Kato T.,Suzuka University of Medical Science
Clinical calcium | Year: 2017
Physical activity may play an important role in maximizing bone mass during adolescence to young adulthood and may have long-lasting benefits on bone health. Because peak bone mass is thought to be attained by the end of the third decade, the early adult years may be the final opportunity for its augmentation. High-impact weight-bearing exercise during youth may provide lifelong benefits in terms of bone mineral content, structure and strength, and consequently reduce fracture risk. Weight-bearing exercise in youth affects bone, and these effects may be preserved as BMC, geometric and structural advantages even after 40 years. In order to evaluate the bone strength enhanced by the exercise and sporting activity, not only measuring the BMD by DXA but also the cross sectional geometric bone analysis may clarify the further contributions.
Ishikawa H.,Nagoya University |
Otaka H.,Nagoya University |
Maki K.,Nagoya University |
Morita T.,Suzuka University of Medical Science |
Aiba H.,Suzuka University of Medical Science
RNA | Year: 2012
Hfq-dependent sRNAs contain, at least, an mRNA base-pairing region, an Hfq-binding site, and a Rho-independent terminator. Recently, we found that the terminator poly(U) of Escherichia coli sRNAs is essential for Hfq binding and therefore for riboregulation. In this study, we tried to identify additional components within Hfq-binding sRNAs required for efficient Hfq binding by using SgrS as a model. We demonstrate by mutational and biochemical studies that an internal hairpin and an immediately upstream U-rich sequence also are required for efficient Hfq binding. We propose that the functional Hfq-binding module of SgrS consists of an internal hairpin preceded by a U-rich sequence and a Rho-independent terminator with a long poly(U) tail. We also show that the Rho-independent terminator alone can act as a functional Hfq-binding module when it is preceded by an internal U-rich sequence. The 3′ region of most known sRNAs share the features corresponding to either a double-or single-hairpin-type Hfq-binding module. We also demonstrate that increasing the spacing between the base-pairing region and the Hfq-binding module reduces or impairs the silencing ability. These findings allowed us to design synthetic Hfq-binding sRNAs to target desired mRNAs. Copyright © 2012 RNA Society.
Satomi Y.,Suzuka University of Medical Science
Anticancer Research | Year: 2012
Background/Aim: The antitumor effect of fucoxanthin, a marine carotenoid found in brown algae, was investigated on prostate cancer cells. Materials and Methods: LNCap prostate cancer cells were treated with fucoxanthin and the effects were evaluated in relation to cell proliferation, cell cycle, expression of growth arrest, DNA damage-inducible protein (GADD45) genes, and phosphorylation status of mitogen-activated protein kinases. Results: Fucoxanthin inhibited the growth of LNCap prostate cancer cells in a dose-dependent manner. Growth-inhibitory effects were accompanied by the induction of GADD45A expression and G 1 cell cycle arrest, but not apoptosis. Furthermore, fucoxanthin activated c-Jun N-terminal kinase (SAPK/JNK), while the inhibition of SAPK/JNK attenuated the induction of G 1 arrest and GADD45A expression by fucoxanthin. Conclusion: These results show that fucoxanthin induces G 1 cell cycle arrest in prostate cancer cells, and suggest that GADD45A and SAPK/JNK might be involved in these effects.
Tashiro R.,Suzuka University of Medical Science |
Ohtsuki A.,Kyoto University |
Sugiyama H.,Kyoto University
Journal of the American Chemical Society | Year: 2010
We have investigated the products of BrU in excess electron transfer and have demonstrated that in DNA the proportion of products changes with the distance between the donor and acceptor. On the basis of a labeling experiment using H2 18O, we have shown that hole migration from Py•+ formed after charge separation is involved in the reaction. © 2010 American Chemical Society.
Komeda S.,Suzuka University of Medical Science
Metallomics | Year: 2011
Platinum coordination compounds are among the most utilized anticancer agents, even though platinum has not been determined to be an essential trace element in any living organism. The success of platinum-based drugs has catalyzed research on other metal-containing agents that can be used to achieve therapeutic goals that cannot be achieved with organic compounds. The antitumor activities of recently reported platinum(ii) complexes indicate that further modification of platinum coordination compounds will lead to the development of anticancer agents with higher efficacies against chemotherapy-insensitive tumors. © 2011 The Royal Society of Chemistry.
Miyazaki T.,Nagasaki University |
Nakayama H.,Suzuka University of Medical Science |
Nagayoshi Y.,Nagasaki University |
Kakeya H.,Nagasaki University |
Kohno S.,Nagasaki University
PLoS Pathogens | Year: 2013
Proper protein folding in the endoplasmic reticulum (ER) is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR), is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata. © 2013 Miyazaki et al.
Morita T.,Suzuka University of Medical Science |
Aiba H.,Suzuka University of Medical Science
Genes and Development | Year: 2011
A major class of bacterial small RNAs (sRNAs), along with RNA-binding protein Hfq and endoribonuclease RNase E, acts on target mRNAs through base-pairing, leading to translational repression and rapid degradation of the mRNAs. In this issue of Genes & Development, Prévost and colleagues (pp. 385-396) demonstrate by using the well-characterized sRNA RyhB that RNase E cleavage at sites distal from the pairing region triggers degradation of target mRNAs. The study has provided an important insight into the initial events of sRNA-induced degradation of target mRNAs. © 2011 by Cold Spring Harbor Laboratory Press.
Sakurai H.,Suzuka University of Medical Science
Journal of Health Science | Year: 2010
This review introduces the development of metal-containing pharmaceutics (metallopharmaceutics) such as anticancer agents containing platinum (Pt) and ruthenium (Ru), and superoxide dismutase (SOD) mimetic, focusing on the recent topics on antidiabetic vanadium (V) and zinc (Zn) complexes as well as antioxidative copper (Cu) and Zn complexes. From the ancient ages, people used many types of inorganic compounds to treat physical disorders or diseases. Since the modern concept of chemotherapy was achieved by Paul Ehrlich, who developed the arsenic (As)-containing compound to treat syphilis in 1910, a wide variety of metallopharmaceutics have been proposed and clinically used worldwide. This review is described for the researchers who are interested in the current states for the development of metallopharmaceutics. © 2010 The Pharmaceutical Society of Japan.
Kuzuhara S.,Suzuka University of Medical Science
Brain and Nerve | Year: 2011
Muro disease refers to the endemic amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in the high incidence ALS focus in the Muro district of the Kii peninsula. Kii paralysis was first described in the 1680s in a folk literature, and as ALS in the medical literature by Kin-no-suke Miura in 1911. Two high-incidence ALS foci were discovered in 1960s by Kimura and Yase, and retro- and anterospective epidemiological surveys were started. Kii ALS was neuropathologically characterized by classical ALS pathology together with many neurofibrillary tangles (NFTs) in the brain, similar to Guamanian ALS. The incidence rates of ALS dramatically declined during the 1950s and 1980s, resulting in the disappearance of the high-incidence foci. In the early 1990s, however, Kuzuhara found existence of high-incidence of ALS in the region, and, in addition, of a high-incidence of PDC with abundant NFTs, similar to Guamanian PDC. The incidence rates of PDC dramatically rose during the 1980s and 1990s, and PDC replaced ALS. Unsuccessful attempts were made to identify cause and pathogenesis of the disease in minerals and environmental factors. More than 70% of patients in the endemic region had a family history of ALS or PDC; therefore, genetic factors were suspected as the cause. The authors analyzed the causative and risk candidate genes in the affected and unaffected family members, but failed to find genes related to ALS/PDC. The changing pattern of Muro disease from ALS with a younger onset and rapid progression to PDC with a later onset and longer survival suggests that some unknown environmental factor(s) might modulate the disease process, which basically might be programmed in the gene(s).
Yamamoto M.,Suzuka University of Medical Science
Yakugaku Zasshi | Year: 2014
It is necessary to offer the proper information about prescription drugs for appropriate use of them in clinical practice. However, a lot of time and labor is required to comprehensively collect the information necessary for clinical application and it could be extremely difficult. If the clinical experience and other information is derived solely on a commercial basis, then it may lead to improper prescription practices. "Academic detailing" is a form of interactive educational outreach to physicians to provide unbiased, non-commercial, evidence-based information about medications and other therapeutic decisions, with the goal of improving patient care. InWestern countries, the public funds are used to support universities and other research institution programs. The experience from such programs spreads to a broader scientific community. In US, "Academic detailing" was pioneered 30 years ago. National Resource Center for Academic Detailing (NaRCAD) is an initiative supported by Agency for Healthcare Research and Quality (AHRQ) grant. Clinical pharmacists are acting as Detailers in Europe and America, and this improves medical quality. The importance of Academic Detailing activity would be also recognized in Japan, and fully-trained (with six-years of specialized training) pharmacists with evaluative and communication skills can be expected to act as such a specialist. © 2014 The Pharmaceutical Society of Japan.