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Biomedical subjects

Yukiko Shimizu

Publications and source records attributed to Yukiko Shimizu.

18 recordsLinked to original sources
PubMed2006

Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins.

Insufficient T-cell response to human T-cell leukemia virus type-I (HTLV-I) is a potential risk factor in adult T-cell leukemia (ATL). We established an assay system for detecting HTLV-I-specific T-cell response by using recombinant glutathione-S-transferase (GST) proteins fused with HTLV-I Tax protein that was divided into three portions, Tax-A, -B, and -C, corresponding to the N-terminal, central and C-terminal regions, respectively. When splenocytes from rats immunized with plasmids encoding Tax cDNA were incubated with these recombinant proteins, strong interferon gamma (IFN-gamma-producing responses occurred against GST-Tax proteins but not against control GST proteins. No such Tax-specific responses were observed in splenocytes from naive rats. Cocktails of oligopeptides corresponding to the Tax-A, -B, and -C regions also induced IFN-gamma-producing responses when incubated with splenocytes from immunized rats, but required higher amounts of antigens and there were a shorter periods of sustained T-cell responses than with GST-Tax protein-based assay. Although splenocytes from immunized rats predominantly reacted against GST-Tax-B protein, they failed to react with peptide cocktails corresponding to the Tax-B region, likely because the major epitope was interrupted in the initially prepared series of peptides. Using a newly prepared peptide series we found that splenocytes predominantly reacted with a peptide located in the Tax-B region that overlaps with a previously identified cytotoxic T lymphocytes (CTL) epitope of this rat strain. Using this system, we examined peripheral blood mononuclear cells (PBMC) from an ATL patient who underwent complete remission following hematopoietic stem cell transplantation (HSCT). PBMC from this patient produced a significant Tax-specific T-cell response predominantly against GST-Tax-A protein. This is consistent with the previous finding that this patient exhibited a strong HLA-A2-restricted CTL response to Tax 11-19 epitope, which is located in the Tax-A region. This study provides a diagnostic tool, useful for monitoring HTLV-I-specific T-cell immunity in patients and for surveying HTLV-I-carriers to identify an immunological group at high risk for ATL development, regardless of their human leukocyte antigen (HLA) types. It is also useful for predicting the location of T-cell epitopes, which may be applicable in future vaccine strategies.

Animals↗
PubMed2006

Steroid sulfatase in breast carcinoma and change of serum estrogens levels after operation.

Fifty-four breast carcinomas were studied for the expression of steroid sulfatase (STS) by immunohistochemistry. Correlations between the expression of STS and clinical parameters were determined. Concentrations of serum estrone (E1), estrone sulfate (E1S), estradiol (E2) and estradiol sulfate (E2S) in 12 postmenopausal patients with STS positive tumor were measured by radioimmunoassay. Positive expression of STS was obtained in 72% of tumors. The incidence of STS positive tumor was significantly more frequent in postmenopausal patients (p = 0.01). In our postmenopausal patients, serum E1, E1S, E2, E2S and E2S levels in STS high score group were decreased postoperatively, and those in both STS high and low score group were stabilized after operation. Results from this study suggest STS in breast carcinoma may play an important enzyme of the intratumoral estrogen synthesis in postmenopausal women, and it would be interesting that locally produced STS might be closely related to the control of estrogens environment in breast carcinoma.

Adult↗
PubMed2006

A pathology study of malignant and benign ovarian tumors among atomic-bomb survivors--case series report.

The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.

Age Distribution↗
PubMed2006

Effect of NaCl on the lipid peroxidation-derived aldehyde, 4-hydroxy-2-nonenal, formation in boiled pork.

Pork was boiled at 100 degrees C for 5, 10 and 15 min and stored at 0 degrees C, and changes in the 4-hydroxynonenal (HNE), malonaldehyde (MA) and fatty acid (FA) contents were analyzed immediately and 3 days later. The HNE, MA and FA contents in all samples were not significantly different from each other. Pork samples containing none (control), 1% and 2% NaCl were boiled at 100 degrees C for 5 min and stored at 0 degrees C, and changes in the HNE, MA and FA contents and cooking yields were immediately analyzed and after 0, 1, 2 and 3 days. Cooking losses in the NaCl-containing samples were significantly lower than those of the control. The HNE contents in the control samples of boiled pork had significantly increased after 3 days of storage, while the contents in the NaCl-containing samples were significantly lower than those of the control after 1, 2 and 3 days of storage. The MA contents in all samples were not significantly different from each other. All FA contents analyzed had decreased in all samples after 3 days of storage. The decrease ratio of highly unsaturated fatty acids was lowest in the sample containing 2% NaCl.

Aldehydes↗
PubMed2005

Identification of two new HLA-A*1101-restricted tax epitopes recognized by cytotoxic T lymphocytes in an adult T-cell leukemia patient after hematopoietic stem cell transplantation.

We previously reported that Tax-specific CD8(+) cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo.

Amino Acid Sequence↗
PubMed2004

Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates.

The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in gamma-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age-time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the gamma-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0-2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.

Adolescent↗
PubMed2004

[A retrospective analysis of infection after corneal transplantation].

PURPOSE: We studied retrospectively the background of postoperative infection after corneal transplantation. METHODS: We reviewed the records of 753 eyes that had undergone corneal transplantation at Kyoto Prefectural University of Medicine or the Baptist Eye Clinic over a period of 6 years from April 1994 to March 2000. Patients who developed microbial keratitis after corneal transplantation were evaluated for the incidence of infection, age, the interval between transplantation and infection, microbiological etiology, the use of topical steroids, therapy, and complications. RESULTS: Follow-up after keratoplasty averaged 43.2+/-25.6 months (mean+/-standard deviation). Among 753 eyes examined, microbial keratitis developed in 27 eyes (3.6%), 14 eyes had bacterial, and 13 had fungal infections. The ages at presentation were 51.4+/-21.5 years for bacterial infections, and 66.5+/-11.1 for fungal infections. The time intervals between transplantation and the onset of infection averaged 7.8+/-7.9 months for bacterial infections, and 24.2+/-17.2 for fungal infections. Infections in 7 (50.0%) of the bacterial eyes were caused by methicillin-resistant Staphylococcus aureus (MRSA) or epidermidis (MRSE), and 9 (69.2%) of the fungal infections by yeast type fungus (8 were Candida species). At onset of keratitis, 3 (21.4%) of the bacterial eyes and 6 (46.2%) of the fungal eyes were treated with fluorometholone, and 11 (78.6%) of the bacterial eyes and 7 (53.8%) of the fungal eyes were treated with betamethazone or dexamethasone. The treatment duration until the focus of disappeared was 32.8+/-19.7 days for bacterial eyes, and 74.8+/-56.3 for fungal eyes. Major complications associated with infection included corneal perforation in 2 eyes of both the bacterial (14.3%) and fungal (15.4%) eyes, graft rejection in 4 (28.6%) bacterial eyes and 1 (7.7%) fungal eye, there was no recurrence of infection in the bacterial eyes but there were 3 (23.1%) cases of recurrence in the fungal eyes. CONCLUSIONS: Infection after corneal transplantation is opportunistic. Fungal infections occurred later than bacterial infections. Also in fungal infections, the mean age at presentation was higher and the recurrence of infection was more frequent.

Adolescent↗
PubMed2003

Second analysis of mortality of nuclear industry workers in Japan, 1986-1997.

IA cohort study of nuclear industry workers was initiated in 1990 to determine the possible health effects of low-level radiation. A total of 5,527 deaths were ascertained among 176,000 male workers who had been retrospectively and/or prospectively followed for an average of 7.9 years during the observation period 1986-1997. Statistical analyses were made mainly on the prospective follow-up outcome of 120,000 workers followed for an average of 4.5 years. The standardized mortality ratio (and its 95% confidence interval) was 0.94 (0.90, 0.97) for 2,934 cases of all causes combined and 0.86 (0.82, 0.91) for 1,305 cases of non-malignant diseases combined, which suggested a healthy worker effect. For 1,191 cases of all cancers combined, it was 0.98 (0.93, 1.04), indicating no difference in mortality from that of the general population. In tests for trend of death rate with increasing radiation dose, no significant correlation was found for all cancers combined. For site-specific cancers, most cancers including leukemia showed no positive correlation with dose, except for cancers of the esophagus, stomach and rectum and multiple myeloma. External causes showed a significant correlation with dose. A separate questionnaire study indicated that these positive findings could be ascribed in part to lifestyle characteristics of the workers. For leukemia only, we attempted to estimate the excess relative risk per unit dose of radiation, which, with reservations because of its wide confidence interval, was within the range of variation of the risks reported in other radiation epidemiological studies. This population must be studied for a longer time and with a consideration of the possible effects of confounding factors.

Age Factors↗
PubMed2003

Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997.

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.

Adolescent↗
PubMed2002

Control of light pulse propagation with only a few cold atoms in a high-finesse microcavity.

Propagation of a light pulse through a high-Q optical microcavity containing a few cold atoms (N<10) in its cavity mode is investigated experimentally. With less than ten cold rubidium atoms launched into an optical microcavity, up to 170 ns propagation lead time ("superluminal"), and 440 ns propagation delay time (subluminal) are observed. Comparison of the experimental data with numerical simulations as well as future experiments are discussed.

Journal Article↗
PubMed2002

Regulation of estrogen activity in human endometrium: effect of IL-1beta on steroid sulfatase activity in human endometrial stromal cells.

We investigated the effect of interleukin 1beta (IL-1beta) on steroid sulfatase (STS) activity and the expression of STS mRNA in human endometrial stromal cells. Endometrial tissue samples were obtained from patients undergoing hysterectomy to remove uterine fibroids. Stromal cells were isolated from the tissue preparation and cultured. IL-lbeta (1 approximately 100 ng/ml) was added into the culture medium and incubated for 24 h. The expression of STS mRNA was measured by competitive RT-PCR. The addition of IL-lbeta at 10 and 100 ng/ml suppressed STS mRNA expression to 55.2 +/- 12.8% and 25.1 +/- 10.9%, respectively, of the control sample to which no IL-lbeta had been added. STS activity was measured by radiolabelled steroid metabolite using thin layer chromatography, and this activity was also significantly suppressed in response to the administration of IL-lbeta in a dose-dependent manner. When IL-1 receptor antagonist (IL-1ra) was added together with IL-1beta to the culture medium, mRNA expression and STS activity were recovered. The present study is the first to demonstrate IL-1beta regulation of STS activity locally in human endometrium. IL-1beta suppressed mRNA and activity of STS in stromal cell culture. This initial demonstration of IL-1beta regulation of STS implies that IL-1beta may control the steroid microenvironment in human uterine endometrium by reducing biologic action of estrogen.

Arylsulfatases↗
PubMed2002

The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells.

Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.

Aromatase↗
PubMed2002

Life-style and other characteristics of radiation workers at nuclear facilities in Japan: base-line data of a questionnaire survey.

To examine confounding on the risk assessment of the radiation workers at nuclear facilities in Japan, a questionnaire survey of their characteristics such as life-style and occupational history was performed for 54,369 male and 470 female workers who were currently engaged in the job and valid answers were obtained from 48,281 males and 428 females. In order to know whether these characteristics were different among different dose groups, the Mantel extension statistical test was performed only for male respondents, with cumulative radiation doses stratified into 5 classes. Increasing trend according to the increasing doses was statistically significant for the percentages of tobacco smokers and of heavy smokers. It was also the case for heavy alcohol drinkers. Percentages of workers who were engaged in jobs dealing with specific toxic materials were also increasing in the higher dose groups. On the other hand, percentage of workers who underwent the X-ray examination of the upper digestive tracts or other radiological examinations tended to be lower in higher dose groups. These results indicate that characteristics of radiation workers such as life-style are different among dose groups and thus may play a role as a confounding factor in the statistical relation between the radiation doses and cancer mortalities.

Adult↗
PubMedDate not supplied

Ceroid accumulation in rat kidneys caused by uptake of ferric nitrilotriacetate.

Ceroid accumulation in kidneys caused by lipid peroxidation in vivo was studied during intraperitoneal (i.p.) injections of ferric nitrilotriacetate (Fe3+-NTA) solution, which is a weak iron chelate compound and generates free radicals in the presence of oxygen. Fe3+-NTA solution (0.5-0.75 mg/100 g body weight) was injected into rats (n=6) for 4 days a week. After 2 weeks of Fe3+-NTA loading, the rats were not treated for 1 month as a rest interval, and then the iron loading was repeated for 35 weeks including the rest intervals. Two rats in each group, Fe3+-NTA loading and control, were sacrificed at 19 and 40 weeks of age, and portions of a kidney and the liver of each rat were fixed in 10% formalin buffered to pH 7.0 for the histological studies. We found ceroid accumulates in greater amounts and more quickly within macrophages and epithelial cells of proximal convoluted tubules of the kidney and Kupffer cells of the liver in iron-loaded rats.

Journal Article↗