• Title/Summary/Keyword: {\alpha}$

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Biosynthesis of $C_{21}$-steroids in Spotted Sen Bass (Lateolabrax maculatus) Ovaries (점농어, Lateolabrax maculatus 난소에서 생성되는 $C_{21}$-스테로이드)

  • BAEK Hea-Ja;AN Cheul-Min;KIM Hyung-Bae
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.34 no.6
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    • pp.638-642
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    • 2001
  • To investigate the production of $C_{21}$-steroids during the spawning period of spotted sea bass, Lateolabrax maculatus, we have incubated maturing and ovulating follicles with radiolabeled pregnenolone and $17\alpha$-hydroxyprogesterone for 24 hours. The resulting metabolites were analyzed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), When maturing follicles ($700\sim800{\mu}m$ in diameters) were incubated with radiolabeled precursors, $C_{21}$-metabolites were corticosteroids and $17\alpha$-hydroxy, $20\beta$-dihydroprogesterone ($17\alpha20\beta OHP$). When ovulation follicles ($1,000\sim1,150{\mu}m$ in diameters) were incubated with radiolabeled precursors, the major $C_{21}$-metabolites were $17\alpha20\beta OHP$, $17\alpha$,$20\beta$, 21-trihydroxy-4-pregnen-3-one ($17\alpha20\beta21P$), and corticosterone. Additional chromatography by TLC and HPLC confirmed the presence of radioactive $17\alpha20\beta OHP$ in the maturing follicles, and $17\alpha20\beta OHP$,$17\alpha20\beta21P$ and corticosterone in ovulating follicles. Although $17\alpha20\beta OHP$ was found in a small peak, the synthesis of this steroid suggests that it may play a role in regulating the oocyte maturation process. Whereas ovulation is regulated by both $17\alpha20\beta OHP$ and $17\alpha20\beta21P$ in the spotted sea bass. In addition, an unusual finding was the biosynthesis of corticosterone. Whether this production is responsible for the ovulation, and is an area requiring continued research.

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Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

Estrus Induction Rates and Conception Rates by MGA Feeding System in Hanwoo (MGA Feeding System에 의한 발정 동기화 방법이 한우의 발정 발현율과 수태율에 미치는 영향)

  • Lee, M.S.;Jung, Y.H.;Park, S.B.;Im, S.K.;Park, J.J.;Jung, J.K.;Moon, S.J.;Kim, C.K.
    • Journal of Embryo Transfer
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    • v.21 no.3
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    • pp.177-182
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    • 2006
  • This study was conducted to investigate the effects of melengesterol acetate (MGA) and $PGF_{2{\alpha}}$ administrations on serum progesterone level, synchrony of estrus and conception rates in Han-woo. Firstly, ten heifers and one freematin were fed 0.5 mg MGA/day for 14 days in a grain carrier, and after 19 days of MGA feeding, a single injection of 25 mg $PGF_{2{\alpha}}$ were treated. Blood samples were collected to evaluate serum progesterone concentrations from the start of feeding of MGA until the end of feeding and subsequent estrous detection and artificial insemination (AI) at 3 days intervals, and on days of $PGF_{2{\alpha}}$ injection, estrous detection, AI, and 15th and 60th days after AI. The level of progesterone in the blood began to increase from 7 days after MGA feeding, and 9 days after feeding it became 5.4 ng/ml and maintained that level thereafter. On the 33th day when the $PGF_{2{\alpha}}$ was injected, it reached the peak level of 7.6 ng/ml. However, 2-3 days after $PGF_{2{\alpha}}$ injection, it dropped to 1.4 ng/ml drastically (p<0.05). Secondly, one hundred and ninety four Hanwoo heifers or cows were divided into two groups to compare estrous induction and conception rates: the one treated with MGA and $PGF_{2{\alpha}}$, (n=104) and the other with $PGF_{2{\alpha}}$ treatment (two injections at 11 days interval, n=90). The heifers or cows treated with MGA and $PGF_{2{\alpha}}$ were identical to those used as above. The percentages of heifers or cows showed estrus were higher in the $MGA+PGF_{2{\alpha}}$ treatment (91.3%) than in the $PGF_{2{\alpha}}$ treatment (72.2%, p<0.05). Conception rates were also higher in the $MGA+PGF_{2{\alpha}}$ treatment (94.2%) than in the $PGF_{2{\alpha}}$ treatment (88.9%, p<0.05). The results of this experiment indicate that estrus synchronization using $MGA+PGF_{2{\alpha}}$ is more effective than that using $PGF_{2{\alpha}}$ (two injections) in Hanwoo.

Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-$\alpha$ (방사선의 항암작용에 대한 재조합 TNF-$\alpha$의 효과)

  • Seong Jinsil;Shin Hang Chul;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.225-231
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    • 1998
  • Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

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Analysis of the Tumor Necrosis Factor-${\alpha}$ Promoter Polymorphism in Children with Henoch-Sch$\"{o}$nlein Purpura (Henoch-Sch$\"{o}$nlein 자반증에서 Tumor Necrosis Factor-${\alpha}$ 유전자 다형성 분석)

  • Yang, Hye-Ran;Ko, Jae-Sung;Seo, Jeong-Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.10 no.1
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    • pp.11-19
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    • 2007
  • Purpose: Henoch-Sch$\"{o}$nlein purpura (HSP) is a systemic vasculitis involving the skin, joints, gastrointestinal tract, and kidney. Although the pathogenesis of HSP is still unclear, tumor necrosis factor (TNF-${\alpha}$) is regarded as an important cytokine contributing to the disease. The goal of this study was to determine the role of TNF-${\alpha}$ in the pathogenesis of HSP, and to evaluate the TNF-${\alpha}$ polymorphism for genetic susceptibility to HSP. Methods: From March 2004 to November 2005, 40 children with HSP and 32 healthy controls were included. Serum TNF-${\alpha}$ levels were measured using the ELISA method during the acute and convalescent phase of HSP. The genotypic and allelic frequencies of the TNF-${\alpha}$ gene polymorphisms at positions -308 and -238 were evaluated in patients and controls. Results: Serum TNF-${\alpha}$ levels were $23.17{\pm}11.31$ pg/mL in the acute phase of children with HSP and $10.56{\pm}5.59$ pg/mL in the convalescent phase (p=0.000). There was no significant correlation between the serum TNF-${\alpha}$ levels and the clinical scores of HSP (r=0.310, p=0.070). The genotypic frequency of the TNF-${\alpha}$ -308 polymorphism in children with HSP was not significantly different compared to healthy controls (GG 80%, GA 20% vs. GG 93.8%, GA 6.2%; p=0.094). The genotypic frequency of the TNF-${\alpha}$ -238 polymorphism in children with HSP was not significantly different (GG 97.5%, GA 2.5% vs. GG 93.8%, GA 6.3%; p=0.429). Conclusion: TNF-${\alpha}$ is assumed to be the main cytokine associated with the pathogenesis of HSP during the acute phase. However, the presence of TNF-${\alpha}$ gene polymorphisms at positions -308 and -238 did not distinguish children with HSP from normal controls.

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Effects of Antioxidants on Oxidation of Tallow by Gamma Irradiation (감마선 조사시 우지 산패억제를 위한 항산화제의 첨가효과)

  • Lee, Kyong-Haeng;Yook, Hong-Sun;Lee, Ju-Woon;Kim, Sung;Kim, Mi-Jung;Byun, Myung-Woo
    • Korean Journal of Food Science and Technology
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    • v.31 no.1
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    • pp.7-12
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    • 1999
  • The effects of antioxidants, ascorbyl palmitate (AP), ${\alpha}-tocopherol\;({\alpha}-Toc)$, BHA and ascorbyl $palmitate+{\alpha}-tocopherol\;(AP+{\alpha}-Toc)$ have been investigated on lipid peroxide formations in tallow immediately and during storage at $50^{\circ}C$ after gamma irradiation with the dose of $1{\sim}10kGy$. Immediately gamma irradiation greatly increased the initiative oxidation of tallow as was expected. But antioxidants were found to be greatly effective in minimizing the radiation-induced peroxidation of tallow and their antioxidative activities were $AP>BHA>AP+{\alpha}-Toc>{\alpha}-Toc$. Especially, AP showed greater antioxidative activity of initiate-oxidation than that of any other antioxidant. Oxidation of tallow during storage at $50^{\circ}C$ after irradiation induced the accelate of autoxidation. But the additions of antioxidants inhibited formation of peroxide. Their antioxidative activities were $BHA>AP+{\alpha}-Toc>{\alpha}-Toc>AP$. Especially $AP+{\alpha}-Toc$ mixture was not significantly different from BHA (p>0.05).

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Lack of Association between Tumor Necrosis Factor-α -308 and -238 Promoter Polymorphisms and Chronic Hepatitis B Virus Infection (종양괴사인자-α -308과 -238 promoter 다형성과 만성 B형 간염 바이러스 감염 간의 연관성 결여)

  • Jang, Won-Hee;Yang, Young-Il;Lee, Youn-Jae;Chun, Jin-Ho;Yea, Sung-Su;Seog, Dae-Hyun;Kim, Hyeong-In
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1207-1211
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    • 2008
  • The pro-inflammatory cytokine tumor necrosis factor-$\alpha$ (TNF-$\alpha$) is an important mediator of the immune response in hepatitis B virus (HBV) infection. Since the production of TNF-$\alpha$ is mostly regulated at the transcriptional level and polymorphisms in the TNF-$\alpha$ promoter alter its expression, TNF-$\alpha$ promoter polymorphisms could affect the pathogenesis of chronic HBV infection. In this study, we investigated the potential association of TNF-$\alpha$ promoter polymorphisms with chronic HBV infection. The study included 181 patients with chronic HBV infection, 201 persons who had been spontaneously recovered from hepatitis B, and 170 unrelated healthy controls. The -308G/A and -238G/A polymorphisms in the TNF-$\alpha$ promoter were analyzed by PCR-restriction fragment length polymorphism. The distribution of both the -308 and -238 genotypes in the patient group was not statistically different from that in the spontaneous recovery and control groups (p>0.05). There was also no significant difference in the allele frequency between the groups (p>0.05). The results suggest that the TNF-$\alpha$ -308 and -238 promoter polymorphisms are not associated with the development of chronic HBV infection in the Korean population.

Mutant Recombinant Hemoglobin (${\alpha}96Val{\rightarrow}Tyr$) Exhibits Low Oxygen Affinity and High Cooperativity

  • Choi, Jong-Whan;Yeh, Byung-Il;Han, Dong-Pyou;Lee, Hyean-Woo;Sohn, Joon Hyung;Jung, Seun-Ho;Kim, Hyun-Won
    • BMB Reports
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    • v.31 no.6
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    • pp.595-599
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    • 1998
  • To investigate conformational information of a low oxygen affinity recombinant hemoglobin (rHb) containing $96Val{\rightarrow}Trp$ mutation at the ${\alpha}96$ position, we ave produced rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr$), using the Escherichia coli expression system and site-directed mutagenesis. The oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Phe$) is similar to that of human normal adult hemoglobin (Hb A). However, the oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Tyr$) showed much lower oxygen affinity than Hb A which is similar to that of rHb (${\alpha}96Val{\rightarrow}Tyr$), providing an opportunity as a potential candidate for a hemoglobin-based blood substitute. Both rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr)$ showed high cooperativity in oxygen binding. IH-NMR spectroscopy shows that both rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr$) have very similar tertiary structure around the heme pockets and uaternary structure in the ${\alpha}_1/{\beta}_2$ subunit interface ompared to Hb A. The low oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Tyr$) has been suggested to be due to a hydrogen bond caused by an extra hydroxyl group not present in rHb (${\alpha}96Val{\rightarrow}Phe$). However, investigation of the carbonmonoxy form of rHb (${\alpha}96Val{\rightarrow}Phe$) and (${\alpha}96Val{\rightarrow}Try$) in the presence of inositol hexaphosphate at low temperature suggests that low oxygen affinity of (${\alpha}96Val{\rightarrow}Try$) may arise from a mechanism different to that of rHb (${\alpha}96Val{\rightarrow}Trp$).

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The Role of Central Postsynaptic ${\alpha}_2$-Adrenoceptor on the Immobility Duration in the Forced-swimming Test Mice (새앙쥐 강제수영시 부동자세 시간에 대한 Central postsynaptic ${\alpha}_2$-Adrenoceptor의 역할에 대한 연구)

  • Rhim, Byung-Yong;Kim, Sang-Kon;Lee, Won-Suk;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.21 no.2
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    • pp.90-98
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    • 1985
  • 1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

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