Barrett's esophagus is considered a precancerous lesion of esophageal adenocarcinoma (EAC). Long-segment Barrett's esophagus, which is generally associated with intestinal metaplasia, has a higher rate of carcinogenesis than short-segment Barrett's esophagus, which is mainly composed of cardiac-type mucosa. However, a large number of cases reportedly develop EAC from the cardiac-type mucosa which has the potential to involve intestinal phenotypes. There is no consensus regarding whether the definition of Barrett's epithelium should include intestinal metaplasia. Basic researches using rodent models have provided information regarding the origins of Barrett's epithelium. Nevertheless, it remains unclear whether differentiated gastric columnar epithelium or stratified esophageal squamous epithelium undergo transdifferentiation into the intestinal-type columnar epithelium, transcommittment into the columnar epithelium, or whether the other pathways exist. Reflux of duodenal fluid including bile acids into the stomach may occur when an individual lies down after eating, which could cause the digestive juices to collect in the fornix of the stomach. N-nitroso-bile acids are produced with nitrites that are secreted from the salivary glands, and bile acids can drive expression of pro-inflammatory cytokines via EGFR or the NF-kappa B pathway. These steps may contribute significantly to carcinogenesis.
Kim, Chul Jang
Tambe, Yukihiro
Mukaisho, Ken-Ichi
Sugihara, Hiroyuki
Isono, Takahiro
Sonoda, Hiromichi
Shimizu, Tomoharu
Kondoh, Gen
Inoue, Hirokazu
Human cyclin D1 generates two major isoforms via alternative splicing: cyclin D1a and cyclin D1b. Cyclin D1b is hardly expressed in normal tissues but is frequently expressed in certain types of cancer tissues. To clarify the oncogenic potential of cyclin D1b variant, we developed cyclin D1b transgenic (Tg) mice and analyzed their phenotypes. We detected rectal tumors in 63% (15/24) of the female Tg mice. All rectal tumors had the histological characteristics similar to human sessile serrated adenoma/polyps (SSA/Ps). Adenocarcinomas were also found in 53% (8/15) of the rectal tumors, suggesting that these adenocarcinomas originated from the SSA/P-like lesions. No rectal tumors were found in the ovariectomized female cyclin D1b Tg mice (0/10), indicating that ovarian hormones played a critical role in rectal carcinogenesis in these Tg mice. Both phosphorylation of Erk, without activating MEK, and expression of estrogen receptor beta were elevated in the rectal tumors of female cyclin D1b Tg mice compared with normal rectums of female wild-type mice. In addition, we established a cell line, D1bTgRT, derived from a rectal cancer of female Tg mouse. Small interfering RNA-induced cyclin D1b knockdown in this cell line suppressed Erk phosphorylation, anchorage-independent growth, cell invasiveness and tumorigenicity in nude mice. In humans, expression of cyclin D1b messenger RNA was detected in 17% (1/6) of colorectal cancer cell lines and 9.7% (3/31) of colorectal cancer tissues. Taken together, these results indicate that cyclin D1b expression contributes to the female- specific rectal carcinogenesis in mouse model. =20
The objective of the present invention is to provide a control device for an internal combustion engine with which it is possible to achieve both a control for suppressing abnormal combustion and a catalyst temperature control when abnormal combustion is detected. With the present invention, the catalyst temperature of a catalyst arranged in the exhaust passage of the internal combustion engine is obtained, and abnormal combustion in the combustion chamber of the internal combustion engine is detected. In addition, the present invention is equipped with: a gas control means that controls the amount of intake air flowing into the combustion chamber and the temperature of the exhaust air flowing into the catalyst; a fuel injection amount control means that controls the amount of injected fuel supplied to the combustion chamber; and an abnormal combustion suppression mode selection means that selects one of three modes on the basis of the catalyst temperature when abnormal combustion is detected. In the first mode abnormal combustion is suppressed by increasing the catalyst temperature by means of the gas control means, in the second mode abnormal combustion is suppressed by suppressing an increase in the catalyst temperature by means of the fuel injection amount control means, and in the third mode abnormal combustion is suppressed by means of the gas control means and the fuel injection amount control means.
Irinotecan is a key drug for patients with advanced and recurrent colorectal carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as there is no useful marker to predict chemosensitivity to the drug. The aim of the present study was to evaluate whether the expression levels of adenosine triphosphate-binding cassette sub-family G (WHITE) member 2 (Junior blood group) (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using the resected primary tumor specimens of 189 patients with colorectal cancer, the association between the immunohistochemical expression of ABCG2 protein and the results of the collagen gel droplet embedded culture drug sensitivity test, performed to evaluate the chemosensitivity to SN-38 (an active metabolite of irinotecan), was investigated. Among the 189 patients, 17 received irinotecan-based chemotherapy, and their responses and progression-free survival (PFS) were analyzed. The tumors of patients with increased ABCG2 expression accounted for 60% of the tumors examined, and were significantly more resistant to SN-38, compared with patients with low ABCG2 expression (P<0.001). In a multivariate logistic regression analysis, increased expression of ABCG2 protein was an independent and significant predictor of resistance to SN-38, increasing the risk of resistance by 12-fold. Increased expression of ABCG2 and a low sensitivity to SN-38 was significantly associated with resistance to irinotecan-based chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with increased expression of ABCG2 was significantly shorter, compared with patients with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased immunohistochemical expression of ABCG2 in primary tumors may be a useful predictive biomarker of resistance to irinotecan-based chemotherapy for patients with recurrent or metastatic colorectal cancer.
A control device (100) of an internal combustion engine (10) is equipped with a supercharger (14) having an idle-stop mechanism (30). In order to suppress excessive elevation of the temperature of a catalyst (16), this control device comprises control means (30) that detects the atmospheric pressure and alters the threshold value relating to a parameter that enables implementation of idle-stop processing by the idle-stop mechanism so that this threshold value is altered in the direction such as to disable idle-stop processing to an extent that is progressively increased as this detected atmospheric pressure assumes lower values.
A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61-year-old man was autopsied after Suffering from myelodysplastic syndrome (chronic myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were suspected as infiltration of leukemia cells before the autopsy. However, blastic leukemia cells were not observed in the lung, although they were seen in the bone marrow and spleen at autopsy. Instead, an unusual amount of cholesterol deposits was observed with mucormycosis and aspergillosis in the lungs. Cholesterol deposition was observed not only in perihilar but also in subpleural regions without apparent bronchial obstruction in both lungs. It is thought that malfunction of monocytes/macrophages resulted in repeated fungal infection and storage of cholesterol caused by tissue destruction and impaired tissue repairing. (C) 2008 Elsevier GmbH. All rights reserved.
In the present study, we developed a novel, simple, and specific detection method using an RP-HPLC at UV 285 nm for the separation and quantification of N-nitroso-bile acids. First, we found that N-nitroso-bile acids have a specific spectrophotometric absorbance at 285 rim. Using this 285 nm detection system, we could especially measure N-nitroso-bile acids, even in co-existence of non-N-nitroso-bile acids. Next, we observed the decomposition of N-nitroso-glychocholate under alkaline, acidic, and neutral conditions. N-nitroso-glychocholate rapidly decomposed under alkaline conditions (pH 9) (t(1/2) = 0.96 h), but remained fairly stable under acidic (PI-I 2) (t(1/2) = 12.8 h) and neutral (pH 7) (t(1/2) = 7.8 h) conditions. This study is the first report, which simply and specifically analyzes N-nitroso-bile acids using an RP-HPLC system.
Background: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors. Methods: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering. Results: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters. Conclusion: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk. (c) 2018 S. Karger AG, Basel
An advanced method of analysis for grid-connected PV systems is developed in this research. To investigate the issues which may arise in the clustered PV systems, a "Demonstration Project on Clustered PV Systems" was initiated in December 2002 in Oota, Japan, involving the installation of more than 500 residential PV systems in the demonstrative research area, and the development of battery-integrated PV systems to avoid restrictions on output power due to the raising of the grid voltage. The annual performance of commercial PV systems without battery was analyzed and a performance ratio of 80% on average was found to have been achieved. Overvoltage of power distribution lines and snow are two major factors capable of causing very low performance ratio on a daily basis. The effects of batteries have also been analyzed, and the results indicate that there will be some reduction of energy losses due to the grid voltage, but the PCS efficiency will be at least 8% worse than that of commercial PV systems. It was also found that nonoptimized battery operation sometimes results in a fully charged situation at noontime and maximum reverse power flow may not be minimized in this situation. (c) 2008 Wiley Periodicals, Inc.
BackgroundRat gastroduodenal reflux models have been used for analyzing Barrett's carcinogenesis. Mice seem to be more useful than rats for studies targeting genes.MethodsWe induced gastroduodenal contents reflux by esophagojejunostomy using C57BL/6J mice. Mice were divided into a standard diet and high-fat diet groups and kept for 60weeks. Bile was sampled from the gallbladder to analyze bile acid fractions, and the esophagus was removed for a histological investigation. Human esophagogastric junction adenocarcinoma cells (OE19) were exposed to taurocholic acid (TCA), after which cell proliferative activity was measured. Rat esophageal cancer cell lines, ESCC-DR and ESCC-DRtca with higher malignant potential induced by continuous TCA exposure, were used to perform comprehensive genetic analysis (CGH).ResultsBarrett's epithelium onset occurred in all mice, and no differences in histological changes were noted between the standard diet and high-fat diet groups. However, no development of adenocarcinoma was noted. Most of the mouse bile acid was taurine conjugates. In the experiment using OE-19 cells, TCA promotes cell proliferation in a dose-dependent manner. Array CGH analysis revealed a large number of chromosomal abnormalities in the ESCC-DR, in addition to genetic abnormalities such as in the UGT2B gene, the substrate of which is bile acid. TCA administration resulted in more chromosomal abnormalities being detected.ConclusionsWe showed the effects of TCA in cancer progression in vitro. However, Barrett's adenocarcinoma onset rates differ between mice and rats despite undergoing similar reflux stimulation including taurine-conjugated bile acids being detected in mouse bile juice. These results suggest that host factors seem to influence Barrett's carcinogenesis.
Takeda, Takashi
Sugihara, Hiroyuki
Suzuki, Yasutaka
Kawamata, Jun
Akutagawa, Tomoyuki
Molecular structures of dicyanomethylenated quinacridone (1) as a solid and in solution were examined on the basis of single-crystal X-ray structural analysis, temperature-dependent (1)H NMR in CD2Cl2, and theoretical calculations. Crystal 1 had a curved, butterfly-shaped molecular structure. Thermally activated flipping between the curved, butterfly-shaped structure and an armchair structure occurred in solution. Electrochemical reduction triggered a dynamic change from the curved, butterfly-shaped conformation in the neutral state to a planar conformation in the dianion state, which represented electrochromic behavior with electrochemical bistability. A large two-photon absorption cross section of compound 1 was observed in the resonance-enhancement region of 423 GM (1 GM =3D 1 * 10(-50) cm(4) s photon(-1) molecule(-1)) at 710 nm. Multiple donor-acceptor charge-transfer pathways of molecule 1 enhanced two-photon absorption. =20
The entity of serrated adenoma of the colorectum was first proposed in 1990, and it was characterized as epithelial neoplasia combining the architectural features of a hyperplastic polyp with the cytological features of an adenoma. Over the past few years, various clinicopathological studies on serrated adenoma have been reported, but its histogenesis remains unclear. Recently the existence of a "serrated neoplasia pathway" leading to malignancy, which is different from the so-called adenoma-carcinoma sequence, has been discussed. Yao et al. reported that hyperplastic polyps and serrated adenomas share a common cell lineage with gastric differentiation. To clarify the existence of the serrated neoplasia pathway, we performed immunohistochemical staining of cytokeratin 7 (CK7) and cytokeratin 20 (CK20), which are commonly used to determine the primary site of a metastatic lesion, and we examined the pattern of CK7/CK20 expression in various colorectal lesions including 44 serrated adenomas, 25 hyperplastic polyps, 20 traditional adenomas, and 48 carcinomas. An obvious difference existed in the pattern of CK7/CK20 expression between the serrated lesions (hyperplastic polyps and serrated adenomas) and others. The majority of serrated adenomas and hyperplastic polyps presented a CK7+/CK20+ pattern, whereas most conventional adenomas and adenocarcinomas expressed CK7-/CK20+. Adenocarcinoma developing in serrated adenoma also presented a CK7+/CK20+ pattern. There are several reports that CK7 is a possible marker of transient dedifferentiation in the gastric carcinogenesis process. Taken together with the present results, a distinct pathway of colorectal carcinogenesis must exist, which is different from the adenoma-carcinoma sequence. CK7 is a possible marker for the serrated neoplasia pathway of colorectal carcinogenesis.
The pathogenic mechanisms responsible for inflammatory bowel disease, especially ulcerative colitis (UC), are poorly understood. As an animal model, the oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to UC. However, the pathogenic factors responsible for DSS-induced colitis and above all, the intestinal microflora in this colitis remain unclear. Therefore, we investigated the relationships between DSS and the intestinal microflora in this study. First, the depolymerization of DSS in mouse feces was analyzed using a pyridylamino-labeling (PA-DSS) and HPLC system. Next, a bacteriological study of the fecal contents using DSS-rich media and subsequently a classification using 16S rRNA were performed. Surprisingly, DSS was depolymerized in mouse feces under aerobic conditions, not under anaerobic conditions. Several kinds of microflora were suggested to be involved in this depolymerization. In particular, Proteus mirabilis can grow in DSS-rich media and has an ability to desulfonate and depolymerize DSS. Then, we produced chemically-modified Mr 2500 DSS from native Mr 5000 DSS. This depolymerized Mr 2500 DSS was administered orally to mice and the colitis was evaluated histologically. The cytotoxicity of Mr 2500 DSS on Caco-2 cells was also investigated. Mr 2500 DSS induced weaker colitis in mice and weak cytotoxicity on Caco-2 cells as compared to Mr 5000 DSS. These findings give insight into the mechanisms responsible for DSS-induced colitis, especially with respect to the molecular mass of DSS.
The voltage of power distribution lines will be increased due to reverse power flow from grid-connected PV systems. In the case of high-density grid connection, the voltage increase will be higher than in a stand-alone grid connection system. To prevent overvoltage on the power distribution lines, the PV system's output will be restricted if the voltage of the power distribution line is close to the upper limit of the control range. Because of this interaction, the output loss will be larger in the high-density case. This research has developed a quantitative analysis method for PV system output and losses in order to clarify the behavior of grid-connected PV systems. All the measured data are classified into loss factors using a 1-minute average of 1-second data instead of the typical 1-hour average. The operation point on the I-V curve is estimated to quantify the loss due to the output restriction, using the module temperature, array output voltage, array output current, and solar irradiance. As a result, the loss due to output restriction is successfully quantified and the behavior of output restriction is clarified. (c) 2006 Wiley Periodicals, Inc.
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