• 제목/요약/키워드: Protein A

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A High Quality Rice Variety "Cheongcheongjinmi" Adaptable to Low Nitrogen Fertilizer Application (질소 소비료적성 고품질 벼 신품종 "청청진미")

  • Cho, Young-Chan;Oh, Myung-Kyu;Choi, Im-Soo;Kim, Yeon-Gyu;Kim, Myeong-Ki;Hwang, Hung-Goo;Hong, Ha-Cheol;Jeong, O-Young;Choi, In-Bae;Choi, Yong-Hwan;Jeon, Yong-Hee;Lee, Jeom-Ho;Lee, Jeong-Heui;Lee, Jeong-Il;Shin, Young-Seop;Kim, Jeong-Ju;Kim, Ki-Jong;Baek, Man-Kee;Roh, Jae-Hwan
    • Korean Journal of Breeding Science
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    • v.41 no.4
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    • pp.654-659
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    • 2009
  • "Cheongcheongjinmi" is a new japonica rice variety developed from a cross between Iri401 and Ilpumbyeo by the rice breeding team of National Institute of Crop Science, RDA. This variety is suitable for ordinary season culture of low level nitrogen application. Heading date of "Cheongcheongjinmi" is August 17, 4 days later than that of Sobibyeo in plain areas. It has culm length of 82 cm, and relatively semi-erect pubescent leaf blade and slightly tough culm tolerant to lodging with good canopy architecture. This variety has 13 tillers per hill, 126 spikelets per panicle and 90.2% of ripened grains. "Cheongcheongjinmi" showed lower spikelet fertility than Sobibyeo when exposed to cold stress. This variety showed slower leaf senescence and lower viviparous germination compared to Sobibyeo during the ripening stage. "Cheongcheongjinmi" is susceptible to blast disease, bacterial blight, virus diseases and planthoppers. The dried plant weight, total nitrogen and RuBisCO activity of "Cheongcheongjinmi" were higher than those of Sobibyeo in low level nitrogen application. The milled rice of "Cheongcheongjinmi" exhibits translucent, clear non-glutinous endosperm and medium short grain. It shows lower protein and amylose contents than those of Sobibyeo, and better palatability of cooked rice compared to Hwaseongbyeo. The milled rice yield of this cultivar is about 5.10 MT/ha at low level nitrogen application of ordinary season culture in local adaptability test for three years. Especially, "Cheongcheongjinmi" has better milling properties such as the percentage of whole grain in milled rice and milling recovery of whole grain, respectively than those of Sobibyeo. "Cheongcheongjinmi" would be adaptable to middle plain areas and middle-western coastal areas of Korea.

Comparison of Growth Characteristics and Productivity of Summer Forage Crops in Sihwa Reclaimed Land (시화 간척지에서 하계 사료작물의 초종 및 품종에 따른 생육특성 및 생산성 비교)

  • Kim, Jong Geun;Jeong, Eun Chan;Kim, Meing Joong;Li, Yan Fen;Kim, Hak Jin;Lee, Su Hwan
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.41 no.2
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    • pp.110-118
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    • 2021
  • This study was conducted to investigate the effects of species and varieties of summer forage crops on growth characteristics and productivity in Sihwa reclaimed land. The summer forage crops used in the trial were silage corn, sorghum×sudangrass hybrid(SSH), and proso millet. For each forage species, Gwangpyeongok(GPO), P15453, P1952 and P2088 were used for silage corn, and 877F, Green star, Honey chew, and Turbo gold cultivars were used for SSH. For proso millet, Ibaekchal, Geumsilchal and Manhongchal developed by the National Institute of Crop Science were used. Silage corn and SSH were sown on May 21, 2019 and proso millet on June 4, and harvested on September 2. There was no significant difference in plant and ear height of silage corn among varieties. P1543 was the highest and P2088 was the lowest in yield of silage corn, but there was no significant difference among treatments. Among the SSH, the plant height of 877F was the highest and Turbo gold variety had the smallest (p<0.05). As for the dry matter(DM) yields, 877F had the highest at 3,862 kg/ha and Green star had the lowest at 2,669 kg/ha (p<0.05). The fresh matter yield of proso millet was 15,778 kg/ha, which was higher than that of corn or SSH, The average dry matter yield was 4,780 kg/ha, and Ibaekchal variety had the highest DM yield compared to other varieties (p<0.05). P2088 had the highest TDN content and GPO was the lowest (p<0.05). As for the SSH, the TDN content of Green star and Honey chew varieties was significantly higher, and the RFV value was the lowest in Turbo gold. The average crude protein content of proso millet was 7.03%, and the highest TDN and RFV values were 64.36% and 106 in Geumsilchal. In the experiment of the germination rate of summer forage crops according to salt concentration, silage corn showed a germination rate of 83.1% even at 0.4% salinity. In particular, P2088 and P1921 varieties had more than 80% germination rate even at 0.6% salt concentration. As for the SSH, the germination rate of 877F was 93.3% even at 0.8% salinity, and 88.3% with Honey chew, indicating higher resistance to salt concentration compared to other varieties. Proso millet showed a high germination rate of 84.0 to 88.7% even at a salt concentration of 0.6%. Considering the above results, proso millet was recommended as the most suitable forage crop species in the Sihwa reclaimed land with high salt concentration, and the Ibaekchal variety is recommended as a suitable forage crop due to its high yield.

Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro (In Vitro 내독소 유도성 급성 폐손상에서 Pentoxifylline과 Neutrophil Elastase Inhibitor의 항염효과)

  • Kim, Young-Kyoon;Kim, Seung-Joon;Park, Yong-Keun;Kim, Seok-Chan;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak;Kim, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.691-702
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    • 2000
  • Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

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Effect of Acutely Increased Glucose Uptake on Insulin Sensitivity in Rats (단기간의 당섭취 증가가 인슐린 감수성에 미치는 영향)

  • Kim, Yong-Woon;Ma, In-Youl;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
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    • v.14 no.1
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    • pp.53-66
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    • 1997
  • Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

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Development of Crushing Device for Whole Crop Silage and the Characteristics of Crushed Whole Crop Silage (총체맥류 분쇄기 개발 및 분쇄 총체맥류 사일리지의 품질 특성)

  • Lee, Sunghyoun;Yu, Byeongkee;Ju, Sunyi;Park, Taeil
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.36 no.4
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    • pp.344-349
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    • 2016
  • This study was conducted to evaluate the possibility of expanding the usage of whole crop silage from beef cattle and dairy cow to hogs and chickens. For this purpose, a crushing device was developed to crush whole crop silage. The crushed silage was sealed, and analyzed for its feed value. The silage varieties used for the experiment included Saessal barley and Geumgang wheat. Whole crop barley and wheat were crushed in the crushing system as a whole without separating stems, leaves, grains, etc.. When the crushed whole crop silages (CWCS) were analyzed, full grain, grains above 10 mm in size, grains 5~10 mm in size, and grains below 5 mm in size accounted for, 20%, 4%, 27%, and 49 %, respectively. In order to facilitate the fermentation of CWCS, inoculated some fermenter into each CWCS sample (barley or wheat). As control, another set of sample was not inoculated. Crude protein (CP), ether extract (EE), crude fiber (CF), neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin, cellulose content, total digestible nutrient (TDN), and relative feed value (RFV) of fermenter-inoculated Saessal barley were 2.45 %, 1.61%, 8.95%, 16.94%, 9.52%, 1.01%, 8.51%, 81.38%, and 447.5%, respectively. The CP, EE, CF, NDF, ADF, lignin, cellulose content, TDN, and RFV in the other sample of Saessal barley without inoculation of fermenter were 2.57%, 1.62%, 9.61%, 18.25%, 10.13%, 1.10%, 9.04%, 80.90%, and 412.9%, respectively. The CP, EE, CF, NDF, ADF, lignin, cellulose content, TDN, and RFV of fermenter-inoculated Geumgang wheat sample were 2.43%, 1.27%, 10.99%, 19.49%, 11.23%, 1.46%, 9.77%, 80.03%, and 382.6%, respectively. The CP, EE, CF, NDF, ADF, lignin, cellulose content, TDN, RFV of the other set sample of Geumgang wheat sample without the inoculation of fermenter were 2.28%, 1.44%, 10.08%, 18.02%, 10.44%, 1.26%, 9.18%, 80.65%, and 416.9%, respectively. The TDN and RFV content in the fermenter-inoculated Saessal barley were 81.38% and 447.5%, respectively, while the one in the fermenter-inoculated Geumgang wheat were 80.03% and 382.6% respectively. When the feed value of whole crop barley and wheat silage without crushing process was compared to the feed value of whole crop barley and wheat silage made from crushing system, the latter appeared to be higher than the former. This could be due to the process of sealing the crushed silage which might have minimized air content between samples and shortened the golden period of fermentation. In conclusion, these results indicate that a crushing process might be needed to facilitate fermentation and improve the quality of silage when making whole crop silage.

PS-341-Induced Apoptosis is Related to JNK-Dependent Caspase 3 Activation and It is Negatively Regulated by PI3K/Akt-Mediated Inactivation of Glycogen Synthase Kinase-$3{\beta}$ in Lung Cancer Cells (폐암세포주에서 PS-341에 의한 아포프토시스에서 JNK와 GSK-$3{\beta}$의 역할 및 상호관련성)

  • Lee, Kyoung-Hee;Lee, Choon-Taek;Kim, Young Whan;Han, Sung Koo;Shim, Young-Soo;Yoo, Chul-Gyu
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.5
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    • pp.449-460
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    • 2004
  • Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

Immunogenicity and Safety of a Haemophilus influenzae Type b Polysaccharide-Tetanus Toxoid Conjugate Vaccine (PRP-T: HiberixTM) in Korean Infants (우리나라 영아에서 PRP-T(HiberixTM)백신의 면역원성 및 안전성에 대한 연구)

  • Chung, Eun Hee;Kim, Yae Jean;Kim, Yun Kyung;Kim, Dong Ho;Seo, Jeong Wan;Lee, Hoan Jong
    • Pediatric Infection and Vaccine
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    • v.10 no.1
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    • pp.71-80
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    • 2003
  • Purpose : Four kinds of Haemophilus influenzae type b protein conjugate vaccines, PRPD, PRP-T, PRP-OMP and PRP-CRM197, have been developed, and PRP-T vaccines are currently produced by two manufacturer, $ActHib^{(R)}$ by Aventis and $Hiberix^{TM}$ by GlaxoSmith-Kline Biologicals. The purpose of this study is to evaluate the immunogenicity and safety of $Hiberix^{TM}$ in Korean infants. Methods : Seventy-three healthy infants(43 male infants) were recruited for this study after parental informed consent was obtained. Each infant was vaccinated at 2, 4 and 6 months of age with the study vaccine. At each visit, infants were also immunized with DTaP, trivalent oral polio vaccine and hepatitis B vaccine when indicated. The serum anti-PRP antibody was measured at prevaccination, 2 month later after the 2nd dose, and 1 month later after the 3rd dose by the ELISA method. The local and systemic adverse reactions of vaccination were monitored for 3 consecutive days after each immunization. Immunogenicity of vaccine was evaluated in infants who received all the scheduled immunization and the adverse reactions were evaluated for infants who received at least one dose of the study vaccine. Results : Among seventy three infants, enrolled in this study; sixty three(37 male infants) completed all the scheduled immunizations. The geometric mean titer(GMT) of anti-PRP antibodies at prevaccination was 0.17 ${\mu}g/mL$(95% confidence interval[CI]; 0.13~0.22). The GMT of anti-PRP antibodies increased to 4.14 ${\mu}g/mL$(95% CI; 2.65~6.48) at 2 month later after the 2nd dose of PRP-T and 14.65 ${\mu}g/mL$(95% CI; 10.83~19.81) at 1 month later after the 3rd dose. Anti-PRP antibody ${\geq}0.15$ ${\mu}g/mL$, was observed in 98.4%(95% CI; 91.8~100) after 2 doses and 100%(95% CI; 100~100) after 3 doses. Anti-PRP antibody ${\geq}1.0$ ${\mu}g/mL$, was obtained in 77.8%(95% CI; 67.5~88.0) after 2 doses, and 98.4%(95% CI; 95.3~100) after 3 doses. Most of the adverse reaction after vaccination were mild. Irritability, the most common systemic reaction, was observed in 45.5%, followed by drowsiness(30.5%), poor feeding(26.7%) and fever(5.6%). Among the local reactions tenderness was observed in 7.9%, redness(${\geq}5$ mm) in 2.8% and swelling(${\geq}5$ mm) in 1.8%. Conclusion : The PRP-T vaccine used in this study was highly immunogenic and safe in Korean young infants. The finding that high GMT and high frequency of infants with a protective titer achieved after 2 doses is consistent with the previous studies which were done with a PRP-T vaccine of other manufacturer. This study suggests that the immunization schedule of PRP-T vaccine for Korean infants may need re-evaluation.

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A Preliminary Study on Depressive Symptoms and Glycemic Controls in Diabetic Patients (당뇨병 환자에서의 우울 및 관련증상에 관한 예비적 연구)

  • Ko, Seung-Hyun;Jeong, Jong-Hyun;Hong, Seung-Chul;Han, Jin-Hee;Lee, Seung-Pil;Ahn, Yoo-Bae;Song, Ki-Ho
    • Korean Journal of Psychosomatic Medicine
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    • v.12 no.2
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    • pp.165-173
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    • 2004
  • Objectives: Diabetes mellitus is a heterogeneous, chronic, progressive disease characterized by hyperglycemia and abnormality in protein, carbohydrate, fat metabolism. Recent studies have reorted two times prevalence of depression in individuals with diabetes compared to individuals without diabetics. This study was designed to investigate glycemic controls, anxiety, alexithymia, stress responses between depressed diabetic patients and non-depressed diabetic patients. Methods The subjects were 60 diabetic patients(mean age : $50.3{\pm}9.7$ years, 31 men and 29 women) who were confirmed to have diabetes depending on the laboratory findings as welt as clinical symptoms at the St. Vincent Hospital Diabetes Clinic, from Mar. 2004 to Sep. 2004. Laboratory test including, blood chemistry. glycated hemoglobin, urinalysis for proteinuria and Korean version of Beck Depression Inventory(BDI), State and Trait Anxiety Inventory(STAI), Toronto Alexithymia Scale(TAS) and Stress Response Inventory(SRI) were used for assessment. Based on BDI scores, all diabetics were divided into 13 depressed-diabetics group(above 20 point) and 47 non-depressed group(below 20 point). We compared demographic data. glycemic controls, STAI, TAS and SRI scores between two groups by independent t-test. Results : 1) Depressed diabetic groups were 13(mean age : $55.4{\pm}7.2$ years, 7 men and 6 women) and non depressed groups were 47(mean age $48.9{\pm}9.8$ years, 24 men and 23 women). In depressed diabetics, compared with non-depressed group, manifested aged(p=0.031), but other demographic data showed no difference between two groups. 2) No significant differences were noted in FBS, PP2h, Hb A1C, total cholesterol, HDL-cholesterol, SGOT/SGPT, BUN levels between depressed and non-depressed groups. But, blood creatine levels of depressed group were significantly increased than non-depressed group(p=0.026). 3) No significant differences were found in the score of STAI, STAI-S, STAI-T, TAS between depressed and non-depressed groups. 4) The SRI scores of depressed groups were significantly higher than non-depressed groups$(59.7{\pm}24.9\;vs.\;31.5{\pm}22.0)(p=0.000)$. Conclusion : The above results suggest that depressed diabetic patients are have more stress responses and higher blood creatine levels. However, there were no differences in laboratory data related to glycemic controls, and anxiety. alexithymia levels between two groups. We suggest that physicians should consider integrated approaches for psychiatric problems in the management of diabetes.

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The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells (수종의 암세포에서 Verapamil이 Tc-99m MIBI와 Tetrofosmin의 섭취에 미치는 영향)

  • Kim, Dae-Hyun;Yoo, Jung-Ah;Suh, Myung-Rang;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.1
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    • pp.85-98
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    • 2004
  • Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.