Decreased Prostaglandin E2 Production by Inflammatory Cytokine and Lower Expression of EP2 Receptor Result in Increased Collagen Synthesis in Keloid Fibroblasts

We investigated the metabolism of arachidonic acid in normal skin-derived fibroblasts (NF) as well as in keloid-derived fibroblasts (KF) in response to macrophage migration inhibitory factor (MIF), a pluripotent cytokine. We found that MIF enhanced cyclooxygenase-2 activity in NF more than in KF. Consistent with this finding, prostaglandin E2 (PGE2), an antifibrogenic molecule, was more significantly increased in NF than in KF by MIF treatment. As regarding E prostanoid receptor 2, the level of expression was significantly lower in KF than in NF. On the other hand, Forskolin, a direct activator of adenylcyclase, decreased collagen synthesis in both NF and KF, which indicates that cAMP plays an important role in regulating collagen synthesis. As PGE2 induces cAMP production, it is conceivable that increased collagen synthesis in KF might be owing to decreased PGE2 and cAMP production. These findings may aid in the development of a therapeutic strategy for the regulation of collagen synthesis in keloid fibroblasts

Graded (metric) tenses in embedded clauses: The case of South Baffin Inuktitut

This work discusses how tenses in South Baffin Inuknitut (SBI; the Eskimo-Aleut family), which are associated with remoteness specifications, are interpreted in embedded clauses. In SBI dependent clauses, the reference point for remoteness specifications may be, but is not necessarily, relativized (shifted) to a time other than external "now". For example, while the hodiernal past (marked by suffix -qqau) designates the day of utterance as its domain of coverage, it may not do so in a subordinate clause. Whether an embedded tense may and must be relativized with regard to remoteness depends on four factors: (i) whether the embedded tense is relativized with regard to temporal direction (the past-present-future opposition), (ii) what the type of the subordinate clause is, (iii) what the tense of the superordinate clause is, and (iv) what the tense of the subordinate clause is. The findings suggest that tense systems across languages may contrast not only with respect to under what circumstances shifting of the directional temporal reference point takes place, but also with respect to under what circumstances shifting of the reference point for temporal remoteness takes place

Prevalence of Exogenous Hormone Use in Japanese Women

Background: There have been few community-based epidemiological studies in which the prevalence of exogenous hormone use, including the use of oral contraceptives (OCs) and hormone replacement therapy (HRT), has been accurately assessed in Japan. Methods: We have been conducting repeated surveys of participants in the Japan Nurses’ Health Study (JNHS), as a nationwide prospective cohort study, since 2001. We determined the prevalence of exogenous hormone use at baseline and during a 10-year follow-up period. A total of 15,019 female nurses participated in the JNHS follow-up cohort. We determined the prevalence of OC use in 14,839 women <60 years of age at baseline and the prevalence of HRT use in 7,915 women, excluding premenopausal women, at the last time they answered a questionnaire. The duration of HRT use was estimated using the Kaplan-Meier method. Results: Six percent of the participants used OCs. The proportion of HRT users who stopped HRT before the baseline survey, the proportion of women using HRT during the follow-up period, and the proportion of all of the participants who had used HRT were 3.2%, 10.6%, and 13.8%, respectively. The median duration of HRT use was 2 years. Conclusions: The lifetime prevalences of exogenous hormone use during this prospective study conducted in Japanese nurses were 6.0% for OCs and 13.8% for HRT. The information obtained in this study will be useful for clarification of the association between exogenous estrogen exposure and estrogen-related diseases as future research

Proteomics-based safety evaluation of multi-walled carbon nanotubes

This study evaluated the biological responses to multi-walled carbon nanotubes (MWCNTs). Human monoblastic leukemia cells (U937) were exposed to As-grown MWCNTs and MWCNTs that were thermally treated at 1800 degrees C (HTT1800) and 2800 degrees C (HTT2800). Cell proliferation was highly inhibited by As-grown but not HTT2800. However, both As-grown and HTT1800, which include some impurities, were cytotoxic. Proteomics analysis of MWCNT-exposed cells revealed 37 protein spots on 2-dimensional electrophoresis gels that significantly changed (p<0.05) after exposure to HTT1800 with a little iron and 20 spots that changed after exposure to HTT2800. Peptide mass fingerprinting identified 45 proteins that included heat shock protein beta-1, neutral alpha-glucosidase AB, and DNA mismatch repair protein Msh2. These altered proteins play roles in metabolism, biosynthesis, response to stress, and cell differentiation. Although HTT2800 did not inhibit cell proliferation or cause cytotoxicity in vitro, some proteins related to the response to stress were changed. Moreover, DJ-1 protein, which is a biomarker of Parkinson's disease and is related to cancer, was identified after exposure to both MWCNTs. These results show that the cytotoxicity of MWCNTs depends on their impurities, such as iron, while MWCNTs themselves cause some biological responses directly and/or indirectly in vitro. Our proteomics-based approach for detecting biological responses to nanomaterials is a promising new method for detailed safety evaluations.ArticleToxicology and Applied Pharmacology. 242(3):256-262 (2010)journal articl

Association between FSH, E1, and E2 levels in urine and serum in premenopausal and postmenopausal women

Objective: We aimed to establish correlations for the levels of follicle-stimulating hormone (FSH), estrone (E1) and estradiol (E2) between urine and serum in premenopausal and postmenopausal women using immunoassays. Methods: In this study of 92 women (61 postmenopausal, 31 premenopausal), both urine and blood specimens were collected on the same day and stored at 4 °C for analysis by chemiluminescent immunoassay, radioimmunoassay and/or electrochemiluminescent immunoassay. Results: There were correlations in the levels of FSH, E1 and E2 between urine and serum in both postmenopausal (r = 0.96 for FSH, r = 0.91 for E1, r = 0.80 for E2) and premenopausal (r = 0.98 for FSH, r = 0.92 for E1, r = 0.90 for E2) women. It is indicated that the correlations were stronger in the premenopausal group compared with the postmenopausal group, especially for FSH. Conclusion: The levels of FSH, E1 and E2 in urine correlated with those in the serum in premenopausal and postmenopausal women. Urine samples could be used instead of serum samples to measure hormone levels, which would reduce the difficulty of conducting large survey studies

Noise reduction effect in super-high resolution LCDs using independent sub-pixel driving technology

We have developed and reported a super-high resolution liquid crystal display (SHR-LCD) using a new resolution enhancement technology of the independent sub-pixel driving (ISD) that utilizes three sub-pixels in each pixel element. This technology realizes the three-times resolution enhancement of monochrome LCDs, and improves the depiction ability of detailed shape such as micro-calcifications of a mammography and bone structures. Furthermore, the ISD technology brings not only resolution enhancement but also noise reduction effect by the high-resolution data sampling in displaying the clinical images. In this study, we examined the efficacy of the newly developed LCDs from the noise power spectrum measurement (NPS), the perceptual comparison of the phantom images and the clinical images. A 15 mega-pixel (MP)SHR-LCD out of a 5MP LCD and a 6MP SHR-LCD out of a 2MP LCD were used for the measurement and the evaluation. In the NPS measurements, the noise of all the SHR-LCDs was improved obviously. The improvement degree of the NPS varied according to the sub-sampling ratio of the data sampling implemented during the image displaying, and the 6MP LCD showed higher improvement. In the perceptual evaluation of the quality-control phantom images and the low-contrast images of the micro-calcifications of the mammography, all the SHR-LCDs provided higher performance than the conventional LCDs. These results proved that the SHR-LCDs using the ISD technology had the excellent ability to display the high-resolution clinical images

Development of a new resolution enhancement technology for medical liquid crystal displays

金沢大学大学院医学系研究科量子医療技術学A new resolution enhancement technology that used independent sub-pixel driving method was developed for medical monochrome liquid crystal displays (LCDs). Each pixel of monochrome LCDs, which employ color liquid crystal panels with color filters removed, consists of three sub-pixels. In the new LCD system implemented with this technology, sub-pixel intensities were modulated according to detailed image information, and consequently resolution was enhanced three times. In addition, combined with adequate resolution improvement by image data processing, horizontal and vertical resolution properties were balanced. Thus the new technology realized 9 mega-pixels (MP) ultra-high resolution out of 3MP LCD. Physical measurements and perceptual evaluations proved that the achieved 9MP (through our new technology) was appropriate and efficient to depict finer anatomical structures such as micro calcifications in mammography

Syntheses of melatonin and its derivatives

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部Two simple synthetic methods for melatonin are newly developed from tryptamine through intermediates, which are promising lead compounds for drug developing research. Novel chemical reactivities of melatonin in its bromination, lithiation, and acylation are also reported

Histological examination of frozen autograft treated by liquid nitrogen removed after implantation

金沢大学医薬保健研究域医学系Background: Several oncological sterilization methods involving autoclaving, irradiation, or pasteurization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones. Methods: We analyzed frozen autografts treated by liquid nitrogen, retrieved at a mean of 19.1 months (2-75 months) after implantation because of complications or local tumor recurrence. The specimens were obtained from six patients with a mean age of 36.2 years (8-68 years). The six grafts comprised three osteoarticular grafts, two intercalary grafts, and one joint graft. We histologically reviewed the autograft-containing sections for tumor cell necrosis, evidence of cortical repair, the cortical junction, and joint cartilage. Results: Tumor cells were completely eradicated from the frozen bone in all cases. In a specimen retrieved 5 months after implantation, a small area of the bone showed active osteocytes and osteoblasts. In three cases retrieved more than 1 year after implantation, osteocytes and osteoblasts were observed in broad portions of the frozen bones, indicating the onset of osteogenesis in the frozen bone at an early stage. The cortical host-graft junction showed incorporation along with continuity of bone trabeculae. In addition, we were able to fi nd normal chondrocytes on the articular surface. Conclusions: The frozen bone specimens in this study thus showed evidence of newly formed bone and earlier osteogenesis than has been previously reported. Our results suggest that frozen autografts may be considered one of the most useful recycled materials for biological reconstruction. © 2009 The Japanese Orthopaedic Association