Kim, Young;Kim, Se Kyu;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Chang, Yoon Soo
Tuberculosis and Respiratory Diseases
/
v.58
no.2
/
pp.120-128
/
2005
Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.
Kim, Haeseop;You, Jeheon;Jo, Yeongcheol;Lee, Youngjae;Park, Inbae;Park, Jeongwook;Jung, Myung-A;Kim, Young-Suk;Kim, Sunoh
Journal of the Korean Society of Food Science and Nutrition
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v.42
no.7
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pp.1029-1035
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2013
The objective of this study was to examine the ability of extracts from Phellinus linteus (PL) and rice with Phellinus linteus mycelium (PLM) to inhibit obesity and diabetes. The efficacy of PL and PLM were evaluated using Oil Red O staining, cholesteryl ester transfer protein (CETP) levels, protein tyrosine phosphate 1B (PTP1B) levels, organ weight, and serum lipid levels. Lipid accumulation significantly decreased by 76% and 59% upon treatment with $300{\mu}g/mL$ of PL and PLM, respectively (P<0.01). The inhibition of CETP activity increased 99% upon treatment with $300{\mu}g/mL$ of PL or PLM. Treatment with 3, 10, 30, 100, and $300{\mu}g/mL$ of PL, changed PTP1B activity by 10, 11, 14, 12, and 18% respectively. Also, treatment with increasing concentrations of PLM led to a significant concentration-dependent inhibition of PTP1B activity (P<0.01). PL and PLM were orally administered for 28 days after a high fat diet (HFD). PL significantly (P<0.05) reduced triglyceride and cholesterol levels. In addition, PLM significantly (P<0.05) reduced triglyceride, cholesterol, and HDL-cholesterol levels. GOT and GPT were not significantly affected. These results indicate that PL and PLM extracts have potent and useful activities for the treatment of obesity and diabetes mellitus.
In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.
Park, Kyeong Seon;Kim, Yu Jin;Yoon, Jin Young;Kyung, Sun Young;An, Chang Hyeok;Lee, Sang Pyo;Park, Jeong Woong;Jeong, Sung Hwan
Tuberculosis and Respiratory Diseases
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v.65
no.6
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pp.504-511
/
2008
Background: Particulate matter may be toxic to human tissue. Ambient air particulate matter ${\leq}10{\mu}m$ in aerodynamic size ($PM_{10}$), which changes under different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also spread unique particulate matter in affected areas. We evaluated production of ROS, $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ by exposing normal epithelial cells to Asian dust particulate matter. Methods: Bronchial epithelial cells were exposed to 0, 50, ${\leq}100{\mu}g/ml$ of a suspension of $PM_{10}$ for 24 h. ROS were detected by measurement of DCF release from DCF-DA by FACScan. $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ were detected by western blotting. Results: $PM_{10}$ exposure increased the expression of $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$. ROS production and $TGF-{\beta}$ levels were significantly higher with 50 or ${\leq}100{\mu}g/ml$$PM_{10}$. Fibronectin and $NF{\kappa}B$ production were significantly higher after ${\leq}100{\mu}g/ml$ of $PM_{10}$. Conclusion: $PM_{10}$ from Asian dust particles might have fibrotic potential in bronchial epithelial cells via ROS induction after $PM_{10}$ exposure.
To investigate differences between the metabolic ratios of normal controls and brain tumors such as astrocytomas and glioblastoma multiforme (GM) by proton MR spectroscopy (MRS) at 37 high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxel technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67$\pm$018 and 1.16$\pm$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (P=0.005). Cho/Cr ratio of glioblastoma multiforme was significantly higher than that of astrocytomas (P=0.001). Lactate was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. This results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.
Effects of acid, salt, heat treatment and natural antimicrobials on survival of E. coli O157:H7 CDF1, A. sobria CDF3 and S. aureus CDF2 isolated from surface of carcass in minced meat was investigated. The growth of E. coli O157:H7 CDF1 and A. sobria CDF3 inhibited in minced meat containing above 4% NaCl but not in 1% lactic acid. The growth of S. aureus CDF2 was not inhibited significantly by addition of 4% NaCl but inhibited completely in minced meat containing 1% lactic acid. Survival of A. sorbia CDF3 did not show any differences during storage at 4 and 10$^{\circ}C$. E. coli O157:H7 CDF10 and A. sobria CDF3 did not detect after heat treatment at 60$^{\circ}C$ for 10 min but S. aureus CDF2 decreased only 1 log after the same treatment. Viable cell of E. coli O157:H7 CDF1 decreased 2 log in TSB containing 0.5% Oolong tea extract after incubation for 12 hr compared with control but A. sobria CDF3 and S. aureus CDF2 did not detect at the same condition. The growth of E. coli O157:H7 CDF1, A. sobria CDF3 and S. aureus CDF2 was not inhibited by addition of 0.3% Oolong tea extract but inhibited by addition of 0.5% Oolong tea extract in minced meat at 20$^{\circ}C$ for 24hr.
Journal of the Korean Academy of Child and Adolescent Psychiatry
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v.13
no.1
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pp.139-152
/
2002
Objectives:This study was conducted to compare the clinical and neuropsychological characteristics by DSM-IV subtypes of attention deficit hyperactivity disorder(ADHD) patients who did not have comorbid psychiatric disorders. Methods:5-15 year old children with ADHD were recruited at psychiatric outpatient clinic of Yeungnam University hospital and the patients with comorbidity or neurological abnormalities were excluded. Finally, total 404 children with ADHD were selected for this study. There were 234 subjects of ADHD-C(57.9%), 156 subjects of ADHD-I(38.6%) and 14 subjects of ADHD-HI(3.5%), who fulfilled the DSM-IV diagnostic criteria. The mean age of the total subjects was 9.63±2.49 years old. The psychopathology, IQ, behavioral problems, neuropsychological executive function were evaluated before pharmacological treatment. The measures were Korean Personality Inventory of Child(K-PIC) for psychopathology, 4 behavioral check lists(ADDES-HV, ACTeRS, CAP, SNAP) for behavioral symptoms of ADHD, K-ABC and KEDI-WISC for IQ and Conner's CPT, WCST, SST for neuropsychological executive functions. Results:1) The prevalence of subtypes was ADHD-C, ADHD-I, ADHD-HI in decreasing order. There was no sex difference of prevalence among three subtypes. The mean age of ADHD-I was older than other subtypes. 2) There was significant differences of psychopathology among subtypes, the ADHD-C and ADHD-HI had higher than the ADHD-I in the scores of delinquent, hyperactivity and psychosis;the ADHD-C had higher than the ADHD-I in the scores of family relation and autism, the scores of ego resilience were lower than the ADHD-I. However, there was no difference in anxiety, depression and somatization scores among them. 3) The results of behavioral symptom check lists, the ADHD-C had higher the score of inattention, hyperactivity and impulsivity than the ADHD-I. Meanwhile the results of ACTeRs, which rated by the teachers, were different. 4) There were significant differences of sequential processing scale and arithmetics among subtypes in IQ using K-ABC, but there was no significant difference between the ADHD-C and the ADHD-I after excluding the ADHD-HI due to small numbers. 5) There was numerical difference among subtypes but did not reach statistical significance in three neuropsychological executive function tests. Conclusion:In conclusion, our results revealed that there was significant difference in clinical features among three subtypes but, no significant difference in executive functions.
Purpose: Flash 3D (pixon(R) method; 3D OSEM) was developed as a software program to shorten exam time and improve image quality through reconstruction, it is an image processing method that usefully be applied to nuclear medicine tomography. If perfoming brain diamox perfusion scan by reconstructing subtracted images by Flash 3D with shortened image acquisition time, there was a problem that SNR of subtracted image is lower than basal image. To increase SNR of subtracted image, we use LEAP collimators, and we emphasized on sensitivity of vessel dilatation than resolution of brain vessel. In this study, our purpose is to confirm possibility of application of LEAP collimators at brain diamox perfusion tomography, identify proper reconstruction factors by using Flash 3D. Materials and methods: (1) The evaluation of phantom: We used Hoffman 3D Brain Phantom with $^{99m}Tc$. We obtained images by LEAP and LEHR collimators (diamox image) and after 6 hours (the half life of $^{99m}Tc$: 6 hours), we use obtained second image (basal image) by same method. Also, we acquired SNR and ratio of white matters/gray matters of each basal image and subtracted image. (2) The evaluation of patient's image: We quantitatively analyzed patients who were examined by LEAP collimators then was classified as a normal group and who were examined by LEHR collimators then was classified as a normal group from 2008. 05 to 2009. 01. We evaluate the results from phantom by substituting factors. We used one-day protocol and injected $^{99m}Tc$-ECD 925 MBq at both basal image acquisition and diamox image acquisition. Results: (1) The evaluation of phantom: After measuring counts from each detector, at basal image 41~46 kcount, stress image 79~90 kcount, subtraction image 40~47 kcount were detected. LEAP was about 102~113 kcount at basal image, 188~210 kcount at stress image and 94~103 at subtraction image kcount were detected. The SNR of LEHR subtraction image was decreased than LEHR basal image about 37%, the SNR of LEAP subtraction image was decreased than LEAP basal image about 17%. The ratio of gray matter versus white matter is 2.2:1 at LEHR basal image and 1.9:1 at subtraction, and at LEAP basal image was 2.4:1 and subtraction image was 2:1. (2) The evaluation of patient's image: the counts acquired by LEHR collimators are about 40~60 kcounts at basal image, and 80~100 kcount at stress image. It was proper to set FWHM as 7 mm at basal and stress image and 11mm at subtraction image. LEAP was about 80~100 kcount at basal image and 180~200 kcount at stress image. LEAP images could reduce blurring by setting FWHM as 5 mm at basal and stress images and 7 mm at subtraction image. At basal and stress image, LEHR image was superior than LEAP image. But in case of subtraction image like a phantom experiment, it showed rough image because SNR of LEHR image was decreased. On the other hand, in case of subtraction LEAP image was better than LEHR image in SNR and sensitivity. In all LEHR and LEAP collimator images, proper subset and iteration frequency was 8 times. Conclusions: We could archive more clear and high SNR subtraction image by using proper filter with LEAP collimator. In case of applying one day protocol and reconstructing by Flash 3D, we could consider application of LEAP collimator to acquire better subtraction image.
A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA ($200{\mu}g$ in $10{\mu}\ell$ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72${\pm}$0.02AU, p<0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39${\pm}$0.03AU, p<0.001; CRH, control:6-OHDA=1:0.76${\pm}$0.07AU, p<0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cg$\alpha$), LH beta subunit (LH-$\beta$), and FSH beta subunit (FSH-$\beta$) in pituitaries from 6-OHDA group compared to control values (Cg$\alpha$, control:6-OHDA=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, control:6-OHDA=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, control:6-OHDA=1:0.84${\pm}$0.05AU, p<0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86${\pm}$0.04AU, p<0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.
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