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      • KCI등재

        Rhabdoid Cholangiocarcinoma: A Variant of Cholangiocarcinoma with Aggressive Behavior

        임범진,김경식,임준석,김명진,박찬일,박영년 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.SUP

        A rhabdoid cholangiocarcinoma is a very rare variant of sarcomatous cholangiocarcinomas. Here, we report a vimentin positive cholangiocarcinoma showing rhabdoid features in the entire tumor, with a very aggressive behavior. A 41-year-old woman was admitted to our hospital due to a huge hepatic mass. The resected liver revealed a 17×15cm sized solid mass with extensive necrosis and an infiltrative border. On microscopic examination, the entire tumor was composed of loosely cohesive round to polygonal cells, with rhabdoid features having abundant eosinophilic glassy cytoplasm and eccentrically located vesicular nuclei. Some tumor cells contained intracytoplasmic mucin vacuoles, but definite areas of glandular differentiation or spindle cell were not found. Immunohistochemical staining showed a diffuse strong positive reaction to pan-cytokeratin and vimentin, and focal positivity for the carcinoembryonic antigen. Other immunohistochemical stainings for cytokeratin 7, cytokeratin 20, S-100 protein, HMB-45, desmin, alpha-smooth muscle actin, c-kit, CD34, alpha-fetoprotein, anti-hepatocyte antigen, chromogranin and synaptophysin were all negative. After two months, the patient developed a local recurrence along the resection margin, and multiple hematogenous metastases to the lung and liver were seen on the follow-up CT scan.

      • KCI등재

        칼시토닌 발현과 아밀로이드 축적을 보인 중이의 유암종 - 1예 보고 -

        임범진,양우익,홍순원,박찬일 대한병리학회 2002 Journal of Pathology and Translational Medicine Vol.36 No.2

        Carcinoid tumor of the middle ear cavity is a rare neoplasm of low malignant potential. It grows slowly and rarely metastasizes. We recently experienced a case of carcinoid tumor of the middle ear cavity occurring in a 51-year-old female who was presented with hearing loss and tinnitus of the right ear. A 1 cm sized pinkish soft mass was noted in the promontory of the middle ear. Histologically, the mass was composed of nests and cords of tumor cells with slightly pleomorphic nuclei and eosinophilic cytoplasm. The extracellular matrix was glassy pink, homogeneous and exhibited apple green birefringence under a polarized light microscope after Congo red staining. The tumor cells showed immunoreactivity for cytokeratin, chromogranin A, synaptophysin, neuron-specific enolase and calcitonin. Electron microscopic examination confirmed the presence of neurosecretory granules. The production of calcitonin and amyloid by the tumor cells suggests the possible relationship of this tumor to the thyroid C cells.

      • KCI등재

        여러 개의 분명한 이종요소를 포함하는 자궁관의 악성혼합 뮬러리안 종양

        임범진,김재욱,양우익,조남훈 대한병리학회 2003 Journal of Pathology and Translational Medicine Vol.37 No.6

        We experienced a case of primary malignant mixed mullerian tumors (MMMT) of the fallopian tube of FIGO stage I. In addition to endometrioid adenocarcinomas, multiple apparent heterologous elements encompassing myxoid chondrosarcoma, osteosarcoma, myxoid liposarcoma and well differentiated angiosarcoma were recognized as separate nodules. These findings have not been described previously in MMMTs of the female genital tract.

      • KCI등재

        External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival

        임범진,이광석,이영화,김수아,민충기,박주영,이혜선,조진선,김선일,정병하,김청수,구교철 대한암학회 2021 Cancer Research and Treatment Vol.53 No.2

        Purpose Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

      • KCI등재

        The spectrum of biopsy-proven renal diseases in Korea

        임범진 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.1

        Biopsy-proven kidney disease has been reported globally. Some of these data are based upon nationwide renal biopsy registries, while single-center-based data have also been provided from countries without registry cohorts. Because of the heterogeneity of study populations and numerous confounding components in retrospective studies, conclusions on the frequencies of renal diseases are not simple.

      • KCI등재

        Toll-Like Receptor 4 Signaling is Involved in IgA-Stimulated Mesangial Cell Activation

        임범진,정현주,이다혜,홍순원 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.4

        Purpose: Deposition of polymeric IgA1 in the kidney mesangium is the hallmark of IgA nephropathy, but the molecular mechanisms of IgA-mediated mesangial responses and inflammatory injuries remain poorly understood. We hypothesize that Toll-like receptor 4 (TLR4) is involved in IgA-induced mesangial cell activation. Materials and Methods: Mouse mesangial cells were stimulated with lipopolysaccharide (LPS) (1 μg/mL), IgA (20 μg/mL), or both, and TLR4 expression was measured by real time RT-PCR and Western blot. Intracellular responses to LPS or IgA were assessed by Western blot for ERK1/2, JNK, p38 MAP kinases (MAPKs), Iκ-Bα degradation and fibronectin secretion. MCP-1 secretion was assessed by ELISA. Small interfering RNA (siRNA) of TLR4 was used to confirm that the effects were caused by TLR4 activity. Results: LPS- or IgA-treatment upregulated the levels of TLR4 mRNA and protein in cultured MMC at 24 h. LPS and IgA induced rapid phosphorylation of MAPKs, but degradation of Iκ-Bα was observed only in LPS-treated MMC. LPS, but not IgA, induced increased secretion of MCP-1 and fibronectin at 24 h or 48 h. Combined LPS and IgA treatment did not cause additional increases in TLR4 mRNA and protein levels or Iκ-Bα degradation,and MCP-1 and fibronectin secretions were less than with LPS alone. LPS- or IgA-induced TLR4 protein levels and MAPK activation were inhibited by transfection with TLR4 siRNA. Conclusion: These results indicate that the activation of MAPKs and MCP-1 secretion are mediated by TLR4, at least in part, in IgA-treated mesangial cells. TLR4 is involved in mesangial cell injury by induction of pro-inflammatory cytokines in IgA nephropathy.

      • KCI등재후보

        미세변화 신증후군 환아에서 사이클로스포린 치료 후 Osteopontin과 Transforming Growth Factor-${\beta}$의 발현

        임범진,김병길,홍순원,정현주,Lim Beom-Jin,Kim Pyung-Kil,Hong Soon-Won,Jeong Hyeon-Joo 대한소아신장학회 2002 Childhood kidney diseases Vol.6 No.2

        목적 : 사이클로스포린(cyclosporine)은 효과적인 면역 억제제로서 현재에는 장기 이식 후 뿐 아니라 다양한 자가면역성 질병에서 그 사용 범위를 넓히고 있다. 신독성은 사이클로스포린의 대표적인 부작용으로서 그 특징적인 조직학적 소견은 간질의 섬유화와 세 동맥의 초자양 변화이다. 간질 섬유화에는 전통적으로 $TGF-{\beta}$가 관여하는 것으로 알려져 있으며 최근에 osteopontin이라는 단백도 관여한다는 사실이 동물 실험을 통해 알려지고 있다. 사이클로스포린에 의한 간질 섬유화에 osteopontin이 관여한다는 사실이 여러 동물실험을 통하여 알려져 있으나 사람에서는 아직까지 분명한 결론을 얻지 못하고 있다. 동일 환자에서 사이클로스포린 치료 전과 후에 두 번 생검을 시행한 신장 조직에서 osteopontin과 $TGF-{\beta}$의 발현을 조사하여 사이클로스포린과 이들의 관계를 밝히는 것이 본 연구의 목적이다. 대상 및 방법 : 연세의대 세브란스 병원 소아과에서 신장 생검으로 미세변화 신증후군으로 진단 받은 19예를 대상으로 하여 사이클로스포린 치료 전 조직 검사 검체를 대조군으로 하고, 치료 후 조직 검사 검체를 비교군으로 하였다. 사구체 메산지움과 세뇨관에서의 osteopontin 발현과 간질에서의 $TGF-{\beta}$ 발현을 면역조직화학염색으로 측정하였다. 결과 : 사이클로스포린 치료 후 사구체 메산지움과 세뇨관에서 osteopontin의 발현이 의의 있게 증가하였지만 간질에서 $TGF-{\beta}$의 증가는 뚜렷하지 않았다. 또한 세뇨관의 osteopontin과 간질의 $TGF-{\beta}$의 변화는 광학현미경으로 관찰되는 간질 섬유화와는 상관관계가 없었다. 따라서 사이클로스포린 사용시 osteopontin의 발현의 증가와 간질 섬유화 간에는 직접적인 연관이 없는 것으로 사료된다. 결론 : 본 연구의 결과 실험 동물에서와는 달리 사람의 신장에서 osteopontin은 간질 섬유화에 직접 관여하기 보다는 신장 손상에 대한 표지자로서의 의미가 있다고 추정된다. Purpose : One of the most important adverse effects of long-term cyclosporine therapy is nephrotoxicity, the morphologic changes of which include interstitial fibrosis and arteriolar hyalinization. Recently, several authors have shown that osteopontin plays an important role in the development of interstitial fibrosis by acting as a macrophage chemoattractant and stimulating the production of $TGF-{\beta}$ in experimental cyclosporine nephrotoxicity. However, the relationship between osteopontin and $TGF-{\beta}$ in humans has not been clearly documented so far. We studied the expression of osteopontin and $TGF-{\beta}$ in children with minimal change nephrotic syndrome treated with cyclosporine to demonstrate whether there is a relationship between cyclosporine toxicity and osteopontin expression as previously shown in animal models. Materials and methods : Nineteen children (15 males and 4 females) were the subject of this study. Renal biopsies had been performed before and after the cyclosporine therapy (mean duration: 15.9 months). In 5 patients, additional biopsies were performed after completing the cyclosporine treatment (mean; 26 months). The expressions of osteopontin and $TGF-{\beta}$ were evaluated by immunohistochemistry in the glomeruli and tubulointerstitium. Results : Osteopontin expression was significantly increased in the glomerular mesangium and tubules after cyclosporine treatment. But there was no statistically significant increase of $TGF-{\beta}$ in the interstitium. There was no significant increase in tubular osteopontin and interstitial $TGF-{\beta}$ expression in those cases developing interstitial fibrosis after cyclosporine treatment compared with cases those not developing interstitial fibrosis. No significant changes in osteopontin or $TGF-{\beta}$ expression were observed in subsequent 5 biopsy samples after discontinuation of cyclosporine compared with the first follow up biopsies. Conclusion : These results suggest that osteopontin is a nonspecific marker of renal injury rather than a mediator of interstitial fibrosis in cyclosporine nephrotoxicity of human.

      • KCI등재

        Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy

        임범진,김민주,홍순원,정현주 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.3

        Background: Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman’s capsule in IgAN cases with mild glomerular histologic change. Methods: To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. Results: In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. Conclusions: Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

      • KCI등재

        Changes of calcific density in pediatric patients with testicular microlithiasis

        임범진,송상훈,송기현,김건석 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.4

        Purpose: Testicular microlithiasis (TM) is a relatively rare clinical entity of controversial significance characterized by the existence of hydroxyapatite microliths located in the seminiferous tubules. The aim of this study was to observe the natural course of changes in the calcific density of pediatric TM. Materials and Methods: We included a total of 23 TM patients undergoing scrotal ultrasound (US) on at least two occasions from July 1997 to August 2014. We retrospectively analyzed the patient characteristics, clinical manifestations, specific pathological features, and clinical outcomes. We measured the calcified area and compared the calcific density between the initial and final USs. Results: The mean age at diagnosis was 11.3±4.6 years, and the follow-up period was 79.1±38.8 months (range, 25.4–152.9 months). During the follow-up period, no patients developed testicular cancer. Calcific density on US was increased in the last versus the initial US, but not to a statistically significant degree (3.74%±6.0% vs. 3.06%±4.38%, respectively, p=0.147). When we defined groups with increased and decreased calcification, we found that diffuse TM was categorized into the increased group to a greater degree than focal TM (10/20 vs. 4/23, respectively, p=0.049). In addition, five of eight cases of cryptorchidism (including two cases of bilateral cryptorchidism) were categorized in the increased calcification group. Conclusions: Diffuse TM and cryptorchidism tend to increase calcific density. Close observation is therefore recommended for cases of TM combined with cryptorchidism and cases of diffuse TM.

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