• Molecules and Cells
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• 제45권10호
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• pp.718-728
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• 2022

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

• Tuberculosis and Respiratory Diseases
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• 제53권3호
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• pp.253-264
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• 2002

연구 배경 : 세포 주기에 영향을 주는 단백질들의 발현이 암의 발생, 진행, 치료 반응 및 생존에 중요하게 관련되어 있다는 보고가 있다. 세포 분열을 촉진하는 CDK4와 이를 억제하는 p27의 발현 정도가 예후와 관련이 있다는 보고가 있고, 최근 새롭게 암억제 유전자로 밝혀진 uteroglobin과 세포 주기와의 관련성이 있는 것으로 생각되며, 이의 발현 여부와 예후와의 관련성에 대한 보고는 아직 없는 실정이다. 그래서 세포 주기와 관련된 단백질의 발현 정도가 비소세포암의 임상 지표와 생존율과의 관련성을 알아 보고자 본 연구를 시행하였다. 방 법 : 수술적 절제를 시행한 110예의 비소세포암 조직을 formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section에서 avidin-biotinylated hooseradish pero xidase complex를 이용한 immuno-peroxidase를 이용한 면역조직화학 염색을 시행하였다. 발현 정도는 양성 염색부위의 면적과 염색 강도에 따라 0:none, 1:weak, 2: moderate, 3:strong로 구분하여 점수로 판정하였다. 염색의 정도에 따라 0,1을 음성군으로, 2와 3을 양성군으로 나누었다. 단백질 각각의 발현과 여러 가지 임상적, 조직학적 지표들과 연관성은 chi-square test를 이용하여 비교하였다. 생존율은 Kaplan-Meier 방법을 이용하였다. 결 과 : 대상군은 수술 후 바소세포암 환자로 전체 110명으로, 성별은 남녀비가 87:23이다. 평균 연령은 $56.43{\pm}9.41$, 조직학적 형태별로는 상피세포암이 43명, 선암이 30명, 대세포암이 9명이고 그 외 다른 암은 28명이다. 세포주기 관련 단백질의 발현율은 p27가 110예 중 83예 (75%), CDK4는 110예 중 98예 (89%), uteroglobin은 110예 중 11예 (10%)로 CDK4가 가장 높았고 uteroglobin 이 가장 적었다. 각 세포주기 관련 단백질 발현율의 세포형에 따른 차이는 통계적으로 유의하지 않았다. 수술적 절제 된 비소세포암에서 시행한 면역 조직학적 염색에서 CDK4 발현이 음성인 군에서 생존기간이 유의하게 높았다(P<0.05). 결 론 : 비소세포폐암에서 세포 주기에 단백질의 발현을 분석한 결과 CDK4 발현 정도가 환자의 예후와 관련되어 있어, 수술 후 치료 계획 및 생존 기간을 예측하는데 좋은 지표로 사용 될 것으로 생각된다.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.91-97
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• 2005

2004 년 3월 9일부터 5월 15일까지 경희의료원 침구과 외래를 내원하여 8주간 연구과정을 마친 환자 29명의 환자를 관찰하여 뜸치료 전, 후의 파킨슨병 증상의 호전도를 여러 임상 척도를 이용하여 살펴 본 결과를 다음과 같이 보고하는 바이다. 1. UPDRS 점수는 침치료 전, 4주 후, 8주 후 각각 $35.41{\pm}22.98$, $31,93{\pm}23.44$, $30.75{\pm}24.55$로 나타나 통계적으로 매우 유의한 차이가 있었다 (p<0.01). 2. HY stage의 변화는 4주후(p=0.046)에는 유의한 변화가 있으나, 8주후에는 (0.063) 유의한 변화가 없었다. 3. Schwab과 England에 의한 ADL의 변화는 4 주후, 8주후 모두 유의한 변화가 없었다(p>0.05). 4. FOCQ의 변화는 치료 4주후에는 유의한 차이가 있었으나(p=0.05) 8주 후에는 유의한 차이가 없었다(p=0.13) 5. 뜸치료를 통해 환자에게서 파킨슨병 임상척도의 변화 외에 움직임의 유연성이나, 덜 피로함과 같은 다양한 변화가 나타났다.

• 동의생리병리학회지
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• 제25권2호
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• pp.345-351
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• 2011

This study was to examine the positive and negative affect related to psychological characteristics of each Sasang types using Positive and Negative Affect Schedule (PANAS) with 78 students from School of Korean Medicine, Pusan National University. After determining the Sasang types by QSCC II, the psychological characteristics of each Sasang types were analysed by PANAS. We did ANOVA analysis with eight related scales and found significant differences between the Tae-Eum type ($18.71{\pm}8.75$, $6.47{\pm}3.36$, $6.31{\pm}2.47$, $3.18{\pm}2.77$, $10.94{\pm}10.08$) and the So-Eum type ($13.38{\pm}6.03$, $4.55{\pm}2.23$, $4.19{\pm}2.16$, $5.81{\pm}4.20$, $1.83{\pm}9.17$, respectively) in Positive Affect (PA) (F=3.931, p=0.024), PA-Joy (F=3.991, p=0.023), PA-Interest (F=5.025, p=0.009), NA-Afraid (F=3.118, p=0.050), and Difference between Positive and Negative Affect (DPN) (F=6.355, p=0.003) scores. The post-hoc analysis showed that the Tae-Eum type ($18.71{\pm}8.75$, $6.47{\pm}3.36$, $6.31{\pm}2.47$, $10.94{\pm}10.08$) has significantly higher score than So-Eum type ($13.38{\pm}6.03$, $4.55{\pm}2.23$, $4.19{\pm}2.16$, $1.83{\pm}9.17$, respectively) in PA (p=0.018), PA-Joy (p=0.021), PA-Interest (p=0.017), and DPN (p=0.002) scores. The So-Eum type ($5.81{\pm}4.20$) showed significantly (p=0.047) higher score than the Tae-Eum type ($3.18{\pm}2.77$) in NA-Afraid. Results demonstrated distinct affect profile differences between Tae-Eum and So-Eum Sasang types using PANAS. This study may serve as the foundation in identifying psychological traits of Sasang types, especially regarding the aspect of affect.

• 대한한의학회지
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• 제29권4호
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• pp.104-113
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• 2008

Objectives: The aim of this study was to investigate the influence of five herbal medicines on cytochrome P450 (CYP) 3A4 drug-metabolizing enzymes in human liver microsomes. Methods: By using of human liver microsomes, we extracted Cnidium officinale Makino, Rhus verniciflua Stokes, Prunus persica Batsch, Corydalis remota Fisch, Carthamus tinctorius Linne, which are called Hwalhyulgeoouhyak(活血祛瘀藥). Then they were incubated and measured for relative enzyme activity under incubation conditions compared to ketoconazole, which is known as a representative inhibitor of CYP 3A4. Results: We showed that all of five traditional herbal medicines had no inhibition effect of CYP 3A4 at 10, 20, 30, 40, and 50${\mu}g/m{\ell}$ doses in human liver microsomes, although Rhus verniciflua Stokes (RVS) showed a little inhibition as about 95% enzyme activity of control. However, this result was not enough to prove that RVS has a CYP 3A4 inhibition effect. Moreover, we can't confirm that those rates have significant induction effect on CYP 3A4. Conclusions: The result of this study could support that those herbal medicines are more reliable than chemical drugs, even if this is a basic step to prove that result.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.796-805
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• 1997

연구배경 : 세포주기의 활성화, 그 중에서도 특히 $G_1$/S 이행에 관여하는 세포주기관련 단백질들은 암발생에 있어서 매우 중요한 역할을 하는 것으로 알려져 있다. $G_1$ 세포주기 관련 단백질 중의 하나인 cdk4 (cyclin dependent kinase 4)의 억제제로 알려져 있는 p16 유전자는 최근에 밝혀진 종양억제유전자중의 하나로서 MTS1 (multiple tumor suppressor 1)이라고도 불린다. p16 유전자는 지금까지 알려진 어느 종양관련 유전자보다도 유전자변이의 빈도가 높은 암억제유전자인데, 특히 비소세포폐암인 경우는 70% 이상의 세포주에서 p16 단백질의 발현이 없는 것으로 밝혀져 있어 p16 유전자는 비소세포폐암 발생에 매우 중요한 역할을 할 것이라고 알려져 있다. 본 연구에서는 비소세포폐암에서 p16을 이용한 유전자치료의 타당성을 입증하기 위하여 다음과 같은 연구를 시행하였다. 방 법 : p16이 결여된 비소세포폐암 세포주 (NCI-H441)에, 정상섬유아세포에서 총 RNA를 추출하여 역전사효소 및 DNA 중합효소반응으로 증폭된 p16 cDNA를 유핵세포 발현 vector인 pRC-CMV plasmid에 subcloning하여 구축된 pRC-CMV-p16 plasmid vector를 lipofectin을 이용하여 유전자 이입한 후, 단백질을 추출하여 Western blot 분석과 면역침전법으로 $G_1$ 세포주기관련 단백질의 변동을 관찰하고, colony 형성능을 비교함으로써 암억제효과를 확인하였다. 결 과 : p16이 유전자주입된 NCI-H441 세포주에서 p16과 cdk4가 복합체를 형성하고 있고 인산화 Rb가 대조 세포주에 비해 감소되어 있음을 확인할 수 있어, p16이 cdk4와 결합함으로써 cdk4에 의한 Rb의 인산화를 방해하고 이에 따른 $G_1$ 세포주기 정체에 의해 종양억제효과가 나타난다는 설명을 뒷받침할 수 있었다. Clonogenic assay 결과는 p16 유전자주입된 NCI-H441 세포주의 colony 형성능이 대조 세포주에 비하여 현격히 감소함을 관찰하였다. 결 론 : 이상의 결과로 p16(MTS1) 유전자를 p16 단백질을 발현하지 못하는 비소세포폐암 세포주에 주입할 경우, 주입한 유전자에서 생성되는 p16 단백질이 cdk와 결합하여 Rb 단백질의 인산화를 저하시켜 궁극적으로 암억제 효과를 일으킬 수 있음이 확인되었고, 이는 향후 비소세포폐암의 유전자치료에 있어서 p16 유전자의 이용 가능성을 확인한 기초자료가 된다고 생각된다.

• 대한한의학회지
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• 제19권2호
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• pp.450-467
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• 1998

To research the characteristics of ion currents induced by inhibitory and excitatory herbs of oriental medicine, we used nystatin-perforated patch clamp technique under voltage clamp condition in periaqueductal gray neuron dissociated from Sprauge-Dawley rat, 10-15 days old. The results are as follows. 1. Ion current induced by $10mg/m{\ell}$ of Bupleuri Radix was inhibited $59.50{\pm}4.29%$ by $10^{-4}M$ bicuculline(p>0.01) but inhibition of $10.75{\pm}4.77%$ by $10^{-4}M$ tubocurarine and $4.75{\pm}4.23%$ by $10^{-4}M$ verapamil had no statistical significance(p>0.05). So ion current induced by Bupleuri Radix revealed only GABA induced $Cl^-$ current, not acetylcholine and $Ca^{2+}$ current. 2. Ion current induced by $20mg/m{\ell}$ of Coptidis Rhizoma was inhibited $47.20{\pm}7.88%$ by $10^{-4}M$ bicuculline(p<0.01) but $3.20{\pm}2.33%$ inhibition by $10^{-4}M$ tubocurarine and $1.00{\pm}1.00%$ inhibition by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Coptidis Rhizoma revealed only GABA induced $Cl^-$ current, not acetylcholine and $Ca^{2+}$ current. 3. Ion current induced by $20mg/m{\ell}$ of Ecliptae Herba was inhibited $55.00{\pm}4.92%$ by $10^{-4}M$ bicuculline (p<0.01), and also inhibited $15.00{\pm}4.26%$ by $10^{-4}M$ tubocurarine(p<0.05), but inhibition of $6.00{\pm}3.03%$ by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Ecliptae Herba showed GABA activated $Cl^-$ current and acetylcholine activated cation current, not $Ca^{2+}$ current 4. Ion current induced by $5mg/m{\ell}$ of Liriopis Tuber was inhibited $15.20{\pm}4.57%$ by $10^{-4}M$ bicuculline<0.05) and also inhibited $14.00{\pm}3.00%$ by $10^{-4}M$ tubocurarine(p<0.05), but inhibition of $5.20{\pm}4.80%$ by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Liriopis Tuber showed GABA. activated $Cl^-$ current and acetylcholine activated cation current, not $Ca^{2+}$ current. 5. Ion current induced by $5mg/m{\ell}$ of Aconiti Tuber was inhibited $97.00{\pm}1.34%$ by $10^{-4}M$ bicuculline(p<0.01), $80.00{\pm}9.83%$ by $10^{-4}M$ tubocurarine(p<0.01), and $24.00{\pm}6.18%$ by $10^{-4}M$ verapamil(p<0.05). So ion current induced by Aconiti Tuber revealed GABA activated $Cl^-$ current and acetylcholine activated cation current and $Ca^{2+}$ current. 6. Ion current induced by $10mg/m{\ell}$ of Zingiberis Rhizoma was inhibited $33.00{\pm}7.43%$ by $10^{-4}$ bicuculline(p<0.05), $10.20{\pm}1.83%$ by $10-^{-4}M$ tubocurarine(p<0.01), and $14.00{\pm}2.16%$ by $10^{-4}M$ verapamil(p<0.01) So ion current induced by Zingiberis Rhizoma revealed GABA activated $Cl^-$ current and acetylcholine activated cation outtent and $Ca^{2+}$ current. 7. Ion current induced by $10mg/m{\ell}$ of Boshniakiae Herba was inhibited $65.00{\pm}13.75%$ by $10^{-4}M$ bicuculline(p<0.05), $38.00{\pm}9.24%$ by $10^{-4}M$ tubocurarine(p<0.05), and $33.25{\pm}7.42%$ by $10^{-4}M$ verapamiHp<0.05). So ion current induced by Bpshniakiae Herba revealed GABA activated $Cl^-$ current and acetylcholine activated cation current and $Ca^{2+}$ current. These results suggest that a point of difference between inhibitory and excitatory herbs is existence of$Ca^{2+}$ current.

• Journal of Preventive Medicine and Public Health
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• 제26권2호
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• pp.179-191
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• 1993

Generally fatty liver is attributed either to chronic alcoholism, diabetes mellitus, or obesity. Based upon this commonly held clinical brief, this study was conducted to investigate the contributing factors of fatty liver and odds ratio (OR) of known contributing factors. A sample of 310 male participants, who visited at Seoul Paik Automated Multiphasic Health Testing System from November 1991 to December 1991, was separated into 112 cases and 198 controls by ultrasonographic fin ding. There were statistically significant difference between fatty liver and normal in triglyceride (TG), body mass index (BMI), alanine aminotransferase (ALT), high density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), alcohol consumption, low density lipoprotein cholesterol (LDL-C), total cholesterol, gamma-glutamyl transferase ($\gamma$-GT), duration of alcohol intake and alkaline phosphatase (Alk.P)(P<0.01, P<0.05). The statistically significant elevated odds ratio were noted for TG (4.48, confidence interval (CI) 2.66-7.55, P=0.000), alcohol consumption(3.24, CI 1.56-6.23, P=0.002), BMI(3.05, CI 1.87-4.97, P=0.000), and FBS (2.59, CI 1.53-4.40, P=0,000). In summary, it is suggested that the fatty liver could be preventive by avoiding such deleterious factors as high fat diet, alcohol and obesity.

• 척추신경추나의학회지
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• 제7권1호
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• pp.27-34
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• 2012

Objectives : The purpose of this study is to find out the relation between 4th lumbar rotational malposition and scoliosis. Methods : We investigated 22 cases of patients who were diagnosed as scoliosis. We used AP & Lateral view X-ray for patients. And we analysed the relation between 4th lumbar rotational malposition and scoliosis. Results : P-value was 0.436 between 4th lumbar rotational amount and lordotic angle, and was 0.758 between 4th lumbar rotational amount and wedge angle(p>0.05). And p-value was 0.022 between 4th lumbar rotational amount and scoliotic apex rotational amount(p<0.05), but was 0.286 between 4th lumbar rotational amount and Cobb's angle(p>0.05). Conclusions : The results suggest that 4th lumbar rotational malposition was statistically correlation with scoliotic apex rotational malposition, was not Cobb's angle, 4th lumbar lordotic & wedge angle.

• 대한예방한의학회지
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• 제10권1호
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• pp.141-153
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• 2006

In order to study the changes in hematology and serum chemistry of rats injected with glycerol, Sprague-Dawley albino rats weighing 240 to 260 gm were injected intramuscularly with a 50% solution of glycerol(8ml/kg). We measured the values of hematology and serum chemistry, and compared the measured values of S1 group(passed for 1day after injection of glycerol), S2 group(passed for 2days after injection of glycerol), S3 group(passed for 3days after injection of glycerol), S4 group(passed for 3days after injection of glycerol) and S5 group(passed for 4days after injection of glycerol) with those of Normal group(non-treated group). The results are summarized as follows : 1. In body temperature, S1, S2, S4 groups showed significantly higher compared with Normal group, especially S2 group was higher than S1 group(p<0.05). But S5 group was lower than Normal group(p<0.05). 2. In RBC, S1 group was lower than Normal group(p<0.05). And in Hct, S1, S2, S3 groups were lower than Normal group(p<0.05), in Hb, S1 and S3 groups were lower than Normal group(p<0.05). 3. In WBC, S1, S2 groups were higher than Normal group(p<0.05). and in WBC differential count, S2, S3, S5 groups were higher than N, S1, S4 groups in monocyte(p<0.05). 4. In GOT, S1 group was higher than Normal group(p<0.05), and S2, S3, S4, S5 groups were lower than S1 group(p<0.05). In GPT, S1 group was higher than Normal group(p<0.05), and S2, S3 groups were lower than S1 group(p<0.05), S4, S5 groups were lower than N, S1, S2, S3 groups(p<0.05). 5. In total cholesterol and creatinine, S4 group was higher than Normal group(p<0.05). According to the above experimental results, we could find the anemia, inflamation, damage of renal function for 4 days by intramuscularly injection with a 50% solution of glycerol(8ml/kg) in rat.