Mast Cells and Subcapsular Cell Hyperplasia in the Adrenal Glands of Mice : マスト細胞とマウス副腎皮膜下細胞過形成

김종수 東京大學 1999 해외박사

Chapter 1 Subcapsular cell hyperplasia (SCH) in the adrenal cortex of aged mice (13-15 months old) was frequent in both sexes of BALB/c, C3H/He, DBA/2J and IQI/Jic mice and in the females of A/J and C57BL/6, although the incidence and severity of SCH were considerably different among mouse strains. Mast cells were closely associated with SCH in the A/J, BALB/c, C57BL/6, DBA/2J and IQI/Jic mice, but not in the C3H/He strain. Compared with other strains, IQI/Jic mice had a significantly larger number of mast cells in the adrenal glands. These findings suggest that mast cells are implicated in the development of SCH in many strains of mouse, and IQI/Jic strain would be appropriate choice for studying the pathogenesis of SCH in the adrenal gland and the role of mast cells in this lesion. Chapter 2 IQI/Jic mice showed a high incidence of subcapsular cell hyperplasia (SCH) in the adrenal cortex accompanied by prominent mast cell infiltration. SCH-positive animals appeared as early as at 3 months of age, with an incidence of 18% in males and 20% in females. Except for one mouse, all females older than 6 months had the lesion. In males, the incidence increased gradually until 9 months, and was then stable at 75-88% thereafter. The severity of SCH increased with age in both sexes, and the lesions were more prominent in females. Mast cells infiltrated mainly at the sites of SCH, and their density was associated with the severity of the lesion. A quantitative morphometric study confirmed a significant correlation between the severity of SCH and the density of mast cells. A histochemical study demonstrated that these mast cells were of the connective tissue-type. These findings indicate that mast cell may play an important role in the pathogenesis of SCH and, IQI/Jic mouse would be a useful strain to elucidate the pathogenesis of SCH in the adrenal cortex in association with mast cell function. Chapter 3 To further characterize subcapsualr cell hyperplasia (SCH) in mice, the author evaluated the morphologic characteristics of SCH in female IQI/Jic mice. IQI/Jic mice showed SCH in the adrenal glands as early as 2 months of age. Hyperplastic subcapsular cells synthesized collagen fibrils, and SCH often accompanied by the infiltration of mast cells but not any other inflammatory cells. Generally, hyperplastic subcapsular cells showed different features in intracytoplasmic contents from adrenocortical endocrine cells. However, they also revealed the features similar to adrenocortical endocrine cells that they had some round mitochondria with tubular cristae, desmosome and basement membrane. Occasionally, adrenocortical endocrine cells which showed rather the characteristic features of hyperplastic subcapsualr cells than the normal endocrine cells were observed in advanced SCH lesions. These findings suggest that the hyperplastic cells would be originated from undifferentiated endocrine cells and/or normal endocrine cells of adrenal cortex. Chapter 4 On the basis of the observations in Chapter 1 and Chapter 2, the author examined the functional significance of mast cell accumulation in the pathogenesis of subcapsular cell hyperplasia (SCH) and the possible interactions between mast cells and hyperplastic cells in the adrenal gland of mice. At first, the author investigated the expression of mRNAs for certain cytokines including SCF and its receptor c-kit, bFGF, NGF, TNF-α; and mast cell-specific proteases such as mMCP-2 and mMCP-7 in the adrenal glands and, for comparison, in the mBMMC. Subsequently, adrenal glands from IQI/Jic mice were evaluated immunohistochemically in GMA tissue sections to identify the expression and localization of their proteins within the SCH lesions. The mRNA for c-kit (SCF receptor) was detected in the IL-3 dependent immature mast cells (mBMMC) but the mRNA for its ligand SCF was not detected. In contrast, the mRNAs for not only c-kit, bFGF, TNF-α, mMCP-2 and mMCP-7 but also SCF and NGF were detected in the adrenal gland specimens. Immunoreactivities of cytokines (SCF, NGF, TNF-α) and proteases (mMCP-2 and mMCP-7) were observed in the adrenal glands. Moreover, positive staining of them were exclusively located to the mast cells at sites of SCH. These findings indicate that mast cells acquired functional maturity to produce SCF and NGF in the SCH lesions. The results of this study suggest that (1) SCH may provide a favorable microenvironment for mast cell differentiation and maturation, and (2) tissue mast cells in SCH lesions synthesize SCF and NGF, and may use them in autocrine fashion for survival and differentiation, and (3) these mast cells can store a range of multifunctional cytokines and proteases, and they contribute to SCH pathogenesis in the adrenal glands of mice.

Color doppler imaging of the liver in neonates with biliary atresia

이무숙 Graduate School, Yonsei University 2008 국내석사

Purpose : To describe color Doppler flow imaging findings of the liver in neonates with biliary atresia and to compare them with those of non-biliary atresiaMethods and Materials : From March 2003 to July 2007, from patients with confirmed biliary atresia, we selected 29 patients (51±24 days, 3-91 days) who were preoperatively evaluated with color Doppler US. We also performed color Doppler US in 35 patients (48±32 days, 3-150 days) with hyperbilirubinemia who did not have biliary atresia. In ultrasonography, we evaluated triangular cord sign, gall bladder length, and diameter of the portal vein and the hepatic artery. In color Doppler imaging, we evaluated presence of hepatic subcapsular flow. Sensitivity, specificity, and positive and negative predictive values were calculated for the TC sign in US and hepatic subcapsular flows in color Doppler imaging. The Mann-Whitney test was used to evaluate differences in the mean diameters of the portal vein and hepatic artery between patients with biliary atresia and non-biliary atresia.Results : In color Doppler images, all patients with biliary atresia demonstrated hepatic subcapsular flow. Among the 35 patients with non-biliary atresia, 30 did not have hepatic subcapsular flow (sensitivity 100%, specificity 85%, positive predictive value 85%, negative predictive value 100%). There was no difference in portal vein diameter between biliary atresia and non-biliary atresia groups. However, there was a statistically significant difference in hepatic artery diameter between the two groups (2.10±0.65mm vs 1.45±0.41 mm, p < .05). Conclusion : The presence of hepatic subcapsular flow is useful to differentiate biliary atresia from other cause of neonatal jaundice.

항 정신병 약물(chloropromazine, haloperidol)의 복용에 따른 안독성

김지훈 부산대학교 대학원 2012 국내석사

Purpose: To evaluate ocular adverse effects of long term antipsychotics-cholopromazine, haloperidol-medication. Subjects and Methods: We studied eye examination for ocular toxicity of 108 eyes of 69 consecutive patients with long term chloropromazine and haloperidol at leat five years. Slit lamp examination revealed pigment and opacity of cornea, cataract change and type of lens opacity. The patients were divided into three groups. Group 1 consisted of patients who had taken only chloropromazine, Group 2 consisted of patients who had taken only haloperidol, Group 3 consisted of patients who had taken chloropromazine and haloperidol. Results: Cataract was found in 61 eyes(56.4%) and anterior subcapsular cataract(ASC) was more prevalent.(n=40, 66%) The anterior subcapsular cataract(ASC) rate was statistically significant in patients used chlorpromazine.(P=0.00) Corneal pigmentation and anterior subcapsular cataract was found in patient using long term chlorpromazine below 300gm Conclusions: long-term chlorpromazine use is related to ocular toxicity especially cataract formation and Patients using even low dose antipsychotic drugs should be investigated to a periodic ophthalmological evaluation . KeyWords : antipsychotics, anterior subcapsular cataract, schizophrenia

(The) association of intravitreal triamcinolone acetonide and posterior subcapsular cataract development

주영광 Graduate School, Yonsei University 2006 국내석사

Intravitreal triamcinolone acetonide(IVTA) is currently used to treat various macular edemas secondary to diabetic retinopathy, branch and central retinal vein occlusion, choroidal neovascularization, and, uveitis, etc.However, the treatment through pars plana injection and the effects of the corticosteroid entails complications such as retinal detachment, vitreous hemorrhage, increased intraocular pressure, pseudohypopyon, endopthalmitis, and cataract formation. Among these complications, treatment with corticosteroids is generally associated with two common and serious ocular side effects; that being elevated intraocular pressure (IOP) and accelerated cataract formation.Therefore, this study is to prospectively investigate the development and progression of posterior subcapsular cataract 6 months after the current maximal 25mg intravitreal pars plana triamcinolone injections in one eye of patients with macular edema secondary to diabetes and retinal vein occlusion and its influence on visual acuity.The prospective interventional case series study included all 38 patients (27 women, 11 men; 76 eyes) who visited the Siloam Eye Hospital''s retina clinic with diabetic retinopathy or retinal branched or central vein occlusion from the beginning of March to the end May 2005. The degree of cataract was depicted before IVTA and after IVTA on monthly bases by the same surgeon. Among the 38 treated eyes, there was an increase of cataract degree by 1 grade at the end of 6 months in 10 patients. The types of progressed cataract were PSC in 7 patients, cortical in 6 patients, and nuclear sclerosis in 1 patient. Four patients had both an increase in grade of PSC and cortical opacities while 6 patients had showed a progression of only one type of cataract.The development and progression of cataract may mask the vision improving effects of high dose intravitreal triamcinolone acetonide injection in certain cases. 유리체내 triamcinolone acetonide 주입술은 당뇨병성망막증, 정맥폐쇄, 노인성 황반증, 포도막염 등으로 인한 황반부종의 치료로 사용되고 있다.그러나, 스테로이드의 사용은 안압 상승이나 백내장의 발생과 같은 합병증을 유발한다고 알려져 있다.그러므로, 본 연구는 현재 사용되는 최고용량인 25 mg triamcinolone acetonide 을 당뇨병 또는 망막정맥폐쇄로 인한 황반부종으로 시력저하를 호소하는 환자들의 안구 유리체내 주입 후 6개월 동안 백내장의 발생과 진행 여부를 관찰하고자 한다.본 연구는 2005년 3월에서 5월 사이에 황반부종과 시력저하로 실로암안과병원을 찾은 총 38명의 환자 (27 여자, 11 남자; 76안)을 대상으로 하였다. 백내장의 정도를 약물 주입 전에 국제공인 방법인 LOC III로 기록하였고 그 후 첫1달은 매주 그리고 그 후는 매달 백내장의 정도를 비교군인 반대 눈과 대조하였다.유리체내 triamcinolone acetonide을 주입한 총 38안중 연구 종료 시점인 6개월 후 1단계이상 백내장의 진행을 보인 환자수는 10명이며 백내장의 유형은 후낭하형이 7, 피질형이 6, 그리고 핵형이 한 명으로 나타났다. 백내장의 유형중 4명은 후낭하형과 피질형이 동시에 진행하였으며 6명은 3중 한가지 형태의 백내장만 진행하는 소견을 보였다.그러므로 유리체내 triamcinolone acetonide의 주입은 통계적으로 유의하게 후낭하형과 피질형 백내장의 발생과 진행에 영향을 주며 이런 백내장의 발생은 치료효과인 시력개선의 저하를 경우에 따라 초래할 수도 있다.

Upregulation of RANKL expression in the thymic subcapsular, paraseptal, perivascular and medullary epithelial cells during thymus regeneration : 가슴샘 재생과정 동안에 가슴샘 피막밑, 사이막옆, 혈관주위 및 속질상피세포에서 RANKL 발현의 증가

김형진 부산대학교 대학원 2004 국내박사

최근 면역세포의 분화와 활성 조절에 관여하는 것으로 밝혀진 사이토카인인 RANKL (receptor activator of nuclear factor-κB ligand)은 뼈 대사 시스템뿐만 아니라 면역시스템에서도 대단히 중요한 역할을 수행한다는 사실이 최근 알려지고 있다. RANKL은 면역계의 여러 세포들 중에서도 특히 T 세포의 분화와 활성의 조절에 중요한 역할을 한다는 사실이 알려졌지만, 미분화된 T 세포 전단계세포에서 성숙한 T 세포로 분화가 이루어지는 장소인 가슴샘에서 RANKL이 존재한다는 사실이 알려져 있지 않을 뿐만 아니라 그 역할에 대해서도 전혀 규명되어 있지 않다. 본 연구에서는 흰쥐에 cyclophosphamide를 투여하여 가슴샘 급성퇴축을 유발한 다음 가슴샘 재생과정 동안에 RANKL 발현을 조사하였다. 면역조직화학염색 결과 가슴샘 재생과정 동안에 가슴샘 피막밑, 사이막옆, 혈관주위 및 속질상피세포에서 RANKL의 발현이 증가된다는 사실을 확인할 수 있었다. 특히, 가슴샘 피막밑, 사이막옆 및 혈관주위 상피세포에서는 cyclophosphamide 투여 후 3일째 그리고 가슴샘 속질상피세포에서는 cyclophosphamide 투여 후 7일째 RANKL의 발현이 가장 현저하게 증가되었다. 또한 Western blot과 RT-PCR 분석에서도 가슴샘 재생과정 동안에 RANKL은 가슴샘 재생과정에서 T 세포의 발달에 중요한 역할을 할 것으로 생각된다.

Expression profile of cytokines and apoptosis mediating molecules in mouse subcapsular kidney allograft : Diagnostic value for allograft rejection

양만길 東國大學校 2004 국내박사

RANKL이 생쥐 가슴샘 피막밑/겉질 상피세포의 증식, 생존 및 가슴샘세로 형성촉진인자 생성에 미치는 효과

이충원 부산대학교 2003 국내박사