Rooj A.K.,University of Alabama at Birmingham |
Kimura Y.,Beppu University |
Buddington R.K.,University of Memphis
BMC Microbiology | Year: 2010
Background. Although probiotic bacteria and their metabolites alter enterocyte gene expression, rapid, non-genomic responses have not been examined. The present study measured accumulation of tracer (2 M) glucose by Caco-2 cells after exposure for 10 min or less to a chemically defined medium (CDM) with different monosaccharides before and after anaerobic culture of probiotic Lactobacilli. Results. Growth of L. acidophilus was supported by CDM with 110 mM glucose, fructose, and mannose, but not with arabinose, ribose, and xylose or the sugar-free CDM. Glucose accumulation was reduced when Caco-2 cells were exposed for 10 min to sterile CDM with glucose (by 92%), mannose (by 90%), fructose (by 55%), and ribose (by 16%), but not with arabinose and xylose. Exposure of Caco-2 cells for 10 min to bacteria-free supernatants prepared after exponential (48 h) and stationary (72 h) growth phases of L. acidophilus cultured in CDM with 110 mM fructose increased glucose accumulation by 83% and 45%, respectively; exposure to a suspension of the bacteria had no effect. The increase in glucose accumulation was diminished by heat-denaturing the supernatant, indicating the response of Caco-2 cells is triggered by as yet unknown heat labile bacterial metabolites, not by a reduction in CDM components that decrease glucose uptake. Supernatants prepared after anaerobic culture of L. gasseri, L. amylovorus, L. gallinarum, and L. johnsonii in the CDM with fructose increased glucose accumulation by 83%, 32%, 27%, and 14%, respectively. Conclusion. The rapid, non-genomic upregulation of SGLT1 by bacterial metabolites is a heretofore unrecognized interaction between probiotics and the intestinal epithelium. © 2010 Rooj et al; licensee BioMed Central Ltd.
Nishio M.,Kyushu University |
Otsubo K.,Kyushu University |
Maehama T.,Japan National Institute of Infectious Diseases |
Mimori K.,Beppu University |
Suzuki A.,Kyushu University
Cancer Science | Year: 2013
The Hippo pathway is an evolutionarily conserved kinase cascade involved in cell growth, apoptosis, development and migration. It is also crucial for stem cell self-renewal and the maintenance of genomic stability. In addition, this pathway has the unique capacities to sense aspects of tissue architecture, such as cell polarity and mechanical tensions imposed by the surrounding microenvironment, and to control organ size and shape. All of these properties are frequently altered in tumor cells. In this review, we summarize how dysregulation of mammalian Hippo signaling is implicated in cancer. © 2013 Japanese Cancer Association.
Hayashi T.,Beppu University |
Furuta Y.,Sanwa Shurui Co. |
Furukawa K.,Beppu University
Journal of Bioscience and Bioengineering | Year: 2011
Respiration-deficient mutant (RDM) strains of Zymomonas mobilis were isolated from antibiotic-resistant mutants. These RDM strains showed various degrees of respiratory deficiency. All RDM strains exhibited much higher ethanol fermentation capacity than the wild-type strain under aerobic conditions. The strains also gained thermotolerance and exhibited greater ethanol production at high temperature (39°C), under both non-aerobic and aerobic conditions, compared with the wild-type strain. Microarray and subsequent quantitative PCR analyses suggest that enhanced gene expression involved in the metabolism of glucose to ethanol resulted in the high ethanol production of RDM strains under aerobic growth conditions. Reduction of intracellular oxidative stress may also result in improved ethanol fermentation by RDM strains at high temperatures. © 2010 The Society for Biotechnology, Japan.
Shirakawa T.,Beppu University
Anti-Cancer Drugs | Year: 2016
Appropriate management of cardiovascular diseases (CVDs) related to chemotherapy for solid tumors is important for safe oncologic treatment. However, prediction of the onset and progression of CVDs has not generally been established in Japan. We carried out a retrospective analysis of advanced or recurrent solid tumor patients who received chemotherapies in a single institution. Patient characteristics, chemotherapy regimens, adverse events, CVDs before chemotherapy, and diagnosis of CVDs in association with chemotherapy were assessed. During the period from April 2006 to March 2012, 394 patients were examined. Cardiac diseases (CDs), hypertension (HT), or arterial thrombosis or venous thromboembolism were prevalent in 37 (9.4%), 22 (5.6%), five (1.3%), and 14 (3.5%) cases, respectively. HT (14.5%) and venous thrombosis (5.8%) were frequent in patients who received bevacizumab-containing chemotherapy. Four cases with left ventricular dysfunction experienced a decrease of ejection fraction and early filling/atrial filling (E/A) and E/A tended to decrease before ejection fraction. Ninety (62.1%) of 145 cases showed an increase in the D-dimer (DD) level before chemotherapy, and a further increase in DD level was found when venous thrombosis occurred. Relative risks of the disease progression of HT, CD, and thromboembolism because of chemotherapy were 1.3, 1.9, and 3.6, respectively. A decrease in E/A and an increase in DD were suggested to be valuable for early diagnosis of the respective onsets of left ventricular dysfunction and venous thrombosis related to chemotherapy. We conclude that patients with previous CD tend to have disease progression of CD during chemotherapy. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Kiyohara C.,Kyushu University |
Horiuchi T.,Beppu University |
Takayama K.,Kyushu University |
Nakanishi Y.,Kyushu University
Cytokine | Year: 2014
Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR=1.64, 95% CI=1.19-2.26) and IL6 rs1800796 (OR=1.41, 95% CI=1.02-1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (Pinteraction=0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer. © 2013 Elsevier Ltd.
Shiozawa S.,Beppu University
WMSCI 2012 - The 16th World Multi-Conference on Systemics, Cybernetics and Informatics, Proceedings | Year: 2012
The self-organized criticality theory explains that systemic autoimmunity, or systemic lupus erythematosus (SLE), necessarily takes place when host's immune system is overstimulated by repeated exposure to antigen, i.e., external disturbance, to levels that surpass the immune system's stability-limit, i.e., self-organized criticality. The autoreactive lymphocyte clones, which we name autoantibody-inducing CD4 T (aiCD4 T) cells, are newly generated via de novo T cell receptor (TCR) revision from thymus-passed non-autoreactive clones at peripheral lymphoid organs. They not only stimulate B cells to generate varieties of autoantibodies but also help final differentiation of CD8 T cell into cytotoxic T lymphocyte (CTL) via antigen cross-presentation to induce tissue injuries identical to SLE. The causative antigen can be individually different, but such antigen must first be correctly presented to T cells and subsequently overdrive the person's CD4 T cells in relation to his/her HLA to generate aiCD4 T cells. The ability of a certain antigen to cause autoimmunity depends on its propensity to be presented and/or cross-presented effectively, resulting in the overstimulation of CD4 and/or CD8 T cells of certain host beyond critical limit, i.e., self-organized criticality.
Takahashi Y.,Beppu University
Nihon Geka Gakkai zasshi | Year: 2012
The single-nucleotide polymorphism (SNP)-based genome-wide association study (GWAS) is now widely performed because of the development of new SNP genotyping technologies from 2007 onward. The GWAS provides a powerful approach to identify regions of the genome that harbor genetic variants conferring risk for disease without prior knowledge of location or function. During the past few years, the GWAS has identified numerous robust associations between specific chromosomal loci and different types of cancer. For nearly all regions identified in the GWAS, the per allele effect sizes estimated are < 1.5 and the mechanism of SNP in carcinogenesis was not clear. Consequently, GWAS findings underscore the complex nature of cancer. The combined effects may be sufficiently great to be useful for risk prediction, targeted screening, and prevention, particularly as more loci are identified. Some loci, such as 8q24, were identified as a cancer susceptibility region for many unrelated cancers, and therefore an investigation of those loci may disclose new mechanisms of carcinogenesis or unknown genes including noncoding RNA. Furthermore, the development of new strategies for GWAS analysis is expected.
Hayashi T.,Beppu University |
Kato T.,Beppu University |
Furukawa K.,Beppu University
Applied and Environmental Microbiology | Year: 2012
We previously isolated respiratory-deficient mutant (RDM) strains of Zymomonas mobilis, which exhibited greater growth and enhanced ethanol production under aerobic conditions. These RDM strains also acquired thermotolerance. Morphologically, the cells of all RDM strains were shorter compared to the wild-type strain. We investigated the respiratory chains of these RDM strains and found that some RDM strains lost NADH dehydrogenase activity, whereas others exhibited reduced cytochrome bdtype ubiquinol oxidase or ubiquinol peroxidase activities. Complementation experiments restored the wild-type phenotype. Some RDM strains seem to have certain mutations other than the corresponding respiratory chain components. RDM strains with deficient NADH dehydrogenase activity displayed the greatest amount of aerobic growth, enhanced ethanol production, and thermotolerance. Nucleotide sequence analysis revealed that all NADH dehydrogenase-deficient strains were mutated within the ndh gene, which includes insertion, deletion, or frameshift. These results suggested that the loss of NADH dehydrogenase activity permits the acquisition of higher aerobic growth, enhanced ethanol production, and thermotolerance in this industrially important strain. © 2012, American Society for Microbiology.
Guan J.-Z.,Chinese People's Liberation Army |
Guan W.-P.,Chinese People's Liberation Army |
Maeda T.,Beppu University |
Makino N.,Beppu University
Aging and Disease | Year: 2012
Telomere shortening has been reported to be related to oxidative stress (OS) associated with the aging process and aging-associated diseases, including Alzheimer's disease (AD). We measured the methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells of 34 AD patients and 49 healthy controls by a Southern blotting analysis, using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII. AD patients bore normal mean telomere lengths and had an unchanged distribution of the telomere length in peripheral leukocytes. However, the subtelomeres in the shortest telomeres were relatively more methylated in AD patients of both genders, compared with age-matched controls. We observed that the pathogenesis of AD was associated with the epigenetic condition of the subtelomere, but not on the overall telomere length and distribution. The relative elevation of subtelomeric methylation of short telomeres in peripheral blood leukocytes may be a characteristic of AD. This implies that leukocytes containing short telomeres with less methylated subtelomeres tend to be removed faster from the peripheral blood in AD patients.
Matsumoto Y.,Beppu University
Spine | Year: 2016
STUDY DESIGN.: Retrospective diagnostic analysis.Objectives. To establish a new scoring system, the Dumbbell scoring system (DSS), for preoperative evaluation of the malignant potential of spinal dumbbell tumors (SDTs). SUMMARY OF BACKGROUND DATA.: Among SDTs, benign tumors such as Schwannomas occur frequently while malignant SDTs, including malignant peripheral nerve sheath tumors (MPNSTs), are uncommon. No scoring system has been developed to preoperatively diagnose the malignant potential of SDTs. METHODS.: We retrospectively reviewed the records of 59 consecutive patients with SDTs. The following imaging features were recorded: tumor size, tumor shape, tumor boundary, pattern of enhancement of intratumoral lesions (homogeneous or heterogeneous), and cyst formation in the tumors on MRI; and enlargement of neural foramina and scalloping or osteolytic destruction of surrounding bones on CT. The prevalence of characteristic imaging features in malignant and benign SDTs were evaluated, and appropriate cut-off points for the DSS score were obtained using receiver operating characteristics. RESULTS.: Twenty cases were confirmed to be malignant tumors. Pathological diagnoses of the malignant SDTs were as follows: 11 cases of MPNST, 3 cases of malignant lymphoma, and 1 case each of extraskeletal Ewingʼs saroma, hemangiopericytoma, hemangioendothelioma, malignant myoepithelioma, neuroblastoma, and plasmacytoma. The DSS was based on four characteristic imaging features confirmed as significant predictors of malignant SDTs, namely, maximal diameter greater than 5?cm, irregularly lobulated tumor, tumor boundary indistinguishable from surrounding tissues, and osteolytic bone destruction. Malignant SDTs showed a higher DSS score (median 5.5 points) than did benign SDTs (median 0 point). The optimum cut-off value for the DSS score was 3 points, and the sensitivity and specificity for the diagnosis of malignant SDTs were 90% and 84.6%, respectively. CONCLUSION.: This scoring system may be helpful for preoperative decision-making. If the DSS score is equal to or higher than 3, biopsies was recommended to confirm the histological diagnosis.Level of Evidence: 4 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.