소아 고위험 고형종양에서의 자가 조혈모세포이식 후 Interleukin-2 치료

신미용,안강모,성기웅,구홍회 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 최근 고용량 화학요법과 자가 조혈모세포이식으로 소아 고위험 고형종양의 치료 성적이 향상되었음에도 불구하고 이식 후 미세잔존종양에 의한 재발이 여전히 문제가 되고 있다. 이에 미세잔존종양을 제거하여 재발을 줄이기 위한 방법으로 rIL-2를 이용한 면역요법이 시도되고 있다. 본 연구에서는 소아 고위험 고형종양에서 고용량 화학요법 및 자가 조혈모세포 이식 후에 rIL-2를 이요한 면역요법을 시행하고 면역학적 변화와 부작용을 평가하고자 하였다. 방법: 5명의 신경모세포종, 1명의 원시신경외배엽성종양, 1명의 재발된 clear cell sarcoma 환아 등 7명의 진행된 고위험 고형종양 환아를 대상으로 하였다. 이 중 6명은 조혈모세포이식 후 6개월 (40일-9개월)후 에 rIL-2를 투여하였으며, 1명은 통상적인 치료를 종결한 후 rIL-2를 투여하였다. 유도요법(d0: 2×10^(6) U/m²/day, d1-d4: 4×10^(6) U/m²/day, 5일간 연속정맥주사)을 72시간 간격으로 2회 시행한 후 유도요법이 끝난 2주 후부터 4주마다 유지요법(2×10^(6) U/m²/day, 4회 이후 : 3×10^(6) U/m²/day; 5일간 피하주사)을 시행하였다. 3명의 신경모세포종 환아는 13-cis-retinoic acid를 병용하였다. 면역학적 변화를 평가하기 위해 림프구아형분석과 혈액검사를 시행하고 부작용을 기록하였다. 결과: NK 세포 수는 유도요법이 끝난 후 현저히 증가하였고(5.3-14.4배), 유지요법 중에서도 대부분 치료전 기저치 보다는 높게 유지되었다. T세포 수와 총 림프구수, T4 세포수, T8 세포수, T4/T8 ratio도 비슷한 양상의 변화를 보였다. 유도요법 중 발열(7명), 피로o식욕부진(7명), 구토(2명), 경한 capillary leak syndrome (1명), 혈소판감소(6명), 빈혈(4명), 경한 간효소치의 상승(4명),경한 혈액응고시간의 연장(3명) 등이 관찰되었으나 rIL-2 투여가 끝난 후 바로 소실되거나 회복되었다. 유지요법 중에는 발열과 피로(7명), 혈소판 감소(2명)외에 다른 부작용은 없었다. 결론: 고위험 고형종양에서 조혈모세포이식 후에 rIL-2는 심각한 부작용 없이 비교적 쉽게 사용할 수 있었고, 면역학적을 NK 세포와 T 세포 수의 증가를 유도하여 미세잔존종양에 의한 재발을 방지하는데 효과가 있을 것으로 기대된다. Background: Although high- dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has improved the outcome of high-risk solid tumors in children, but in some patients tumor relapse after HDCT and ASCT is due to minimal residual disease (MRD). To reduce tumor recurrence due to growth of MRD, immunotherapy with recombinant human Interleukin-2 (rIL-2) was introduced. The purpose of this study was to evaluate the immunologic changes and side effects of r-IL-2 therapy after HDCT and ASCT in children with high-risk solid tumor. Methods: Seven patients with high-risk solid tumor(5 neuroblastomas, 1 promotive neuroecto-dermal tumor, 1 recurred clear cell sarcoma) were enrolled in this study. Six patients received rIL-2,since 6 months (40 days-9 months) after HDCT and ASCT, and 1 patients received rIL-2 after completion of conventional treatments. After 2 courses of induction treatment (d0: 2×10^(6) U/m²/day, d1-d4: 4×10^(6) U/m²/day, CIV) with 72 hours interval, maintenance treatment (1st-3trd; 2×10^(6) U/m²/day, 4for 5 days, 4th-; 3×10^(6) U/m²/day for 5 days, SC) was done every 4 weeks. In 3 patients with neuroblastoma, 13-cis-retionoic acid was used simultaneously. Blood tests including enumeration of lymphocyte subpopulation were done to evaluate immunologic and hematologic change, and various side effects were recorded. Results: The number of natural killer(NK) cells increased 5.3 to 14.4 fold after 2 courses of induction treatment, and maintained at higher level during maintenance treatment than before treatment. The number of total lymphocyte and T cell, T4 cell, T8 cell, and T4/T8 ratio changed in similar pattern. Fever (7), fatigue (7), anorexia (7), vomiting (2), local erythema of injection site (3), rash (2), mild capillary leak syndrome (1), thrombocytopenia (6), mild anemia (4), mild elevation of liver enzyme (4) and mild prolongation of coagulation time (3) were observed during induction, but disappeared or recovered soon after completion of induction treatment. There was no significant side effects other than fever (7), fatigue (7), and thromocytopenia (2) during maintenance treatment. Conclusion: This study demonstrated the feasibility of rIL-2 therapy after HDCT and ASCT in children with high-risk solid tumor without significant side effects. we expect that rIL-2 therapy has effects to control and remove MRD, and therefore prevent tumor recurrence.

Prevalence and Causes of Childhood Urticaria

신미용,이수영 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.3

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The Influence of the Presence of Wheat Flour on the Antigenic Activities of Egg White Proteins

신미용,이정옥,안강모,이상일,한영신 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.1

Purpose: It is known that ovomucoid, an egg allergen, is heat resistant and remains soluble after heating. However, a recent study showed thatthe antigenic activity of ovomucoid could be reduced by heating when egg white (EW) was mixed with wheat flour. This study was performed to determinethe influence of wheat flour on the antigenic activities of EW proteins when EW is heated, and the influence of the duration of heat treatment. Methods: A mixture of EW and wheat flour was kneaded for 10 minutes and then baked at 180°C for 10 minutes and 30 minutes. The EWwithout wheat flour was also heated at 180°C for 10 minutes and 30 minutes. The proteins were separated by sodium dodecyl sulfate polyacrylamidegel electrophoresis (SDS-PAGE), and IgE immunoblotting was performed with the pooled sera of 5 egg-allergic patients. The antigenic activitiesof ovomucoid in different EW samples were measured by inhibition enzyme-linked immunosorbent assay (ELISA). Results: 1) SDS-PAGE: theintensity of the 37-50 kD bands (overlapped bands of ovomucoid and ovalbumin) decreased significantly in the mixture of EW and wheat flour bakedfor 30 minutes, compared with the mixture baked for 10 minutes, heated EW and raw EW. 2) IgE immunoblot: in the mixture of EW and wheat, a remarkabledecrease of IgE reactivity to 37-50 kD was observed when baked for 30 minutes. 3) Inhibition ELISA: the antigenic activity of ovomucoiddecreased significantly in the mixture of EW and wheat baked for 30 minutes, but not in the heated pure EW. Conclusions: This study showedthat the antigenic activity of ovomucoid can be reduced by baking EW with wheat flour. The decrease in ovomucoid antigenicity in the baked mixtureof EW and wheat flour was dependent on the time of heat treatment, indicating that heating should be prolonged to achieve a reduction in ovomucoidantigenic activity.

영상의학과 검사 안내 동영상 프로그램 개발

신미용,김미경,한유미,신은경,김양미,윤지원,권지혜,이은혜 한국의료QA학회 2009 가을학술대회 Vol.2009 No.2

A Case of Hereditary Angioedema in a 7-Year-Old Korean Girl

신미용,안강모 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.1

Hereditary angioedema (HAE) is a rare autosomal dominant disease that usually occurs in adolescence and early adulthood. It is characterized by recurrentnon-pitting edema involving the skin and intestinal tract, especially the extremities and face. It is not associated with urticaria and pruritus. The cause is known to be the deficiency of C1 inhibitor. We herein report a 7-year-old girl with HAE who had recurrent episodes of swelling of theextremities and face without urticaria and pruritus. Her great grandmother had suffered from the same symptoms. The level of serum C4 was 8.01mg/dL (normal: 10-40 mg/dL). The level of C1 inhibitor was 5.0 mg/dL (normal: 18-40 mg/dL). To our knowledge, this is the first pediatric case withtypical clinical symptoms of HAE and C1 esterase inhibitor deficiency in Korea.

Combined Effects of Lactobacillus rhamnosus and Egg Oral Immunotherapy in a Mouse Model of Egg Allergy

신미용 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Recent clinical trials have successfully used oral immunotherapy (OIT) to treat food allergies. Probiotics have immunomodulatory effects by balancing Th1/Th2 immunity and enhancing regulatory T-cell activity. In this study, we analyzed the effects of OIT, probiotics alone, and probiotics administered simultaneously with OIT in a mouse model of egg allergy. Methods: C3H/HeJ mice were sensitized by intragastric administration of ovomucoid (OM) with cholera toxin. For the OIT regime, increasing doses of OM were administered orally to sensitized mice. Lactobacillus casei variety ramnosus (Lcr35) was also administered. The mice were divided into 4 groups: control (no OIT), OIT, Lcr35, and OIT plus Lcr35 (OIT + Lcr35). The effects of OIT and Lcr35 treatment were estimated based on the symptom score, rectal temperature, serum levels of OM-specific immunoglobulin (Ig)E, IgA, IgG1, and IgG2a immediately after and 2 weeks after ceasing treatment and histological staining of the small intestine. Results: The severity of anaphylaxis decreased in all treatment groups. Simultaneous administration of Lcr35 and OIT decreased the severity of anaphylaxis compared to controls and the OIT group. The protective effects were sustained 2 weeks after ceasing treatment in all treatment groups. A significant decrease in OM-specific IgA, IgG1, and IgG2a levels was observed in both the OIT and OIT plus Lcr35 groups. However, a significant decrease in the OM-specific IgE level was observed only in OIT plus Lcr35 treated mice and was sustained 2 weeks after ceasing treatment. Mucin amounts in the small intestine decreased after OIT, OIT plus Lcr35, and Lcr35 treatment with the lowest in the OIT plus Lcr35 group. Conclusions: Lcr35 treatment during OIT had some synergic effect for protection against anaphylaxis in a mice model of egg allergy. These findings should be confirmed in future animal studies including more detailed immunological profiles and human studies.

The Influence of the Time and Temperature of Heat Treatment on the Allergenicity of Egg White Proteins

신미용,한영신,안강모 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.2

Purpose: The present study was performed to determine the factor, either duration or the temperature of heat treatment, exerting maximal and significantinfluence on the composition and allergenicity of egg white (EW) proteins. Methods: Raw EW and 4 kinds of heated EW (fried EW, boiledEW for 10 minutes, boiled EW for 30 minutes, and baked EW for 20 minutes at 170°C) were prepared, and subsequently protein extraction was carriedout. The proteins were separated by SDS-PAGE, and then immunoglobulin E (IgE) immunoblots were performed with the sera of 7 egg-allergicpatients. Furthermore, the antigenic activities of ovalbumin (OVA), ovomucoid (OM), and ovotransferrin (OT) in different EW samples were measuredby inhibition enzyme-linked Immuno-sorbent assay (ELISA). Results: In SDS-PAGE analysis, the intensity of the protein band at 45 kD (correspondingto OVA) decreased significantly in boiled EW (30 minutes) and baked EW, but no change was observed in the case of boiled EW for 10 minutes. In IgE immunoblots, the IgE response to 34-50 kD (OM and OVA) in boiled EW for 30 minutes decreased significantly, when compared with raw EWand other heated EWs. In inhibition ELISA, a significant decrease in the OVA antigenic activity was observed in boiled EW for 30 minutes amongstother heated EW samples. However, OM antigenic activity in all kinds of heated EW including boiled EW for 30 minutes did not reduce after heattreatment. The OT antigenic activity nearly disappeared in heated EWs except in the case of boiled EW for 10 minutes. Conclusions: Amongst 4kinds of heated EWs, the boiled EW for 30 minutes showed the most significant changes both in composition and reduction in allergenicity. Our resultsrevealed that the duration of heat treatment had more influence on the composition and allergenicity of EW proteins than the temperature.

Lymphoproliferative Disorder as an Unusual Cause of Stridor in a Post-Liver Transplant Child

신미용,정진아,안강모,최연호,이상일,서연림,고영혜,손영익,이석구 대한 소아알레르기 호흡기학회 2004 Allergy Asthma & Respiratory Disease Vol.14 No.3

소아 무기폐에서 굴곡성 기관지내시경 소견 및 치료적 유용성

신미용,황종희,정은희,문정희,이주석,박용민,안강모,이상일,Shin, Mee Yong,Hwang, Jong Hee,Chung, Eun Hee,Moon, Jeong Hee,Lee, Ju Suk,Park, Yong Min,Ahn, Kang Mo,Lee, Sang Il 대한소아청소년과학회 2002 Clinical and Experimental Pediatrics (CEP) Vol.45 No.9

목 적: 저자들은 무기폐로 굴곡성 기관지내시경을 시행받은 소아 환자들의 임상 양상, 기관지내시경 소견과 기관지내시경의 치료적 유용성을 알아보고자 하였다. 방 법 : 단순 흉부 방사선 촬영에서 한달 이상 지속된 만성 무기폐, 급성 광범위 무기폐, 또는 우연히 발견되어 지속기간을 알 수 없는 무기폐를 보여 진단 및 치료 목적으로 굴곡성 기관지내시경을 시행 받은 66명의 소아를 후향적으로 분석하였다. 결 과 : 무기폐가 발생한 기저 질환으로는 폐렴 후에 발생한 경우가 32례(60.4%)로 가장 많았고 그 외에 결핵, 만성폐질환, 수술, 천식, 교통사고와 연관되어 나타났다. 무기폐는 우중엽(24.6%)과 우상엽(24.6%)에 가장 많이 발생하였다. 기관지내시경 소견은 정상 기도를 보인 경우가 26례(39.4%)로 많았고, 염증성 기도 변화를 보인 경우가 29례(경도의 염증성 기관지 협착 15례, 기도 점막의 부종과 과다 분비물을 보인 경우가 14례, 작은 육아종 3례, 점액마개가 3례)로 이상 소견의 대부분을 차지하였으며 그 외 선천성 기도 기형, 기관지내결핵, 기관지의 외인성 압박과 혈전 등이 관찰되었다. 폐렴과 연관되어 발생한 무기폐의 기관지내시경 소견도 정상 기도를 보인 경우가 32례 중 14례(43.7%)였으며 기도 점막의 부종과 과다 분비물, 기관지 협착 등의 염증성 변화가 역시 이상 소견의 대부분을 차지하였다. 치료적 목적으로 분비물의 흡입, 기관지 세척 및 N-acetylcystein($Mucomyst^{(R)}$) 주입을 시행받은 39례 중 18례(46.1%)에서 무기폐가 부분적으로 혹은 완전히 호전되었고, 폐렴과 동반되어 나타난 무기폐의 경우에는 치료적 처치를 시행 받은 23명 중 13명(56.5%)에서 무기폐가 호전을 보였다. 결 론: 굴곡성 기관지내시경술을 시행받은 소아들에서 무기폐는 대부분 폐렴과 만성폐질환, 천식 등의 염증성 호흡기질환과 동반되어 발생하였다. 기관지내시경 소견상 이상 소견으로는 경도의 기관지 협착과 다량의 염증성 분비물 등의 염증성 기도 변화가 대부분이었으나 약 40%에서는 정상소견을 보였다. 굴곡성 기관지내시경은 소아에서도 무기폐의 진단에 유용하였고, 만성 무기폐나 급성 광범위 무기폐의 치료에도 효과적임을 알 수 있었으며 특히 폐렴 후 발생한 지속적 무기폐의 치료에 기관지내시경이 유용할 것으로 판단된다. Purpose : We evaluated the clinical manifestations, bronchoscopic findings and therapeutic effects of flexible fiberoptic bronchoscopy in atelectasis of children. Methods : Sixty six children who received bronchoscopy due to persistent atelectasis, acute severe atelectasis and incidental atelectasis on plain chest radiography were studied retrospectively. Results : The most common causative underlying disease was pneumonia(60.4%). Other underlying conditions were pulmonary tuberculosis, chronic lung disease, postoperative state, bronchial asthma and chest trauma. The most common abnormal findings were inflammatory changes such as bronchial stenosis(n=15), mucosal edema and large amount of secretion(n=14), granulation tissue( n=3) and mucus plug(n=3) although 39.4% showed normal airways. Other findings were congenital airway anomalies, endobronchial tuberculosis, extrinsic compression and obstruction by blood clot. In 32 children with pneumonia-associated atelectasis, 43.7% revealed normal airways, and the most common abnormal findings were also inflammatory changes. Eighteen out of 39 patients who received therapeutic intervention such as suctioning of secretion, bronchial washing and intrabronchial administration of N-acetylcysteine($Mucomyst^{(R)}$) had complete or partial resolution of their atelectasis. In 32 patients with pneumonia-associated atelectasis, 56.5% showed improvement by therapeutic intervention. Conclusion : In this study, atelectasis was mainly associated with inflammatory airway diseases such as pneumonia. The most common abnormal bronchoscopic findings were inflammatory changes such as mucosal edema and large amounts of secretion and bronchial stenosis, although about 40% revealed normal airway. Flexible bronchoscopy is helpful for either diagnosis or treatment, especially in pneumonia-associated atelectasis.

26 일 ( 토 ) 일반연제 , 구연 B : 그랜드볼룸 4 : < 좌장 : 윤혜선 , 박중원 > ( 10:10 - 10:40 ) : 현재 유통 중인 콩 제품에서 PCR 을 이용한 유전자 재조합 콩의 검출

신미용,전경희,정은희,손대열,안강모,이상일 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 2001 춘계학술대회 초록집 Vol.2001 No.-