29 research outputs found
Epinephrine-induced Metabolic Acidosis during Orthognatic Surgery: A case report
Epinephrine has a variety of clinical uses one is its use as a topical hemostatic agent on bleeding surfaces, such as in the mouth. We report a temporal association between the administration of topical epinephrine and the development of metabolic acidosis during general anesthesia. A 21 year-old patient, with facial asymmetry, had undergone orthognatic surgery. During the operation, serial blood gas analysis revealed the onset of a metabolic acidosis following the local infiltration (0.036 mg) and topical application of a high dose of epinephrine-Bosminโ (1:1,000 epinephrine). The metabolic acidosis resolved within 5 hours.ope
Effect of BMI and patient positioning on airway pressures and respiratory compliance during laparoscopic surgery
BACKGROUND: Conventional laparoscopic surgery requires a pneumoperitoneum with CO2 and a change in the patient positioning. Because of the pneumoperitoneum, the peak and plateau airway pressure and respiratory compliances can change compared with initial value. Obesity also affects the patient's respiratory mechanics. The aim of this study was to determine the correlation between the patient's positioning and a pneumoperitoneum with the changes in the respiratory mechanics, and to examine the relationship between the patient's BMI and the changes in therespiratory mechanics.
METHODS: Fifty patients undergoing a laparoscopic cholecyctectomy and had no pulmonary pathology were enrolled in this study. The patient's basic data were obtained and the Body Mass Index (BMI) was calculateed. Conventional induction and maintenance of anesthesia were carried out, and each patient was fully relaxed with a rocuronium during the procedure. The change in the respiratory mechanics was checked 5 minutes after induction, the time that the pneumoperitoneum had been induced, and the end of surgery with the supine and 10ยฐ tilting of the Trendelenburg and reverse Trendelenburg position.
RESULTS: There was approximately a 30% reduction in dynamic compliances before and after inducing pneumoperitoneum with CO2 at each position and a negative correlation between the BMI and the dynamic compliance. There were no significant differences in the respiratory mechanics withe the different patient positions.
CONCLUSIONS: The respiratory mechanics are influenced by an increase in the patient's BMI and induced pneumoperitoneum but not by a 10ยฐ tilting of the reverse Trendelenburg and Trendelenburg position.ope
In vivo study on the biocompatibility of new resin-based root canal sealers ์ ๊ฐ๋ฐ ๋ ์ง ๊ณ์ด ๋ดํจ์ ์ ์์ฒด์นํ์ฑ์ ๊ดํ ์ฐ๊ตฌ :
Thesis (master`s)--์์ธ๋ํ๊ต ๋ํ์ :์น์ํ๊ณผ ์น๊ณผ๋ณด์กดํ์ ๊ณต,2002.Maste
(The) study for the velocity measurement of the horizontal saccadic eye movement
์ํ๊ณผ/์์ฌ[ํ๊ธ]
Saccade ์๊ตฌ์ด๋์ ์๋-์งํญ์ ํน์ง์ผ๋ก ์ ์๋ ์ ์๋ค. Saccade ์ต๋์๋ ์ธก์ ์
์ค์์ฑ์๋ ๋ถ๊ตฌํ๊ณ ๊ทธ ์๋-์งํญ๊ด๊ณ๋ ์ผ๋ฐ์ ์ผ๋ก ์ผ์ ํ ์ธก์ ๊ฐ์ด ๋์ค์ง ๋ชปํ๊ณ ์
์ผ๋ฉฐ, ํนํ saccade์ ์ด๋๋ฐฉํฅ์ ๋ํ ์๋-์งํญ์ธก์ ๊ฐ์ ๋์ฑ ๋ค์ํ ์ธก์ ๊ฐ์ด ๋ณด๊ณ ๋
๊ณ ์๋ค. ์ด์๊ฐ์ ๋ค์ํ ์ธก์ ๊ฐ์ ์ด๋ ์ ๋๋ ํ๋ณธํฌ๊ธฐ์ ๊ด๊ณ๊ฐ ์์ผ๋ ๊ฐ์ฅ ์ค์ํ
์์ธ์ ์ฌ์ฉ๋ ๊ธฐ๋ก๋ฐฉ๋ฒ์ด ๋ค๋ฅด๊ธฐ ๋๋ฌธ์ผ๋ก ์๊ฐ๋๋ค.
๋ณธ ์ฐ๊ตฌ์ ๋ชฉ์ ์ saccade ์ด๋๋ฐฉํฅ์ด ์ํ saccade ์ต๋์๋์ ์ํฅ์ ๋ฏธ์น ์ ์๋๊ฐ
๋ฅผ ์ถ๊ตฌํ ๊ฒ์ด๋ค. ์ด๋ฅผ ์ํ์ฌ ์ํ saccade ์ด๋์ 6๊ฐ์ง ๊ธฐ๋ณธ๋ฐฉ์์ ์ ํ๊ณ ๊ฐ๋ณ์ 10
ยฐ์ ๋ํ์ฌ ์ด ๊ธฐ๋ณธ๋ฐฉ์์ ๋ฐฉํฅ๊ณผ ์๋๋ฅผ ๊ธฐ๋กํ์ฌ ๊ณ ์ฐฐํ๋ค.
์๊ตฌ์ด๋์ ์ธก์ ํ๊ธฐ ์ํ์ฌ ์๊ตฌ์ด๋ ๋ชจ๋ํฐ, ์ํ๋ฐ์์ฅ์น, ๊ธฐ๋ก๊ธฐ ๊ธฐํ ๊ฐ์ข
๊ณ ์ ์ฅ
์น์ ๋ถ๋์ฅ์น๋ก ์ธก์ ์ฒด๊ณ๋ฅผ ๊ตฌ์ฑํ๊ณ 3๋ช
์ ๊ฑด๊ฐํ ํ๊ตญ์ฑ์ธ์ ํผ๊ฒ์๋ก ์ ์ ํ์ฌ 4์ฃผ๋
์ ์์ค์์ ์คํ์ ์ค์ํ๋ค. ๊ธฐ๋ก์ง์์ saccade ์์น, ์ต๋์๋๋ฅผ ๋ฉด๋ฐํ ๊ด์ฐฐํ๊ณ ,
์๋ฃ๋ ํต๊ณ์ ์ผ๋ก ์ฒ๋ฆฌํ์ผ๋ฉฐ, t-๊ฒ์ ์ ๊ฑฐ์ณ 5%์ ์๋ฏธ์๋ ๋ ๋ฒจ์ ๊ตฌํ์ฌ ๋ค์๊ณผ ๊ฐ์
์คํ๊ฒฐ๊ณผ๋ฅผ ์ป์๋ค.
1. ๊ฐ๋ณ์ 10ยฐ์ ๋ํ์ฌ saccade ์๊ตฌ์ด๋์ ์ต์ข
์์น๋ฏธ๋ฌ์ด๋ ์์ ์ด๋์ ๋ฐ์์จ์ด
๋ฎ์์ผ๋ฉฐ ๊ฑฐ์๊ฐ ์ ์ ์๊ตฌ์ด๋ํํ๋ฅผ ๋ํ๋๋ค.
2. Saccade ์ต๋ ์๋์ ๋ํฏ๊ฐ์ 295.6deg/sec์ด๋ค.
3. ์ด์ธก๊ณผ ๋น์ธก๋ฐฉํฅ์ ์ด๋์ ๋ํ์ฌ saccade ํ๊ท ์ต๋์๋๊ฐ์ ๋น์ธก์ด ์ฝ๊ฐ ๋ ๋น ๋ฅด๋
ํต๊ณ์ ์ผ๋ก ์ ์๋ฏธํ ๋ณํ๋ ์๋๋ค.
4. ์ค์ฌ์, ์ด์ฌ์, ์ค์ฌํต๊ณผ๋์นญ์ ์ด๋์ฌ์ด์ saccade ํ๊ท ์ต๋์๋๊ฐ์ ๋น์ธก์ด ์ฝ๊ฐ
๋ ๋น ๋ฅด๋ ํต๊ณ์ ์ผ๋ก ์ ์๋ฏธํ ๋ณํ๋ ์๋๋ค.
5. ๋ณธ ์ฐ๊ตฌ์ ๊ฒฐ๊ณผ๋ฅผ ์ข
ํฉํ๋ฉด, ๊ฐ๋ณ์ 10ยฐ์ด๋์ ๋ํ์ฌ saccade ํ๊ท ์ต๋์๋๋ ๋ฐฉ
ํฅ์ ๋ฐ๋ผ ๋ณํ๊ฐ ์๋ค.
๋ณธ ์ฐ๊ตฌ์ ๊ฒฐ๊ณผ๋ ์ ๊ฒฝ๊ณ์ ๊ด๊ณ๋ ์๊ณผ์งํ์ ์ง๋จ๊ณผ ์ฐ๊ตฌ์ ์ ์ฉํ๊ฒ ์ด์ฉ๋ ์ ์์ผ
๋ฆฌ๋ผ๊ณ ์๊ฐ๋๋ฉฐ ์ด๋ฅผ ์ํ์ฌ ์์ผ๋ก ๋ณด๋ค ๊ด๋ฒ์ํ ๊ฐ๋ณ์์ ๋ํ ํ์ค์น์ ํ๋ฆฝ์ด ํ์
ํ๋ค.
[์๋ฌธ]
Saccadic eye movement may be defined entirely on the basis of velocity-amplitude
characteristics. Despite the obvious importance of saccadic peak velocity
measurements, there is lack of agreement about saccadic velocity-amplitude
relationships in general and particularly with regard to the direction of movement.
The variability of the results is attributed mostly to different recording
techniques used and partly to the sample size.
The aim of this study is to investigate the effect of saccadic direction for the
determination of their possible influence upon the horizontal saccadic peak
velocity. Therefore, six basic patterns of horizontal saccadic movement were
determined and the direction and velocity of these basic patterns of the angular
distance of 10 degrees were recorded and discussed.
The experimental apparatus consisted of Biometrics Eye Movement Monitors, target
function generators, oscillographic recorders and the other fixation devices. The
experimental subjects were three Korean adults. All experiments had been performed
in the dark room for 4 weeks.
The position and peak velocity of saccadic eye movement in the records were
carefully observed and the data were analyzed statistically for significant change
with the use of t-test at the 5 per cent level and the main results are as follows:
1. In the horizontal saccadic eye movement in the angular distance of 10 degrees,
the production rate of undershoot or corrective movement is low and most of the
saccadic eye movement are normal.
2. The mean of the saccadic peak velocity is 295.6 deg/sec in the angular
distance of 10 degrees.
3. The mean horizontal saccadic peak velocity is faster in the nasal direction,
as compared with the temporal direction, but the difference is not statistically
significant.
4. The mean saccadic peak velocity is greater in the nasal than in the temporal
direction among the velocities of the centering, decentering and symmetry but the
difference is not statistically significant.
5. The analysis of the results showed that the mean horizontal saccadic peak
velocity has no statistically significant difference between the nasal and the
temporal direction in the angular distance of 10 degrees.
Author feels that the methods and results of this study may be useful tools in
the diagnosis and research of eye disease related to the nervous system and that
further study to establish the standard data of saccadic peak velocity should be
performed at the various angular distances.restrictio
Effects of fatty acids on the activity of K+-channels in vascular smooth muscle cells
์ํ๊ณผ/๋ฐ์ฌ[ํ๊ธ]
์์์ ์ผ๋ก ํํ ์ํ์ ๋น ์ง ๊ฒฝ์ฐ ๊ด์ ๋๋งฅ์ ํ๋ฅ๋์ด ํ์ ํ ์ฆ๊ฐํ๋ ๊ฒ์ด ๋ง์
์ฐ๊ตฌ์๋ค์ ์ํด ๋ณด๊ณ ๋์์ผ๋ฉฐ, ์ด๊ฐ์ ํ๋ฅ๋ ์ฆ๊ฐ ํ์์ ํํ์ ์ฆ๊ฐํ๋ ๋์ฌ๋ฌผ์ง(is
chemic metabolites)๋ค์ด ๊ด์๋๋งฅ์ ๊ธด์ฅ๋๋ฅผ ๊ฐ์์์ผ ๋ํ๋๋ ๊ฒ์ผ๋ก ์๊ฐ๋๊ณ ์์ผ
๋ ์์ง ๊ทธ ๊ธฐ์ ์ ๋ช
ํ์น ์๋ค.
์ด๊ฐ์ ํํ์ฑ ๋์ฌ๋ฌผ์ง ์ค์ ํ๋์ธ ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ์ฌ๋ฌ ์ข
๋ฅ์ ion channel ํ์ฑ ์กฐ์
์ ์ค์ํ ์ญํ ์ ํ๊ณ ์์ผ๋ฉฐ, ํนํ ์ธํฌ์ ๋ง์ ์์ ๊ณผ๋ถ๊ทน์์ผ ์ฃผ๋ ion channel์ ํ
์ฑ์ ์ฆ๊ฐ์์ผ์ฃผ๋ ๋ง์ ์์ ํ๋ถ๊ทน์ ์ด๋ํ๋ ion channel์ ํ์ฑ์ ์ต์ ํ๋ ๊ฒ์ด ๋ง
์ ์ฐ๊ตฌ์๋ค์ ์ํด ๋ณด๊ณ ๋์๋ค. ๊ทธ๋ฐ๋ฐ ๋ง์ด ์กฐ์ง์ผ๋ก์ ํ๋ฅ๋์ ๊ด๋ฅ์์ด ์ผ์ ํ ๊ฒฝ์ฐ
ํ๊ด์ ๊ธด์ฅ๋์ ์ํด ์กฐ์ ๋๊ฒ ๋๋ฉฐ, ์ด๊ฐ์ ํ๊ด์ ๊ธด์ฅ๋๋ ํ๊ด ํํ๊ทผ ์ธํฌ์ ๋ง์
์์ ํฌ๊ธฐ์ ์ปค๋ค๋ ์ํฅ์ ๋ฐ๊ฒ ๋๋ค. ํ๊ด ํํ๊ทผ ์ธํฌ์ ๋ง์ ์์ ์ฌ๋ฌ ์ธ์๋ค์ ์ํด
์กฐ์ ๋๊ณ ์์ผ๋ฉฐ, ํนํ ํ๊ด ํํ๊ทผ์ธํฌ๋ง์ ๋๋ฆฌ ์กด์ฌํ๋ Ca**++ -activated K**+ -ch
annel์ ํ์ฑ ์ ๋์ ๋ฐ๋ผ ํฌ๊ฒ ์ํฅ์ ๋ฐ๊ฒ ๋๋ค.
๋ฐ๋ผ์ ํํ์ ์ฆ๊ฐํ๋ arachidonic acid ๋ฐ ๊ธฐํ ์ ๋ฆฌ ์ง๋ฐฉ์ฐ์ด ํ ๋ผ ๊ด์ ๋๋งฅ ํํ
๊ทผ ์ธํฌ์ Ca**++ -activated K**+ -channel์ ํ์ฑ์ ๋ฏธ์น๋ ์ํฅ์ patch clamp ๋ฐฉ๋ฒ์ผ
๋ก ์ธก์ ํ์ฌ ๋ค์๊ณผ ๊ฐ์ ๊ฒฐ๊ณผ๋ฅผ ์ป์๋ค.
1. ๋ณธ ์คํ ์กฐ๊ฑด์์ ๊ด์ ๋๋งฅ ํ๊ด ํํ๊ทผ ์ธํฌ์์ ์ฃผ๋ก ๊ด์ฐฐ๋๋ ion channel์,
์ธํฌ๋ด Ca**++ ๋๋ ๋ฐ ๋ง์ ์์ ํ๋ถ๊ทน์ ๋น๋กํ์ฌ ๊ทธ์ ํ์ฑ์ด ์ฆ๊ฐ๋๋ large conduct
ance K**+ -channel(BK channel)์ด ์ฃผ๋ก ๊ด์ฐฐ๋์๋ค.
2. ๊ด๋ฅ์ก์ ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ์ฒจ๊ฐํ ๊ฒฝ์ฐ BK channel์ ํ์ฑ์ด ํ์ ํ ์ฆ๊ฐํ์์ผ๋ฉฐ, ์ด
๊ฐ์ ์ฆ๊ฐ ํจ๊ณผ๋ ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ์ฉ๋งค๋ก ์ฌ์ฉํ dimethylsulfoxide(DMSO)์๋ ๋ฌด๊ดํ์๋ค.
3. ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ๋๋๋ฅผ 0.5ฮผM์์ 4ฮผM๊น์ง ์ฆ๊ฐ์ํจ ๊ฒฝ์ฐ ํฌ์ฌ ๋๋์ ๋น๋กํ์ฌ BK
channel์ ํ์ฑ์ด ์ฆ๊ฐํ์์ผ๋ฉฐ, ์ ๋ฆฌ ์ง๋ฐฉ์ฐ์ ๋๋๋ฅผ 10ฮผM๊น์ง ์ฆ๊ฐ์ํจ ๊ฒฝ์ฐ์๋ ์ค
ํ๋ ค BK channel์ ํ์ฑ์ด ๊ฐ์ํ์๋ค.
4. ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ BK channel ํ์ฑ ์ฆ๊ฐ ํจ๊ณผ๋ ๊ทธ์ ํ์์๊ฐ ํฐ ๊ฒฝ์ฐ ๋์ฑ ํ์ ํ์์ผ
๋ฉฐ, ํฌํ ์ฌ๋ถ๋ ์ปค๋ค๋ ์ํฅ์ ๋ผ์น์ง ๋ชปํ์๋ค.
5. ๊ด๋ฅ์ฉ์ก๋ด ^^Ca++ ๋๋ ๋ฐ ^^Mg++์ ์กด์ฌ ์ฌ๋ถ๋ ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ BK channel์ ํ์ฑ
์ฆ๊ฐํจ๊ณผ์ ๋ณ๋ค๋ฅธ ์ํฅ์ ๋ผ์น์ง ๋ชปํ์๋ค.
6. ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ BK channel์ ํ์ฑ ์ฆ๊ฐ ํจ๊ณผ์ด์ธ์ small conductance K**+ -channel
์ ํ์ฑ ์ญ์ ์ฆ๊ฐ์์ผ ์ฃผ์๋ค.
์ด์์ ์คํ ๊ฒฐ๊ณผ๋ก ๋ณด์ ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ํ๊ด ํํ๊ทผ์ BK channel์ ํ์ฑ ์กฐ์ ์ ๊ด์ฌ
ํ๋ endogenous regulator๋ก ์์ฉํ๋ฉฐ, ํนํ ํํ์ํ์ ๊ฐ์ด ์ธํฌ๋ด ์ ๋ฆฌ์ง๋ฐฉ์ฐ์ ๋๋
๊ฐ ์ฆ๊ฐํ๋ ๊ฒฝ์ฐ ํ๊ด ๊ธด์ฅ๋ ์กฐ์ ์ ์ค์ํ ์ญํ ์ ํ ๊ฒ์ผ๋ก ์๊ฐ๋๋ค.
[์๋ฌธ]
A variety of fatty acids regulate the activity of ion channels in a different
preparations, and the concentration of fatty acid is greatly increased during
myocardial ischemia. These reports suggest that fatty acid may contribute to the
ischemic regulation of coronary blood flow.
To test this possibility, we studied the effect of fatty acid on the Ca**++
-activated K**+ -channel(BK channel) from rabbit coronary smooth muscle cells by
using a patch clamping method.
Arachidonic acid dissolved in DMSO activated BK channel in a dose-dependent
manner(from 0.5 to 10ฮผM), and DMSO(0.1%) alone had no effect on the activity of BK
channel. The effect of arachidonic acid were also examined in both cell-attached
and excised, inside-out patch. Arachidonic acid activated BK channel in both
cell-attached and inside-out patches, but onset and recovery of this effect were
slower in cell-attached patch configuration. BK channel activity was also increased
by other fatty acids, including myristic acid, linoleic acid, palmitoleic acid and
palmitic acid. Long chain fatty acids were more effective than short chain fatty
acid(myristic acid), and there is no stastical difference between
saturated(palmitic acid) and unsaturated fatty acid(palmitoleic acid) on BK channel
activity. The concentration of Ca**++ and Mg**++ in the bathing solution had no
appreciable effect on the arachidonic acid-induced increase of BK channel activity.
From the above results, it may be concluded that fatty acid act as an "endogenous
regulator" of BK channel and also contribute to the ischemic coronary
vasodilatation by increasing the activity of BK channel in coronary smooth muscle
cells.restrictio
์๊ถ๊ฒฝ๋ถ์์์ Bcl-2, Bax, VEGF, PCNA ๋จ๋ฐฑ์ ๋ฐํ ๋ฐ Apoptosis ์์๊ณผ ์ ํํญ์ํํ์๋ฒ ๋ฐ์๋์์ ์๊ด๊ด๊ณ์ ๊ดํ ์ฐ๊ตฌ
ํ์๋
ผ๋ฌธ(์์ฌ)--์์ธ๋ํ๊ต ๋ํ์ :์ํ๊ณผ ์ฐ๋ถ์ธ๊ณผํ์ ๊ณต,2000.Maste
๋๋ ๊ฐ๊ณต ์ํ์ผ๋ก๋ถํฐ ์นํ ํฌ๋ก๋งํ ๊ทธ๋ํผ๋ฅผ ์ด์ฉํ CP4 5-enolpyruvylshikimate-3-phosphate์ ๊ฒ์ถ
Thesis (master`s)--์์ธ๋ํ๊ต ๋ํ์ :๋์๋ช
๊ณตํ๋ถ,2003.The Round-up Readyยฃยฟ soybean, which has the tolerance against an herbicide,
glyphosate, is widely used for soybean processing. Recently, detection of
genetically modified (GM) food becomes more important because of mandatory
labeling. In general, there are two quantitation methods of genetically modified
soybean in soybean food products; one is based on PCR analysis at DNA level and
the other is an immunoassay for the CP4 5-enolpyruvylshikimate-3-phosphate
synthase (CP4 EPSPS) at protein level. However, these two methods have
limitations when GM soybean is processed to Korean traditional foods.
Therefore, development of a new detection method is needed for soybean food
products. Affinity chromatography could be a possibility as an alternative
detection method at protein level using the shikimate 3-phosphate as a ligand.
Especially, because CP4 EPSPS is intact after the heat-treatment for 90 min at
95 ยกรC, tofu can be applied onto affinity chromatography. An affinity
chromatography column was made by immobilizing shikimate 3-phosphate to the
beaded agarose gel through the carbodiimide condensation. Since the shikimate 3-
phosphate was not available commercially, it was synthesized enzymatically by
shikimate kinase II and purified by ion exchange chromatography. The protein
samples isolated from GM soybean were applied to an affinity chromatography
column and CP4 EPSPS was analyzed by SDS-PAGE. It seemed that CP4 EPSPS was
adsorbed onto affinity chromatography column. However, Because shikimate 3-
phosphate was purified with low level, the efficiency of affinity chromatography
column was not good. To prepare a large quantity of shikimate 3-phoshate, an
affinity chromatography can be a successful detection method for CP4 EPSPS from
GM soybeans and its food products. For the better analysis of CP4 EPSPS, the
changes of ligand immobilizing method and protein elution condition should be
considered.Maste
์์น-ํน์ด์ ๋์ฐ๋ณ์ด ์ ๋์ N-๋ง๋จ ์์ญ ์ ๊ฑฐ๋ฅผ ํตํ Arthrobacter sp. S37 ์ ๋์ endoinulinase์ ๊ธฐ๋ฅ ๋ถ์
Thesis (master`s)--์์ธ๋ํ๊ต ๋ํ์ :๋์๋ช
๊ณตํ๋ถ,2003.Endoinulinase from Arthrobacter sp. S37 (EnIAb), a member of
family 32 glycosidase, catalyzes hydrolysis of inulin using two
catalytic residues, a nucleophile and an acid/base catalyst, as indicated
in the bell-shaped pH dependence profile. Sequence alignment of
EnIAb with other members of the family followed by a site-directed
mutagenesis and the pH dependence studies of mutants proposed a
detailed catalytic mechanism. Complete loss of enzyme activity in
D460A mutant and noticeable changes in the alkaline limb from 8.8 to
7.0 of pH dependence in D460E mutant revealed that Asp460 residue,
a component of the fully conserved RDP (Asn-Asp-Pro) motif among
family 32, elevates the pKa of the acid/base catalyst of EnIAb with
electrostatic interaction. Together with observations that only a kcat not
a Km value was reduced more than 100-fold in E323A, E519A, D460N
and D460E mutants, the active site of the enzyme is proposed to be a
triad of carboxylate groups Glu323 (nucleophile), Glu519 (acid/base
catalyst) and Asp460. Various single residue and truncated mutants of
the unique N-terminal domain (residue 1 ~ 240) suggested that the
domain has dual roles as a carbohydrate-binding domain and a direct
involvement in catalysis. Significant reductions in enzyme efficiency
(kcat/Km) were observed in W75K, W141A, and W141K mutants,suggesting these highly conserved aromatic residues W75 and W141
play a key role in substrate binding. In addition, N-terminal truncated
mutants ฮ15, ฮ45, ฮ70 as well as ฮ240 were almost inefficient in
enzyme catalysis, necessitating the structural integrity of the Nterminal
domain for catalysis. These results provide a model of the
active site common to a family 32 and a unique functional role of the
N-terminal domain in EnIAb.Maste
A Study on the Activity of HBV DNA-polymerase and Effect of Adenine Arabinoside-5'-monophosphate (Ara-AMP) Therapy in Chronic HBV Infection
์ํ๊ณผ/์์ฌ[์๋ฌธ]
[ํ๊ธ]
Hirschman ๋ฑ (1971)์ด Australia ํญ์ ์์ฑ์ธ ํ์์ ํ์ฒญ์์ DNA-polymerase์ ์กด์ฌ
๋ฅผ ๋ณด๊ณ ํ ์ด๋ DNA-polymerase์ ํ์ฑ๋๊ฐ ํ๋์ Bํ ๊ฐ์ผ๋ฐ์ด๋ฌ์ค์ ํ์์๋ก์ ๋ฐ์ด
๋ฌ์ค์ ์ฆ์์ ๋๋ฅผ ๋ฐ์ํ๊ณ eํญ์์ ์์ฑ์ฌ๋ถ์ ๋ฐ์ ํ ์ฐ๊ด์ฑ์ ๊ฐ์ง๋ ์ํ์ธ์๋ก ๋ณด
๊ณ ๋๊ณ ์๋ค(Hindman, 1976). ๋ํ ๊ทผ๋๊น์ง ๋์ฆ์ ๋ฐ ๋ณด์ ์ ์น๋ฃ์๋ง ์์กดํด์ค๋ ๋ง์ฑ
ํ๋์ฑ ๊ฐ์ผ์ ์น๋ฃ๋ก์ ์ต๊ทผ ํญ๋ฐ์ด๋ฌ์ค์ ์ธ adenine arabinoside 5'-monophosphate (
์ดํAra-AMP๋ก ์ฝํจ)๊ฐ ๊ฐ์ผ ๋ฐ์ด๋ฌ์ค ํ์์์ ์์ค ๋ด์ง๋ ์ ํ์ ํจ๊ณผ๊ฐ ์๋ค๊ณ ๋ณด๊ณ
๋๊ณ ์์ผ๋ฉฐ (Pollard๋ฑ, 1976; Bassendinee ๋ฑ, 1978) ์ด ์ฝ๋ฌผ์ด clfydhy๊ณผ์ ๊ฒฝ๊ฐ์ DN
A-polymeass์ ํ์ฑ๋๊ฐ ๊ฐ์ฅ ๋ฏผ๊ฐํ๋ค๊ณ ์๋ ค์ ธ ์๋ค(Scullard ๋ฑ, 1981).
์ ์๋ 1985๋
1์๋ถํฐ 1986๋
5์๊น์ง ์ฐ์ธ๋ํ๊ต ์๊ณผ๋ํ ์๋์ธ๋ธ๋์ค๋ณ์์ ์
์
ํ์๋ HB^^s Ag ์์ฑ์ด๋ฉฐ ๋ณต๊ฐ๊ฒ์ฌ๋ฅผ ์ธก์ ํ์์ผ๋ฉฐ ๊ทธ์ค e ํญ์์ด ์์ฑ์ด ๋ง์ฑ ํ๋์ฑ
๊ฐ์ผ, ๋ง์ฑ ์ง์์ฑ ๊ฐ์ผ ๋ฐ ๊ฐ๊ฒฝ๋ณ์ฆ์ผ๋ก ํ์ง๋ ํ์ 80์๋ฅผ ๋์์ผ๋ก DNA-polymerase์
ํ์ฑ๋๋ฅผ ์ธก์ ํ์์ผ๋ฉฐ ๊ทธ์ค e ํญ์์ด ์์ฑ์ธ ๋ง์ฑ ํ๋์ฑ ๊ฐ์ผํ์ 37์๋ฅผ ๋์์ผ๋ก Ar
a-AMP๋ฅผ ํฌ์ฌํ ํ ์ฅ๊ธฐ๊ฐ ์ฃผ๊ธฐ์ ์ผ๋ก DNA-polymerase์ ํ์ฑ๋๋ฅผ ์ธก์ ํ์ฌ ๋ค์๊ณผ ๊ฐ์
๊ฒฐ๊ณผ๋ฅผ ์ป์๋ค.
1) ํ์ฒญ e ํญ์์ด ์์ฑ์ด์๋ ํ์๊ตฐ์ DNA-polymerase์ ํ์ฑ๋๋ 4994.3ยฑ789.8 dpm/
ml์๊ณ ์์ฑ์ด์๋ ํ์๊ตฐ์ 606.2ยฑ190.1 dpm/ml๋ก์ ์๊ตฐ์ฌ์ด์ ํต๊ณํ์ ์ผ๋ก ์ ์ํ
์ฐจ์ด๋ฅผ ๋ณด์๋ค(p<0.05).
2) ๋ง์ฑ ํ๋์ฑ ๊ฐ์ผ, ๋ง์ฑ ์ง์์ฑ ๊ฐ์ผ ๋ฐ ๊ฐ๊ฒฝ๋ณ์ฆ ํ์๊ตฐ์ DNA-polymerase์ ํ์ฑ
๋๋ ๊ฐ๊ฐ 4889.6ยฑ930.6 dpm/ml, 5040.9ยฑ1449.3 dpm/ml ๊ทธ๋ฆฌ๊ณ 1895.6ยฑ1075.8 dpm/ml
๋ก์ ๊ฐ๊ตฐ ์ฌ์ด์ ํต๊ณ์ ์ ์์ฑ์ ๋ณด์ด์ง ์์๋ค(p>0.05).
3) Ara-AMP๋ก ์น๋ฃํ ๊ตฌ์์์ DNA-polymerase์ ํ์ฑ๋๋ ์น๋ฃํ 1์ฃผ์งธ๋ถํฐ ์์์๊ฒ
๊ฐ์ํ๊ธฐ ์์ํ์ฌ 24์ฃผ์ด์ ์ถ์ ์ด ๊ฐ๋ฅํ๋ 16๋ช
์ ๊ฒฝ์ฐ์์ 10์(62.5%)๋ ์ ์๋ฒ์ฃผ์
DNA-polymerase์ ํ์ฑ๋๋ฅผ ๋ํ๋์ผ๋ฉฐ ๊ทธ์ค 6์๊ฐ e ํญ์์ด ์์ ๋์๊ณ , DNA-polymeras
e์ ์ฌ์์น์ ๋ณด์๋ ๋๋จธ์ง 6์ (37.5%)๋ ๋์กฐ๊ตฐ์์์ ๊ฐ์ด 1์๋ง์ด e ํญ์์ ์์ ์
๋ณด์๋ค.
4) Ara-AMP์ ๋ถ์์ฉ์ผ๋ก๋ 37์์ค ์์๋ถ์ง์ด 8์(21.6%)๋ก ๊ฐ์ฅ ๋ง์๊ณ ์ค์ฌ๊ณผ ๋ฌด๊ธฐ
๋ ฅ๊ฐ์ด ๊ฐ๊ฐ 6์(16.2%)์์ผ๋ฉฐ 1์(2.7%)์์ ์ง๊ฐ์ด์, ๊ณผ๋ฆฝ๋ฐฑํ๊ตฌ ๊ฐ์์ฆ ๋ฐ ํ์ํ๊ฐ
์์ฆ์ ๋์์ ๋ณด์์ผ๋ ํฌ์ฝ์ค์งํ ์ ์์ผ๋ก ํ๋ณต๋์๋ค.
์ด์์ ๊ฒฐ๊ณผ DNA-polymerase์ ํ์ฑ๋๋ eํญ์์ ์์ฑ์ฌ๋ถ์ ์ฐ๊ด์ฑ์ ๋ณด์ด๋ฉฐ ๋ง์ฑ ํ
๋์ฑ ๊ฐ์ผํ์์๊ฒ Ara-AMP๋ก 4์ฃผ๊ฐ ๋จ๊ธฐ์น๋ฃ๋ฅผ ์ํํจ์ผ๋ก์ Bํ ๊ฐ์ผ๋ฐ์ด๋ฌ์ค์ ์ฆ์์
ํจ๊ณผ์ ์ผ๋ก ์ต์ ํ ์ ์์๋ค.
A Study on the Activity of HBV DNA-polymerase and Effect of Adenine
Arabinoside-5'-monophosphate (Ara-AMP) Therapy in Chronic HBV Infection
Yong Bum Kim, M.D.
Department of Medical Science
The Graduate School, Yonsei University
(Directed by Prof. Jin Kyung Kang, M.D.)
Since the presence of DNA-polymerase has been reported by Hirschman et al. in
concentrated preparations containing Au antigen, the activity of DNA-polymerase has
been used as the index of degree of the viral replication and as the most sensitive
marker for the effects of antiviral therapy.
The activity of DNA-polymerase was measured through radiological assay in 80
patients with HBaAg positive chronic HBV infection (57 patients with chronic active
hepatitis, 12 with chronic persistent hepatitis and 11 with liver cirrhosis) and
serially checked for about one year in 37 patients with HBeAg positive chronic
active hepatitis, who received 4 weeks Ara-AMP there apy.
The following results were obtained
1. The mean DNA-polymerase activity of the HBeAg positive chronic hepatitis
patients was significantly higher than that of the HBeAg negative patients (p<0.05)
but differences of the SGOT and SGPT levels between the both groups were not
significant (p>0.05).
2. The differences of mean DNA-polymerase activities among the chronic active
hepatitis, chronic persistent hepatitis and liver cirrhosis were not
significant(p>0.05).
3. During the 4 weeks of Ara-AMP therapy, the mean levels of DNA-polymerase
activity, SGOT and SGPT fell dramatically. 10 of 16 patients who could follow up
for over 24 weeks maintained DNA-polymerase activity normal however, remaining 6
relapsed. From 1 to 9 months after therapy, 7 of 16 patients became HBeAg negative,
while only one of 6 controls became HBeAg negative.
4. Side effects of Ara-AMP such as anorexia (21.6%), nausea(16.2%), general
weakness(16.2%), paresthesia(2.7%), granulocytopenia(2.7%), and
thrombocytopenia(2.7%) were observed.
In conclusion, the measurement of DNA-polymerase activity will be helpful in
evaluation of infectivity of chronic viral hepatitis and effect of antiviral
therapy. More work is needed to determine whether the use of Ara-AMP in more
prolonged or repeated courses, or both, and application earlier in the course of
the iliness might be more effect in the eradication of virus and in stopping
progression of chrniceliver disease. Alternatively, Ara-AMP may be more effective
when combined with other antiviral agents, and controlled studies to evaluate
various combination regimens are required.restrictio
The U.S. Antitrust Policy of Telecommunications:1974~1984 AT&T antitrust divestiture
ํ์๋
ผ๋ฌธ(์์ฌ) --์์ธ๋ํ๊ต ๋ํ์ :์ธ๊ตํ๊ณผ,2007.Maste