Toxicologic Pathology最新文献

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Toxicologic Neuropathology of Novel Biotherapeutics. 新型生物治疗药物的毒理神经病理学。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-02-21 DOI: 10.1177/01926233241230542
Dinesh S Bangari, Lisa G Lanigan, Sarah D Cramer, Jessica L Grieves, René Meisner, Arlin B Rogers, Elizabeth J Galbreath, Brad Bolon
{"title":"Toxicologic Neuropathology of Novel Biotherapeutics.","authors":"Dinesh S Bangari, Lisa G Lanigan, Sarah D Cramer, Jessica L Grieves, René Meisner, Arlin B Rogers, Elizabeth J Galbreath, Brad Bolon","doi":"10.1177/01926233241230542","DOIUrl":"10.1177/01926233241230542","url":null,"abstract":"<p><p>Biotherapeutic modalities such as cell therapies, gene therapies, nucleic acids, and proteins are increasingly investigated as disease-modifying treatments for severe and life-threatening neurodegenerative disorders. Such diverse bio-derived test articles are fraught with unique and often unpredictable biological consequences, while guidance regarding nonclinical experimental design, neuropathology evaluation, and interpretation is often limited. This paper summarizes key messages offered during a half-day continuing education course on toxicologic neuropathology of neuro-targeted biotherapeutics. Topics included fundamental neurobiology concepts, pharmacology, frequent toxicological findings, and their interpretation including adversity decisions. Covered biotherapeutic classes included cell therapies, gene editing and gene therapy vectors, nucleic acids, and proteins. If agents are administered directly into the central nervous system, initial screening using hematoxylin and eosin (H&E)-stained sections of currently recommended neural organs (brain [7 levels], spinal cord [3 levels], and sciatic nerve) may need to expand to include other components (e.g., more brain levels, ganglia, and/or additional nerves) and/or special neurohistological procedures to characterize possible neural effects (e.g., cell type-specific markers for reactive glial cells). Scientists who evaluate the safety of novel biologics will find this paper to be a practical reference for preclinical safety testing and risk assessment.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"414-431"},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913491","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
Toxicologic Pathology Forum Opinion: Rational Approaches to Expanded Neurohistopathology Evaluation for Nonclinical General Toxicity Studies and Juvenile Animal Studies. 毒理病理学论坛意见:非临床一般毒性研究和幼年动物研究中扩大神经组织病理学评估的合理方法。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-30 DOI: 10.1177/01926233231225239
Brad Bolon
{"title":"Toxicologic Pathology Forum Opinion: Rational Approaches to Expanded Neurohistopathology Evaluation for Nonclinical General Toxicity Studies and Juvenile Animal Studies.","authors":"Brad Bolon","doi":"10.1177/01926233231225239","DOIUrl":"10.1177/01926233231225239","url":null,"abstract":"<p><p>Existing nervous system sampling and processing \"best practices\" for nonclinical general toxicity studies (GTS) were designed to assess test articles with unknown, no known, or well-known neurotoxic potential. Similar practices are applicable to juvenile animal studies (JAS). In GTS and JAS, the recommended baseline sampling for all species includes brain (7 sections), spinal cord (cervical and lumbar divisions [cross and longitudinal sections for each]), and 1 nerve (sciatic or tibial [cross and longitudinal sections]) in hematoxylin and eosin-stained sections. Extra sampling and processing (ie, an \"expanded neurohistopathology evaluation\" [ENHP]) are used for agents with anticipated neuroactivity (toxic ± therapeutic) of incompletely characterized location and degree. Expanded sampling incorporates additional brain (usually 8-15 sections total), spinal cord (thoracic ± sacral divisions), ganglia (somatic ± autonomic, often 2-8 total), and/or nerves (2-6 total) depending on the species and study objectives. Expanded processing typically adds special neurohistological procedures (usually 1-4 for selected samples) to characterize glial reactions, myelin integrity, and/or neuroaxonal damage. In my view, GTS and JAS designs should sample neural tissues at necropsy as if ENHP will be needed eventually, and when warranted ENHP may incorporate expanded sampling and/or expanded processing depending on the study objective(s).</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"363-374"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576489","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
Historical Control Background Incidence of Spontaneous Neoplastic Lesions of Sprague-Dawley Rats in 104-Week Toxicity Studies. 在为期 104 周的毒性研究中,Sprague-Dawley 大鼠自发性肿瘤病变的历史对照背景发生率。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-28 DOI: 10.1177/01926233231224466
Amit Kumar, Marie Bockenstedt, Victoria Laast, Alok Sharma
{"title":"Historical Control Background Incidence of Spontaneous Neoplastic Lesions of Sprague-Dawley Rats in 104-Week Toxicity Studies.","authors":"Amit Kumar, Marie Bockenstedt, Victoria Laast, Alok Sharma","doi":"10.1177/01926233231224466","DOIUrl":"10.1177/01926233231224466","url":null,"abstract":"<p><p>Data collected from approximately 1800 male and 1800 female Sprague-Dawley (SD) rats used in 104-week carcinogenicity studies were archived in a historical control database at Labcorp Early Development, Inc, and the neoplastic microscopic observation data from these rats were retrospectively evaluated. Historical control data can provide useful information on the range and incidence of spontaneously occurring background neoplasms in the species and strain of the test animal used in different types of toxicity studies, including studies of differing lengths, delivery of test article, and test animal. Some of the most common malignant findings noted included fibrosarcoma of skin/subcutis and thyroid C-cell carcinoma in males (2.1% each) while mammary gland carcinoma and pituitary carcinoma (25% and 2.6%) were most common in females. Pituitary adenoma of pars distalis was found to be the most prevalent benign neoplasm in both males and females (56.4% and 77.1%). Fibroadenoma of mammary gland (35.6%) and thyroid C-cell adenoma (8.5%) were the second and third most common benign tumors in female SD rats. In males, the thyroid C-cell adenoma (10.9%) and benign pheochromocytoma (8.9%) were the second and third most common tumors.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"329-356"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571509","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
Early-Onset Asymptomatic Polypoid Cystitis in Two Adolescent Male Beagle Dogs. 两只青春期雄性比格犬早期出现的无症状多发性膀胱炎
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-09 DOI: 10.1177/01926233231224462
Giulia Tosi, Jennifer Rachael Barnes
{"title":"Early-Onset Asymptomatic Polypoid Cystitis in Two Adolescent Male Beagle Dogs.","authors":"Giulia Tosi, Jennifer Rachael Barnes","doi":"10.1177/01926233231224462","DOIUrl":"10.1177/01926233231224462","url":null,"abstract":"<p><p>This brief communication describes a rare spontaneous background lesion in the lower urinary tract of two male laboratory beagles. Proliferative lesions comprising a constellation of histological features consistent with polypoid cystitis were observed in the bladder of two adolescent dogs from a routine preclinical toxicology study. Both animals were clinically asymptomatic and had only minor alterations in urinalysis parameters. While chronic polypoid cystitis is well-recognized in adult pet dogs, this is the first reported case in purpose-bred laboratory beagles. An awareness of this uncommon background finding is important for toxicological pathologists to distinguish it from potential test article-related findings.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"357-360"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404509","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
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective. 毒理病理学论坛观点文章:在非临床毒性研究中使用虚拟对照组:解剖病理学的视角。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-31 DOI: 10.1177/01926233231224805
Armelle Grevot, Julie Boisclair, Magali Guffroy, Peter Hall, Gabriele Pohlmeyer-Esch, Matt Jacobsen, Ute Bach, Anna Lena Frisk, Noel Dybdal, Xavier Palazzi
{"title":"Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective.","authors":"Armelle Grevot, Julie Boisclair, Magali Guffroy, Peter Hall, Gabriele Pohlmeyer-Esch, Matt Jacobsen, Ute Bach, Anna Lena Frisk, Noel Dybdal, Xavier Palazzi","doi":"10.1177/01926233231224805","DOIUrl":"10.1177/01926233231224805","url":null,"abstract":"<p><p>In the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinical and anatomic pathologists, and regulators to support approaches that will facilitate a staggered implementation of VCGs in nonclinical toxicity studies. Notably, the authors believe that a validated database for VC animals will need to include histopathology (digital) slides for microscopic assessment. Ultimately, the most important step lies in the validation of the concept by performing VCG and the full control group in parallel for studies of varying duration over a reasonable timespan to confirm there are no differences in outcomes (dual study design). The authors also discuss a hybrid approach, whereby control groups comprised both concurrent and VCs to demonstrate proof-of-concept. Once confidence is established by sponsors and regulators, VCs have the potential to replace some or all CC animals.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"390-396"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642955","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
Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies? 在动物研究中,历史对照组数据可以用来代替同期对照吗?
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2023-10-31 DOI: 10.1177/01926233231208987
Thomas Steger-Hartmann, Matthew Clark
{"title":"Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies?","authors":"Thomas Steger-Hartmann, Matthew Clark","doi":"10.1177/01926233231208987","DOIUrl":"10.1177/01926233231208987","url":null,"abstract":"<p><p>The availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately evident, the potential challenges need to be carefully considered to avoid any effect which could lower the sensitivity of an animal study to detect adverse events, safety thresholds, target organs, or biomarkers. In our brief communication, we summarize the current discussion regarding VCGs and propose a path forward how the replacement of concurrent control with VCGs resulting from historical data could be systematically assessed and to come to conclusions regarding the scientific value of the concept.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"361-362"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413999","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
Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology. 评估用于毒理病理学的整张切片图像扫描仪的色彩再现性和色彩变异缓解情况。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-30 DOI: 10.1177/01926233231224468
Mei-Lan Chu, Xing-Yue M Ge, Jeffrey Eastham, Trung Nguyen, Reina N Fuji, Ruth Sullivan, Daniel Ruderman
{"title":"Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology.","authors":"Mei-Lan Chu, Xing-Yue M Ge, Jeffrey Eastham, Trung Nguyen, Reina N Fuji, Ruth Sullivan, Daniel Ruderman","doi":"10.1177/01926233231224468","DOIUrl":"10.1177/01926233231224468","url":null,"abstract":"<p><p>Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"313-328"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576460","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
Toxicologic Pathology Forum: Opinion on Interpretive Challenges for Procedure-Related Effects Associated With Direct Central Nervous System Delivery of Oligonucleotides to Rodents, Dogs, and Nonhuman Primates. 毒理病理学论坛:关于啮齿动物、狗和非人灵长类动物中枢神经系统直接给药寡核苷酸的程序相关效应的解释性挑战的意见。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-08-01 Epub Date: 2024-01-05 DOI: 10.1177/01926233231218953
Lisa D Berman-Booty, Stephanie K Klein, Curt Mazur, Joseph Schroeder, Sven Korte, Florian T Ludwig, Annette Romeike, Brad Bolon, Jessica L Grieves
{"title":"Toxicologic Pathology Forum: Opinion on Interpretive Challenges for Procedure-Related Effects Associated With Direct Central Nervous System Delivery of Oligonucleotides to Rodents, Dogs, and Nonhuman Primates.","authors":"Lisa D Berman-Booty, Stephanie K Klein, Curt Mazur, Joseph Schroeder, Sven Korte, Florian T Ludwig, Annette Romeike, Brad Bolon, Jessica L Grieves","doi":"10.1177/01926233231218953","DOIUrl":"10.1177/01926233231218953","url":null,"abstract":"<p><p>Direct delivery of therapeutics to the central nervous system (CNS) greatly expands opportunities to treat neurological diseases but is technically challenging. This opinion outlines principal technical aspects of direct CNS delivery via intracerebroventricular (ICV) or intrathecal (IT) injection to common nonclinical test species (rodents, dogs, and nonhuman primates) and describes procedure-related clinical and histopathological effects that confound interpretation of test article-related effects. Direct dosing is by ICV injection in mice due to their small body size, while other species are dosed IT in the lumbar cistern. The most frequent procedure-related functional effects are transient absence of lower spinal reflexes after IT injection or death soon after ICV dosing. Common procedure-related microscopic findings in all species include leukocyte infiltrates in CNS meninges or perivascular (Virchow-Robin) spaces; nerve fiber degeneration in the spinal cord white matter (especially dorsal and lateral tracts compressed by dosing needles or indwelling catheters), spinal nerve roots, and sciatic nerve; meningeal fibrosis at or near IT injection sites; hemorrhage; and gliosis. Findings typically are minimal to occasionally mild. Findings tend to be more severe and/or have a higher incidence in the spinal cord segments and spinal nerve roots at or close to the site of administration.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"375-389"},"PeriodicalIF":1.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098676","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
Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies. 在NHP中用预先存在的或治疗出现的抗衣壳抗体给药基因治疗载体的安全性发现。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-07-01 Epub Date: 2023-11-03 DOI: 10.1177/01926233231202995
Sundeep Chandra, Brian R Long, Carlos Fonck, Andrew C Melton, Jeremy Arens, Jill Woloszynek, Charles A O'Neill
{"title":"Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies.","authors":"Sundeep Chandra, Brian R Long, Carlos Fonck, Andrew C Melton, Jeremy Arens, Jill Woloszynek, Charles A O'Neill","doi":"10.1177/01926233231202995","DOIUrl":"10.1177/01926233231202995","url":null,"abstract":"<p><p>Replication-incompetent adeno-associated virus (AAV)-based vectors are nonpathogenic viral particles used to deliver therapeutic genes to treat multiple monogenic disorders. AAVs can elicit immune responses; thus, one challenge in AAV-based gene therapy is the presence of neutralizing antibodies against vector capsids that may prevent transduction of target cells or elicit adverse findings. We present safety findings from two 12-week studies in nonhuman primates (NHPs) with pre-existing or treatment-emergent antibodies. In the first study, NHPs with varying levels of naturally acquired anti-AAV5 antibodies were dosed with an AAV5-based vector encoding human factor VIII (hFVIII). In the second study, NHPs with no pre-existing anti-AAV antibodies were dosed with an AAV5-based vector carrying the beta subunit of choriogonadotropic hormone (bCG); this led to the induction of high-titer antibodies against the AAV5 capsid. Four weeks later, the same NHPs received an equivalent dose of an AAV5-based vector carrying human factor IX (hFIX). In both of these studies, the administration of vectors carrying hFVIII, bCG, and hFIX was well-tolerated in NHPs with no adverse clinical pathology or microscopic findings. These two studies demonstrate the safety of AAV-based vector administration in NHPs with either low-titer pre-existing anti-AAV5 antibodies or re-administration, even in the presence of high-titer antibodies.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"246-256"},"PeriodicalIF":1.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427091","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
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs. 微型猪自发性AA淀粉样变性的病理学特征。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2023-07-01 Epub Date: 2023-10-24 DOI: 10.1177/01926233231204019
Misaki Inoue, Shinya Miyazaki, Natsumi Kobayashi, Akihisa Kangawa, Tomoaki Murakami
{"title":"Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs.","authors":"Misaki Inoue, Shinya Miyazaki, Natsumi Kobayashi, Akihisa Kangawa, Tomoaki Murakami","doi":"10.1177/01926233231204019","DOIUrl":"10.1177/01926233231204019","url":null,"abstract":"<p><p>The minipig has been used as a non-rodent species in nonclinical toxicology studies, but little is known about amyloid A (AA) amyloidosis in this species. Among domestic pigs, reports of AA amyloidosis have been limited to animals with mutations in the N-terminal residue of serum AA (SAA), which is thought to be a primary etiological factor. In this study, we histologically examined 26 microminipigs aged 0.6 to 10 years and observed amyloid deposition in one 0.6-year-old and six 5-year-old or older microminipigs. The amyloid deposits were identified as AA based on mass spectrometry (MS) and immunohistochemistry (IHC). The 0.6-year-old microminipig showed severe deposition in the renal cortex and spleen, whereas 5-year-old or older animals had severe deposition in the renal medulla. MS and IHC detected serum amyloid P-component (SAP) in amyloid deposits in older animals but not in a 0.6-year-old animals. Based on the proteomic analysis and gene sequencing, amino acid mutations of SAA, previously found in domestic pigs, were not involved in the pathogenesis of AA amyloidosis in microminipigs. This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"257-263"},"PeriodicalIF":1.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692445","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
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