Journal of Pathology and Translational Medicine

Original Articles

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment: Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim; J Pathol Transl Med. 2021;55(5):338-348. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.26

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Background
Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).
Methods
A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.
Results
As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.
Conclusions
Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Citations

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Construction and validation of a novel signature based on epithelial-mesenchymal transition–related genes to predict prognosis and immunotherapy response in hepatocellular carcinoma by comprehensive analysis of the tumor microenvironment
Biao Gao, Yafei Wang, Shichun Lu
Functional & Integrative Genomics.2023;[Epub] CrossRef
Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma
Biao Gao, Yafei Wang, Shichun Lu
Scientific Reports.2023;[Epub] CrossRef

Causes of necrotic features in fine-needle aspirates from cervical lymph nodes: Young Jin Seo, Hyeongchan Shin, Hye Won Lee, Hye Ra Jung; J Pathol Transl Med. 2021;55(1):60-67. Published online November 27, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.28

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Abstract PDF

Background
Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult.
Methods
We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis.
Results
When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients.
Conclusions
Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

Citations

Citations to this article as recorded by

The Potential Use of Peptides in the Fight against Chagas Disease and Leishmaniasis
Hayelom Berhe, Mahesh Kumar Cinthakunta Sridhar, Mulate Zerihun, Nir Qvit
Pharmaceutics.2024; 16(2): 227. CrossRef
Does the Necrotic Portion of Metastatic Lymphadenopathy from Squamous Cell Carcinoma Still Have Tumoral Oncologic Information? Differential Diagnosis of Benign Necrotic Lymphadenopathy Using microRNA
Eun Shin, Seung Hoon Han, Il-Seok Park, Jee Hye Wee, Joong Seob Lee, Heejin Kim
Biomedicines.2023; 11(9): 2407. CrossRef
Impact of HPV status in T1–2 oropharyngeal squamous cell carcinoma with bulky N3 nodes: a multicenter GETTEC study
Charles Hurel, Florent Carsuzaa, Julia Salleron, Philippe Gorphe, Christian Righini, Maximilien Rogé, Erwan de Mones, Sylvain Morinière, Sébastien Vergez, Juliette Thariat, Xavier Dufour
European Archives of Oto-Rhino-Laryngology.2023; 280(2): 847. CrossRef

Placental Lesions in Meconium Aspiration Syndrome: Binnari Kim, Soo-young Oh, Jung-Sun Kim; J Pathol Transl Med. 2017;51(5):488-498. Published online August 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.20

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Abstract PDF

Background
Meconium aspiration syndrome (MAS) is defined by respiratory distress requiring supplemental oxygen in a meconium-stained neonate. MAS is clinically subclassified as mild, moderate, and severe according to the oxygen requirement. The aims of this study were to compare the histological findings in the placentas of MAS neonates with those of meconium-stained but non-MAS neonates and to analyze the correlation between the severity of MAS and the grade of its histological parameters. Methods: We collected 160 singleton term placentas from neonates with meconium staining at birth from a tertiary medical center, Seoul, Republic of Korea. We reviewed hematoxylin and eosin sections of tissue samples (full-thickness placental disc, chorioamniotic membranes, and umbilical cord). Results: Funisitis was present more frequently in MAS than in non-MAS (p < .01), of which the stage was correlated with the severity of MAS (p < .001). The histological findings consistent with maternal underperfusion and chronic deciduitis were more frequent in MAS than in non-MAS (p < .05). There was a correlation between the degree of chorionic vascular muscle necrosis and the severity of MAS (p < .05). Conclusions: Our results suggest that fetal inflammatory response evidenced by funisitis occurs prenatally in MAS and that the stage of funisitis and of chorionic vascular muscle necrosis may be a predictive marker of the severity of MAS.

Citations

Citations to this article as recorded by

Machine learning‐based placental clusters and their associations with adverse pregnancy outcomes
Julie M. Petersen, Samantha E. Parker, Kimberly A. Dukes, Jennifer A. Hutcheon, Katherine A. Ahrens, Martha M. Werler
Paediatric and Perinatal Epidemiology.2023; 37(4): 350. CrossRef
The risk of meconium aspiration syndrome (MAS) increases with gestational age at term
Clara Ward, Aaron B. Caughey
The Journal of Maternal-Fetal & Neonatal Medicine.2022; 35(1): 155. CrossRef
Protective placental inflammatory and oxidative stress responses are attenuated in the context of twin pregnancy and chorioamnionitis in assisted reproduction
Hayley R. Price, Nick Pang, Hugh Kim, Michael W. H. Coughtrie, Abby C. Collier
Journal of Assisted Reproduction and Genetics.2022; 39(1): 227. CrossRef
Correlation between Pregnancy Outcome and Placental Pathology in COVID-19 Pregnant Women
Sara A. Al-Rawaf, Enas T. Mousa, Noora M. Kareem, Atif Amin Baig
Infectious Diseases in Obstetrics and Gynecology.2022; 2022: 1. CrossRef
Differential impact of antiretroviral therapy initiated before or during pregnancy on placenta pathology in HIV-positive women
Nadia M. Ikumi, Thokozile R. Malaba, Komala Pillay, Marta C. Cohen, Hlengiwe P. Madlala, Mushi Matjila, Dilly Anumba, Landon Myer, Marie-Louise Newell, Clive M. Gray
AIDS.2021; 35(5): 717. CrossRef
Meconium Aspiration Syndrome: A Narrative Review
Chiara Monfredini, Francesco Cavallin, Paolo Ernesto Villani, Giuseppe Paterlini, Benedetta Allais, Daniele Trevisanuto
Children.2021; 8(3): 230. CrossRef
Isolated acute funisitis in the absence of acute chorioamnionitis: What does it mean?
Tracy B. Grossman, Debra S. Heller, Rebecca N. Baergen
Placenta.2019; 75: 42. CrossRef
Influence of foetal inflammation on the development of meconium aspiration syndrome in term neonates with meconium-stained amniotic fluid
Kyoko Yokoi, Osuke Iwata, Satoru Kobayashi, Kanji Muramatsu, Haruo Goto
PeerJ.2019; 7: e7049. CrossRef

TNF-α and TNF-β Polymorphisms are Associated with Susceptibility to Osteoarthritis in a Korean Population: Lin Han, Joo Hyoun Song, Jung Hwan Yoon, Yong Gyu Park, Suk Woo Lee, Yoo Jin Choi, Suk Woo Nam, Jung Young Lee, Won Sang Park; Korean J Pathol. 2012;46(1):30-37. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.30

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Abstract PDF

Background

The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA.

Methods

We investigated the genotypes TNF-α and TNF-β in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively.

Results

For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224).

Conclusions

The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.

Citations

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Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review
Phaniendra Alugoju, V. K. D. Krishna Swamy, Naga Venkata Anusha Anthikapalli, Tewin Tencomnao
Critical Reviews in Food Science and Nutrition.2023; 63(31): 10709. CrossRef
Complete sequence and comparative analysis of the mitochondrial genome of the rare and endangered Clematis acerifolia, the first clematis mitogenome to provide new insights into the phylogenetic evolutionary status of the genus
Dan Liu, Kai Qu, Yangchen Yuan, Zhiheng Zhao, Ying Chen, Biao Han, Wei Li, Yousry A. El-Kassaby, Yangyang Yin, Xiaoman Xie, Boqiang Tong, Hongshan Liu
Frontiers in Genetics.2023;[Epub] CrossRef
Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis
Daniela Pacheco dos Santos Haupenthal, Marcus Barg Resmini, Leandro Almeida Da Silva, Mateus Cardoso Colares, Laura de Roch Casagrande, Ligia Milanez Venturini, Thiago Antônio Moretti de Andrade, Fernando Russo Costa do Bomfim, Anand Thirupathi, Paulo Emi
Current Drug Targets.2023; 24(3): 287. CrossRef
Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status
Mohammed H. Hassan, Amer Alkot Mostafa Elsadek, Marwa Ahmed Mahmoud, Bakheet E. M. Elsadek
Biochemical Genetics.2022; 60(2): 611. CrossRef
Complement System Inhibition Modulates the Inflammation Induced by the Venom of Premolis semirufa, an Amazon Rainforest Moth Caterpillar
Joel J. M. Gabrili, Isadora Maria Villas-Boas, Giselle Pidde, Carla Cristina Squaiella-Baptistão, Trent M. Woodruff, Denise V. Tambourgi
International Journal of Molecular Sciences.2022; 23(21): 13333. CrossRef
Azilsartan prevented AGE‐induced inflammatory response and degradation of aggrecan in human chondrocytes through inhibition of Sox4
Jie Lei, Mengyin He, Liangzhou Xu, Chengjian He, Jie Li, Wei Wang
Journal of Biochemical and Molecular Toxicology.2021;[Epub] CrossRef
TNF-α Carried by Plasma Extracellular Vesicles Predicts Knee Osteoarthritis Progression
Xin Zhang, Ming-Feng Hsueh, Janet L. Huebner, Virginia B. Kraus
Frontiers in Immunology.2021;[Epub] CrossRef
Genetic association between TNF-α G-308A and osteoarthritis in Asians: A case–control study and meta-analysis
Chih-Chien Wang, Chih-Yun Huang, Meng-Chang Lee, Dung-Jang Tsai, Chia-Chun Wu, Sui-Lung Su, Mingqing Xu
PLOS ONE.2021; 16(11): e0259561. CrossRef
Sex-, Age-, and Metabolic Disorder-Dependent Distributions of Selected Inflammatory Biomarkers among Community-Dwelling Adults
So Mi Jemma Cho, Hokyou Lee, Jee-Seon Shim, Hyeon Chang Kim
Diabetes & Metabolism Journal.2020; 44(5): 711. CrossRef
Tumor necrosis factor-α: Molecular assessment of gene expression, genetic variants and serum level in Egyptian patients with knee osteoarthritis
Nermin Raafat, Amal F. Gharib, Doaa S. Atta, Shimaa M. AbdElwahab, Doaa M. Sharaf
Gene Reports.2020; 21: 100922. CrossRef
Effect of a functional variant of tumor necrosis factor‐β gene in temporomandibular disorders: A pilot study
Kaan Yerliyurt, Ayse Feyda Nursal, Akin Tekcan, Nevin Karakus, Mehmet K. Tumer, Serbulent Yigit
Journal of Clinical Laboratory Analysis.2019;[Epub] CrossRef
Interleukin-6 (-572) and Tumor Necrosis Factor α (-308 and -238) Polymorphisms and Risk of Knee Osteoarthritis in a Pakistani Population: A Case–Control Study
Syeda Kanwal Batool Naqvi, Maria Bibi, Iram Murtaza, Qamar Javed
Iranian Journal of Science and Technology, Transactions A: Science.2019; 43(4): 1485. CrossRef
Role of resistin genetic variations in knee osteoarthritis pathogenesis, a cross sectional study
Syeda Kanwal Batool Naqvi, Iram Murtaza, Qamar Javed
Molecular Biology Reports.2019; 46(3): 2657. CrossRef
Relationship Between Genetic Polymorphisms of the TNF Gene and Hallux Valgus Susceptibility
Jie Yang, Junhu Wang, Xiaojun Liang, Hongmou Zhao, Jun Lu, Qiang Ma, Feng Tian
Genetic Testing and Molecular Biomarkers.2019; 23(6): 380. CrossRef
Functional status and severity of osteoarthritis in elderly is associated to the polymorphism of TNFA gene
Marcos Tadeu Parron Fernandes, Karen Barros Parron Fernandes, Fernanda Freitas Anibal, Walquíria Shimoya-Bittencourt, Viviane Martins Santos, Priscila Daniele de Oliveira Perrucini, Regina Célia Poli-Frederico
Advances in Rheumatology.2019;[Epub] CrossRef
Association of TNF-α-308 G > A and −238G > A polymorphisms with knee osteoarthritis risk: A case-control study and meta-analysis
Mohammad Reza Sobhan, Masoud Mahdinezhad-Yazdi, Kazem Aghili, Masoud Zare-Shehneh, Shohreh Rastegar, Jalal Sadeghizadeh-Yazdi, Hossein Neamatzadeh
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Association between tumor necrosis factor alpha rs1800629 polymorphism and risk of osteoarthritis in a Chinese population
Jie Chen, Yu Wu, Jiannong Yu, Jinming Shen
Brazilian Journal of Medical and Biological Research.2018;[Epub] CrossRef
Association of cytokine gene polymorphisms with osteoarthritis susceptibility
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TNF‑α increases the expression of inflammatory factors in synovial fibroblasts by inhibiting the PI3K/AKT pathway in a rat model of monosodium iodoacetate‑induced osteoarthritis
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Experimental and Therapeutic Medicine.2018;[Epub] CrossRef
The single-nucleotide polymorphism (SNP) of tumor necrosis factor α −308G/A gene is associated with early-onset primary knee osteoarthritis in an Egyptian female population
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Clinical Rheumatology.2017; 36(11): 2525. CrossRef
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Meta-analysis of tumor necrosis factor alpha -308 polymorphism and knee osteoarthritis risk
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Wei-Ping Chen, Yan Xiong, Yong-Xiang Shi, Peng-Fei Hu, Jia-Peng Bao, Li-Dong Wu
International Immunopharmacology.2014; 19(1): 174. CrossRef
Variations in the TNFα gene and their interactions with the IL4R and IL10 genes in relation to hand osteoarthritis
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BMC Musculoskeletal Disorders.2014;[Epub] CrossRef
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Chinese Medical Journal.2014; 127(9): 1761. CrossRef
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Case Report

Adnexal Clear Cell Carcinoma with Comedonecrosis: A Case Report.: Seo Hee Kim, Sun Hee Han, Jung Suk An, Ju Han Lee, Eung Seok Lee, Heum Rye Park, Young Sik Kim; Korean J Pathol. 2010;44(1):92-96.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.92

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Abstract PDF: Adnexal clear cell carcinoma with comedonecrosis (ACCCC) is a very rare malignancy of the skin with an aggressive clinical course and a predilection for the scalp. This is the first reported case of ACCCC in Korea. A 79-year-old male presented with left abdominal masses that proved to be two subcutaneous nodules. The tumors histologically consisted of epithelial nests that showed a distinctive zonal arrangement. The centrally located clear cell areas with comedonecroses were merged with the peripheral squamoid cells, often exhibiting retraction artifacts and an infiltrating border. Nuclear pleomorphism and frequent mitoses were prominent. The clear cells were immunopositive for carcinoembryonic antigen and epithelial membrane antigen. We report here on a case of ACCCC involving the abdominal skin, and this tumor should be distinguished from the more indolent squamous cell and tricholemmal carcinomas.

Original Article

Immunohistochemical Study of IL-4, IL-6, and TNF Expression in Cardiac Myxoma: Emphasis on Constitutional Symptoms of the Myxoma Patients.: Min Sun Cho, Soo Yeon Cho, Mi Jung Kim, Sung Sook Kim, Jeong Wook Seo, Woon Sup Han; Korean J Pathol. 1995;29(5):563-571.

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Abstract: It is well documented that cardiac myxomas are associated with immunologic features that can simulate systemic autoimmune diseases. Recently, it was reported that cardiac myxomas produce IL-6 constitutively, which could partly explain the immunologic features observed in these patients. However, only a few investigators have studied cytokines in regards to symptoms they may cause in patients with cardiac myxoma. Also there is very little information in the literature on the immunohistochmical localization of IL-6. We performed immunobistochemical stains for IL-4, TNF, and IL-6 on paraffm embbeded tissue of cardiac myxoma tissue. A bioassay of IL-6 activity in patient's serum and in cultured cells from fresh myxoma tissue was performed to ascertain the role of these cytokines in myxomas. In this study, we demonstrated inununohistochemically that there was a local overproduction of IL-4, TNF, and IL-6 in cytoplasm of the tumor cells in about half cases. Bioassays of the serum and cultured tumor cells revealed elevated IL-6 activities. Also these findings correlate to production of patient's constitutional symptoms with statistical significance (P<0.05). In conclusion, these results are of considerable importance in understanding the role of IL-4, TNF, and IL-6 in cardiac myxoma patient with constitutional symptoms, and have an impact on strategies for diagnosis and therapy of cardiac myxoma.

Case Reports

Subcutaneous Fat Necrosis Associated with Pancreatic Adenocarcinoma: A case report.: Hee Jung Kim, Kwang Gil Lee; Korean J Pathol. 1996;30(2):155-160.

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Abstract PDF: Subcutaneous fat necrosis is manifested by erythematous tender nodules on the legs, buttock or trunk and is associated with pancreatic disease including acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, pancreatic stone and other diseases. Its histologic findings are pathognomonic and reveal foci of subcutaneous fat necrosis with "ghost-like" anucleated cells with thick "shadowy wall" and surrounding inflammatory infiltrate consisting of polymorphonuclear cells, eosinophils, lymphocytes, histiocytes, foam cells and foreign body giant cells. We experienced a case of subcutaneous fat necrosis associated with pancreatic adenocarcinoma manifested by subcutaneous nodules in the buttock and lower extremities and by arthralgia of the left knee in a 67-year-old woman. Therefore, we are reporting to emphasize the importance of the skin findings of the internal disease.

Idiopathic Entero-colic Lymphocytic Phlebitis: A case report.: Seung Sam Paik, Young Ha Oh, Eun Kyung Hong, Jung Dal Lee; Korean J Pathol. 1996;30(6):533-538.

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Abstract PDF: Localized enterocolic lymphocytic phlebitis is characterized by selective phlebitis involving the small to medium-sized veins and venules, infiltration exclusively by lymphocytes, and no other systemic vasculitis or inflammatory bowel disease. This vasculitis can be a rare cause of intestinal ischemia. We experienced a case of enterocolic lymphocytic phlebitis in a 72-year-old woman, who presented with abdominal pain and distension. The resected colon and terminal ileum showed striking lymphocytic phlebitis affecting the veins and venules of the bowel and mesentery which resulted in ischemic injury of the bowel. This vasculopathy was the only demonstrable cause of ischemia. Arteritis and arteriolitis was not found. There is no clinical or laboratory evidence or a history of extraintestinal vasculitis. The etiology of this clinicopathological entity has not been elucidated. Herein, we report the clinicopathological findings in this patient who presented with ischemic intestinal necrosis caused by localized intestinal lymphocytic phlebitis associated with thrombosis.

Original Articles

The Effect of Photodynamic Therapy in BALB/-c Mice Adenocarcinoma in Homograft Model.: Chang Ho Cho, O Jun Kwon; Korean J Pathol. 2000;34(7):481-487.

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Abstract PDF: Among the efficient cancer treatments, photodynamic therapy (PDT) is one of the therapies inducing rapid apoptosis of cancer cells while causing minimal damage to surrounding normal tissue. We studied the effect of PDT on the adenocarcinoma in BALB/-c mice of homograft model, and the following results were obtained. Apoptosis occurred up to 3 mm in depth from the surface in the first 1 hour after PDT applied, and subsequently the counts were increased in the deeper portion. A remarkable apoptosis observed up to 6 mm in depth shows that the light in use could not penetrate more than 6 mm of tissue. Tissue necrosis was identified in the deeper area of the tumor 6 hours later or thereafter. This necrosis seemed to occur as an indirect effect of vascular obstruction resulting from the damage of endothelial cells which was induced by selective collection of photosensitizer in the endothelial cells of newly forming vessels as well as in the cancer cells. These results indicate that the effective depth of PDT is greater than the depth of light penetration.

Expression of Inducible Nitric Oxide Synthase and Nitric Oxide Mediated Apoptosis in Neuronal PC12 Cells after Lipopolysaccharide/Tumor Necrosis Factor-/Interferon- Treatment.: Jiyeon Kim, Jiyoung Kim, Kuseong Kang, Eunkyoung Kwak, Jiyoung Park, Taein Park, Yoonkyung Sohn; Korean J Pathol. 2002;36(4):249-256.

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Abstract PDF: BACKGROUND
Inducible nitric oxide synthase (iNOS) has been detected in a number of pathologic conditions in the central nervous system. This study was investigated the patterns of iNOS expression in the neuronal PC12 cell and the effects of nitric oxide on the apoptosis of PC12 cells.
METHODS
The stimulating agents for induction of iNOS expression in PC12 cells were bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-), and interferon-gamma (IFN-).
RESULTS
The expression iNOS mRNA and protein in PC12 cells stimulated with LPS/TNF-/IFN- were profoundly increased. The expression of iNOS mRNA arose at 6 hours, peaked at 12 hours, and declined to 48 hours after LPS/TNF-/ IFN- treatment. iNOS protein was increased up to 24 hours in LPS/TNF-/IFN- treated PC12 cells while the expression of nNOS was unaffected. Accumulation of NO derivatives in the culture media was markedly increased at least at up to 48 hours after LPS/TNF-/IFN- treatment. The induction of iNOS expression and NO production in differentiated PC12 cells was correlated with apoptotic cell death judged by transmission electron microscopy and DNA fragmentation from the results of the Terminal deoxynucleotidyl-transferase-mediated dUDP biotin nick end-labeling (TUNEL) method. After treatment with NOS inhibitor, N-monomethylarginine (NMMA), a profound decrease in NO production by LPS/TNF-/IFN- treated PC12 cells was noted. And the LPS/TNF-/IFN- induced apoptosis was prevented by the NMMA treatment.
CONCLUSIONS
From the above results it is concluded that the expression of iNOS in differentiated PC12 cells is induced by the combined application of LPS, TNF-, and IFN-. And the apoptosis of cultured PC12 cells is mediated by iNOS-derived NO.

Apoptosis and Cell Proliferation in Experimental Acute Tubular Necrosis Induced by Intramuscular Glycerol Injection.: Wan Seop Kim, Jung Woo Noh, Moon Hyang Park; Korean J Pathol. 2003;37(1):41-49.

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Abstract PDF: BACKGROUND
Acute tubular necrosis (ATN) is the most common cause of acute renal failure. It is characterized by the destruction of tubular epithelial cells. To examine apoptosis and proliferative activity of tubular cells in the course of acute tubular necrosis, we induced acute renal failure by intramuscular hypertonic glycerol injection to New Zealand White rabbits.
METHODS
The immunohistochemistry was done for Ki-67 and tissue-transglutaminase (tTG), and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed using a total of 77 renal specimens including 29 gun biopsies and 48 nephrectomiy specimens.
RESULTS
Widespread tubular injury with pigment casts and interstitial hemorrhage were noted. The tubular proliferation index was increased at 2 hours after glycerol injection, and the index peaked at 3 hours. The second cell proliferation peak was noted at 3 days. Apoptotic cells were identified by TUNEL and tTG staining. The apoptotic index was significantly increased, and it peaked at 24 hours after glycerol injection. There was a significant correlation between the proliferation index (MIB-1) the and the apototic index (TUNEL)(p= 0.001). A DNA ladder pattern was observed at 6 to 8 hours.
CONCLUSIONS
Tubular cell proliferation and apoptosis occur in the early phase after the induction of acute tubular necrosis, and the excess hyperplastic epithelial cells appear to be eliminated by apoptosis.

Case Report

An Unusual Type of Acute Renal Failure due to Extensive Crystal Deposition in the Renal Tubular Epithelium and Interstitium: A Case Report.: Ja Seung Koo, Eunah Shin, Shin Woo Kang, Hyeon Joo Jeong; Korean J Pathol. 2004;38(5):337-340.

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Abstract PDF: Acute tubular necrosis is a major cause of acute renal failure. Acute renal failure that is caused by crystal deposition can result from drug toxicity, lymphoplasmacytic neoplasms, ingestion of industrial organic solvents, or intratubular obstruction due to degenerated red blood cells and red blood cell casts. We herein present an uncommon case of acute renal failure in a 57-year-old woman showing an unusually massive accumulation of variable-sized, round, ellipsoid or rhomboid, pale-pink, refractile bodies in the proximal and distal tubular epithelial cells, interstitial macrophages and Bowman's spaces. These bodies were electron dense with a maximum diameter of 3 micrometer. The information we gathered from the patient history, the laboratory data and the various histochemical and immunohistochemical analyses failed to reveal the exact nature of these crystal-like structures.

Original Articles

Expression of Tumor Necrosis Factor-alpha, Interleukin-1beta and Inducible Nitric Oxide Synthase after Stereotaxic Injection of Lipopolysaccharide in Rat Hippocampus.: Hoon Kyu Oh, Ku Seong Kang, Ji Yeon Kim, Eun Kyoung Kwak, Jung Wan Kim, Ji Young Park, Yoon Kyung Sohn; Korean J Pathol. 2004;38(3):157-164.

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Abstract PDF: BACKGROUND
Brain inducible nitric oxide synthase (iNOS) might be detectable in several pathologic conditions, and it is thought to play an important role in their pathophysiology. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are believed to be essential factors of iNOS induction of the brain.
METHODS
After intrahippocampal stereotaxic injection of lipopoly-saccharide (LPS), the rat brains were removed at 6, 12 and 24 h. The rat brain tissues were examined to clarify the expression patterns of TNF-alpha, IL-1beta and iNOS.
RESULTS
The inflammatory cells which were stained with anti-TNF-alpha antibody, appeared in 6 h and increased for 24 h after LPS injection. The iNOS positive cells appeared after 12 h of LPS injection. A semiquantitative analysis of reverse transcription-polymerase chain reaction (RT-PCR) revealed that the TNF-alpha and IL-1beta mRNA arose at 1 h, peaked at 6 h and then declined until 48 h after LPS injection. The iNOS mRNA arose after 6 h, peaked at 12 h, and declined until 48 h after LPS injection.
CONCLUSIONS
We conclude that the induction of inflammatory events by intrahippocampal injection of LPS activates TNF-alpha and IL-1beta secretion, and this is followed by an induction of iNOS expression. TNF-alpha and IL-1beta seem to be related with iNOS expression in brain inflammation.

A Study on the Pathogenesis of Renal Papillary Necrosis Induced by Endotoxin.: Kyung Rak Sohn, Tae Joong Sohn; Korean J Pathol. 1989;23(4):416-454.

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Abstract PDF: The author carried out an experimentation to clarify a possible pathogenesis of renal papillary necrosis induced by an univisceral Shwartzman reaction. The experimental animals were healthy white rabbits in weighing between 1.7 kg and 3.0 kg. Under the condition of ureterostomy, animals were pretreated with 0.5 cc of 50% ethyl alcohol and followed by administration of 0.2 ~ 1.5 mg endotoxin (E. coli 026 : B6, bacto lipopolysaccharide B. Difco, U.S.A.) as preparation in the renal pelvis. And then sacrificed at 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours and 24 hours after intravenous injection of 0.2 mg or 0.6 mg endotoxin through the ear veins, subjection to examine light and electron microscopically. The obtained results were summarized as follows: Papillary necrosis was developed in 88% among 18 cases excluding 6 cases died before sacrification. There were two types of necrosis, namely papillary and medullary type, but the former and combined forms of both types were the most common findings. Initial main target site of injury in renal papilla induced by endotoxiin was the endothelium of vasa recta and then followed by the Henle's loop, interstitial cell and collecting tubule respectively. Vascular injuries such as swelling and detachment of endothelium were observed since 10 minutes after endotoxin injection. Henle's loop showed stratification of basement membrane without consistent features with time lapses and initially observed fatty vaculoes at 1 hour after endotoxin injection were more eminent in 24 hours group. Main changes of interstitial cells were decrease of lipid droplets while increase of fatty vacuoles; the latter were initially observed in 1 hour group and more eminent in 24 hours group. Collecting tubule showed many fatty vacuoles especially in 24 hours group. It is thought that emergence of fatty vacuoles seems to be a kind of immature lipid droplets to compensate the increased demand of PC release due to continuous ischemic condition. In conclusion, it is thought that ischemic injury due to the vascular changes is pathogenic mechanism producing renal papillary necrosis. Endotoxin induced univisceral Shwartzman reaction in the kidney may be a good experimental model in studying renal papillary necrosis.

Case Report

Delayed Radionecrosis of the Brain: A case simulating recurrent glioma.: Shin Kwang Khang, Jun Ho Song, Kyu Ho Lee, In Wook Choo, Je G Chi; Korean J Pathol. 1988;22(3):360-366.

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Abstract PDF: An appreciation of the radiation changes in the brain adjacent to radiated glioma is of considerable importance from both clinical and pathological standpoint because the alteration in the brain parenchyma may result in a picture that mimics recurrence of the neoplasm. A 35 years old woman was admitted because of deterioration of consciousness which has started about 20 days ago. Past history revealed removal of left frontal brain tumor 4 years earlier and the diagnosis was grade II astroma. Postoperative radiation was done at that time. Sine then, she has been doing well. Computerized tomogram showed an ill defined huge low density mass at right frontal and left posterior parietal areas, which was irregularly enhanced in postcontrast study. Unlikely to the usual brain tumors, there was no mass effect on adjacent structures. Histologically acellular necrotic zone was alternating with hypercellular zone and most striking changes were vascular and glial reaction. Most of the vessels showed acellular hyliane thickening of their wall and some vessels were almost completely occluded. There was marked glial proliferation with considerable cellular and nuclear irregularities. Gemistocytic astrocytes were frequently seen and some were multinucleated.

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