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Biomedical subjects

Takeo Sakurai

Publications and source records attributed to Takeo Sakurai.

At least 19 recordsLinked to original sources

Effect of dietary cyclic nigerosylnigerose on intestinal immune functions in mice.

We examined the dietary effects of cyclic nigerosylnigerose (CNN), a dietary indigestible oligosaccharide with four D-glucopyranosyl residues linked by alternating alpha-(1-->3)- and alpha-(1-->6) glucosidic linkages, on the intestinal immune function of mice, and the effects were compared with those of alpha-(1-->3)-linked oligosaccharide (nigerooligosaccharides, NOS) or alpha-(1-->6)-linked oligosaccharide (isomaltooligosaccharides, IMO). BALB/c mice were fed with 1-5% CNN, 5% IMO, or 12.5% NOS for 4 weeks, and the intestinal mucosal immune responses were determined. In the 1-5% CNN fed groups, the amounts of IgA in feces increased significantly. In addition, IgA, transforming growth factor-beta1 (TGF-beta1), and interleukin-6 (IL-6) secretion by Peyer's patch (PP) cells were enhanced in CNN fed mice. In the 5% CNN group, pH in the cecum decreased, and the amounts of lactic acid and butyric acid increased. These findings were not observed in the NOS- or IMO-fed group of mice. They suggest that CNN supplementation changes the intestinal environment of microflora and indirectly enhances the immune function in the gut.

Animals↗

A novel phenomenon predicting the entry into a state of hibernation in Syrian hamsters (Mesocricetus auratus).

When Syrian hamsters (Mesocricetus auratus) are bred in a cold and short-day environment, most animals go into hibernation after a certain period of time. However, to date it has not been possible to predict which hamster will enter hibernation. In this study, we subcutaneously implanted thermo-loggers in hamsters bred in the cold environment, and recorded the subcutaneous temperature at short intervals until they went into hibernation. A time series analysis of temperature disclosed that a fall of 0.4 to 0.8 degrees C in subcutaneous temperature was seen 5 to 16 days before entering hibernation, and this phenomenon continued for three days or more. No hamster went into the hibernation without displaying this signal. Although the mechanism by which this phenomenon takes place is not clear, it is a sign from the body, which is useful for indicating if a hamster will enter hibernation shortly.

Acclimatization↗

Geo-referenced multimedia environmental fate model (G-CIEMS): model formulation and comparison to the generic model and monitoring approaches.

A spatially resolved and geo-referenced dynamic multimedia environmental fate model, G-CIEMS (Grid-Catchment Integrated Environmental Modeling System) was developed on a geographical information system (GIS). The case study for Japan based on the air grid cells of 5 x 5 km resolution and catchments with an average area of 9.3 km2, which corresponds to about 40,000 air grid cells and 38,000 river segments/catchment polygons, were performed for dioxins, benzene, 1,3-butadiene, and di-(2-ethyhexyl)phthalate. The averaged concentration of the model and monitoring output were within a factor of 2-3 for all the media. Outputs from G-CIEMS and the generic model were essentially comparable when identical parameters were employed, whereas the G-CIEMS model gave explicit information of distribution of chemicals in the environment. Exposure-weighted averaged concentrations (EWAC) in air were calculated to estimate the exposure ofthe population, based on the results of generic, G-CIEMS, and monitoring approaches. The G-CIEMS approach showed significantly better agreement with the monitoring-derived EWAC than the generic model approach. Implication for the use of a geo-referenced modeling approach in the risk assessment scheme is discussed as a generic-spatial approach, which can be used to provide more accurate exposure estimation with distribution information, using generally available data sources for a wide range of chemicals.

Benzene↗

Calcitonin receptor gene and breast cancer: quantitative analysis with laser capture microdissection.

There is a growing body of evidence indicating that calcitonin (CT) and its receptor (CTR) is involved in cell growth, differentiation and tissue development. Using laser capture microdissection (LCM) and real-time reverse transcription polymerase chain reactions (RT-PCR), we have investigated CTR mRNA expression in 60 primary breast cancers, including 14 pairs of matched cancers and unaffected ductal epithelia from the same patients. Our results demonstrate that CTR mRNA was constantly expressed in normal ductal epithelium and in breast cancer. In the 14 cases where matched samples were available, a decrease in CTR mRNA expression was found in 9 breast cancers (64.3%), an increased CTR expression in 2 cases (14.3%) and no significant change in 3 cases (21.4%). In 60 cases of primary breast cancers, decreased CTR expression was found in 44 (73.3%), increased CTR expression was detected in 10 cases (16.7%) and no change was observed in 6 cases (10%). Decreased CTR expression was found more often in cases with lymph node metastasis (p = 0.0498) and lymphatic invasion (p = 0.0179). Also there was a decreased CTR expression in cases with an extensive intraductal component (p = 0.0543) and a high nuclear grade (p = 0.1934), although this was not statistically significant. Overall, we conclude that CTR mRNA was constantly expressed in unaffected ductal epithelium, whereas decreased CTR mRNA expression was frequently found in breast cancers, particularly in cases with lymph node metastasis and lymphatic invasion. These results suggest that CTR might be of great potential significance in breast cancer progression.

Adult↗

Dioxins in aquatic sediment and soil in the Kanto region of Japan: major sources and their contributions.

Major sources of dioxins (tetra- to octa-chlorinated dibenzo-p-dioxins and dibenzofurans) were quantitatively identified, and the contributions of each source were estimated in aquatic surface sediment and soil in the Kanto region of Japan, where a major part of the municipal, industrial, and agricultural activities in Japan take place. Detailed chromatographic peak-specific data corresponding to all dioxin compounds were used throughout the analysis to achieve source specificity. Four major sources were identified by using principal component analysis. Three of them were combustion processes, impurities in pentachlorophenol, and impurities in the diphenyl ether herbicide CNP. One, characterized by polychlorinated dibenzo-p-dioxins with 1,2,6,9-chlorine substitution, remained unattributed to any known source or transformation process. The composition of the unattributed source resembled those reported in sediment samples free from anthropogenic impacts. Contributions from the four major sources were estimated by using a mass balance receptor model, and the source contributions to each homologue varied among samples. Tokyo Bay sediment was characterized by the highest relative contribution from pentachlorophenol impurities in the region. The unattributed source contribution was most prominent in the Lake Kasumigaura sediment. The results indicated considerable contributions in aquatic surface sediment in the studied region from dioxin impurities in herbicides used in the past.

Agriculture↗

Magnetic resonance axillography for preoperative diagnosis of the axillopectoral muscle (Langer's axillary arch): a case report.

The axillary arch of Langer is the most common muscular variation in the axilla. Recognition of anatomic variations is important for surgeons to perform safe axillary surgery. We describe a case of a woman with breast cancer, in whom sentinel lymph node biopsy was successfully performed and the presence of this anomaly preoperatively diagnosed by magnetic resonance axillography.

Axilla↗

Anastrozole-induced remission of diaphragmatic paralysis from metastatic breast cancer treated with multiple prior therapies.

We describe a woman with metastatic breast cancer treated with multiple rounds of prior cytotoxic and endocrine therapies, who presented with ipsilateral diaphragmatic paralysis. The use of anastrozole, a highly selective nonsteroidal aromatase inhibitor (1 mg daily), successfully induced remission of metastatic tumors in our patient, who is partially recovering from diaphragmatic paralysis.

Anastrozole↗

Source and behavior analyses of dioxins based on congener-specific information and their application to Tokyo Bay basin.

Identification of pollution sources and estimation of their contribution to dioxin pollution are important for taking better countermeasures against such sources. The information based on seventeen 2,3,7,8-chlorine-substituted congeners and 10 homologues is usually not sufficient for source identification. The usefulness of detailed congener-specific information of tetra- to octachlorinated polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans was examined by principal component analysis and compared with conventional dioxin information. It was revealed that congener-specific information was far more effective for source identification than conventional information. For source apportioning, it was shown that multiple regression analysis with detailed source congener profiles could be carried out successfully when calculations were performed for individual homologues. This was because of the large variation in homologue composition in source dioxin profiles in addition to the difference in environmental behavior among the homologues. The newly proposed methods for statistical analysis were applied to the estimation of dioxin mass balance in Tokyo Bay basin. It was found that Tokyo Bay sediment core contained dioxins from three major sources: combustion, pentachlorophenol (PCP), and chloronitrophen (CNP). PCP and CNP contained large amounts of dioxin as impurity and were used extensively as paddy field herbicides in Japan in the past. The total dioxin load from the two herbicides to the basin during the past 45 years (1951-1995) was estimated to be five times larger than that from combustion source in terms of toxic equivalents (WHO-TEQ). However, in the surface sediment of the bay, the contribution from the herbicides was nearly equal to that from combustion. The herbicide contribution peaked during the 1960s and 1970s and gradually decreased thereafter.

Agriculture↗

Prognostic value of thymidine phosphorylase expression in breast carcinoma.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyuridine and their analogs. TP has also angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. We examined TP expression using immunohistochemistry (654-1 Mab) in 182 invasive breast carcinomas (67 N0 and 115 N1/2; median follow-up 78 months [range, 3-177]; 51 patients treated with adjuvant systemic cyclophosphamide, methotrexate and 5-fluorouracil [CMF] chemotherapy and 82 with tamoxifen). High TP expression was found in 142 cases (78%) and correlated with lower histologic grade and low p53 expression. No correlation was found between TP expression and vascular density. TP-positive tumors had a significant increase in both disease-free survival (DFS; p = 0.0025) and overall survival (OS; p = 0.0070) in the total cohort of patients and in the subgroups of node-positive patients and patients treated with CMF adjuvant therapy; no significant difference in either DFS or OS was observed in patients without CMF treatment. Our findings suggest that TP has little effect on tumor angiogenesis of breast carcinoma, whereas it could represent an interesting marker that could predict response to CMF chemotherapy.

Antineoplastic Agents, Hormonal↗

MR-axillography oriented surgical sampling for assessment of nodal status in the selection of patients with breast cancer for axillary lymph nodes dissection.

BACKGROUND: We have reported that magnetic resonance axillography (MR-axillography) is the best method for assessing lymph node size and representing the relation of the lymph node to normal anatomy. METHODS: The four largest nodes on MR-axillography were sampled in 62 consecutive patients with breast cancer undergoing axillary clearance. Axillary clearance yielded a mean of 17.0 (range 5-28) nodes. RESULTS: A method of preliminary sampling of four nodes in the axilla oriented by MR-axillography was assessed in all cases, 22 of whom were histologically node positive. Based on the sampled nodes, lymph node metastases were detected in 20 of 22 (91%) of the node-positive patients. Based on the sampled nodes, of the 19 patients with macrometastatic nodes, lymph node metastases were detected in all 19 (100%), but only in 1 of the 3 (33%) patients with only one micrometastatic node. CONCLUSIONS: This experience indicates that sampling the four largest nodes by MR-axillography orientation accurately identifies patients with macrometaststic nodes. This result may be comparable to that of surgical sampling performed by the most skilled surgeons.

Adult↗

Thymidine phosphorylase is regulated by tamoxifen in T47D breast cancer cell line.

BACKGROUND: Thymidine phosphorylase (TP) has diverse functions within cells, including increasing the sensitivity of cancer cells to cytotoxic drugs including 5-fluorouracil (5-FU) and methotrexate. However, the regulators of TP still remains largely unknown. METHOD: In this study, we examined whether tamoxifen has specific effects on TP expression in the T47D breast cancer cell line. We studied the TP expression in the T47D cell line before and after tamoxifen treatment using Western blot analysis and ELISA. RESULTS: We found that TP expression is significantly up-regulated in tamoxifen-treated cells compared with control. CONCLUSIONS: Our findings suggest that tamoxifen may increase chemotherapy sensitivity through TP up-regulation for treatment regimens including doxifluridine, capecitabine, and/or methotrexate.

Blotting, Western↗

p63 expression in normal, hyperplastic and malignant breast tissues.

BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study. METHODS: Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining. RESULTS: p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas. CONCLUSION: The results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.

Biopsy, Needle↗

Chromosome 3p and breast cancer.

Solid tumors in humans are now believed to develop through a multistep process that activates oncogenes and inactivates tumor suppressor genes. Loss of heterozygosity at chromosomes 3p25, 3p22-24, 3p21.3, 3p21.2-21.3, 3p14.2, 3p14.3, and 3p12 has been reported in breast cancers. Retinoid acid receptor beta2 (3p24), thyroid hormone receptor beta1 (3p24.3), Ras association domain family 1A (3p21.3), and the fragile histidine triad gene (3p14.2) have been considered as tumor suppressor genes (TSGs) for breast cancers. Epigenetic change may play an important role for the inactivation of these TSGs. Screens for promoter hypermethylation may be able to identify other TSGs in chromosome 3p. Alternatively, use of an "epigenetic modifier" may enhance the response to another type of agent for breast cancer.

Breast Neoplasms↗

Examination of dioxin fluxes recorded in dated aquatic-sediment cores in the Kanto region of Japan using multivariate data analysis.

Past dioxin (coplanar polychlorinated biphenyl (Co-PCB), 2,3.7,8-substituted polychlorinated dibenzo-p-dioxin (PCDD) and 2,3,7,8-substituted polychlorinated dibenzofuran (PCDF)) fluxes recorded in dated aquatic-sediment cores were analyzed using principal component analysis (PCA). The data set consisted of samples from four cores collected from the Kanto region of Japan. Time trends and spatial differences in the dioxin flux were examined, and the potential relationship to emission sources was investigated. Twenty-five compounds and 58 core slices, corresponding to the later half of the 20th century, were subjected to the analysis. The PCA of both log-transformed and maximum-value-standardized data successfully divided the dioxin compounds into a small number of groups, and three similar clusters of Co-PCBs. PCDDs and penta- to hepta-CDFs were identified. PCB formulations used in the past are judged to have been responsible for the major part of the Co-PCB flux recorded in the sediment cores. However, the relationship to emission sources needs further investigation. It is suggested that most 2,3,7,8-substituted PCDDs and PCDFs are different from Co-PCBs in their emission sources or movements in the environment. The subcore clusters obtained from the PCA of log-transformed data show that the cores from different sampling areas exhibited distinct dioxin fluxes and compositions. Common time trends among the cores were more effectively summarized by the PCA of maximum-value-standardized data focusing on relative time trends. PC scores show that recently the flux of each dioxin compound in the four cores has been generally declining after having reached a peak.

Benzofurans↗

Retinoid, retinoic acid receptor beta and breast cancer.

Retinoids have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoic acid (RA) can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. The regulation of cell growth and differentiation of normal, premalignant, and malignant cells by retinoids is mediated by the RA receptors (RARs) and retinoid X receptor. One of the target genes of retinoid receptors is RARbeta2. A growing body of evidence supports the hypotheses that the RARbeta2 gene is a tumor suppressor gene and the chemopreventive effects of retinoids are due to induction of RARbeta2. RARbeta2 expression is reduced in many malignant tumors including breast carcinoma. This paper will briefly discuss basic aspects of retinoids and retinoid acid receptor. In particular, we review what is now known for inactivation mechanism of RARbeta2 and its role in tumor cell growth inhibition.

Breast Neoplasms↗

The Fragile Histidine Triad gene and breast cancer.

The Fragile Histidine Triad (FHIT) Gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumor suppressor gene involved in different tumor types. Abnormalities of the FHIT locus were found in many established cancer cell lines and tumors including breast cancer. In sporadic breast cancer, loss of heterozygosity within the FHIT gene has been observed at different frequencies and has been correlated with tumor progression. Aberrant FHIT transcripts have been reported in breast cancer. Furthermore, Fhit protein loss is correlated with prognosis. We summarized the research advances of FHIT genetic, epigenetic change and aberrant Fhit protein expression in breast cancer. Fhit protein may be a novel prognostic factor for breast cancer. FHIT gene therapy may potentially be clinically useful for treatment of breast cancer, suggesting further research involving FHIT introduction should be performed in breast cancer.

Acid Anhydride Hydrolases↗

Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer.

PURPOSE: The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast carcinomas. In this study, we would like to delineate more precisely its role in breast tumorigenesis. EXPERIMENTAL DESIGN: To confirm the tumorigenic role of FHIT, 46 sporadic invasive ductal carcinomas of the breast were tested for the "two hits" required to inactivate this gene. Microsatellite loss of heterozygosity (LOH) was considered as the first hit. To examine the possibility that hypermethylation serves as the second hit for FHIT inactivation, methylation of 5'-CpG islands of FHIT was analyzed by methylation-specific PCR. RESULTS: LOH was detected in 8 of 40 informative tumors, and hypermethylation was observed in 22 of 46 (48%) cases. Aberrant FHIT protein expression was found in 31 of 46 (67%) cases examined. All seven tumors showing both LOH and hypermethylation showed complete loss of Fhit protein expression. In addition, a significant positive association was found between the existence of LOH and 5'-CpG island hypermethylation (P = 0.04), which was consistent with the two-hit model. CONCLUSIONS: To our knowledge, this study provides the first evidence that biallelic inactivation of FHIT by LOH and hypermethylation leads to the complete inactivation of FHIT gene in patients with breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in primary breast carcinomas, especially those with LOH. These findings support a role for this tumor suppressor gene in sporadic breast tumorigenesis.

Acid Anhydride Hydrolases↗

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma.

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.

Adult↗