• 약학회지
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• 제50권2호
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• pp.93-98
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• 2006

Human foamy virus (HFV) integrase mediates integration of viral c-DNA into cellular DNA. In this process, HFV prointegration complex (PIC) in which integrase is a key component moves to nuclei of the infected cells and leads to integration of viral DNA to the cellular genome, which is essential in viral life cycle. In general nuclear localization signals (NLS) have been suggested to be involved in localizing retroviral PIC to nuclei, but the mechanisms for nuclear localization of the HFV PIC remains unclear. To functionally identify the NLS of HFV integrase, various subdomains of the protein were expressed as GFP fusions and their subcellular locations were analyzed with confocal laser scanning microscopy. Wild type HFV integrase was karyophilic by targeting the fusion protein to nuclei of the COS-1 and 293T cells. Our results showed that strong NLS of HFV integrase was mapped to the C-terminal regions. In addition the karyophilic properties of N-terminal and central regions are not individually strong enough to direct localization of the fusion proteins to nuclei, but their cooperative activity for nuclear import was confirmed.

• 대한의용생체공학회:의공학회지
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• 제11권2호
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• pp.195-202
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• 1990

The hypothesis of asymmetric resistance to explain the phenomenon of lung hyperinflation (LHI) during hlgh frequency ventilation (HFV) was quantitatively studied. LHI was predicted by modeling the ism-volume pressure-flow (IVPF) data from 5 human subjects using the empirical Rohrer's equation. Non-steadiness during HFV was compensated by em- ploying recently proposed volume-frequency diagram. Tidal volume and ventilation frequency were 100 ml and 20 Hz, respectively. Airflow pattern was a symmetric sinusoid. The predic- tion results of mean pressure drop across the airways were averaged for those 5 subjects, and compared with zero by one-sided student's t-test. A marginally significant (P<0.1) increase in mean pressure drop was observed during HFV at low lung volumes (below FRC) , which could increase mean lung volume up to one liter When the lung volume was above FRC, no significant LHI (P >0.25) was resulted. LHI seemed to be inversely related to the lung volume. These results recommend to clinically apply HFV only at lung volumes above FRC.

• 약학회지
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• 제48권1호
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• pp.13-19
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• 2004

A bacterial expression vector for the human foamy virus (HFV) integrase was constructed and expressed in Escherichia coli. By two-step purification using a nickel-chelated column and a SP-sepharose chromatography; the HFV into-grase protein of 43 kDa was purified to near homogeneity, and used to investigate biochemical characteristics of the enzymatic activities, such as endonucleolytic and disintegration activities. Oligonucleotide substrates were specifically and efficiently cleaved by the purifed HFV integrase in the presence of Mn $^{+2}$, but not in the presence of Mg $^{+2}$, indicating that the HFV integrase is not able to use Mg $^{+2}$ as a cofactor Endonucleolytic reaction was almost completed in 60 min at 37 $^{\circ}C$. In addition, the maximum enzymatic activities were observed at 5 mM Mn $^{+2}$ in the buffer of which pH was from 7.0 to 9.0. The endonucleolytic activities were dose-dependently blocked in the addition of baicalein or chicolic acid which is a well-known inhibitor of human immunodeficiency virus integrase.

• Molecules and Cells
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• 제19권2호
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• pp.246-255
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• 2005

Retroviral integrases insert viral DNA into target DNA. In this process they recognize their own DNA specifically via functional domains. In order to analyze these functional domains, we constructed six chimeric integrases by swapping domains between HIV-1 and HFV integrases, and two point mutants of HFV integrase. Chimeric integrases with the central domain of HIV-1 integrase had strand transfer and disintegration activities, in agreement with the idea that the central domain determines viral DNA specificity and has catalytic activity. On the other hand, chimeric integrases with the central domain of HFV integrase did not have any enzymatic activity apart from FFH that had weak disintegration activity, suggesting that the central domain of HFV integrase was defective catalytically or structurally. However, these inactive chimeras were efficiently complemented by the point mutants (D164A and E200A) of HFV integrase, indicating that the central domain of HFV integrase possesses potential enzymatic activity but is not able to recognize viral or target DNA without the help of its homologous N-terminal and C-terminal domains.

• 약학회지
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• 제49권3호
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• pp.198-204
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• 2005

Human foamy virus (HFV) integrase mediates integration of viral c-DNA into cellular DNA. In this process, HFV integrase recognizes its own viral DNA specifically and catalyzes insertion of viral c-DNA. In order to study catalytic domains and residues, three deletion mutants and two point mutants of HFV integrase were constructed and analyzed with respect to enzymatic activities. The C-terminal deletion mutant showed decreased enzymatic activities while the N-terminal deletion mutant lost the activities completely, indicating that the N-terminal domain is more important than the C-terminal domain in enzymatic reaction. The point mutants, in which an aspartic acid at the 164th position or a glutamic acid at the 200th position of the HFV integrase protein was changed to an alanine, lost the enzymatic activities completely. However, they were well complemented with other defective deletion mutants to recover enzymatic activities partially. Therefore, these results suggest that the aspartic acid and glutamic acid at the respective 164th and 200th positions are catalytic residues for enzymatic reaction.

• 대한의용생체공학회:의공학회지
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• 제11권2호
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• pp.203-208
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• 1990

A possible asymmetry in airway inertance was modeled based on previously reported radiographic visualization data of the airway wall fluctuation in intact dogs. Effects of asymmetric Inertance on mean lung volume during high frequency ventilation (HFV) were evaluated in terms of mean inertive pressure drop across the airways. It was found that a negligible inertlve pressure drop was expected ($<1{\;}cmH_20$) in normal subjects, while a sig- nificant rise in mean alveolar pressure compared to mean mouth pressure by approximately $3{\;}cmH_20$ was resulted for about 40% airway fluctuation representing bronchoconstriction state by Histamine induction. These results demonstrate that asymmetric Inertance could lead patients with airway diseases to a significant lung hyperinflation (LHI), and bronchodilation treatment is recommended prior to applying HFV to prevent those patients from a possible barotrauma.

• 대한의용생체공학회:의공학회지
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• 제14권1호
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• pp.89-96
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• 1993

During high frequency ventilation (HFV), mean alveolar pressure has been measured to increase with mean airway opening pressure controlled at a constant level in both humans and experimental animals. Since this phenomenon could potentiate barotrauma limiting advantages of HFV, the present study theoretically predicted the difference between menu alveolar and airway opening pressures ($MP_{alv}$). In a Weibel's trumpet airway model, approximated formula for $MP_{alv}$ was derived based on momentum conservation assuming a uniform velocity profile. The prediction, equation was a func pion of gas density($\rho$), mean flow rate(Q), and diameter of the airway opening where the pressure measurement was made($D_0$) : $MP_{alv}=4{\rho}(Q/D_0^{2})^2$. This was a result of the difference in crosssectional area between the alveoli and the airway opening. A simple aireway model experiment was performed and the results well fitted to the prediction, which demonstrated the validity of the present analysis. Previously reported $MP_{alv}$ data from anesthetized dogs in supine position were comparable to the predicted values, indicating that the observed dissociation between mean alveolar and airway opening pressures during HFV can be explained by this innate geometric (or cross-sectional area) asymmetry of the airways. In lateral position, however, the prediction substantially underestimated the measurements suggesting involvement of other important physiological mechanisms.

• Neonatal Medicine
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• 제17권1호
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• pp.21-33
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• 2010

목 적 : 최근 신생아중환자실에서 생존률이 향상됨에 따라서 기관지폐이형성증의 발생률이 증가하고 있고, 그 중에서도 특히 비전형적 기관지폐이형성증의 발생률이 증가하고 있다. 그러나, 전형적인 기관지폐이형성증 환아와 비전형적 기관지폐이형성증 환아의 비교 연구는 많지 않다. 이에 저자들은 두 군간의 차이점을 알아보고자 본 연구를 시행하였다. 방 법: 2004년 5월부터 2007년 4월까지 서울대학교병원과 분당 서울대학교병원에서 출생하여 신생아중 환자실에 입원한 월경 후 주령 32주 미만인 환아를 대상으로 하였고, 이를 전형적인 군과 비전형적인 군으로 나누었다. 그리고, 기관지 폐이형성증의 발생률을 조사하고, 전형적인 군과 비전형적인 군에서 주산기적 요인과 출생 후 치료를 비교하였다. 결 과:총 연구 대상은 260명이었고 이 중 141명(54.2%)이 기관지폐이형성증으로 진단되었다. 이 중 전형적 기관지폐이형성증은 64명, 비전형적 기관지폐이형성증은 77명이었다. 전형적 기관지폐이형성증 환아에서 신생아 호흡곤란 증후군, 동맥관 개존증, 자궁내 성장지연이 더 많이 동반되었고, 1분과 5분 Apgar 점수가 낮았고, 고진동 인공환기기 사용이 더 많았다. 비전형적 기관지폐이형성증 환아에서는 산전 스테로이드 사용이 더 많았고, 조기 양막파수, 임상적 융모양막염과 병리학적 융모양막염의 동반이 더 많았다. 다중 로지스틱 회귀분석을 시행하였을 때 고진동 인공환기기 사용은 전형적 기관지폐이형성증 환아에서 독립변수였고, 산전 스테로이드 사용, 임상적 융모양막염과 병리학적 융모양막염은 비전형적 기관지폐이형성증 환아에서 독립변수였다. 결 론:본 연구에서는 산전 요인(산전 스테로이드 사용, 임상적 융모양막염, 병리학적 융모양막염)은 비전형적인 기관지폐이형성증과 유의한 관계를 보였고, 산후요인(더 흔한 고진동 인공환기기 사용)은 전형적 기관지폐이형성증과 유의한 관계를 보였다. 앞으로, 위와 같은 임상 연구들을 바탕으로 기관지폐이형성증의 예방과 치료에 대한 더 많은 연구가 필요하리라 생각된다.

• Journal of Yeungnam Medical Science
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• 제6권2호
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• pp.47-55
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• 1989

고빈도 진동환기가 동맥혈의 가스분압에 미치는 영향을 알아보고자 저자들은 9마리의 고양이를 대상으로 진동빈도, 일회분출량 및 bias flow를 다양하게 변화시켜 아래와 같은 결과를 얻었다. 1) 일회분출량과 bias flow를 고정시킨 후 진동빈도를 점차 증가시켜 도 $PaCO_2$의 변동은 없었다(Table 1). 2) 진동빈도를 고정시킨 후 일회분출량과 bias flow를 변화시켜 관찰하였던 바 $PaCO_2$는 bias flow의 변화와는 상관관계가 없으나, 일회분출량의 변화와는 유의한 상관관계가 있었다(p<0.01)(Table 2, Fig. 1). 3) $PaCO_2$는 진동빈도를 15Hz로 고정시킨 상태하에서는 1회 분출량 및 bias flow를 증가시켜도 큰 변동없이 정상으로 유지되었다(Table 2). 이상의 결과로 고빈도 진동환기법에서 $PaCO_2$의 결정인자는 진동빈도와 bias flow와는 무관하였고 일회분출량과는 상관관계가 있음을 알 수 있었다.

• Journal of Yeungnam Medical Science
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• 제6권2호
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• pp.39-46
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• 1989

고빈도환기법시에 생길 수 있는 기관 및 기관지의 손상의 정도를 알아 보고자 저자들은 13마리의 고양이를 대상으로 CMV와 HFOV을 각각 6시간동안 사용후 폐의 조직 병리소견을 비교하여 다음과 같은 결과를 얻었다. 1) CMV와 HFOV 사용군에서 기관 및 기관지 손상의 정도의 차이에는 통계적으로는 유의한 차이가 없었다. 2) 상피 세포내 점액의 소실은 CMV군에서 다소 더 심하였다. 3) 폐실질병변으로 폐기종은 CMV군에서 더 심하였다. 이상의 결과로 건강한 고양이에서 비교적 짧은 기간동안에 사용한 CMV와 HFOV군에서 기관 및 손상의 차이는 저명하지 않았으나, CMV군에서 다소 더 세포기능의 장애가 초래되었을 것으로 생각되며 또한 폐압손상도 더 받았을 것으로 추측된다.