• Clinical and Experimental Pediatrics
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• 제48권10호
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• pp.1038-1049
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• 2005

Asthma is characterized by a chronic inflammatory disorder of the airways that leads to tissue injury and subsequent structural changes collectively called airway remodelling. Characteristic changes of airway remodelling in asthma include goblet cell hyperplasia, deposition of collagens in the basement membrane, increased number and size of microvessels, hypertrophy and hyperplasia of airway smooth muscle, and hypertrophy of submucosal glands. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines, chemokines, and growth factors. Through a variety of inflammatory mediators, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce airway structural remodelling. The end result of chronic airway inflammation and remodelling is an increased thickness of the airway wall, leading to a increased the bronchial hyperresponsiveness and fixed declined lung function.

• 대한세포병리학회지
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• 제5권2호
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• pp.180-183
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• 1994

A case of metastatic mucoepidermoid carcinoma of the lung, originating from the hard palate, was diagnosed by sputum and bronchial washing cytology. Although the cytologic features of mucoepidermoid carcinoma have been well described, it is easy to confuse mucoepidermoid carcinoma with the more common primary adenocarcinoma or squamous cell carcinoma of the lung. The features distinguishing mucoepidermoid carcinoma from other primary neoplasms include 1) mucus-secreting cells individually and in clusters admixed with other cell components, 2) epidermoid cells identified by the presence of abundant spread-out cytoplasm and an oval dark nucleus and 3) intermediate cells resembling normal ductal epithelial cells with moderate-to-scanty cytoplasm, a central, round vesicular nucleus and a prominent nucleolus. The morphologic features of metastatic mucoepidermoid carcinoma in this case were similar to those of primary salivary mucoepidermoid carcinoma.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.238-245
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• 2007

Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.

• Animal cells and systems
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• 제2권1호
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• pp.1-8
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• 1998

Hepatocyte growth factor (HGF), originally discovered and cloned as a powerful mitogen for hepatocytes, is a four kringle-containing growth factor which specifically binds to membrane-spanning tyrosine kinase, c-Met/HGF receptor. HGF has mitogenic, motogenic (enhancement of cell movement), morphogenic (e.g., induction of branching tubulogenesis), and anti-apoptotic activities for a wide variety of cells. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues, including liver, kidney, lung, gut, mammary gland, and tooth. In adult tissues HGF elicits an organotrophic function which supports regeneration of organs such as liver, kidney, lung, and vascular tissues. HGF is also a novel member of neurotrophic factor in nervous systems. Together with the preferential expression of HGF in mesenchymal or stromal cells, and c-Met/HGF receptor In epithelial or endothelial cells, the HGF-Met coupling seems to orchestrate dynamic morphogenic processes through epithelial-mesenchymal (or-stromal) interactions for organogenesis and organ regeneration. HGF or HGF gene may well become unique therapeutic tools for treatment of patients with various organ failure, through its actions to reconstruct organized tissue architectures. This review focuses on recently characterized biological and physiological functions integrated by HGF-Met coupling during organogenesis and organ regeneration.

• 대한세포병리학회지
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• 제8권1호
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• pp.83-86
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• 1997

Signet ring cell carcinoma is a variant of adenocarcinoma and has been rarely reported in the lung as a primary site. Recently, we experienced two cases of primary signet ring cell carcinoma in the lung without any other extrapulmonary lesion. Sputum cytology was performed and the tumor cells which have eccentrically located nuclei and abundnat mucinous cytoplasm were dispersed in diffuse sheets. On resected specimen, the signet ring cells occupied about $50{\sim}80%$ of all tumor cell nests. Histochemical staining revealed that the mucin produced by tumor cells was mostly carboxylated acid mucins. Ultrastructurally, the tumor cells contained variable sized membrane-bound mucin granules with weak central osmilophilic density and showed numerous surface microvilli, which represented that tumor cells arose from bronchial epithelial cells. In general, this tumor has diffusely infiltrative nature and the prognosis is fatal due to widespread metastasis before clinical discovery.

• 대한세포병리학회지
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• 제2권1호
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• pp.28-35
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• 1991

So-called sclerosing hemangioma of the lung is a rare benign neoplasm which usually presents with a coin lesion detected through routine chest X-ray. We report two cases showing characteristic cytologic appearances which have been rarely reported. Both cases were young females with coin lesions in the lung. Fine needle aspiration of each case revealed unique but some different cytologic features. Case 1 showed bland-looking polygonal epithelial cells resembling bronchioloalveolar cells haying predominantly papillary configurations with loosely arranged solid sheets or isolated cells. Cytoplasms were plump, cyanophilic, and finely granular, with eccentric nuclei. The nuclei were usually monotonous, round-to-ovoid, and vesicular with a small but conspicuous nucleolus. In comparison to case 1, case 2 revealed largely loose pavement-like solid sheets or clusters rather than papillary patterns in the hemorrhagic background. The size of tumor cells were a little smaller than that of case 1. Bronchioloalveolar carcinoma and papillary adenocarcinoma of metastatic origin were considered to be one of the important differential diagnoses with these cytologic features. Histologically, both cases exhibited findings compatible with so-called sclerosing hemangioma of the lung.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.903-909
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• 2002

Research in the cytokine field has grown exponentially in recent years, and the validity of such studies relies heavily on the appropriate measurement of levels of cytokines in various biological samples. Transforming growth factor (TGF)-$\beta$, a hormonally active polypeptide found in normal and transformed tissue, is a potent regulator of cell growth and differentiation. The most widely used bioassay for TGF-$\beta$ is the inhibition of the proliferation of mink lung epithelial cells. Though detection of [$^3$H]thymidine incorporation is more sensitive than the MTT assay, it presents some disadvantages due to the safety and disposal problems associated with radioisotopes. In this study, we attempted to ascertain the experimental conditions which could be used for measuring the in vitro biological activity of TGF-$\beta$ in a safer and more sensitive way compared with the currently available methods. We compared the commonly used method, the MTT assay, to the XTT assay using different parameters including cell number, incubation time and the wave length used for detecting the product. We examined the anti-proliferative activities of TGF-$\beta$ in three different cell lines: Mv-1-Lu mink lung epithelial cells, MCF10A human breast epithelial cells and H-ras-transformed MCF10A cells. Herein, we present an experimental protocol which provides the most sensitive method of quantifying the biological activity of TGF-$\beta$, with a detection limit of as low as 10 pg/ml: Mv-1-Lu or H-ras MCF10A cells ($1{\times}10^5/well$) were incubated with TGF-$\beta$ at $37^{\circ}C$ in a humidified $CO_2$ incubator for 24 hr followed by XTT treatment and determination of absorbance at 450 or 490 nm. Our results may contribute to the establishment of an in vitro bioassay system, which could be used for the satisfactory quantitation of TGF-$\beta$.

• Tuberculosis and Respiratory Diseases
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• 제56권2호
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• pp.187-197
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• 2004

연구배경 : Nitric Oxide(NO)는 매우 다양한 생물학적 조절기능을 수행하는 분자로서 심혈관계, 신경계, 면역기능 등에 관여함은 물론 최근 세포 사에도 직 간접적으로 영향을 미치고 있음이 알려져 있다. NO의 이렇게 복잡한 생물학적 기능 수행은 reactive oxygen species(ROS), metal ions 및 단백질 등과 복잡한 상호작용에 의한 것이며 NO가 나타내는 생물학적 효과는 용량-의존적이며, 세포-특이적이라고 밝혀져 있다. NO는 간세포 및 현관내피세포에서는 아포프토시스를 억제하지만 종양세포 및 신경세포 등에서는 아포프토시스를 유도하는 것으로 보고되고 있다. NO는 여러 호흡기질환의 병태생리에도 관여하는 것으로 알려져 있는바 천식과 같은 염증성 기도 질환에서 호기 NO가 증가되어있는 반면 흡연자나 일차성 폐 고혈압 환자에서는 감소되어 있다고 보고되고 있다. 이러한 배경에서 NO가 폐 상피 세포의 세포 사에 미치는 영향과 신호전달 경로를 밝히기 위하여 본 연구를 시행하였다. 방 법 : 폐 상피 세포로는 A549 세포 주를, NO donor로서는 SNAP (S-nitroso-N-acetyl-penicillamine)과 SNP(sodium nitroprusside)를 사용하였다. 세포 독성 검사는 crystal violet assay를 이용하였고 아포프토시스 assay는 Hoechst 33342와 propium iodide(PI) 이중 염색 후 형광현미경을 이용하여 핵의 형태학적변화를 관찰함으로써 괴사(necrosis)와 감별하였다. 철에 의한 NO 유도성 세포 사 억제 효과를 관찰하기 위하여 RBC와 FeSO4를 이용하였다. NO 유도성세포사의 신호전달 경로에 bcl-2와 p53이 미치는 영향을 평가하기 위하여 bcl-2 과 발현 세포 주 (A549-bcl-2)와 p53 knock out 세포 주 (A549-E6)를 대상으로 세포독성을 비교하였고 p53 활성화는 Western blot을 이용하여 확인하였다. 결 과 : A549 세포 주에서 SNAP과 SNP 모두 농도-의존적 세포독성을 관찰할 수 있었다. 아포프토시스 assay에서 SNAP은 저 농도에서는 아포프토시스를, 고농도에서는 괴사를 유도함을 관찰하였고 SNP는 농도에 상관없이 세포사가 괴사의 형태를 나타냄을 확인하였다. 이는 SNP가 순순한 NO donor가 아니라 cyanide에 의한 세포독성의 결과라고 생각되며 고농도의 SNAP에 의한 괴사 유도는 peroxynitrite 생성에 의한 결과임을 시사한다. SNAP에 의한 세포 사는 RBC와 FeSO4등 철에 의해 억제됨을 확인하였고 bcl-2에 의해서 억제되었으며 p53을 활성화시키고 p53 knock out에 의해 차단되었다. 결 론 : 폐상피세포에서 NO는 저 농도에서는 아포프토시스를 고농도에서는 괴사에 의한 세포 사를 유도하며 철이 중요한 억제제이며 bcl-2 및 p53이 신호전달 경로에 있어서 중요한 역할을 담당하는 것으로 생각된다.

• 대한세포병리학회지
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• 제3권1호
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• pp.30-36
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• 1992

Pulmonary hamartoma is the most common benign tumor of the lung but rarely encountered in routine cytologic work-up. We recentely experienced a case of fine needle aspiration cytology of pulmonary hamartoma in a 65-year old male patient. The characteristic cytopathologic features were 1) The mesenchymal components with cuboidal epithelial cells in a clean background, 2) The presence of fibromyxoid mesenchymal component composed of fibroblasts in a loose fibrillary stroma, and 3) Antler-liker fibromyxoid cluster having the rimming of epithelial cells which correspond to the epithelial glowing in cleft-like fashion in pulmonary hamartoma.

• Tuberculosis and Respiratory Diseases
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• 제61권4호
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• pp.366-373
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• 2006

연구배경 : Paraquat는 P-450 reductase에 의해 반응성 산소유리기(ROS)를 발생시켜 세포막, 단백질, 핵산 등과 반응함으로써 세포손상을 유도하며 급성 폐 손상을 일으킨다. 최근 급성 폐 손상 및 급성 호흡곤란 증후군에 있어서 폐상피세포의 아포프토시스가 중요한 역할을 한다고 알려지기 시작하였다. 이에 반응성 산소유리기에 의한 폐 손상의 대표적 물질인 paraquat로 인한 폐상피세포의 세포죽음이 아포프토시스인지 확인하고 dexamethasone, N-acetylcysteine, 그리고 bcl-2가 paraquat로 인한 폐상피 세포죽음에 어떠한 영향을 미치는지 등을 연구하였다. 방법 : 폐상피세포주인 A549와 BEAS-2B 세포주, 그리고 bcl-2 construct를 유전자 주입한 A549 pcDNA3-bcl-2 세포주를 이용하였다. 아포프토시스는 Annexin V assay를 이용하여서 판정하였으며 세포독성 검사는 MTT assay를 이용하였다. Paraquat는 0, $1{\mu}M$, $10{\mu}M$, $100{\mu}$M, 1 mM, 10 mM의 농도로 사용하였다. Dexamethasone은 $1{\mu}M$의 농도로 paraquat 투여 12시간 전에 전처치하였고, N-acetylcysteine은 1 mM의 농도로 paraquat 투여 1시간 전에 전처치하였다. 결과 : 양 세포주 모두에서 paraquat는 농도와 시간 경과에 따라서 세포죽음을 증가시켰고, 이러한 세포죽음은 아포프토시스였다. N-acetylcysteine과 dexamethasone은 시간과 농도에 따라 약간의 차이가 있으나 전반적으로 10~30%의 방어효과가 있었다. Bcl-2를 과발현시킨 A549-bcl-2 세포주에서 A549-neo 세포주에 비해 paraquat에 의한 세포독성이 약 20~30% 정도 차단되었다. 결론 : Paraquat는 폐상피세포에서 아포프토시스를 유도하며, paraquat에 의한 아포프토시스는 마이토콘드리아 경로에 의해 일어날 것으로 추정된다.