Journal of Toxicologic Pathology最新文献_第3页

Molecular autopsy for sudden death in Japan. 日本猝死的分子解剖。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2023-08-30 DOI: 10.1293/tox.2023-0080

Takuma Yamamoto, Yuko Emoto, Takehiko Murase, Takahiro Umehara, Aya Miura, Minori Nishiguchi, Kazuya Ikematsu, Hajime Nishio

{"title":"Molecular autopsy for sudden death in Japan.","authors":"Takuma Yamamoto, Yuko Emoto, Takehiko Murase, Takahiro Umehara, Aya Miura, Minori Nishiguchi, Kazuya Ikematsu, Hajime Nishio","doi":"10.1293/tox.2023-0080","DOIUrl":"10.1293/tox.2023-0080","url":null,"abstract":"Japan has various death investigation systems; however, external examinations, postmortem computed tomography, macroscopic examinations, and microscopic examinations are performed regardless of the system used. These examinations can reveal morphological abnormalities, whereas the cause of death in cases with non-morphological abnormalities can be detected through additional examinations. Molecular autopsy and postmortem genetic analyses are important additional examinations. They are capable of detecting inherited arrhythmias or inherited metabolic diseases, which are representative non-morphological disorders that cause sudden death, especially in infants and young people. In this review, we introduce molecular autopsy reports from Japan and describe our experience with representative cases. The relationships between drug-related deaths and genetic variants are also reviewed. Based on the presented information, molecular autopsy is expected to be used as routine examinations in death investigations because they can provide information to save new lives.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10811381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66318311","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

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats 结合病理、生化和行为评估，评估异烟肼治疗大鼠的外周神经毒性

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-12-29 DOI: 10.1293/tox.2023-0094

Akane KASHIMURA, Satomi NISHIKAWA, Yuhei OZAWA, Yui HIBINO, Takashi TATEOKA, Mao MIZUKAWA, Hironobu NISHINA, Tetsuya SAKAIRI, Takanori SHIGA, Naoyuki AIHARA, Junichi KAMIIE

{"title":"Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats","authors":"Akane KASHIMURA, Satomi NISHIKAWA, Yuhei OZAWA, Yui HIBINO, Takashi TATEOKA, Mao MIZUKAWA, Hironobu NISHINA, Tetsuya SAKAIRI, Takanori SHIGA, Naoyuki AIHARA, Junichi KAMIIE","doi":"10.1293/tox.2023-0094","DOIUrl":"https://doi.org/10.1293/tox.2023-0094","url":null,"abstract":"In drug development, assessment of non-clinical peripheral neurotoxicity is important to ensure human safety. Clarifying the pathological features and mechanisms of toxicity enables the management of safety risks in humans by estimating the degree of risk and proposing monitoring strategies. Published guidelines for peripheral neurotoxicity assessment do not provide detailed information on which endpoints should be monitored preferentially and how the results should be integrated and discussed. To identify an optimal assessment method for the characterization of peripheral neurotoxicity, we conducted pathological, biochemical (biomaterials contributing to mechanistic considerations and biomarkers), and behavioral evaluations of isoniazid-treated rats. We found a discrepancy between the days on which marked pathological changes were noted and those on which biochemical and behavioral changes were noted, suggesting the importance of combining these evaluations. Although pathological evaluation is essential for pathological characterization, the results of biochemical and behavioral assessments at the same time points as the pathological evaluation are also important for discussion. In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139053869","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

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease 环孢素诱发慢性肾病大鼠肾小管上皮细胞中 CD44 的表达

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-12-18 DOI: 10.1293/tox.2023-0111

Kohei MATSUSHITA, Takeshi TOYODA, Hirotoshi AKANE, Tomomi MORIKAWA, Kumiko OGAWA

{"title":"CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease","authors":"Kohei MATSUSHITA, Takeshi TOYODA, Hirotoshi AKANE, Tomomi MORIKAWA, Kumiko OGAWA","doi":"10.1293/tox.2023-0111","DOIUrl":"https://doi.org/10.1293/tox.2023-0111","url":null,"abstract":"Renal tubular epithelial cell (TEC) injury is the most common cause of drug-induced kidney injury (DIKI). Although TEC regeneration facilitates renal function and structural recovery following DIKI, maladaptive repair of TECs leads to irreversible fibrosis, resulting in chronic kidney disease (CKD). CD44 is specifically expressed in TECs during maladaptive repair in several types of rat CKD models. In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague–Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fibronectin 1 (Fn1). Immunohistochemistry revealed that epithelial and mesenchymal markers of TECs of fibrotic lesions were downregulated and upregulated, respectively, and that these TECs were surrounded by a thickened basement membrane. In situ hybridization revealed an increase in Fn1 mRNA in the cytoplasm of TECs of fibrotic lesions, whereas fibronectin protein was localized in the stroma surrounding these tubules. Enzyme-linked immunosorbent assay revealed increased serum CD44 levels in CyA-treated rats. Collectively, these findings suggest that CD44 contributes to renal fibrosis by inducing fibronectin secretion in TECs exhibiting partial epithelial-mesenchymal transition and highlight the potential of CD44 as a biomarker of renal fibrosis. \u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824096","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

Drug review process advancement and required manufacturer and contract research organization responses 药品审评过程的进展和要求生产商和合同研究组织的回应

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-11-22 DOI: 10.1293/tox.2023-0106

Takayuki ANZAI, Glenn J. MYATT, Frances HALL, Brenda FINNEY, Kenshi NAKAGAWA, Hijiri IWATA, Reo ANZAI, Anne DICKINSON, Matthew FREER, Dai NAKAE, Hiroshi ONODERA, Takaaki MATSUYAMA

{"title":"Drug review process advancement and required manufacturer and contract research organization responses","authors":"Takayuki ANZAI, Glenn J. MYATT, Frances HALL, Brenda FINNEY, Kenshi NAKAGAWA, Hijiri IWATA, Reo ANZAI, Anne DICKINSON, Matthew FREER, Dai NAKAE, Hiroshi ONODERA, Takaaki MATSUYAMA","doi":"10.1293/tox.2023-0106","DOIUrl":"https://doi.org/10.1293/tox.2023-0106","url":null,"abstract":"The United States Senate passed the “FDA Modernization Act 2.0.” on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient safety. Nonetheless, society is becoming increasingly opposed to animal testing, and efforts will be made to use fewer animals and conduct fewer animal tests as a natural and reasonable response. These changes eventually alter the shape of new drug applications. Based on the assumption that fewer animal tests will be conducted or fewer animals will be used in testing, this study explored bioinformatics and new technologies as alternatives to compensate for reduced information and provide a picture of how future new drug applications may look. The authors also discuss the directions that pharmaceutical companies and nonclinical contract research organizations should adopt to promote the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibitions.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518799","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

Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model. 确定数据集，以确定MPTP诱导的帕金森病猴模型中枢神经系统毒性的最佳组织病理学检查时间。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-05-24 DOI: 10.1293/tox.2023-0010

YasunoHironobu, MasudaYasushi, OzakiHarushige, SanoTomoya, ShinozawaTadahiro, WatanabeTakeshi

{"title":"Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model.","authors":"YasunoHironobu, MasudaYasushi, OzakiHarushige, SanoTomoya, ShinozawaTadahiro, WatanabeTakeshi","doi":"10.1293/tox.2023-0010","DOIUrl":"10.1293/tox.2023-0010","url":null,"abstract":"Determining the optimal timing for histopathological examination following exposure to a test article is crucial for assessing neurotoxicity. However, no study has focused on identifying an ideal dataset to define the optimal timing for histopathological examination of central nervous system (CNS) toxicity in monkeys. Therefore, this study aimed to define a predictive endpoint that would guide us in selecting the optimal timing for histopathological examination of CNS toxicity in monkeys. Four cynomolgus monkeys were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intravenously at a dosage of 0.6 mg/kg twice at 1-week intervals. Necropsies were performed 1 week after the final dose. The Parkinsonian rating (PR) score and temporal changes in neurofilament light chain and glial fibrillary acidic protein concentrations in the cerebrospinal fluid (CSF) and serum were evaluated and compared with the histopathological findings in the brain. The PR score of all animals administered MPTP increased from days 10 to 11, with some degree of individual variability. Microscopically, all animals showed axonal swelling and vacuolation, with or without microgliosis in the nigrostriatal bundle. However, substantial neurodegenerative findings were observed only in animals with high PR scores at necropsy. A slight increase in CSF biomarker levels at necropsy was also observed in animals with high PR scores. However, their correlation with microscopic findings in these animals was unclear. These data suggest that comprehensive clinical observations, such as PR score alone or combined with other CSF biomarkers, could be further evaluated as potential indicators for triggering anatomic CNS evaluations in monkeys following toxic insults.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66318039","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

Retraction: Nuclear Morphometric Analysis of Leydig Cells of Male Pubertal Rats Exposed In Utero to Di(n-butyl) Phthalate. 收缩：暴露于邻苯二甲酸二正丁酯的雄性青春期大鼠睾丸间质细胞的核形态计量学分析。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-10-06 DOI: 10.1293/tox.36.R1

Shin Wakui, Masaya Motohashi, Takemi Satoh, Masaru Shirai, Tomoko Mutou, Hiroyuki Takahashi, Michael F Wempe, Hitoshi Endou, Tomoo Inomata, Masao Asari

引用次数: 0

Pathological analysis of lesions in the exocrine pancreas of rats induced by Zinc Maltol. 麦芽酚锌致大鼠外分泌胰腺损伤的病理学分析。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-07-13 DOI: 10.1293/tox.2023-0063

FujiwaraSakura, MorokiTakayasu, HitomiMasaya, SatoMakoto, TerayamaYui, YoshikawaTsuyoshi

引用次数: 0

Smooth muscle hamartoma of the lungs in a Wistar Hannover rat. 汉诺威Wistar大鼠肺平滑肌错构瘤。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-07-07 DOI: 10.1293/tox.2023-0056

MiyazakiShinya, FujiwaraChinatsu, KatohYoshitaka, ItoTsuyoshi, KoyamaAya, TakahashiNaofumi, ShigaAtsushi, HaradaTakanori

{"title":"Smooth muscle hamartoma of the lungs in a Wistar Hannover rat.","authors":"MiyazakiShinya, FujiwaraChinatsu, KatohYoshitaka, ItoTsuyoshi, KoyamaAya, TakahashiNaofumi, ShigaAtsushi, HaradaTakanori","doi":"10.1293/tox.2023-0056","DOIUrl":"10.1293/tox.2023-0056","url":null,"abstract":"Hamartomas are tumor-like masses comprising disorganized normal tissue elements. To date, spontaneous hamartomas have been reported in several organs and tissues in rodents but not in the lungs. Here, we report the first case of a hamartoma in the lungs of a 108-week-old female Wistar Hannover rat. Grossly, a white spot, 7 mm in diameter, was observed on the costal surface of the left lung. Histopathologically, the nodular lesions adjacent to the bronchioles comprised mature smooth muscle cells. The lesion was not encapsulated and spread along the alveolar walls and ducts without compression of the surrounding tissue. In the nodules, elastic fibers enclosed small lumens lined with factor VIII-related antigen-positive endothelial cells. This structure suggested that the nodule mimicked an artery. Moreover, structural abnormalities were observed within the bronchioles and arterioles owing to the increased number of smooth muscle cells in the surrounding tissues. These features suggested that this was a case of tissue malformation rather than a neoplasm, leading to the diagnosis of a smooth muscle hamartoma of the lung.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66318292","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

Histopathology of fused triplet placenta in rat. 大鼠融合三联体胎盘的组织病理学。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-06-05 DOI: 10.1293/tox.2023-0026

FurukawaSatoshi, TsujiNaho, HayashiSeigo, KurodaYusuke, KimuraMasayuki, KojimaChisato, TakeuchiKazuya

引用次数: 0

Analyses of damage-associated molecular patterns, particularly biglycan, in cisplatin-induced rat progressive renal fibrosis. 在顺铂诱导的大鼠进行性肾纤维化中，损伤相关的分子模式，特别是多糖的分析。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-07-01 DOI: 10.1293/tox.2022-0148

Minto Nakagawa, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate

{"title":"Analyses of damage-associated molecular patterns, particularly biglycan, in cisplatin-induced rat progressive renal fibrosis.","authors":"Minto Nakagawa, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate","doi":"10.1293/tox.2022-0148","DOIUrl":"https://doi.org/10.1293/tox.2022-0148","url":null,"abstract":"Damage-associated molecular patterns (DAMPs) and their receptors (TLR-2 and -4) may play important roles in renal fibrosis, of which the pathogenesis is complicated. We used rat renal lesions induced by a single intraperitoneal injection of cisplatin at 6 mg/kg body weight; consisting of tissue damage of renal tubules on days 1 and 3, further damage and regeneration with inflammation mainly on days 5 and 7, and interstitial fibrosis on days 9, 12, 15, and 20. Microarray analyses on days 5 (the commencement of inflammation) and 9 (the commencement of interstitial fibrosis) showed that DAMPs increased by more than two-fold relative to control included common extra-cellular matrix (ECM) components such as laminin (Lamc2) and fibronectin, and heat shock protein family, as well as fibrinogen, although it was limited analysis; Lamc2, an element of basement membrane, may be regarded as an indicator for damaged renal tubules. In the real-time RT-PCR analyses, TLR-2 significantly increased transiently on day 1, whereas TLR-4 significantly increased on days 9 and 15, almost in agreement with the increased biglycan (a small leucine-rich proteoglycan as ubiquitous ECM component). As M1/M2 macrophages participated in renal lesions, such as inflammation and fibrosis, presumably, TLR-4, which may be expressed in immune cells, could play crucial roles in the formation of renal lesions in association with biglycan.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/d6/tox-36-181.PMC10412960.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9990958","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