and in vivo, in spontaneous and experimental metastatic abilities, in immunogenicity, and in the capacity of intercellular communication in vitro. Although no. 11 clone overgrew other clones in vivo, this was not the case when clones were mixed and maintained in vitro. We conclude that clonal interactions in vivo may be responsible for the dominance of no. 11 clone in the tumor. It is likely that the preferential metastasis of no. 11 clone to the lung may be a simple reflection of the proliferative advantage of the dominant clone in the tumor in situ.

Animals↗
PubMed1990

Lack of evidence for the involvement of type-C and type-B retroviruses in radiation leukemogenesis of NFS mice.

Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.

Animals↗
PubMed1989

Overexpression and amplification of the c-myc gene in mouse tumors induced by chemicals and radiations.

We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 alpha-tocopherol-induced sarcomas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification.

Animals↗
PubMed1989

Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells.

E-Cadherin is a member of the cadherin family, which plays a key role in intercellular adhesion in various tumors as well as in normal tissues. Here, we examined the expression of this adhesion molecule in a murine ovarian tumor line OV2944, whose sublines show different degrees of spontaneous metastasis from subcutaneous sites; sublines LM-1 and LM-3 exhibit a low metastatic activity but a variant subline HM-1 has a high metastatic activity. When the expression of E-cadherin in these cells was examined by immunoblot analysis, the highly metastatic HM-1 cells was found to express an extremely small amount of this molecule, as compared with a high level of E-cadherin expression in the weakly metastatic LM-1 and LM-3 cells. Northern blot analysis showed that the amount of tanscripts from the E-cadherin gene is proportional to the amount of proteins detected in these cells. Immunofluorescence staining revealed that cells of the highly metastatic line were heterogeneous, that is, their cultures contained both E-cadherin-positive and negative cells. In contrast, cells of the weakly metastatic lines homogeneously expressed E-cadherin. When the highly metastatic line was subcloned, all the subclones consisted of E-cadherin-positive and negative cells. These results suggest that the expression of E-cadherin gene is not stably controlled in the highly metastatic line.

Animals↗
PubMed1989

A small nuclear RNA, U5, can transform cells in vitro.

Low-molecular-weight RNA exhibiting transforming potential was identified in chemically induced lymphoma cells by the transformation of mink lung cells after transfection. The RNA was sequenced by the direct chemical method and was shown to be a small nuclear RNA, U5. The transforming potential of the RNA was further studied in quantitative transformation assays using 3Y1, a rat fibroblastic cell line. Transformed foci appeared with a latency of 3 to 4 weeks after transfection. U5-transformed 3Y1 cells frequently carried an amplified c-myc oncogene. In addition, U5 induced chromosome aberrations in transfected cells, indicating that the RNA acts as a clastogen. Transforming and clastogenic potentials were specifically inactivated when U5 was incubated with RNase H in the presence of a complementary oligonucleotide. We discuss a possible mechanism of U5-induced cell transformation.

Animals↗
PubMed1989

Mechanism of suppression of the long terminal repeat of Moloney leukemia virus in mouse embryonal carcinoma cells.

Sequence-specific DNA-binding proteins that bind to the long terminal repeat (LTR) of Moloney leukemia virus in undifferentiated and differentiated mouse embryonal carcinoma (EC) cells were identified by gel retardation assay. The proteins that bind to the CCAAT box were present in both undifferentiated and differentiated EC cells. The amounts and the number of species of the proteins that bind to the enhancer and the GC-rich region were far lower in undifferentiated EC cells than in the differentiated counterparts. These proteins were supposed to be transcriptional activators. Proteins that bind upstream of the enhancer, namely, the -352 to -346 region and the -407 to -404 region, were identified. These proteins were designated the embryonic LTR-binding protein (ELP) and the LTR-binding protein, respectively. The ELP was present only in undifferentiated EC cell lines. The LTR-binding protein was detected in all cell lines tested. The mechanism of suppression of the LTR was investigated by the chloramphenicol acetyltransferase assay. The enhancer and the GC-rich region of the LTR functioned poorly in undifferentiated cells. When eight copies of ELP-binding sequences were inserted upstream of the enhancer region, expression of the chloramphenicol acetyltransferase gene was reduced about threefold in ECA2 cells. From these data, we concluded that two mechanisms, the shortage of activator proteins and the presence of a negative regulatory protein (ELP), are involved in the suppression of the LTR in undifferentiated EC cells.

Animals↗
PubMed1989

Teratogenic effect of californium-252 irradiation in rats.

The teratogenicity of californium-252 (Cf-252) irradiation which generates approximately 70% 2.3 MeV fast neutron and 30% gamma rays was evaluated. A single whole body exposure of Cf-252 at various doses was given to pregnant rats on day 8 or 9 of pregnancy, followed by microscopic autopsy of the fetuses at the terminal stage of pregnancy to search for external and internal malformations. For comparison, pregnant rats were irradiated with various doses of cobalt-60 (Co-60) standard gamma rays at the same dose rate (1 rad/min.). The doses were 20-120 rad of Cf-252 and 80-220 rad of Co-60. Using frequency of radiation induced malformations observed on day 8 of pregnancy as an index, relative biological effectiveness (RBE) of 2.3-2.7 was obtained from the straight line obtained by modifying by the least squares method the frequency curves of malformed fetuses in total implants and in surviving fetuses. The types of malformations induced by Cf-252 and Co-60 irradiation were alike. Using fetal LD50 as an index, 2.4 was obtained as RBE when irradiated on day 8 of pregnancy and 3.1 as that when irradiated on day 9. The results showed that Cf-252 had stronger a teratogenic effect than Co-60 gamma rays.

Abnormalities, Radiation-Induced↗
PubMed1989

Acute and late effects of A-bomb radiation studied in a group of young girls with a defined condition at the time of bombing.

Ninety girl students have been identified, who were 14-15 years old when exposed to the atomic bomb while at the Central Telephone Office in Hiroshima located at a distance of 550 meters from the hypocenter. The mortality rate of the students exposed on the second floor of the building was estimated to be 50.9% and those exposed on the first floor (ground level) 33.3%. Doses to the students exposed on the second floor were estimated from cytogenetic evidence to be around 6 Gy in the T65 Dose system or appear to be 4 Gy in the DS86 system. These data indicate that LD50 is around 4 Gy in these young females. Among 28 students who were confirmed to be alive in 1965 and followed to the end of 1988, six students had breast cancer, mostly of invasive ductal type carcinoma. The incidence of breast cancer in the adolescent group was very high, the relative risk being 23.1 with 95% confidence limits of 12.9 to 42.2.

Adolescent↗
PubMed1989

Human cells of neural origin are permissive for bovine leukemia virus.

Bovine leukemia virus (BLV) propagated in a cell clone of fetal lamb kidney origin was transmitted by cell contact to different mammalian cells including human cells. The transmission of the BLV genome was effectively achieved by cocultivation of mitomycin-C-killed, virus-producing cells of the cell clone with recipient cells. In particular, human cells of neural origin were highly susceptible to BLV infection, while some other cells were resistant. The transmission of the BVL genome from virus-nonproducing cells failed which suggests the existence of virus specific receptors on the cells. The donor cells contained three integrated BLV proviruses. In recipient cells only one provirus was found. The majority of cells contained both unintegrated and integrated BLV provirus. In the cells containing the transmitted BLV, the viral genome was expressed to its protein products. The results indirectly suggest that retroviruses with similar properties could cause various neural diseases in man.

Animals↗