• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.101-101
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• 2004

• 생명과학회지
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• 제13권4호
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• pp.463-472
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• 2003

제5인자와 지질막 phosphatidylserine과의 상호작용은 prothrombinase 복합체의 활성을 조절하는데 중요하다. 본 연구에서 제5인자의 지질 결합부위에 위치한 Trp2063과 Trp2064를 동시에 돌연변이 시킨 재조합 제5인자를 과발현 시키고 정제하였다. 돌연변이된 제5인자는 1-10%의 phosphatidylserine을 포함하는 지질막에서 아주낮은 활성을 보였다. surface plasmon resonance에 의해서 지질막과의 결합을 측정한 결과 돌연변이된 제5인자가 본래의 제5인자보다 고정된 지질막에의 결합이 현저하게 떨어지는 것을 관찰하였다. 제5인자가 phosphatidylserine을 포함하는 지질막에 높은 친화력으로 결합하기 위해서는 Trp2063과 Trp2064가 필수적이고 이러한 상호작용은 생리적인 phosphatidylserine 농도를 포함하는 지질막 위에서 prothrombinase 복합체의 형성에 필요하다는 결론을 내렸다.

• Toxicological Research
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• 제25권4호
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• pp.175-180
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• 2009

Lead (Pb) is a ubiquitously occurring environmental heavy metal which is widely used in industry and human life. Possibly due to a global industrial expansion, recent studies have revealed the prevalent human exposure to Pb and increased risk of Pb toxicity. Once ingested by human, 95% of absorbed Pb is accumulated into erythrocytes and erythrocytes are known to be a prime target for Pb toxicity. Most of the studies were however, focused on $Pb^{2+}$ whereas the effects of $Pb^{4+}$, another major form of Pb on erythrocytes are poorly understood yet. In this study, we investigated and compared the effects of $Pb^{4+}$, $Pb^{2+}$ and other heavy metals on procoagulant activation of erythrocytes, an important factor for the participation of erythrocytes in thrombotic events in an effort to address the cardiovascular toxicity of $Pb^{4+}$. Freshly isolated erythrocytes from human were incubated with $Pb^{4+}$, $Pb^{2+}$, $Cd^{2+}$ and $Ag^+$ and the exposure of phosphatidylserine (PS), key marker for procoagulant activation was measured using flow cytometry. As a result, while $Cd^{2+}$ and $Ag^+$ did not affect PS exposure, $Pb^{4+}$ and $Pb^{2+}$ induced significantly PS exposure in a dose-dependent manner. Of a particular note, $Pb^{4+}$ induced PS exposure with a similar potency with $Pb^{2+}$. PS bearing microvesicle (MV), another important contributor to procoagulant activation was also generated by $Pb^{4+}$. These PS exposure and MV generation by $Pb^{4+}$ were well in line with the shape change of erythrocyte from normal discocytes to MV shedding echinocytes following $Pb^{4+}$ treatment. Meanwhile, nonspecific hemolysis was not observed suggesting the specificity of $Pb^{4+}$-induced PS exposure and MV generation. These results indicated that $Pb^{4+}$ could induce procoagulant activation of erythrocytes through PS exposure and MV generation, suggesting that $Pb^{4+}$ exposure might ultimately lead to increased thrombotic events.

• Journal of Yeungnam Medical Science
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• 제36권3호
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• pp.273-280
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• 2019

Cerebral venous sinus thrombosis (CVT) is a rare cerebrovascular condition accounting for 0.5-1% of all types of strokes in the general population. Hyperthyroidism is associated with procoagulant and antifibrinolytic activity, thereby precipitating a hypercoagulable state that predisposes to CVT. We report the case of a 31-year-old Korean man with massive CVT and diagnosis of concomitant Graves' disease at admission. Early diagnosis and prompt treatment of CVT are important to improve prognosis; therefore, CVT should be considered in the differential diagnosis in all patients with hyperthyroidism presenting with neurological symptoms.

• Archives of Pharmacal Research
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• 제29권12호
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• pp.1158-1163
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• 2006

More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drink-ing water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to $22.39{\pm}2.26\;{\mu}g/dL$. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.

• Journal of Interdisciplinary Genomics
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• 제3권2호
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• pp.41-46
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• 2021

Inherited platelet function disorders (IPFDs) are a disease group of heterogeneous bleeding disorders associated with congenital defects of platelet functions. Normal platelets essential role for primary hemostasis by adhesion, activation, secretion of granules, aggregation, and procoagulant activity of platelets. The accurate diagnosis of IPFDs is challenging due to unavailability of important testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. Among several IPFDs, Glanzmann thrombasthenia (GT) is a most representative IPFD and is relatively frequently found compare to the other types of rarer IPFDs. GT is an autosomal recessive disorder caused by mutations of ITGA2B or ITGB3. There are quantitative or qualitative defects of the GPIIb/IIIa complex in platelet, which is the binding receptor for fibrinogen, von Willbrand factor, and fibronectin in GT patients. Therefore, patients with GT have normal platelet count and normal platelet morphology, but they have severely decreased platelet aggregation. Thus, GT patients have a very severe hemorrhagic phenotypes that begins at a very early age and persists throughout life. In this article, the general contents about platelet functions and respective IPFDs, the overall contents of GT, and the current status of genetic diagnosis of GT in Korea will be reviewed.

• Clinical and Experimental Pediatrics
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• 제49권10호
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• pp.1093-1099
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• 2006

목 적 : 호모시스테인은 성인에서 관상동맥 질환을 포함한 심혈관 질환의 독립적인 위험 인자로서, 혈관 내피세포 손상과 혈액 응고 촉진, 혈전 형성 등의 기전으로 동맥경화증의 위험을 증가시킨다고 알려져 있으나 이러한 호모시스테인이 소아에 미치는 영향은 아직까지 연구된 바가 없다. $TNF-{\alpha}$는 전염증성 사이토카인으로서 혈관 내피세포 손상과 관상동맥의 염증 반응을 초래한다. 본 연구에서는 호모시스테인이 가와사키병의 관상동맥 합병증에 미치는 영향과 $TNF-{\alpha}$의 연관성에 대해 알아보고자 하였다. 방 법 : 가와사키병 환아 24명(관상동맥 확장이 없는 군(1군) : 8명, 관상동맥 확장이 있는 군(2군) : 16명)에 대한 임상 양상과 면역글로불린 투여 전과 후, 회복기에서의 호모시스테인과 $TNF-{\alpha}$ 혈중 농도를 비교하였다. 대조군은 같은 시기에 내원한 열이 없는 정상 소아(3군 : 10명)와 열성 질환 소아(4군 : 11명)로 정하였다. 결 과 : 면역글로불린 투여 전의 호모시스테인은 1군($14.0{\pm}7.0{\mu}mol/L$)에서 3군($5.9{\pm}1.1{\mu}mol/L$)에 비해 유의하게 높았으며(P<0.05), 2군($17.4{\pm}8.0{\mu}mol/L$)에서는 3군($5.9{\pm}1.1{\mu}mol/L$)과 4군($9.2{\pm}2.0{\mu}mol/L$) 각각에 비해 유의하게 높았다(P<0.05). $TNF-{\alpha}$에서도 면역글로불린 투여 전 2군($858.4{\pm}934.0pg/mL$)이 3군($8.0{\pm}1.1pg/mL$)과 4군($54.1{\pm}146.3pg/mL$)에 비해 유의하게 높았다(P<0.05). 2군에서 시간 경과에 따른 호모시스테인과 $TNF-{\alpha}$를 비교해 보면 면역글로불린 투여 전에 각각 $17.4{\pm}8.0{\mu}mol/L$, $858.4{\pm}934.0pg/mL$로 가장 높았고, 면역글로불린 투여 후와 회복기로 갈수록 감소하였다. 또한 가와사키병 급성기에서 호모시스테인과 $TNF-{\alpha}$는 양의 상관관계를 가진다(r=0.488, P<0.05). 결 론 : 호모시스테인의 혈중 농도가 높을수록 가와사키병에서 관상동맥 병변이 발생할 가능성이 더 높았으며 $TNF-{\alpha}$와 같은 사이토카인도 관상동맥 병변의 형성에 중요한 역할을 할 것으로 생각된다.