Eun Suk Koh

Role of Lung Apolipoprotein A-I in Idiopathic Pulmonary Fibrosis Antiinflammatory and Antifibrotic Effect on Experimental Lung Injury and Fibrosis

RATIONALE Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. METHODS Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. MEASUREMENTS AND MAIN RESULTS Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006-0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control animals. Immunohistochemical analysis showed positive staining on intraalveolar macrophages and epithelial cells of the lungs. Intranasal treatment with Apo A-I protein reduced the bleomycin-induced increases in number of inflammatory cells and collagen deposition in sham-treated mice in a dose-dependent manner. CONCLUSIONS Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.

Comparison of Experimental Lung Injury from Acute Renal Failure with Injury due to Sepsis

Background: Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS. Objectives: The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF. Methods: We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs. Results: Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-α increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions. Conclusions: We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.

Overexpression of Apolipoprotein A1 in the Lung Abrogates Fibrosis in Experimental Silicosis

The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1) protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0). ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group) or day 15 (ApoA1_D15 group). The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.

Circulating IL-33 level is associated with the progression of lung cancer

OBJECTIVES Interleukin (IL)-33 protects against infection and inflammation; however, few studies have explored the relevance of IL-33 in lung cancer patients. We evaluated relation of plasma IL-33 levels with development and progression of lung cancer. MATERIALS AND METHODS A total of 160 patients with lung cancer and 160 controls with normal lungs were enrolled. Plasma IL-33 levels were measured using a specific sandwich ELISA; these levels were followed-up in 18 patients who underwent surgery and in 14 patients treated with chemotherapy. Malignant lesions and normal lung tissues from 10 cancer patients were subjected to immunohistochemical staining for IL-33. RESULTS IL-33 levels were significantly lower in cancer patients than normal controls (0.08 vs. 0.38 ng/mL, p=0.005). Among cancer patients, IL-33 decreased in a stage-dependent manner from 0.76 ng/mL in stage I patients to 0.25 ng/mL in those with stage II, 0.08 ng/mL in those with stage III, and 0.08 ng/mL in those with stage IV (p=0.002). The levels were higher at stage I (p=0.041) and markedly lower at stages III and IV than those of controls (p=0.005 and p=0.001, respectively). A similar pattern was observed when IL-33 levels were analyzed by T stage; the levels were 0.39 ng/mL at T1/T2 vs. 0.08 ng/mL at T3/T4 (p=0.001). However, no difference was noted when stage N1 levels were compared with N2 and N3 levels (p=0.058), or between stage M0 and M1 levels (p=0.147). IL-33 levels gradually decreased after surgical resection of malignant lesions (from 1.075 to 0.756 ng/mL, p=0.006), but were unchanged after chemotherapy (0.705 vs. 0.829 ng/mL, p=0.875). On immunohistochemical staining, bronchial epithelial and vascular endothelial cells of normal lung tissues mainly expressed IL-33. CONCLUSIONS Plasma IL-33 levels are associated inversely with progression of lung cancer. The observed decreases may be attributed to lung volume reduction containing bronchial epithelium and vascular endothelium as the sources of IL-33.

Metabolic Profiling Regarding Pathogenesis of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease characterized by fibrosis of the lung parenchyma and loss of lung function. IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair process including uncontrolled proliferation of lung (myo) fibroblasts and excessive deposition of extracellular matrix proteins in the interstitial space; however, the pathogenic pathways involved in IPF have not been fully elucidated. In this study, we attempted to characterize metabolic changes of lung tissues involved in the pathogenesis of IPF using gas chromatography-mass spectrometry-based metabolic profiling. Partial least-squares discriminant analysis (PLS-DA) model generated from metabolite data was able to discriminate between the control subjects and IPF patients (R(2)X = 0.37, R(2)Y = 0.613 and Q(2) (cumulative) = 0.54, receiver operator characteristic AUC > 0.9). We discovered 25 metabolite signatures of IPF using both univariate and multivariate statistical analyses (FDR < 0.05 and VIP score of PLS-DA > 1). These metabolite signatures indicated alteration in metabolic pathways: adenosine triphosphate degradation pathway, glycolysis pathway, glutathione biosynthesis pathway, and ornithine aminotransferase pathway. The results could provide additional insight into understanding the disease and potential for developing biomarkers.

Detection of distant metastasis to skeletal muscle by 18F-FDG-PET in a case of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a rare malignancy that originates from the epithelial cells of the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma can metastasize in lymphatic chains, including the hepatoduodenal ligament, and it often invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenal glands, and brain. However, distant skeletal muscle metastasis is very rare. Moreover, a metastatic skeletal muscle tumor rarely shows specific symptoms, making it difficult to identify in a routine examination. A 45-year-old man with a chief complaint of right upper quadrant abdominal pain was admitted to our hospital. Abdominal ultrasound and computed tomography with contrast enhancement showed a malignant mass in the right hepatic lobe, and 2-[18F] fluoro-2-deoxy-D-glucose positron-emission tomography revealed distant skeletal muscle metastases in the thorax and buttock. The patient underwent an ultrasound-guided percutaneous needle biopsy for the metastatic low-echo masses in the skeletal muscle.

Primary pulmonary T-cell lymphoma: a case report.

Primary pulmonary T-cell lymphoma is an extremely rare malady, and we diagnosed this in a 52-year-old male who was admitted to our hospital with cough for the previous two weeks. The chest CT demonstrated multiple variable sized mass-like consolidations with low density central necrosis in the peripheral portion of both the upper and lower lobes. Positron emission tomography (PET) showed multiple areas of hypermetabolic fluorodeoxyglucose (FDG) uptake in both lungs with central metabolic defects, which correlated with central necrosis seen on CT. The histological sample showed peripheral T-cell lymphoma of the not otherwise specified form. The follow-up CT scan showed an increased extent of the multifocal consolidative lesions despite that the patient had undergone chemotherapy.

Infrasellar craniopharyngioma originating from the pterygopalatine fossa with invasion to the maxillary sinus

Craniopharyngiomas that originate in the nasopharynx and sphenoid bone (known as infrasellar craniopharyngiomas) are rare and comprise only 5% of all craniopharyngiomas. The involvement of the maxillary sinus has been reported only twice. We present a very rare case that involved the maxillary sinus.

Sclerosing Stromal Tumor in an Elderly Postmenopausal Woman

Sclerosing stromal tumor (SST) of the ovary is a rare tumor derived from the sex cord stroma. This tumor was first described by Chalvaridjian and Scully in 1973. SST of the ovary is prevalence of 1.5% to 6% of ovarian stromal tumors. Patients are most commonly diagnosed in their 20s and 30s. There have been reports of SST postmenopausal women aged 65-, 67-, and 71 in the Republic of Korea; however, no report of this disease has been reported in women older than 80. In this study, we would like to report an 80-year-old postmenopausal woman who did not previously complain of any symptoms, and was finally diagnosed with SST. She was involved in a traffic accident, and huge pelvic mass was found during the evaluation of intra-abdominal hemorrhage. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed ; a final pathologic diagnosis reported SST.

A Case of Capillary Hemangioma of Lingular Segmental Bronchus in Adult

Capillary hemangioma of the tracheobronchial tree is an extremely rare benign tumor in adults, especially those located in the bronchus. Characteristics and treatment of capillary hemangiomas of adult tracheobronchial trees have not been well known. We present a 61-year-old man with hemoptysis, which was caused by a small tiny nodule in the left lingular segmental bronchus. The nodule was removed by a forcep biopsy, via flexible bronchoscopy, and it was revealed to be capillary hemangioma. A small isolated endobronchial capillary hemangioma can be treated with excisional forcep biopsy, but a risk of massive bleeding should not be overlooked.