• YAKHAK HOEJI
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• v.50 no.2
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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.

• Journal of Biomedical Engineering Research
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• v.11 no.2
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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.

• YAKHAK HOEJI
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• v.48 no.1
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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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• v.19 no.2
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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.

• YAKHAK HOEJI
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• v.49 no.3
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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.

• Journal of Biomedical Engineering Research
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• v.11 no.2
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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.

• Journal of Biomedical Engineering Research
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• v.14 no.1
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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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• v.17 no.1
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• pp.21-33
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• 2010

Purpose : The increased survival of preterm infants in the neonatal intensive care unit recently has resulted in an increased frequency of bronchopulmonary dysplasia (BPD), especially with atypical forms. However, there have been few studies compairing classic and atypical BPD. The aim of this study was to investigate the differences between these two types of BPD. Methods : Infants with a gestational age less than 32 weeks born at the Seoul National University Hospital and Bundang Seoul National University Hospital from May 2004 to April 2007 were included. The data were categorized in 2 groups, classic and atypical BPD. We determined the incidence of BPD, and compared perinatal factors and postnatal managements between two groups. Results : Among 260 study subjects, 141 (54.2%) infants had BPD. Classic BPD infants were 64 and atypical BPD infants were 77. Comparison of differences between 2 groups, classic BPD infants were associated with respiratory distress syndrome, patent ductus arteriosus, intrauterine growth restriction, more high-frequency ventilator (HFV) use, low 1 and 5 minute Apgar scores. Atypical BPD infants were associated with antenatal steroid use, maternal premature rupture of membrane and chorioamnionitis (CAM). In multivariate analysis, more HFV use was associated with classic BPD. Antenatal steroid use, clinical CAM and histological CAM were associated with atypical BPD. Conclusion : The results of this study showed that antenatal factors (antenatal steroid use, clinical CAM, histological CAM) were associated with atypical BPD and postnatal factors (HFV used more) were associated with classic BPD. Further studies are needed for prevention and treatment of BPD.

• Journal of Yeungnam Medical Science
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• v.6 no.2
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• pp.47-55
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• 1989

High frequency ventilation (HFV) is a new ventilatory technique that uses very small tidal volume(less than the anatomic dead space) and high frequency, and classified 4 distinct types according to frequency and mode of gas delivery. The mechanism of gas transport of high frequency oscillation ventilation(HFOV) is somewhat different to other types of HFV. To evaluate the determinants of $PaCO_2$ in HFOV, a study was done with a HFOV on 9 cats, and the results are : 1) $PaCO_2$ was not correlated with frequency at the constant stroke volume(6 voltage) and bias flow (6L/minutes). 2) $PaCO_2$ was correlated with stroke volume but not with bias flow under the constant frequency(15Hz/min) and bias flow(3 to 6L/min). From above results, the main determinant of $PaCO_2$ on artificial ventilation with HFOV was stroke volume, but further study between flow, the site of delivery to the airway and humidification of bias flow and $CO_2$ elimination is required in future research.

• Journal of Yeungnam Medical Science
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• v.6 no.2
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• pp.39-46
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• 1989

The tracheobronchial histopathologic findings in 7 healthy cats used with high frequency oscillation ventilation (HFOV) were compared with those in 6 cats used with conventional mechanical ventilation (CMV). 4-point, 9-variable scoring system was used to evaluate the injury in the trachea, right & left main bronchi and parenchyme. The following results were obtained ; 1) The tracheobronchial tree received HFOV had no significant damage compared with CMV (P>0.05). 2) Intraepithelial mucus loss and emphysema were s lightly more prominent in CMV groups. As above results ; the tracheobronchial histopathologic difference was not prominent between CMV and HFOV groups received with relatively short period, however, the cellular function and barotrauma may be more prominent in CMV groups. From now on, as causes of tracheobronchial injury in HFV, interaction between humidification and mechanical trauma considers further study.