No abstract available.
Breast Neoplasms* ; Breast*

OBJECTIVES: The reproductive history of women has been suggested to have a possible influence on the risk of osteoporotic fractures. The purpose of this study was to assess the association between reproductive history and hip fractures in the elderly women. METHODS: The study subjects were drawn from women members of the Korean Elderly Pharmacoepidemiologic Cohort (KEPEC), aged 65 years or over, whose reproductive histories were available, and who were beneficiaries of the Korea Medical Insurance Corporation (KMIC) in 1993 and lived in Busan city, Korea. The information on reproductive histories, and possible confounders, were collected from mailed questionnaires. Potential hip fracture cases were collected from the claims data obtained between 1993 and 1998, with a hospital survey conducted to confirm the final diagnoses. Rate ratios and their 95% confidence intervals, were calculated using a Cox's proportional hazard model. RESUJLTS: Following up 5,219 women for 6 years, 51 cases were confirmed with hip fractures. When adjusted for age, weight and physical activity, the rate ratio of hip fractures in women who had given birth three or more times was 0.56 (95% CI: 0.25 - 1.25), compared with those who had given birth two or less times. When adjusted for age, number of births, weight and physical activity, the rate ratio in women who first gave birth when younger than 22 years was 0.60 (95% CI: 0.34 - 1.08) compared with those who had giving birth at 22 years or older. CONCLUSIONS: According to these findings, an early age when first giving birth might decrease the risk of hip fractures in elderly Korean women.
Aged* ; Busan ; Cohort Studies* ; Diagnosis ; Female ; Hip Fractures ; Hip* ; Humans ; Insurance ; Korea* ; Motor Activity ; Osteoporotic Fractures ; Parturition ; Postal Service ; Proportional Hazards Models ; Surveys and Questionnaires ; Reproductive History*

OBJECTIVES: The reproductive history of women has been suggested to have a possible influence on the risk of osteoporotic fractures. The purpose of this study was to assess the association between reproductive history and hip fractures in the elderly women. METHODS: The study subjects were drawn from women members of the Korean Elderly Pharmacoepidemiologic Cohort (KEPEC), aged 65 years or over, whose reproductive histories were available, and who were beneficiaries of the Korea Medical Insurance Corporation (KMIC) in 1993 and lived in Busan city, Korea. The information on reproductive histories, and possible confounders, were collected from mailed questionnaires. Potential hip fracture cases were collected from the claims data obtained between 1993 and 1998, with a hospital survey conducted to confirm the final diagnoses. Rate ratios and their 95% confidence intervals, were calculated using a Cox's proportional hazard model. RESUJLTS: Following up 5,219 women for 6 years, 51 cases were confirmed with hip fractures. When adjusted for age, weight and physical activity, the rate ratio of hip fractures in women who had given birth three or more times was 0.56 (95% CI: 0.25 - 1.25), compared with those who had given birth two or less times. When adjusted for age, number of births, weight and physical activity, the rate ratio in women who first gave birth when younger than 22 years was 0.60 (95% CI: 0.34 - 1.08) compared with those who had giving birth at 22 years or older. CONCLUSIONS: According to these findings, an early age when first giving birth might decrease the risk of hip fractures in elderly Korean women.
Aged* ; Busan ; Cohort Studies* ; Diagnosis ; Female ; Hip Fractures ; Hip* ; Humans ; Insurance ; Korea* ; Motor Activity ; Osteoporotic Fractures ; Parturition ; Postal Service ; Proportional Hazards Models ; Surveys and Questionnaires ; Reproductive History*

OBJECTIVES: The potential association between choline acetyltransferase(CHAT) polymorphism and the risk of mild cognitive impairment(MCI) has not been investigated in Korea. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E(APOE) polymorphism in the development of MCI in elderly Korean sample. METHODS: We analyzed CHAT 2384G > A polymorphism and APOE polymorphism among 149 MCI subjects with MCI and 298 normal controls. We tested the association between MCI and CHAT A allele status using a logistic regression model. In addition, we employed generalized multifactor dimensionality reduction(GMDR) to investigate the interaction between CHAT and APOE with regard to the risk of MCI. RESULTS: The CHAT A allele was associated with AD risk(OR = 1.59, 95% CI = 1.02-2.48, p = 0.042). No significant gene-gene interaction between CHAT and APOE was found in GMDR method(testing balanced accuracy = 0.540, p = 0.055). CONCLUSION: The CHAT A allele was associated with MCI risk in the Korean elderly. Its interaction with the APOE epsilon4 allele was not significant with regard to the development of MCI.
Aged ; Alleles ; Apolipoproteins ; Apolipoproteins E ; Choline ; Choline O-Acetyltransferase ; Humans ; Korea ; Logistic Models ; Mild Cognitive Impairment

NFI-C null mice demonstrate aberrant odontoblast differentiation and abnormal dentin formation, and thus develop molars lacking roots. However, other tissues and organs in the body including ameloblasts appear to be unaffected. Abnormal dentin in NFI-C null mice shares morphological similarities to the osteodentin that is formed in dental caries. However, little is known about the relationship between NFI-C and osteodentin formation. In this study, to elucidate the molecular characteristics of abnormal odontoblast in NFI-C null mice, we examined the levels of Ask-1, Cdc-2, Smad2/3, and TGF-betaR1 in cell culture and tissue sections from NFI-C null mice using immunofluorescence and immunohistochemistry. NFI-C protein was localized in the nucleus and cytoplasm of normal odontoblasts in vitro. Ask-1 and Cdc-2 proteins were shown in the perinuclear cytoplasm of both normal and NFI-C null mice. There were no differences in the pattern of production of Ask-1 and Cdc-2 proteins between normal and NFI-C null mice. Smad2/3 was not found in the odontoblast and subodontoblastic cells of the normal mice, whereas NFI-C null mice showed Smad2/3 immunoreactivity in the odontoblasts and subodontoblastic cells of the tooth pulp. TGF-betaR1 was weakly immunopositive in the odontoblast and subodontoblastic cells of normal mice, whereas it was detected strongly in the subodontoblastic cells of the NFI-C null mice. These results suggest that disruption of NFI-C increased the expression of Smad2/3 and TGF-betaR1 in developing odontoblasts and consequently caused abnormal dentin formation, similar to osteodentin.
Ameloblasts ; Animals ; Cell Culture Techniques ; Cytoplasm ; Dental Caries ; Dentin ; Fluorescent Antibody Technique ; Immunohistochemistry ; Mice ; Molar ; Odontoblasts ; Tooth

The aim of the present study was to identify a new candidate anti-inflammatory compound for use in the active stage of thyroid-associated ophthalmopathy (TAO). Benzylideneacetophenone compound JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] was synthesized based on a structural modification of yakuchinone B, a constituent of the seeds of Alpinia oxyphylla, which belongs to the ginger family (Zingiberaceae), has been widely used in folk medicine as an anti-inflammatory phytochemical. Orbital fibroblasts were primarily cultured from patients with TAO, and the potential of JC3 to suppress the interferon (IFN)-gamma-induced protein (IP)-10/CXCL10 production in these cells was determined. IFN-gamma strongly increased the level of IP-10/CXCL10 in orbital fibroblasts from patients with TAO. JC3 exerted a significant inhibitory effect on the IFN-gamma-induced increase in IP-10/CXCL10 in a dose-dependent manner; its potency was greater than that of an identical concentration of yakuchinone B with no toxicity to cells at the concentration range used. Moreover, the constructed dimer and trimer polystructures of JC3, showed greater potency than JC3 in suppressing the IFN-gamma-induced production of IP-10/CXCL10. JC3 significantly attenuated the IP-10/CXCL10 mRNA expression induced by IFN-gamma, and a gel-shift assay showed that JC3 suppressed IFN-gamma-induced DNA binding of signal transducer and activator of transcription-1 (STAT-1) in TAO orbital fibroblasts. Our results provide initial evidence that the JC3 compound reduces the levels of IP-10/CXCL10 protein and mRNA induced by IFN-gamma in orbital fibroblasts of TAO patients. Therefore, JC3 might be considered as a future candidate for therapeutic application in TAO that exerts its effects by modulating the pathogenic mechanisms in orbital fibroblasts.
Cells, Cultured ; Chalcone/chemical synthesis/*pharmacology ; Chemokine CXCL10/genetics/*metabolism ; Diarylheptanoids/chemistry/pharmacology ; Fibroblasts/*drug effects/metabolism ; Graves Ophthalmopathy/*metabolism ; Humans ; Interferon-gamma/*metabolism ; Orbit/cytology ; RNA, Messenger/genetics/metabolism ; STAT1 Transcription Factor/genetics/*metabolism

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
Apoptosis ; Autophagy ; Blotting, Western ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Cell Survival ; DNA Damage ; Fluorescent Antibody Technique ; Humans ; Phosphotransferases ; Protein Isoforms ; Stomach Neoplasms

PURPOSE: Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. MATERIALS AND METHODS: This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. RESULTS: The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. CONCLUSION: Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.
Administration, Oral ; Breast Neoplasms* ; Breast* ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Korea* ; Multivariate Analysis ; Retrospective Studies

Objective: This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. Materials and Methods: Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann–Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. Results: The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%–26.4%]) than that in controls (26.8% [25.6%–27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70–2.05 cm3 ] vs. 2.21 cm3 [1.86– 3.46 cm3 ]; p = 0.003) and brainstem (9.98 cm3 [9.45–11.00 cm3 ] vs. 11.05 cm3 [10.10–11.53 cm3 ]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39–0.48 cm3 ] vs. 0.48 cm3 [0.45–0.54 cm3 ]; p = 0.004) and brainstem (1.45 cm3 [1.28–1.59 cm3 ] vs. 1.54 cm3 [1.42–1.67 cm3 ]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). Conclusion MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.