Journal of Toxicologic Pathology最新文献_第7页

Histopathology of acute colchicine intoxication: novel findings and their association with clinical manifestations. 急性秋水仙碱中毒的组织病理学:新发现及其与临床表现的关系。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-04-03 DOI: 10.1293/tox.2022-0007

Shojiro Ichimata, Yukiko Hata, Kojiro Hirota, Naoki Nishida

{"title":"Histopathology of acute colchicine intoxication: novel findings and their association with clinical manifestations.","authors":"Shojiro Ichimata, Yukiko Hata, Kojiro Hirota, Naoki Nishida","doi":"10.1293/tox.2022-0007","DOIUrl":"https://doi.org/10.1293/tox.2022-0007","url":null,"abstract":"A 32-year-old woman attempted suicide by ingesting Gloriosa bulbs and died approximately 2 days later. Toxicological examination revealed a potentially fatal blood concentration of colchicine (0.096 mg/L). In addition to the increased mitotic figures in the gastrointestinal mucosa, a unique finding for acute colchicine intoxication, pathological examination showed microvesicular lipid droplets in the liver, kidney, heart, and conduction system. Furthermore, central chromatolysis of neurons was observed in the pontine nucleus, medial accessory olivary nucleus, nucleus of the solitary tract, and nucleus ambiguus. Grumose degeneration of the cerebellar dentate nucleus was also evident. These pathological findings may help identify colchicine intoxication, even in the absence of evidence suggesting ingestion during autopsy. Moreover, pathological changes in the heart and central nervous system may be associated with the development of serious complications of acute colchicine intoxication.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 3","pages":"255-262"},"PeriodicalIF":1.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/8d/tox-35-255.PMC9255996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

A simple specimen preparation method for histopathological evaluation of vestibular organs. 一种用于前庭器官组织病理学评估的简单标本制备方法。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-05-07 DOI: 10.1293/tox.2022-0008

Shinichi Onishi, Atsuko Murai, Aki Kito, Yuka Kawashima, Yusuke Ohmori, Atsuhiko Kato

引用次数: 1

Response biomarkers of inhalation exposure to cigarette smoke in the mouse lung. 小鼠肺部吸入暴露于香烟烟雾的反应生物标志物。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-05-21 DOI: 10.1293/tox.2021-0077

Shugo Suzuki, Kazuhisa Asai, Min Gi, Kazuya Kojima, Anna Kakehashi, Yuji Oishi, Taisuke Matsue, Nao Yukimatsu, Kazuto Hirata, Tomoya Kawaguchi, Hideki Wanibuchi

{"title":"Response biomarkers of inhalation exposure to cigarette smoke in the mouse lung.","authors":"Shugo Suzuki, Kazuhisa Asai, Min Gi, Kazuya Kojima, Anna Kakehashi, Yuji Oishi, Taisuke Matsue, Nao Yukimatsu, Kazuto Hirata, Tomoya Kawaguchi, Hideki Wanibuchi","doi":"10.1293/tox.2021-0077","DOIUrl":"https://doi.org/10.1293/tox.2021-0077","url":null,"abstract":"Cigarette smoking is known to increase the risk of cancer and chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of short-term nose-only inhalation exposure to cigarette smoke in mice. Male 10-week-old C57BL mice were exposed to clean air (control) or mainstream cigarette smoke for 1 h/day, 5 days/week, for 2 or 4 weeks. Exposure to cigarette smoke increased the number of inflammatory cells, especially neutrophils, in the bronchoalveolar lavage fluid, increased inflammatory cell infiltration foci, and caused an increase in the thickness of the peripheral bronchial epithelium. Microarray gene expression analysis indicated that smoke exposure induced inflammatory responses, including leukocyte migration and activation of phagocytes and myeloid cells, as early as two weeks after the initiation of exposure. Importantly, chemokine (C-C motif) ligand 17, resistin-like alpha, and lipocalin 2 were upregulated and may serve as useful markers of the toxic effects of exposure to cigarette smoke before pulmonary histological changes become evident.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 3","pages":"247-254"},"PeriodicalIF":1.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/29/tox-35-247.PMC9256000.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Histopathologic effect of in ovo exposure to methotrexate at early embryonic stage on optic tectum of Japanese quail (Coturnix japonica). 早期胚胎期卵暴露于甲氨蝶呤对日本鹌鹑(Coturnix japonica)视屏的组织病理学影响。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-04-23 DOI: 10.1293/tox.2022-0011

Masakatsu Nohara, Mayo Iwasaki, Mahiro Nishio, Akihiko Sugiyama

引用次数: 1

The potential of organoids in toxicologic pathology: Histopathological and immunohistochemical evaluation of a mouse normal tissue-derived organoid-based carcinogenesis model. 类器官在毒理学病理学中的潜力:小鼠正常组织来源的类器官癌变模型的组织病理学和免疫组织化学评估。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-04-22 DOI: 10.1293/tox.2022-0021

Rikako Ishigamori, Mie Naruse, Akihiro Hirata, Yoshiaki Maru, Yoshitaka Hippo, Toshio Imai

{"title":"The potential of organoids in toxicologic pathology: Histopathological and immunohistochemical evaluation of a mouse normal tissue-derived organoid-based carcinogenesis model.","authors":"Rikako Ishigamori, Mie Naruse, Akihiro Hirata, Yoshiaki Maru, Yoshitaka Hippo, Toshio Imai","doi":"10.1293/tox.2022-0021","DOIUrl":"https://doi.org/10.1293/tox.2022-0021","url":null,"abstract":"Recently, we introduced an organoid-based chemical carcinogenesis model using mouse normal tissue-derived organoids. In the present review article, the histopathological and immunohistochemical characteristics of mouse normal tissue-derived organoids and tumors derived from these organoids after their in vitro treatment with genotoxic carcinogens and injection into nude mouse are reviewed. In organoids treated in vitro with genotoxic carcinogens, we confirmed macroscopic tumorigenicity and histopathological findings, including neoplastic characteristics, such as multilayered epithelia and/or invasion of epithelia into the surrounding interstitium. In contrast glandular/cystic structures with monolayered epithelia were clearly demarcated from the surrounding Matrigel/interstitium in the untreated control groups. In addition to macroscopic tumorigenicity, these microscopic epithelial changes, which are characteristic of the early stages of carcinogenesis, are included in the requirements for carcinogenicity-positive judgement of the organoid-based carcinogenesis model. Immunohistochemistry of cytokeratins (CKs), used to determine the origin of epithelia and distribution of extraductal invasive lesions, or oncogenic kinases, which reflect molecular activation in epithelia following chemical treatment, is helpful for accurate diagnosis and molecular evaluation in the early stages of carcinogenesis. This information improves our biological understanding of organoid-based chemical carcinogenesis models.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 3","pages":"211-223"},"PeriodicalIF":1.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/5b/tox-35-211.PMC9255998.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40503981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Testicular alterations in cryptorchid/orchiopexic rats chronically exposed to acrylamide or di-butyl-phthalate 慢性暴露于丙烯酰胺或邻苯二甲酸二丁酯的隐睾/睾丸缺乏大鼠睾丸改变

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-04-13 DOI: 10.1293/tox.2021-0045

Thania R. R. Lima, Nathália P. Souza, Ana P. Ferragut Cardoso, Lígia M. M. Gomide, Merielen G. Nascimento e Pontes, Hélio A. Miot, Lora L. Arnold, Samuel M. Cohen, João Lauro V. de Camargo

{"title":"Testicular alterations in cryptorchid/orchiopexic rats chronically exposed to acrylamide or di-butyl-phthalate","authors":"Thania R. R. Lima, Nathália P. Souza, Ana P. Ferragut Cardoso, Lígia M. M. Gomide, Merielen G. Nascimento e Pontes, Hélio A. Miot, Lora L. Arnold, Samuel M. Cohen, João Lauro V. de Camargo","doi":"10.1293/tox.2021-0045","DOIUrl":"https://doi.org/10.1293/tox.2021-0045","url":null,"abstract":" Exposure of Sprague-Dawley (SD) rats to acrylamide (AA) or di-butyl-phthalate (DBP) from the 12th gestational day to the 16th postnatal week (PNW) has been shown to reduce the effectiveness of orchiopexy in recovering the testicular alterations associated with experimental cryptorchidism established at weaning. Herein, we provide information about the long-term effects of AA or DBP on the testes of cryptorchid/orchiopexic rats. Male offspring exposed in utero to 10 mg/kg/day AA or 500 mg/kg/day DBP underwent bilateral surgical cryptorchidism at the 3rd PNW and orchiopexy at the 6th week, with continuous exposure to the chemicals through diet until the 58th week. Regardless of the test chemical, there were severe qualitative/quantitative alterations in the seminiferous tubules and increased numbers of Leydig cells. There was an increase and decrease in the number of tubules with c-Kit- and placental alkaline phosphatase-labeled germ cells, respectively, as compared to those in the control group, suggesting an imbalance between apoptosis and cell proliferation processes. The histological scores of the testicular lesions at the end of this one-year study were higher than those in the previous 16-week study, indicating that exposure of rats to the toxicants AA or DBP enhanced the testicular alterations induced by the chemicals beginning at the intra-uterine life, and impaired the effectiveness of orchiopexy in restoring the testes to normal morphology. Although the present experimental protocol does not completely replicate the natural human undescended testes, our findings may contribute to understanding the alterations occurring in cryptorchid/orchiopexic testes potentially exposed to exogenous chemicals for extended periods.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"122 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LPS-TLR4/MD-2–TNF-α signaling mediates alcohol-induced liver fibrosis in rats LPS-TLR4/ MD-2-TNF -α信号介导酒精性大鼠肝纤维化

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-02-26 DOI: 10.1293/tox.2021-0018

Wensheng Mou, Shi-ru Chen, Zhengqi Wu, Libin Hu, Ji-ye Zhang, Hong-Jie Chang, Hang Zhou, Y. Liu

{"title":"LPS-TLR4/MD-2–TNF-α signaling mediates alcohol-induced liver fibrosis in rats","authors":"Wensheng Mou, Shi-ru Chen, Zhengqi Wu, Libin Hu, Ji-ye Zhang, Hong-Jie Chang, Hang Zhou, Y. Liu","doi":"10.1293/tox.2021-0018","DOIUrl":"https://doi.org/10.1293/tox.2021-0018","url":null,"abstract":"Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)–tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2–TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin–eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2–TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2–TNF-α signaling pathway.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"193 - 203"},"PeriodicalIF":1.2,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48268443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

rasH2 mouse: reproducibility and stability of carcinogenicity due to a standardized production and monitoring system. rasH2小鼠:由于标准化的生产和监测系统，致癌性的重复性和稳定性

IF 0.9 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-01-01 Epub Date: 2021-11-19 DOI: 10.1293/tox.2021-0068

Hideki Tsutsumi, Ryo Inoue, Masahiko Yasuda, Riichi Takahashi, Masami Suzuki, Koji Urano

{"title":"rasH2 mouse: reproducibility and stability of carcinogenicity due to a standardized production and monitoring system.","authors":"Hideki Tsutsumi, Ryo Inoue, Masahiko Yasuda, Riichi Takahashi, Masami Suzuki, Koji Urano","doi":"10.1293/tox.2021-0068","DOIUrl":"10.1293/tox.2021-0068","url":null,"abstract":"The rasH2 mouse was developed as a model for carcinogenicity studies in regulatory science. Its phenotype is stable during high-volume production and over successive generations. To produce rasH2 mice, three strains of mice (C57BL/6J-TgrasH2, C57BL/6J, and BALB/cByJ) were maintained individually. Since the homozygous c-HRAS genotype is lethal, hemizygous transgenic mice were maintained by crossing with inbred C57BL/6J mice. After breeding, male B6-transgenic mice were mated with female BALB/cByJ mice to obtain transgenic mice. Pups that were rasH2-Tg (tg/wt) or rasH2-Wt (wt/wt) were confirmed by genotyping. Frozen embryos were preserved by the Central Institute for Experimental Animals (CIEA) and sent to two facilities, CLEA Japan and Taconic Biosciences, where the mice were produced. Production colonies are created in both facilities and supplied to customers worldwide. To prevent genetic drift, the colonies were renewed for up to 10 generations, and renewals were carried out four times every five years from 2005 to 2021. To ensure the uniformity and maintenance of the phenotype of rasH2 mice, the carcinogen susceptibilities were monitored in every renewal of colonies by CIEA based on a standard protocol of the short-term carcinogenicity study using the positive control compound N-methyl-N-nitrosourea (MNU). Furthermore, simple carcinogenicity monitoring targeting the forestomach, the organ most sensitive to MNU, was performed approximately once a year. Based on the optimally designed production and monitoring systems, the quality of rasH2 mice with reproducibility and stability of carcinogenicity is maintained and supplied globally.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"19-24"},"PeriodicalIF":0.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45880536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of a uniform thymic malignant lymphoma model with C57BL/6J p53 gene deficient mice C57BL/6J p53基因缺陷小鼠胸腺恶性淋巴瘤模型的建立

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-01-01 DOI: 10.1293/tox.2021-0022

Susu Liu, Jianjun Lyu, Qian-qian Li, Xi Wu, Yanwei Yang, Guitao Huo, Qingfen Zhu, Ming Guo, Yuelei Shen, Sanlong Wang, Changfa Fan

{"title":"Generation of a uniform thymic malignant lymphoma model with C57BL/6J p53 gene deficient mice","authors":"Susu Liu, Jianjun Lyu, Qian-qian Li, Xi Wu, Yanwei Yang, Guitao Huo, Qingfen Zhu, Ming Guo, Yuelei Shen, Sanlong Wang, Changfa Fan","doi":"10.1293/tox.2021-0022","DOIUrl":"https://doi.org/10.1293/tox.2021-0022","url":null,"abstract":"Lymphoma is the third most common cancer diagnosed in children, and T-cell lymphoma has the worst prognosis based on clinical observations. To date, a lymphoma model with uniform penetrance has not yet been developed. In this study, we generated a p53 deficient mouse model by targeting embryonic stem cells derived from a C57BL/6J mouse strain. Homozygous p53 deficient mice exhibited a higher rate of spontaneous tumorigenesis, with a high spontaneous occurrence rate (93.3%) of malignant lymphoma. Because tumor models with high phenotypic consistency are currently needed, we generated a lymphoma model by a single intraperitoneal injection of 37.5 or 75 mg/kg N-methyl-N-nitrosourea to p53 deficient mice. Lymphoma and retinal degeneration occurred in 100% of p53+/− mice administered with higher concentrations of N-methyl-N-nitrosourea, a much greater response than those of previously reported models. The main anatomic sites of lymphoma were the thymus, spleen, bone marrow, and lymph nodes. Both induced and spontaneous lymphomas in the thymus and spleen stained positive for CD3 antigen, and flow cytometry detected positive CD4 and/or CD8 cells. Based on our observations and previous data, we hypothesize that mice with a B6 background are prone to lymphomagenesis.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"25 - 36"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46485370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Malignant stromal cell tumor of the spleen in a WBN/Kob rat WBN/Kob大鼠脾脏恶性间质细胞瘤

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-01-01 DOI: 10.1293/tox.2021-0067

Yui Terayama, T. Matsuura, K. Ozaki

引用次数: 0