[Clinicopathological value of ER alpha, ER beta and those isoforms in breast cancer].
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Biomarkers, Tumor↗
Biomedical subjects
Y Omoto
Publications and source records attributed to Y Omoto.
Clinical Significance of Estrogen Receptor Àin Breast Cancer.
To estimate the clinical significance of estrogen receptor (ER) beta in breast cancer we reviewed some reports and compared them with our preliminary results. The structure of ERbetais similar to that of ER alpha. The DNA binding domain of ER beta is 96% conserved compared with ER alpha, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen responsiveelements on target genes and that they may also bind similar ligand. The targettissues of ER beta such as testis, prostate, lung, brain, thymus, and ovary, are different from those of ER alpha, ovary, uterus, endometrium, and breast. Although the function of ER beta in breast cancer progression is not well understood, 30-50% of breast cancers may express ER beta mRNA signals. Additionally, ER beta may be auseful prognostic factor in patients with breast cancer, because tumors that co-expressed ER alpha and ER beta might be node positive and tend to be of higher grade.Further characterization of the function of ER beta and its isoforms in breast cancer is warranted.
Journal Article↗
Consecutively Occurring Multiple Fibroadenomas of the Breast Distinguished from Phyllodes Tumors by Clonality Analysis of Stromal Tissue.
We present a woman with consecutively occurring multiple fibroadenomas of thebreast distinguished from phyllodes tumor by clonality analysis of stromal tissue. Fifty-three masses developed in her right breast in an 11.5 year period since first onset. A clonality analysis, performed by polymerase chain reaction (PCR), focused on the Hpa II site within exon 1 of the androgen receptor (AR) gene. Estrogen receptor (ER) alpha immunohistochemistry was performed with a specific polyclonal antibody against the hormone binding domain of the protein. Since all of the nodules were polyclonal in stromal tissues, they were hyperplastic rather than true neoplasms such as phyllodes tumors. The co-existence of abundant adenosisfoci and numerous sub-clinical small nodules in the adjacent breast tissue alsosuggested proliferative stimuli throughout the breast. ER alpha protein was expressed only in the nuclei of epithelial cells. The possible influence of ER positive epithelial cells on stromal cell growth is discussed.
Journal Article↗
DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers.
Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to polymerase chain reaction (PCR) amplification. To confirm the results of PCR-based methylation analysis, Southern hybridization was also performed. Twenty of 29 patients with ER-alpha-positive tumours and five of 27 with ER-alpha-negative tumours were unmethylated at the P1 promoter region of the ER-alpha gene. The incidence of methylation was highly negatively correlated with ER-alpha expression (P = 0.0002). A similarly negative correlation was observed at the P0 promoter region of the ER-alpha gene (P = 0.0154). Additionally, the tumours with the ER-alpha gene hypermethylated at both promoter regions had definitely negative ER-alpha values. It was suggested that this epigenetic change might control ER-alpha expression, and might play an important role in the loss of hormone-dependence in breast cancer.
Breast Neoplasms↗
Detection of DNA Fragmentation in Human Breast Cancer Tissue by an Antibody Specific to Single-stranded DNA.
While there have been many reports concerning the clinical significance of bcl-2 expression in human breast cancer, little is known about apoptosis in primary breast cancers. We immunohistochemically examined DNA fragmentation in 107 primary human breast cancers from Japanese women using an antibody specific to single-stranded DNA. The apoptosis index calculated as the product of the positive cell number and the cellularity coefficient, ranged from 0 to 48. The average incidence of apoptosis was calculated as 0.1% of tumor cells. No relationships were observed among the apoptosis index, expression of bcl-2, and the histological grade of the tumors. Almost all apoptotic cells were phagocytosed by surrounding tumor cells immediately after DNA fragmentation. Apoptotic body formation was rare. The apoptotic cells seemed to be degraded within phagocytes, leaving no trace of apoptosis except the tiny shells of nuclei. The intensive phagocytic reaction might be one of the main reasons for the low incidence of apoptosis in human breast cancers.
Journal Article↗
Genetic and epigenetic alterations of the estrogen receptor gene and hormone independence in human breast cancer.
The existence of hormone-independent tumors is a substantial problem for the present endocrine treatment of breast cancers. Estrogen receptor (ER) gene mutation can change the biochemical activity of the protein and can affect hormone responsiveness. However, quite a few mutations of significance have been described in breast cancer. Recently, numerous variant ERs have been detected at the mRNA level with alternative splicing, yielding deletion of exon 3, 5, or 7. The truncated ER protein induced from variant mRNA could mainly be exhibited as a repressor through dominant negative effects on normal ER protein. The mechanism of the loss of hormone dependency is, however, still very complex. Further work to assess the correlation between clinical behavior and ER variants is required to determine whether these variants play a role in hormone-resistant disease. Additionally, the DNA methylation of the ER gene itself may control ER expression. These epigenetic changes can play an important role in the loss of hormone dependence in breast cancer.
Alternative Splicing↗
[Prognostic significance of loss of heterozygosity in breast cancer].
Loss of heterozygosity (LOH) was analyzed in 113 cases of sporadic breast cancer using 35 microsatellite markers on 20 chromosomes. LOH was frequently seen in 17p (44%), 16q (31%), 17q (29%) and 13q (23%). Individual patients were scored according to the incidence of LOH at the above four chromosomal markers; with no LOH as 1, with one or two LOH as 2, and with three of four LOH as 3. A high LOH score was well associated with high histological grade (p = 0.019) and a significantly poor prognosis (p = 0.0035). These data suggest that accumulation of LOH occurs at a later stage of breast cancer progression, and that the LOH score may be a useful prognostic marker of breast cancer.
Breast Neoplasms↗
The Clinical Value of Microsatellite Instability and a Loss in Heterozygosity in Sporadic Breast Cancers.
We analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) in 108 cases of sporadic breast cancers using 22 microsatellite markers on 12 chromosomes. LOH was frequently seen in 1p(13%), 6p(18%), 8p(11%), 11p(18%), 13q(21%),16q(31%), 17p(44%) and 17q(29%). Individual patients were scored according to the degree of LOH at the above eight chromosomal markers. Patients with no LOH were scored as 1, patients with one to three LOH were scored as 2, and patients with four or more LOH were scored as 3. A high LOH score correlated with a high histological grade (p=0.019) and a poor prognosis (p=0.0035). Eleven(10.2%) of 108 patients with breast cancer showed MI, with 6 cases showing MI at a single locus and 5 at multiple loci. Of the 11 MI-positive patients only one had lymph node involvement(p=0.015), none had histological grade 3 disease, and MI-positive patients tended to have a better prognosis than MI-negative ones. These data suggest that MI may be an early event in mammary tumorigenesis, and that LOH occurs at a later stage. The LOH score may be a useful prognostic marker of operable breast cancer.
Journal Article↗
Microsatellite instability in in situ and invasive sporadic breast cancers of Japanese women.
We studied the timing of microsatellite instability (referred to as replication error; RER) presentation during human breast carcinogenesis using tissue microdissected from both in situ and invasive breast cancers of Japanese women. We analyzed 100 breast cancer specimens for RER at nine genomic loci on seven chromosomes. Eight of the 100 cases (8%) were RER-positive at one or more chromosomal loci. Additionally; we obtained genomic DNA from two of four RER-positive patients with an intraductal component, both of which showed microsatellite instability in in situ foci. This finding indicates that microsatellite instability may be an early event during human breast carcinogenesis.
Breast Neoplasms↗
CD4 T-lymphocyte activation is associated with peak expiratory flow variability in childhood asthma.
BACKGROUND: Asthma has been recognized as a chronic inflammatory disorder of the airway. We have investigated the relationships among the activation markers on lymphocytes, eosinophils, their serum products in the peripheral blood, and the variability of airway obstruction in childhood asthma. METHODS: Twenty-two patients with atopic asthma (mean age, 12 years) were treated regularly and asked to measure their peak expiratory flow (PEF) twice daily for 7 days, Peripheral venous blood was obtained on day 8. RESULTS: The absolute counts of CD4 T lymphocytes expressing the activation marker CD25 in the peripheral blood on day 8 correlated significantly with the values of the coefficient of variation (CV) of both morning PEF (p < 0.01) and night PEF (p < 0.05) obtained over 7 days, but those of CD8+/CD25+ T lymphocytes, those of CD23+ B lymphocytes, and the serum concentrations of soluble CD25 did not. The absolute counts of peripheral blood eosinophils also demonstrated a significant correlation with the CV values of both morning PEF (p < 0.01) and night PEF (p <0.05). CONCLUSION: CD4 T-lymphocyte activation and increased counts of eosinophils in peripheral blood correlate with CV of PEF in patients with asthma, suggesting that CV of PEF is a good marker for assessing not only the variability of airway obstruction but also the degree of airway inflammation.
Adolescent↗
Immunocytochemical localization of prostaglandin endoperoxide synthase in the bovine intestine.
The localization of prostaglandin (PG) endoperoxide synthase in bovine intestine was examined immunocytochemically with polyclonal antibody raised against PG endoperoxide synthase purified from bovine seminal glands. The most intense positive staining reaction for the enzyme was present in mast cells. Mast cells were found to be widely distributed in the intestinal wall, and were particularly numerous in the lamina propria. Most of the mast cells in the lamina propria of the intestinal villi were elongated and oriented with their long axis parallel to the plane of the absorptive epithelium. In whole mount preparations of jejunal villi, mast cells were seen to form a two-dimensional network in the lamina propria. In addition to mast cells, smooth muscle cells of the inner circular muscle layer and muscularis mucosae, nerve cells and fibers, endothelial cells of arterioles, and serosal epithelial cells also showed faint to moderate staining for the enzyme. These results suggested that mast cells are the major source of PGs in the bovine intestinal wall. The characteristic arrangement of mast cells in the intestinal villi may be related to their functions in this portion of the bovine intestine.
Animals↗
Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat.
Plasma post-heparin diamine oxidase (DAO) activity and plasma levels of plant sterols were examined in streptozotocin diabetic rats fed with chow containing plant sterols, to investigate the enzyme activity in relation to the morphological changes of small intestine as well as sterol absorption in the diabetic rats. Diabetic rats showed increased small intestinal mass and surface area compared with control rats. Plasma post-heparin DAO activity and plant sterol level were also increased more than 2.5-fold in the diabetic rats. Insulin treatment improved these abnormalities. Plasma DAO activity correlated to both the small intestinal hyperplastic change and plasma plant sterol levels. These results indicate that plasma post-heparin DAO activity may be used as a marker of intestinal hypertrophy as well as ability to absorb dietary sterols.
Amine Oxidase (Copper-Containing)↗
Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide-stimulated rat Kupffer cells.
In response to stimulation with lipopolysaccharide, isolated rat Kupffer cells released increased amounts of prostaglandin E2, prostaglandin D2, 6-keto-prostaglandin F1 alpha, and thromboxane B2. There was a lag of 2-6 hours before a significant release of these metabolites into the medium was detected. Nonstimulated Kupffer cells converted exogenous arachidonic acid to prostaglandins and thromboxane B2, and a major product was prostaglandin D2. Twenty-four hours after stimulation with lipopolysaccharide, Kupffer cells produced approximately 7 times more prostaglandin E2 and 2 times more prostaglandin D2, 6-keto-prostaglandin F1 alpha; and thromboxane B2 than nonstimulated cells. Western immunoblotting of microsomal proteins prepared from the stimulated rat Kupffer cells showed a 70-kilodalton component that was immunoreactive with a polyclonal anticyclo-oxygenase antibody. The intensity of the band increased with the time of the lipopolysaccharide stimulation. These results suggest that the accelerated arachidonate metabolism in lipopolysaccharide-stimulated rat Kupffer cells might be attributed to an induction of the cyclo-oxygenase enzyme.
6-Ketoprostaglandin F1 alpha↗
[The synthesis of cytokines by human lens epithelial cells--interleukin 1 (IL-1), tumor necrosis factor (TNF) interleukin 6 (IL-6), and epidermal growth factor (EGF)].
We proposed the hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by cytokines and/or prostaglandins, synthesized by residual lens epithelial cells (LEC). To test our hypothesis, we measured IL-1 alpha, TNF-alpha, IL-6 and EGF in the culture media of human LEC, obtained by capsulotomy during cataract surgery, by ELISA. IL-1 alpha was detected in one of the two pools of 2-week cultures (20.7 pg/10(5) cells), in two of the three pools of 3-week cultures (12.0 pg/10(5) cells and 13.9 pg/10(5) cells), and in one pool of 4-week cultures (11.1 pg/10(5) cells). IL-6 was detected in 1-week culture (195 pg/10(5) cells) and in 7-week culture (81.6 pg/10(5) cells). TNF-alpha and EGF were not detected. During culture, the cells proliferated and underwent fibroblast-like changes on exposure to the plastic wells. IL-1 and IL-6 may be also produced in vivo by residual LEC contacting with posterior chamber lens after cataract surgery, and these mediators may play a role in postoperative inflammation including fibrin reaction.
Cells, Cultured↗
Visual load of working with visual display terminals--introduction of VDT to newspaper editing and visual effect.
In the Japanese newspaper industry, since the late 1970s, computerization has been started in large scale. The system, called Computerized Typesetting System (CTS), has been introduced. With this system, all information in the newspaper is input into a computer, called up on a cathode ray display (CRT) to edit, and then output to film or printing plates by CTS. Thus, the work of newspaper production has undergone a major transformation from industrial work to clerical work. It was reported that newspaper production staff working with VDTs complained more than staff working with the older key system about visual and physical problems which affected their job and their daily life. The complaint rates were highest for editors, who used VDT constantly throughout the day. This study was performed to clarify the health impact of VDT use and to prevent health disorders caused by the introduction of CTS. It is concluded that 5 m corrected vision and sphere refraction of CTS workers who used CTS over 2 or 4 hr daily, significantly became worse in a year after the introduction. Therefore, it is indicated that the control of CTS work time is important to prevent the visual disorder.
Adult↗
[Detection of methicillin-resistant Staphylococcus aureus by the Showa disk].
The Showa disk susceptibility test using two penicillinase-resistant penicillins (PRPs: methicillin and oxacillin) and four cephalosporins (cefazolin, cefmetazole, ceftizoxime, and latamoxef) was evaluated to discriminate between the strains of Staphylococcus aureus resistant to methicillin (MRSA) and those susceptible (MSSA). Among 129 MRSA and 112 MSSA strains, significant numbers of MRSA found to be false-susceptible to PRPs, especially when incubated at 37 degrees C. Using agar plates supplemented with 5% NaCl, oxacillin disk correctly categorized all the MRSA and MSSA strains, but two MSSA strains were mischaracterized with methicillin disk. All the MSSA strains found to be susceptible against cephalosporins tested, but significant numbers of MRSA were also interpreted to be susceptible. Only the result of ceftizoxime disk susceptibility test highly correlated with methicillin resistance, when incubated at 35 degrees C. All the MRSA did not produce any significant bacterial growth inhibitory zone around the disk, whereas all the MSSA found to be susceptible (19 mm or more), e.g., 100% correlation. With these data, we recommend that ceftizoxime disk susceptibility test, incubated at 35 degrees C, provides a more reliable method to characterize the strains of MRSA and MSSA. The interpretive breakpoint would be used as; less than or equal to 16 mm (greater than or equal to 25 micrograms/ml) for MRSA.
Methicillin Resistance↗
[Application of middlebrook 7H-10 agar medium for rapid detection of mycobacteria].
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Agar↗
[Re-evaluation of nursing education: in an example in training at a public health clinic at the School of Nursing, Keio Gijuku University School of Medicine].
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Education, Nursing↗