Clinical Significance of Classification of Graves` Disease According to the Characteristics of TSH receptor Antibodies

(Won Bae Kim),(Hyun Kyung Chung),(Young Joo Park),(Do Joon Park),(Hong Kyu Lee),(Bo Youn Cho) 대한내과학회 2001 The Korean Journal of Internal Medicine Vol.16 No.3

N/A Background:It has been widely accepted that the epitope (s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves` patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluatedyet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves` disease. Methods:We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1+2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves` disease. Results: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n=41) was characterized by moderate TSAb activities bothin CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n=16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n=19) patients had low TSAb activities bothin CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n=30) could be categorized as `mild disease` group, as they had low activities in all kinds of TSHRAb assay and had low antim icrosomal antibody activities. 5) Group 5 (n=14) was characterized by moderate TSAb activities with atypical epitope (s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n=10) patients had veryhigh TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n=6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p<0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p<0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50%vs.27.5%,p=0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. Conclusion:These results suggest that the differences inepitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves` disease. Although the pathogenic mechanism is not clearyet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves` disease.

Freud의 'Rat Man' 증례를 통해 본 강박신경증의 정신분석적 이해

조도연 한국정신분석학회 1994 精神分析 (Psychoanalysis) Vol.5 No.1

甲狀腺炎과 Lithium 治療에 의한 甲狀腺機能低下症

鄭道彦,禹鍾仁,李定均,趙普衍,高昌舜,金勇一 大韓神經精神醫學會 1982 신경정신의학 Vol.21 No.2

A case of a female Manic Depressive Illness patient with goitrous hypothyroidism is presented. After ten and half months of lithium maintenance therapy starting during her first psychiatric admission, she was admitted again due to acute recurrent manic episode. On admission, she complained of easy fatigability and cold intolerance, and thyroid gland was palpable and enlarged in moderate degree. Thyroid function test revealed markedly increased TSH and moderately decreased thyroxine levels. TRH stimulation test showed an exaggerated response. Needle biopsy specimen revealed chronic lymphocytic and immune complex thyroiditis. However, antithyroglobulin and antimicrosomal antibodies were negative. In pretreatment thyroid evaluation on her first admission, neither goiter nor thyroid function abnormality was detectable and no signs of underlying thyroid disease or hereditary predisposition to hypothyroidism were present. Within three weeks of discontinuation of lithium, goiter was no more palpable and within five weeks, thyroid function test returned to normal range. The possibility that patients with underlying thyroiditis may be particularly susceptible to a rapid onset of lithium-induced hypothyroidism is discussed.

불응성 자가면역질환에서의 자가조혈모세포이식

민도준,양동원,민창기,김완욱,이상헌,박성환,김동욱,이종욱,조철수,민우성,김범생,김호연,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 기존의 치료에 불응하고 예후가 불량한 자가면역질환 환자들에게 최근 고용량 면역억제 및 조혈모 세포이식이 새로운 치료방법으로 대두되고 있다. 저자들은 다발성 경화증(multiple sclerosis, MS) 및 류마티스 관절염(rheumatoid arthritis, RA) 등 2명의 자가면역질환 환자들에서 자가조혈모세포 이식을 시행하였다. 방법: 말초혈액 조혈모세포 가동화를 위하여 cyclophosphamide (4 g/㎡) 및 granulocyte colony stimulating factor (10 g/kg/day)를 투여하였고, CD34+ 세포를 분리·채집 하였다, 이식 전처치로 MS 환자에서 BEAM 및 antihymocyte globulin (ATG) (3.75 mg/kg), RA 환자에서 fludarabine (180 mg/㎡), ATG (10 mg/kg)와 busulfan (8 mg/kg)을 투여하였다. 결과: 호중구 수가 500/㎕ 이상으로 회복되는 기간은 MS 환자에서 9일, RA 환자에서 15일이었다. 혈소판이 20.000/㎕ 이상으로 회복되는 가간은 RA 환자에서 9일 이었고, MS 환자에서는 혈소판 감소증이 발생하지 않았다. 비혈액학적 독성으로 MS 환자에서 WHO 1도의 오심 및 점막염이 관찰되었다. MS 환자는 이식 6개월 후까지 시력감소가 남아있었으나, 이식전에 관찰되던 감각이상 및 운동장애 등의 신경학적 이상 소견은 더 이상 관찰되지 않았다. RA 환자는 이식 1개월 후 관절 증상 및 검사소견의 호전을 보였다. 결론: 불응성 자가면역질환 환자에서 고용량 면역억제 및 조혈모세포이식은 적은 독성으로 높은 치료효과를 기대할수 있으며, 향후 이 시술의 임상적 의의를 규명하기 위하여 전향적이고 장기적인 연구가 필요할 것으로 사료된다. Background: High-dose immunosuppressive therapy followed by autologous hemathpoietic stem cell transplantation (HSCT) has been proposed as a new approach to treat severe, refractory autoimmune diseases. We describe two patients with refractory autoimmune diseases (one multiple sclerosis 〔MS〕and one rheumatoid arthritis〔RA〕) who underwent T-cell-depleted autologous peripheral bleed stem cell transplantation for the first time in Korea. Methods: We mobilized autologous stem cells with cyclophisphamide (4 g/㎡) and granulocyte colony-stimulating factor (10 ㎍/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after high-dose chemotherapy with BEAM and antithymocyte globulin (ATG) (3.75 mg/kg) in MS, or fludarabine (180 mg/㎡), ATG (10 mg/kg) and busulfan (8 mg/kg) in RA. Results: The engraftment with an absolute nerutrophil count greater than 500㎕ occurred on day 9 in MS and 15 in RA, respectively. The time to nontransfused platelet count greater than 2.000/㎕ was 9 day in RA. MS patient did not show ant episode of thrombocytopenia. Regimen-related non-hematopoietic toxicity was minimal. For 6 months since HSCT, them patient with MS had been free from previously existed sensory and motor abnormalities except decreased visual acuity. Then patient with RA and only one tender joint and two mildly swollen joints with improvement in laboratory parameters at one month after HSCT. Conclusion: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of intractable autoimmune diseases. The durability of remission, however, remains to be clarified.

Metal Oxide Sensor Array를 이용한 사과와 귤의 신선도 분석

임향주,한도수,조성동,김기윤 조선대학교 기초과학연구소 2000 自然科學硏究 Vol.23 No.1

The Electronic Nose has been designed to provide objective and reproducible aroma discrimination on a wide variety to human nose. The sensor array in combination with sophisticated chemometrics and artificial neural network software provides the output displaying the closeness of difference in aroma patterns of different samples. As an application the system has been used to discriminate of the fresh and decomposing apples and oranges. The discrimination has been successfully demonstrated.

슬관절 골관절염 증상이 환자에게 미치는 우울 효과

박영규,이윤영,이계우,김정아,윤도경,박승회,조경환,홍명호,박용규 대한노인병학회 2001 대한노인병학회지 Vol.5 No.4

슬관절 골관절염 환자에서 근육내 자극요법의 치료 효과

박영규,우종웅,안승렬,김정아,윤도경,박승회,조경환,홍명호 대한노인병학회 2001 대한노인병학회지 Vol.5 No.4

일차성 갑상선기능 저하증 환자에서 사람 TSH 수용체 항체를 발현하는 Chinese Hamster Ovary ( CHO ) 세포를 이용한 갑상선 자극차단 항체 활성의 측정

조보연,김원배,박도준 대한내분비학회 1997 Endocrinology and metabolism Vol.12 No.1

Background: The Chinese hamster ovary cells transfected with human TSH receptor cDNA (hTSHR-CHO), expressing functional human TSH receptors, are known to be more sensitive in detection of thyroid stimulating antibodies than FRTL-5 cells. There has been no report on the usefulness of these cells to measure thyroid stimulation blocking antibody(TSBAb) activity which is frequently found in patients with primary myxedema, Methods: We established the optimal assay condition of measurement of TSBAb using hTSHR- CHO cells, and simultaneously measured TSBAb activities with FRTL-5 cells and with hTSHR- CHO cells in 49 patients with primary myxedema, compared them with their thyrotropin binding inhibitor immunoglobulin(TBII) activities. Results: 1) hTSHR-CHO cells specifically bound bTSH and were stimulated by bTSH in terms of cyclic AMP generation in a dose dependent manner. 2) Myxedema IgG suppressed TSH-stimulated cAMP production of hTSHR-CHO cells in a dose dependent manner reaching plateau at the concentration of I g/L. Normal pooled IgG has no suppressive action at the concentration of less than 1 g/L, but caused significant suppression at the concentration of greater than 1g/L. 3) TSBAb activities measured by hTSHR-CHO cells in 49 patients with primary myxedema were as follows: Four of 25 TBII-negative cases(16%) and 22 of 24 TBII-positive cases(92%) had TSBAb activities. Most of TSBAb positive patients(95%), especially in TBII positive cases, showed very high activities of more than 90%. 4) TSBAb activities measured by hTSHR-CHO cells and those by FRTL-5 cells were both positive in 24 patients(49%), both negative in 18 patients(37%), and were discrepant in 7 patients(14%). The TSBAb activities measured with hTSHR-CHO cells and those measured with FRTL-5 cells were significantly correlated(r=0.71, p$lt; 0.01). 5) Forty five percent of patients with primary myxedema had all of 3 kinds of activities(TBII, hTSHR-CHO cell TSBAb, FRTL-5 cell TSBAb), 37% of them had none of 3 activities and 18% of them had 1 or 2 kinds of activities only. Conclusion: The usefulness of hTSHR-CHO cells in measurements of TSBAb activities were confirmed. The TSBAb activities of most patients with primary myxedema measured by hTSHR- CHO cells were concordant with those measured by FRTL-5 cells. However, a small subset of patients(18%) had discrepant results in assays of TSH receptor antibodies according to the differences in TSH receptors(rat, human and porcine) used in assay. Such discrepancy may be explained by heterogeneity in epitopes for blocking TSH receptor antibodies. (J Kor Soc Endocrinol 12:18-32, 1997)

Liquid biopsy using cfDNA to predict radiation therapy response in solid tumors

Won Kyung Cho(Won Kyung Cho),Junnam Lee(Junnam Lee),Sung-Min Youn(Sung-Min Youn),Dongryul Oh(Dongryul Oh),Do Hoon Lim(Do Hoon Lim),Han Gyul Yoon(Han Gyul Yoon),Eun-Hae Cho(Eun-Hae Cho),Jae Myoung Noh( 대한방사선종양학회 2023 Radiation Oncology Journal Vol.41 No.1

Purpose: This study explored the potential feasibility of cell-free DNA (cfDNA) in monitoring treatment response through the measurement of chromosomal instabilities using I-scores in the context of radiation therapy (RT) for other solid tumors. Materials and Methods: This study enrolled 23 patients treated with RT for lung, esophageal, and head and neck cancer. Serial cfDNA monitoring was performed before RT, 1 week after RT, and 1 month after RT. Low-depth whole-genome sequencing was done using Nano kit and NextSeq 500 (Illumina Inc.). To measure the extent of genome-wide copy number instability, I-score was calculated. Results: Pretreatment I-score was elevated to more than 5.09 in 17 patients (73.9%). There was a significant positive correlation between the gross tumor volume and the baseline I-score (Spearman rho = 0.419, p = 0.047). The median I-scores at baseline, post-RT 1 week (P1W), and post-RT 1 month (P1M) were 5.27, 5.13, and 4.79, respectively. The I-score at P1M was significantly lower than that at baseline (p = 0.002), while the difference between baseline and P1W was not significant (p = 0.244). Conclusion: We have shown the feasibility of cfDNA I-score to detect minimal residual disease after RT in patients with lung cancer, esophageal cancer, and head and neck cancer. Additional studies are ongoing to optimize the measurement and analysis of I-scores to predict the radiation response in cancer patients.

Acanthosis Nigricans Associated with Vitiligo

Do Youn Cho,Sung Han Kim,Kyu Cherl Choi,Byoung Soo Chung 대한피부과학회 2005 Annals of Dermatology Vol.17 No.1