Okahashi Y.,Nara Medical University
Nucleic acids research | Year: 2010
Estrogen-DNA adducts are potential biomarkers for assessing the risk and development of estrogen-associated cancers. 4-Hydroxyequilenin (4-OHEN) and 4-hydroxyequilin (4-OHEQ), the metabolites of equine estrogens present in common hormone replacement therapy (HRT) formulations, are capable of producing bulky 4-OHEN-DNA adducts. Although the formation of 4-OHEN-DNA adducts has been reported, their quantitative detection in mammalian cells has not been done. To quantify such DNA adducts, we generated a novel monoclonal antibody (4OHEN-1) specific for 4-OHEN-DNA adducts. The primary epitope recognized is one type of stereoisomers of 4-OHEN-dA adducts and of 4-OHEN-dC adducts in DNA. An immunoassay with 4OHEN-1 revealed a linear dose-response between known amounts of 4-OHEN-DNA adducts and the antibody binding to those adducts, with a detection limit of approximately five adducts/10(8) bases in 1 microg DNA sample. In human breast cancer cells, the quantitative immunoassay revealed that 4-OHEN produces five times more 4-OHEN-DNA adducts than does 4-OHEQ. Moreover, in a mouse model for HRT, oral administration of Premarin increased the levels of 4-OHEN-DNA adducts in various tissues, including the uterus and ovaries, in a time-dependent manner. Thus, we succeeded in establishing a novel immunoassay for quantitative detection of 4-OHEN-DNA adducts in mammalian cells.
Honoki K.,Nara Medical University
Expert Review of Anticancer Therapy | Year: 2010
Stem cells are defined by their unique characteristics, which include their abilities to self-renew and differentiate. Normal somatic stem cells have been isolated from various tissues such as bone marrow, adipose tissue, mammary glands and the nervous system. They are considered naturally resistant to chemotherapeutic agents because they express high levels of membrane transporter molecules, detoxifying enzymes and DNA repair proteins. Several recent studies have identified the presence of side populations in various cancer tissues, the so-called 'cancer stem cells', which are defined as the counterparts of stem cells in tumor tissues. These cancer stem cells possess stem-like properties, such as self-renewal and differentiation abilities, as well as playing a role in tumor initiation. Most sarcomas, which are thought to originate from mesenchymal stem cells, are highly malignant and approximately 30-40% of them show local and/or distant relapse (metastasis), even in the case of relatively chemosensitive tumors such as osteosarcomas and Ewing sarcomas. Several studies have suggested the presence of stem-like cell populations in sarcomas, based on their tumorigenicity and drug resistance. This review explores the issues of drug resistance of cancer stem cells in sarcomas and the possibilities of targeting cancer stem cells for the future treatment of sarcomas. © 2010 Expert Reviews Ltd.
Yamashita M.,Nara Medical University
Biochemical and Biophysical Research Communications | Year: 2011
Neural progenitor cells and developing neurons show periodic, synchronous Ca 2+ rises even before synapse formation, and the origin of the synchronous activity remains unknown. Here, fluorescence measurement revealed that the membrane potential of the nuclear envelope, which forms an intracellular Ca 2+ store, changed with a release of Ca 2+ and generated spontaneous, periodic bursts of fluctuations in potential. Furthermore, changes in the nuclear envelope's potential underlay spike burst generations. These results support the model that voltage fluctuations of the nuclear envelope synchronize Ca 2+ release between cells and also function as a current noise generator to cause synchronous burst discharges. © 2011 Elsevier Inc.
Takeshima Y.,Nara Medical University
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society | Year: 2012
Destructive spondyloarthropathy may occur in long-term hemodialysis patients, but focal amyloid deposits in the spine are rare. We present a case of upper cervical extradural amyloidoma with a history of long-term hemodialysis presenting with progressive and intractable radiculopathy. We describe a 51-year-old female with a long-term history of hemodialysis treatment. She suffered progressive and intolerable right occipital headache. Neurological examination revealed right C2 radiculopathy. Magnetic resonance imaging (MRI) of the cervical spine showed a solid focal extradural mass lesion at the C2 level. She underwent subtotal resection of the extradural mass lesion and decompression of the right C2 nerve root by a posterior approach. Histological examination revealed amyloid deposits. The occipital headache immediately disappeared after surgery. Follow-up MRI 10 months after surgery demonstrated no recurrence of the extradural amyloidoma. Development of an upper cervical extradural amyloidoma after long-term hemodialysis is extremely rare. Prompt evaluation of long-term hemodialysis patients suffering from progressive cervical pain should be recommended, and treatment is required if there are signs or symptoms of compression of a nerve root or the spinal cord.
Osaki S.,Nara Medical University
Physical Review Letters | Year: 2012
We overcome the difficulties in pulling long draglines from spiders, twist bundles of dragline filaments, and succeed in preparing violin strings. The twisting is found to change the cross section shapes of filaments from circular to polygonal and to optimize the packing structure with no openings among filaments providing mechanically strong and elastic strings. The spider string signal peaks of overtones for the violin are relatively large at high frequencies, generating a soft and profound timbre. Such a preferable timbre is considered to be due to the unique polygonal packing structure which provides valuable knowledge for developing new types of materials. © 2012 American Physical Society.