한국인에서 전신성 경화증과 HLA-DR 유전자의 연관성에 관한 연구

강성하 ( Sung Ha Kang ),박명희 ( Myoung Hee Park ),송영욱 ( Yeong Wook Song ),차훈석 ( Hoon Suk Cha ),한창완 ( Chang Wan Han ),이은봉 ( Eun Bong Lee ),백한주 ( Han Joo Baek ) 대한류마티스학회 1998 대한류마티스학회지 Vol.5 No.1

Objective: This study was conducted to elucidate the associations of HLA with systemic sclerosis (SSc) in Koreans. Methods: HLA associations with SSc according to SSc-specific autoantibody status and clinical subsets (diffuse and limited) were investigated. HLA-A, B, and C antigens were typed by the serological method using microlymphocytotoxicity test, and HLA-DR by DNA typing method using PCR-reverse hybridization and PCR-SSCP in 56 Korean patients with SSc and 226 healthy controls. For SSc patients, anti-Scl-70 and anticentromere antibodies were tested by double immunodiffusion and indirect immunofluorescence, respectively. Results: The results of HLA class I antigen typing showed that the frequencies of HLA-A24, B52 and B62 were increased, whereas those of A33, B44 and B58 were decreased in SSc patients compared to healthy controls. The frequency of HLA-DR2 was significantly increased, whereas that of HLA-DR13 was decreased in patients with SSc compared to controls. Among HLA-DR2 alleles, both HLA-DRB1*1501 and *1502 were increased in SSc patients compared to controls. According to clinical status, HLA-DRB1*1501 was increased in limited SSc patients and that of DRB1*1502 was increased both in diffuse and limited SSc patients compared to controls. According to autoantibody status, HLA-DRB1*1502 was significantly increased in anti-Scl-70-positive SSc patients and that of DRB1*1501 was increased in anti-Scl-70-negative SSc patients compared to controls. The association of HLA-DR2 alleles with SSc according to clinical subsets and anti-Scl-70 antibody status revealed that the frequency of HLA-DRB1*1501 was significantly increased in anti-Scl-70-negative limited SSc patients compared to controls. Conclusions: These results suggest that different HLA-DR2 alleles are associated with different types of SSc in Koreans. HLA-DRB1*1502 shows strong association with anti-Scl-70-positive SSc, and DRB1*1501 with anti-Scl-70-negative limited SSc. It is concluded that the pathogenesis of SSc in Koreans is in part, based on the same genetic background.

테놀민 정(아테놀올 50 mg)에 대한 신일아테놀올 정의 생물학적 동등성

곽혜선,강성하,전인구,Gwak, Hye-Sun,Kang, Sung-Ha,Chun, In-Koo 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets

액체크로마토그래프법에 의한 사람 혈장 중 테라조신의 정량 및 테라토닌^® 정의 생물학적 동등성

조은숙,강성하,전인구,Cho, Eun-Sook,Kang, Sung-Ha,Chun, In-Koo 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

개선된 HPLC분석법을 이용한 세파클러 모노하이드레이트 250 mg 캡슐의 생물학적동등성

김태완,한선영,송옥경,신관석,강성하,이범진,Kim, Tae-Wan,Cao, Qing-Ri,Han, Sun-Young,Song, Ok-Kyoung,Sin, Kwan-Seog,Kang, Sung-Ha,Lee, Beom-Jin 한국임상약학회 2005 한국임상약학회지 Vol.15 No.1

A bioequivalence study of CKD $Cefaclor^{(R)}$ capsule (Chong Kun Dang Pharm Co., Ltd) to $Ceclor^{(R)}$ capsule (Lilly Korea Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the cefaclor dose of 250 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. An improved high-performance liquid chromatorgraphy (HPLC) analytical method with UV detection was used to determine plasma cefaclor concentration in human volunteers for 8 hr after oral drug administration. The area under the plasma concentration-time curve from time zero to 8 hr ($AUC_{0-8hr}$) was calculated by the linear trapezoidal rule. the $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{0-8hr}\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The $90{\%}$ confidence intervals of the $AUC_{0-8hr}$ ratio and the $C_{max}$ ratio for CKD $Cefaclor^{(R)}$ and $Ceclor^{(R)}$ were $0.9400{\leq}{\delta}{\leq}1.0345$ and $0.8858{\leq}{\delta}{\leq}1.1021$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the of CKD $cefaclor^{(R)}$ capsule was bioequivalent to $Cefaclor^{(R)}$ capsule with respect to its bioavailability.

Hb Dieppe에 의한 우성유전 베타 지중해빈혈 1례

최유경,이홍진,박원일,이경자,강성하,김지연,박성섭,Choi, You Kyoung,Lee, Hong Jin,Park, Won Il,Lee, Kyung Ja,Kang, Sung Ha,Kim, Ji Yeon,Park, Sung Sup 대한소아청소년과학회 2002 Clinical and Experimental Pediatrics (CEP) Vol.45 No.5

저자들은 상염색체 우성으로 유전되는 경한 저색소성 소구성 빈혈을 보이고 ${\beta}$ 유전자의 127번째 코돈 이 CAG에서 CGG로 치환되는 과오돌연변이로 인하여 매우 불안정한 베타 사슬 변이체를 만드는 우성유전 베타 지중해빈혈을 경험하였기에 문헌고찰과 함께 보고하는 바이다. ${\beta}$ thalassemias are usually transmitted as autosomal recessive traits. However, some dominant forms of ${\beta}$ thalassemia have been identified in individuals who have inherited a single copy of an abnormal ${\beta}$ globin gene. Thalassemia intermedia with mild anemia, jaundice, and splenomegaly has been observed in these patients. Electrophoresis has shown elevated Hemoglobin(Hb) $A_2$ and Hb F levels. In particular, there are inclusion bodies in the erythroid precursors and peripheral red blood cells after splenectomy. The molecular basis of these dominant ${\beta}$ thalassemias is heterogeneous. The authors studied the first Korean case of dominantly inherited ${\beta}$ thalassemia due to Hb Dieppe. Hb Dieppe is a missense mutation of ${\beta}$ codon $127(CAG{\rightarrow}CGG)Gln{\rightarrow}Arg$. The patient in this case was characterized by moderate anemia, hypochromia, microcytosis, elevated Hb $A_2$ levels, elevated Hb F levels and splenomegaly. The father of the patient also has the same disease. We report this case and review related literature.

춘천 지역에서 발생한 쯔쯔가무시병의 임상적 특징

이호권 ( Ho Gwon Lee ),민슬기 ( Seul Ki Min ),공승진 ( Seung Jin Kong ),이수정 ( Su Jung Lee ),송헌호 ( Hun Ho Song ),윤종우 ( Jong Woo Yoon ),이명구 ( Myung Goo Lee ),신동훈 ( Dong Hoon Shin ),강성하 ( Sung Ha Kang ),이정열 ( Jeo 대한내과학회 2005 대한내과학회지 Vol.69 No.2

목적 : 쯔쯔가무시병 환자의 일부는 중증감염으로 중환자실 집중치료를 필요로 하며 이 중 사망하는 환자들도 있다. 본 연구는 춘천 및 인근 지역에서 발생한 쯔쯔가무시병 환자의 임상적인 특징과 이 중 중증환자들의 특징을 분석하여 지역사회의 쯔쯔가무시병의 진단과 치료 및 교육에 도움이 되고자 하였다. 방법 : 1997년 4월부터 2002년 12월까지 한림대학교 부속 춘천성심병원에서 쯔쯔가무시 병으로 진단되었던 81예의 환자들의 의무기록 열람을 통한 후향적 분석을 시행하였다. 81예 환자들의 내원시 임상소견을 분석하였고, 이 중 본 병원에서 치료 받았던 79예의 환자들의 치료결과를 분석하였으며, 내원시 일반병실로 입원한 환자와 중환자실로 입원하였던 환자의 임상소견을 비교하여 중증환자들의 특징을 비교하였다. 결과 : 73예의 환자가 가을에 발생하였으며, 70예에서 발열이 있었고, 가피가 발견된 경우는 58예(71.6%)였다. Doxycycline 치료 후 45예의 환자가 48시간내 열이 없어졌으나 13예에서는 5일이상 열이 지속되었다. 79예 중에서 중환자실로 입원한 경우가 25예 였으며 이 중 8예에서 기계환기 치료를 받았고, 3예가 다발성 장기부전으로 사망하였다. 중환자실에 입원한 중증환자들은 백혈구수가 많았고, BUN과 크레아티닌이 높았고, 알부민 수치가 낮았다. 결론 : 쯔쯔가무시병은 중증질환으로 이환될 수 있으며 특히 고령이거나 만성질환을 가지고 있는 환자에게서는 치명적인 결과를 초래할 수 있으므로 감염발생의 위험이 있는 지역사회에서 유행 시기에 발열 등의 증상이 있을 때 조기 진단이 필수적이며 이를 위한 교육이 필요하다. 그리고 중증환자에서 백혈구수, 혈청 알부민, BUN, 크레아틴 등에서 차이를 나타내어 쯔쯔가무시 병의 예후를 예측하는 요소로 사료된다. Background : Tsutsugamushi disease is an acute febrile disease in Korea. Some patients with tsutsugamushi disease have severe illness, which needs care in intensive care unit, and may die due to the disease. We analyzed the cases with tsutsugamushi disease who lived in Chuncheon and neighboring communities to find out clinical manifestations, laboratory findings especially in severe cases. Methods : We reviewed the clinical records of the 81 cases who were diagnosed as tsutsugamushi in Chuncheon Sacred Heart Hospital from April, 1997 to December, 2002. We analyzed the clinical and laboratory findings of the 81 cases, and the treatment results of 79 cases who recieved the treatment in this hospital. We also compared the characteristics of the patients between admission to general ward and intensive care unit (ICU). Results : Seventy three cases developed the disease in autumn. Seventy cases had fever. 58 cases had eschar in their bodies. With the doxycycline treatment, forty five cases subsided the fever within 48 hours, but in 13 cases, fever continued after 5 days of treatment. Twenty five cases were admitted to ICU, 8 cases among them were treated with ventilator, 3 cases died due to the multi-organ failure. When we compared the clinical characteristics of the patients admitted to ICU with those to general wards, leukocyte count, the level of BUN and creatinine were higher, the albumin level was lower in ICU patients than those of general ward patients. Conclusion : Tsutsugamushi disease can progress to severe disease, and be fatal to the patients. So it is necessary to diagnose early and treat carefully. We suggest that leukocyte count, BUN, creatinine, or albumin can be used to predict the prognosis.(Korean J Med 69:190-196, 2005)

B항원이 발현되지 않은 Cis-AB형 1예

강성하,이영경,박민정,신동훈,조현찬,이규만,한규섭 大韓輸血學會 2001 大韓輸血學會誌 Vol.12 No.2

액체크로마토그래프법에 의한 사람 혈장 중 테라조신의 정량 및 테라토닌^�정의 생물학적 동등성

조은숙,강성하,전인구 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ㎕-portions of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range 5∼60 ng/ml were 0.49∼2.92 and 0.38∼5.12%, respectively. The bioequivalence of two terazosin tablets, the Hytrine?? (Il Yang Pharmaceutical Co., Ltd.) and the Teratonin?? (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers (24.6±2.0 years old) were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. C_max and T_max were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_max and T_max between the two preparations were 0.21%, 5.53% and 8.82%, respectively. The powers (1-β) for AUC_t, C_max and T_max were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences (Δ, %) at α=0.1 and 1-β=0.8 and the 90% confidence intervals were all less than ±20% except for T_max, AUC_t and C_max met the criteria of KDFA for bioequivalence, indicating that Teratonin?? tablets are bioequivalent to Hytrine?? tablets.

테놀민 정(아테놀올 50㎎)에 대한 신일아테놀올 정의 생물학적 동등성

곽혜선,강성하,전인구 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, Tenormin^?? Tablets in 20 healthy Korean volunteers. The volunteers received a single 50㎎ dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration (C_max), time to reach peak plasma concentration (T_max), and terminal first order elimination half-life (t_1/2). No statistically significant difference was obtained between the T_max values, and the logarithmic transformed AUC and C_max values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and C_max values of Sinil Atenolol Tablets over those of Tenormin^?? Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of T_max in Tenormin^?? Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of t_1/2 between the two products were found comparable, and the mean t_1/2 values of Tenormin^?? Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to Tenormin^?? Tablets in both the rate and extent of absorption, indicating that Sinil Atenolon Tablets were bioequivalent to the reference product, Tenormin^?? Tablets.

Microalbumin 검사를 위한 요 검체의 보관

신동훈,박재웅,송원근,강성하,박종선,윤갑준 대한임상검사정도관리학회 2000 臨床檢査와 精度管理 Vol.22 No.1