• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.57-57
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• 2003

In growing number of diseases it has been shown that aggregation of specific proteins has an important role in pathogenesis of the disorder. This has been demonstrated in structural details with the liver cirrhosis of ${\alpha}$$_1$-antitrypsin deficiency, and it is now believed that similar protein aggregation underlies many neurodegenerative disorders such as autosomal dominant Parkinson disease, prion diseases, Alzheimer disease, and Huntington disease. ${\alpha}$$_1$-Antieypsin, a member of serine pretense inhibitor (serpin) family, functions as an inhibitor of neutrophil elastase.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.4
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• pp.234-241
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• 2000

The Saccharomyces cerevisiae PMR1 gene encodes a Ca2+-ATPase localized in the Golgi. We have investigated the effects of PMR1 disruption in S. cerevisiae on the glycosylation and secretion of three heterologous glycoproteins, human ${\alpha}$1-antitrypsin (${\alpha}$1-AT), human antithrombin III (ATHIII), and Aspergillus niger glucose oxidase (GOD). The pmr1 null mutant strain secreted larger amounts of ATHIII and GOD proteins per a unit cell mass than the wild type strain. Despite a lower growth rate of the pmr1 mutant, two-fold higher level of human ATHIII was detected in the culture supernatant from the pmr1 mutant compared to that of the wild-type strain. The pmr1 mutant strain secreted ${\alpha}$1-AT and the GOD proteins mostly as core-glycosylated forms, in contrast to the hyperglycosylated proteins secreted in the wild-type strain. Furthermore, the core-glycosylated forms secreted in the pmr1 mutant migrated slightly faster on SDS-PAGE than those secreted in the mnn9 deletion mutant and the wild type strains. Analysis of the recombinant GOD with anti-${\alpha}$1,3-mannose antibody revealed that GOD secreted in the pmr1 mutant did not have terminal ${\alpha}$1,3-linked mannose unlike those secreted in the mnn9 mutant and the wild type strains. The present results indicate that the pmr1 mutant, with the super-secretion phenotype, is useful as a host system to produce recombinant glycoproteins lacking high-mannose outer chains.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.70-76
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• 1995

A few researchers have reported that major depression may be associated with higher levels of positive acute phase proteins(APPs), such as haptoglobin(Hp), ${\alpha}1$-antitrypsin(${\alpha}1AT$), ceruloplasmin(Cp) and lower levels of negative APPs(visceral proteins), such as albumin(Alb) and transferrin(Tf). Elevated levels of positive APPs and a drop in negative APPs constitute important indicators of immune activation. This study was designed to investigate whether altered serum concentrations of positive APPs and of negative APPs reflect the state of depression. Twenty patients who fulfilled DSM-III-R criteria for major depressive disorder and for dysthymic disorder and twelve normal healthy controls were included. The authors measured positive APPs(Hp, ${\alpha}1AT$, Cp) and negative APPs(Alb, Tf) using rate nephelometry and bromcresol green method. 1) There were significant increases of ${\alpha}1AT$, Cp in major depressed patients as compared with normal controls. Trends towards higher Hp and lower Alb, Tf in major depressed patients were observed. 2) No significant difference of APPs concentrations between dysthymic patients and normal controls was found. 3) Severity of depression(HDRS, BDI score) was related to Hp, Cp, ${\alpha}1AT$ value positively. Our findings are partially compatible with the hypothesis that major depression may be accompanied by acute phase response with higher levels of positive APPs and lower levels of negative APPs.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.615-623
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• 2001

Background : Pneumoconiosis is a parenchymal lung disease that results from the accumulation of coal dust in the lungs and the consequent tissue reaction. To evaluate the role of various personal factors in pneumoconiosis and the significance of some serologic markers for assessing the disease activity related to pneumoconiosis, the Rheumatoid Factor(RF), ${\alpha}_1$-AT, C-Reactive Protein(CRP), ceruloplasmin and fibrinogen levels were measured. Method : All the patients were males, 45-76 years old, and the mean duration of coal dust exposure was 23.2 years. 51 patients were classified as having Simple Pneumoconiosis (SP), 59 had Progressive Massive Fibrosis (PMF). Fifty eight men with ages ranging from 26-70 years were used as normal controls. The serum RF and CRP were titrated using an Autochemistry analyzer (HITACHI 7150 : Japan) and the ${\alpha}_1$-AT and ceruloplasmin levels were measured using a Nephelometer (Behring Nephelometer : Germany) and the fibrinogen levels were estimated by using an Autoanalyzer for hematologic coagulation. Result : There was a higher RF level in the SP, and PMF groups than in the control groups but there was no statistical difference. The CRP, ${\alpha}_1$-AT, and ceruloplasmin levels were also higher in the SP, and PMF groups. However, the fibrinogen concentration was within the normal ranges in both the SP and PMF groups. Conclusion : The CWP (Ed note : Define CWP) patients had significantly higher CRP, ${\alpha}_1$-AT, and ceruloplasmin levels compared to the control group. It is believed that these serologic changes could be used as a marker of the disease activity.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.40-40
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• 2003

형질전환체 제작 시 발현벡터가 삽입되는 위치에 따라 발현 또는 억제되는 현상인 ‘position effect(위치효과)’를 극복하기 위해 Matrix Attachment Region(MAR)을 포함하는 발현벡터를 제작하였다 MAR는 핵 기질(nuclear matrix) 부착 부위로 발현조절에 관여하는 전사인자 등이 존재하는 핵 기질 부착부위로, 삽입된 발현벡터가 전사활성을 할 수 있는 게놈 환경을 제공해 주어 형질전환 유전자 발현을 향상시켜 준다고 보고되고 있다. 본 연구에서는 사람에서 이미 분리되어 염기서열이 밝혀진 MAR를 PCR로 증폭하였다. 증폭된 1,270 bp의 human alpha-1-antitrypsin MAR와 1,080 bp human corticosteroid binding globulin promoter MAR를 T vector에 클로닝하여 염기서열을 확인했으며 발현벡터 클로닝에 사용하였다. 유용 유전자와 세포 형질전환에 사용할 선별 유전자로 neo를 포함하며, 그 외 벡터골격은 pGL3 control vector를 사용하여 기본 발현벡터를 제작하였다. 이 벡터에 MAR를 5', 3' 양쪽 또는 한쪽만 포함하도록 클로닝하였다. 이는 MAR의 위치에 따른 게놈내 삽입 및 발현효과를 확인하여 형질전환동물 생산용 발현벡터로 활용하고자 한다.

• Biomedical Science Letters
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• v.15 no.4
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• pp.309-317
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• 2009

Occupational exposure to inorganic dusts such as coal and silica has been identified as a chronic obstructive pulmonary disease (COPD) risk factor. This risk factor causes lung inflammation and protease-antiprotease imbalance. This abnormal inflammatory response of the lung induces parenchymal tissue destruction and leads to progressive airflow limitation that is characteristics of COPD. The aim of this study was to determine the relationship of proteases such as neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 and antiproteases such as alpha-1 antitrypsin (AAT) and tissue inhibitors of metalloproteinase (TIMP)-1 with lung function. The study population contained 223 retired workers exposed to inorganic dusts. We performed lung function test, including percent of forced expiratory volume in one second ($%FEV_1$) predicted and $%FEV_1$/forced vital capacity (FVC). We analyzed serum MMP-9, AAT, TIMP-1 and plasma NE concentrations by sandwich enzyme immunoassay. NE, AAT, and TIMP-1 concentrations in workers, who had $%FEV_1$<80% predicted, were higher than those of workers who had $%FEV_1{\geq}80%$ (P<0.05). Both AAT and TIMP-1 concentrations in workers with airflow limitation were higher than those of workers with normal airflow (P<0.05). $%FEV_1$ predicted showed significant negative correlation with AAT (r=-0.255, P<0.0l), TIMP-1 (r=-0.232, P<0.01), and NE (r=-0.196, P<0.01). $%FEV_1$/FVC predicted showed significant negative correlation with NE (r=-0.172, P<0.05). From the results of stepwise multiple regression analysis about $%FEV_1$ and $%FEV_1$/FVC, significant independents were NE (r=-0.135, P=0.001) and AAT (r=-0.100, P=0.013) in $%FEV_1$, and NE (r=-0.160, P=0.014) in $%FEV_1$/FVC. In the present study, there were significant correlations between airflow limitation and protease concentration and between airflow limitation and antiprotease concentration. Serum protease and antiprotease concentrations, however, may be affected by the biological and inflammatory responses. It is necessary to evaluate specimens more reflected the effects of proteases and antiproteases in the lung such as lung tissue, bronchoalveolar lavage fluid, and exhaled breath condensate (EBC).

• Journal of the Korean Arthroscopy Society
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• v.2 no.2
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• pp.181-184
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• 1998

This is a report on a aseptic synovitis diagnosed and treated arthroscopically following the meniscal repair using biodegradable Meniscus Arrow$^{(R)}$(Bionix Inc, Malvern, USA). Histological examination revealed chronic nonspecific synovitis and birefringent material. Immunohistochemical tests were positive in lysozyme, ${\alpha}$-1-antitrypsin and ${\alpha}$-1-antichymotrypsin. The patient was received arthroscopic synovectomy, and then pain and swelling of the knee joint was relieved. Range of motion was improved to full range. As far as we know, this is the first case of aseptic synovitis after meniscal repair using biodegradable Meniscus Arrow$^{(R)}$.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.63-63
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• 2003

$\alpha$$_1$-Antityrpsin is a member of the serine protease inhibitor (SERPIN) family that shares a common tertiary structure. The reactive site loop (RSL) of serpins is exposed at one end of the molecule for protease binding. Upon cleavage by a target protease, the RSL is inserted into the major $\beta$-sheet A, which is a necessary process for formation of a tight inhibitory complex. Various biochemical and structural studies suggest that the rate of the RSL insertion upon binding a target protease is critical for inhibitory activity, and it is thought that helix F region (thFs3A and helix F) located in front of $\beta$-sheet A, should be lifted for the loop insertion during complex formation.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.36-46
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• 1998

Solid and papillary epithelial neoplasm of pancreas is a rare tumor, usually affecting young women, and its histogenesis is still controversial. This study was performed to define the clinicopathologic features and cellular origin of this tumor. Eight female cases of solid and papillary epithelial neoplasm of pancreas were studied by analyzing the clinicopathologic findings and immunohistochemical and electron-microscopic findings. The age of eight cases ranged from 21 to 54 years (mean, 34 years). The tumors developed in the tail (4 cases), body-tail (2 cases), body (1 case) and head (1 case). The mean diameter of tumors was 9.3 em (range, 5.5 to 13 cm). Tumors showed solid, cystic and hemorrhagic areas. Histologically, the tumor cells were uniformly round or polygonal in shape, and formed solid sheets and papillary pattern. On the immunohistochemical stain, 8 cases (100%) were immunoreactive for ${\alpha}1$-antitrypsin, 7 cases (87.5%) for cytokeratin, 7 cases (87.5%) for progesterone receptor, 6 cases (75%) for vimentin, and 1 case (12.5%) for synaptophysin, respectively. None of them were immunoreactive for estrogen receptor. Electron microscopic examination showed many mitochondria, annulate lamellae and canaliculi-like gap. These findings suggest that solid and papillary epithelial tumor of pancreas possibly originates from totipotent stem cells.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.64-64
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• 2003

In growing number of diseases it has been shown that the aggregation of specific proteins has an important role in the pathogenesis of the disorder. This has been demonstrated in structural detail with the liver cirrhosis of ${\alpha}$$_1$-antitrypsin deficiency, and it is now believed that similar protein aggregation underlies many neurodegenerative disorders such as autosomal dominant Parkinson disease, prion diseases, Alzheimer disease, Huntington disease.