Yumei Cao , Lei Qiao , Yingying Song , Yuanye Yan , Yewen Ni , Huiyu Xi , Jiayu Chen , Suyan Li , Haiyang Liu
{"title":"Caspase-1 Inhibition Ameliorates Photoreceptor Damage Following Retinal Detachment by Inhibiting Microglial Pyroptosis","authors":"Yumei Cao , Lei Qiao , Yingying Song , Yuanye Yan , Yewen Ni , Huiyu Xi , Jiayu Chen , Suyan Li , Haiyang Liu","doi":"10.1016/j.ajpath.2024.06.009","DOIUrl":"10.1016/j.ajpath.2024.06.009","url":null,"abstract":"<div><div>Retinal detachment (RD) is a sight-threatening condition that occurs in several retinal diseases. Microglia that reside in retina are activated after RD and play a role in the death of photoreceptor cells. The involvement of microglial pyroptosis in the early pathological process of RD is still unclear. VX-765, an inhibitor of caspase-1, may exert neuroprotective effects by targeting microglial pyroptosis in nervous system disease; however, whether it plays a role in RD is uncertain. This study detected and localized pyroptosis to specific cells by immunofluorescence co-staining and flow cytometry in rat RD models. The majority of gasdermin D N-terminal (GSDMD-N)-positive cells exhibited IBA1-positive or P2RY12-positive microglia in the early stage of RD, indicating the pyroptosis of microglia. Administration of VX-765 shifted the microglia phenotype from M1 to M2, inhibited microglial migration toward the outer nuclear layer (ONL) post-RD, and most importantly, inhibited microglial pyroptosis. The thickness of ONL increased with VX-765 administration, and the photoreceptors were more structured and orderly under hematoxylin and eosin staining and transmission electron microscopy, revealing the protective effects of VX-765 on photoreceptors. Overall, this study demonstrated that inflammation induced by pyroptosis of microglia is the early pathological process of RD. VX-765 may serve as a candidate therapeutic approach for the treatment of RD by targeting microglia.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 10","pages":"Pages 1924-1937"},"PeriodicalIF":4.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002426/pdfft?md5=b47bc1de32cf108f260e7adf3d118fb0&pid=1-s2.0-S0002944024002426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sourabh Soni , Laura Antonescu , Kaylin Ro , Jeffrey C. Horowitz , Yohannes A. Mebratu , Richard S. Nho
{"title":"Influenza, SARS-CoV-2, and Their Impact on Chronic Lung Diseases and Fibrosis","authors":"Sourabh Soni , Laura Antonescu , Kaylin Ro , Jeffrey C. Horowitz , Yohannes A. Mebratu , Richard S. Nho","doi":"10.1016/j.ajpath.2024.06.004","DOIUrl":"10.1016/j.ajpath.2024.06.004","url":null,"abstract":"<div><div>Respiratory tract infections represent a significant global public health concern, disproportionately affecting vulnerable populations such as children, the elderly, and immunocompromised individuals. RNA viruses, particularly influenza viruses and coronaviruses, significantly contribute to respiratory illnesses, especially in immunosuppressed and elderly individuals. Influenza A viruses (IAVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to pose global health threats due to their capacity to cause annual epidemics, with profound implications for public health. In addition, the increase in global life expectancy is influencing the dynamics and outcomes of respiratory viral infections. Understanding the molecular mechanisms by which IAVs and SARS-CoV-2 contribute to lung disease progression is therefore crucial. The aim of this review is to comprehensively explore the impact of IAVs and SARS-CoV-2 on chronic lung diseases, with a specific focus on pulmonary fibrosis in the elderly. It also outlines potential preventive and therapeutic strategies and suggests directions for future research.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 10","pages":"Pages 1807-1822"},"PeriodicalIF":4.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002359/pdfft?md5=61c329fee97e91f660fccea1512054cc&pid=1-s2.0-S0002944024002359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Areej Alsaafin, Peyman Nejat, Abubakr Shafique, Jibran Khan, Saghir Alfasly, Ghazal Alabtah, Hamid R. Tizhoosh
{"title":"Sequential Patching Lattice for Image Classification and Enquiry","authors":"Areej Alsaafin, Peyman Nejat, Abubakr Shafique, Jibran Khan, Saghir Alfasly, Ghazal Alabtah, Hamid R. Tizhoosh","doi":"10.1016/j.ajpath.2024.06.007","DOIUrl":"10.1016/j.ajpath.2024.06.007","url":null,"abstract":"<div><div>Digital pathology and the integration of artificial intelligence (AI) models have revolutionized histopathology, opening new opportunities. With the increasing availability of whole-slide images (WSIs), demand is growing for efficient retrieval, processing, and analysis of relevant images from vast biomedical archives. However, processing WSIs presents challenges due to their large size and content complexity. Full computer digestion of WSIs is impractical, and processing all patches individually is prohibitively expensive. In this article, we propose an unsupervised patching algorithm, Sequential Patching Lattice for Image Classification and Enquiry (SPLICE). This novel approach condenses a histopathology WSI into a compact set of representative patches, forming a collage of WSI while minimizing redundancy. SPLICE prioritizes patch quality and uniqueness by sequentially analyzing a WSI and selecting nonredundant representative features. In search and match applications, SPLICE showed improved accuracy, reduced computation time, and storage requirements compared with existing state-of-the-art methods. As an unsupervised method, SPLICE effectively reduced storage requirements for representing tissue images by 50%. This reduction can enable numerous algorithms in computational pathology to operate much more efficiently, paving the way for accelerated adoption of digital pathology.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 10","pages":"Pages 1898-1912"},"PeriodicalIF":4.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002384/pdfft?md5=85185165c783af61b921a36727aebaa6&pid=1-s2.0-S0002944024002384-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khun Zaw Latt , Teruhiko Yoshida , Shashi Shrivastav , Amin Abedini , Jeff M. Reece , Zeguo Sun , Hewang Lee , Koji Okamoto , Pradeep Dagur , Yu Ishimoto , Jurgen Heymann , Yongmei Zhao , Joon-Yong Chung , Stephen Hewitt , Pedro A. Jose , Kyung Lee , John Cijiang He , Cheryl A. Winkler , Mark A. Knepper , Tomoshige Kino , Jeffrey B. Kopp
{"title":"Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice","authors":"Khun Zaw Latt , Teruhiko Yoshida , Shashi Shrivastav , Amin Abedini , Jeff M. Reece , Zeguo Sun , Hewang Lee , Koji Okamoto , Pradeep Dagur , Yu Ishimoto , Jurgen Heymann , Yongmei Zhao , Joon-Yong Chung , Stephen Hewitt , Pedro A. Jose , Kyung Lee , John Cijiang He , Cheryl A. Winkler , Mark A. Knepper , Tomoshige Kino , Jeffrey B. Kopp","doi":"10.1016/j.ajpath.2024.06.006","DOIUrl":"10.1016/j.ajpath.2024.06.006","url":null,"abstract":"<div><div>Although hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the <em>Slc12a3</em> gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice. The percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (<em>P</em> < 0.05); in Vpr Tg mice, <em>Slc12a3</em> expression was not significantly different in DCT cells. The <em>Pvalb</em><sup>+</sup> DCT1 subcluster had fewer cells in Vpr Tg mice compared with those in WT mice (<em>P</em> < 0.01). Immunohistochemistry revealed fewer <em>Slc12a3</em><sup>+</sup> <em>Pvalb</em><sup><em>+</em></sup> DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT samples in the DCT cluster showed down-regulation of the <em>Ier3</em> gene, which is an inhibitor of apoptosis. The <em>in vitro</em> knockdown of <em>Ier3</em> by siRNA transfection induced apoptosis in mouse DCT cells. These observations suggest that the salt-wasting effect of Vpr in Vpr Tg mice is likely mediated by <em>Ier3</em> down-regulation in DCT1 cells and loss of <em>Slc12a3</em><sup>+</sup> <em>Pvalb</em><sup>+</sup> DCT1 segments.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 10","pages":"Pages 1844-1856"},"PeriodicalIF":4.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002372/pdfft?md5=a8ea8d28868ba18519b4cecc36a25926&pid=1-s2.0-S0002944024002372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Geister , Dalton Ard , Heer Patel , Alyssa Findley , Godfrey DeSouza , Lyndsay Martin , Henry Knox , Natasha Gavara , Aurelia Lugea , Maria Eugenia Sabbatini
{"title":"The Role of Twist1 in Chronic Pancreatitis–Associated Pancreatic Stellate Cells","authors":"Emma Geister , Dalton Ard , Heer Patel , Alyssa Findley , Godfrey DeSouza , Lyndsay Martin , Henry Knox , Natasha Gavara , Aurelia Lugea , Maria Eugenia Sabbatini","doi":"10.1016/j.ajpath.2024.06.003","DOIUrl":"10.1016/j.ajpath.2024.06.003","url":null,"abstract":"<div><div>In healthy pancreas, pancreatic stellate cells (PaSCs) synthesize the basement membrane, which is mainly composed of type IV collagen and laminin. In chronic pancreatitis (CP), PaSCs are responsible for the production of a rigid extracellular matrix (ECM) that is mainly composed of fibronectin and type I/III collagen. Reactive oxygen species evoke the formation of the rigid ECM by PaSCs. One source of reactive oxygen species is NADPH oxidase (Nox) enzymes. Nox1 up-regulates the expression of Twist1 and matrix metalloproteinase-9 (MMP-9) in PaSCs from mice with CP. This study determined the functional relationship between Twist1 and MMP-9, and other PaSC-produced proteins, and the extent to which Twist1 regulates digestion of ECM proteins in CP. Twist1 induced the expression of MMP-9 in mouse PaSCs. The action of Twist1 was not selective to MMP-9 because Twist1 induced the expression of types I and IV collagen, fibronectin, transforming growth factor, and α-smooth muscle actin. Luciferase assay indicated that Twist1 in human primary PaSCs increased the expression of MMP-9 at the transcriptional level in an NF-κB dependent manner. The digestion of type I/III collagen by MMP-9 secreted by PaSCs from mice with CP depended on Twist1. Thus, Twist1 in PaSCs from mice with CP induced rigid ECM production and MMP-9 transcription in an NF-κB–dependent mechanism that selectively displayed proteolytic activity toward type I/III collagen.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 10","pages":"Pages 1879-1897"},"PeriodicalIF":4.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"This Month in AJP","authors":"","doi":"10.1016/j.ajpath.2024.07.001","DOIUrl":"10.1016/j.ajpath.2024.07.001","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Page 1607"},"PeriodicalIF":4.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002335/pdfft?md5=1b52ea14a6b2b8c06ac4821f96abdafd&pid=1-s2.0-S0002944024002335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Multiscale Connected UNet for the Segmentation of Lung Cancer Cells in Pathology Sections Stained Using Rapid On-Site Cytopathological Evaluation","authors":"","doi":"10.1016/j.ajpath.2024.05.011","DOIUrl":"10.1016/j.ajpath.2024.05.011","url":null,"abstract":"<div><p>Lung cancer is an increasingly serious health problem worldwide, and early detection and diagnosis are crucial for successful treatment. With the development of artificial intelligence and the growth of data volume, machine learning techniques can play a significant role in improving the accuracy of early detection in lung cancer. This study proposes a deep learning-based segmentation algorithm for rapid on-site cytopathological evaluation (ROSE) to enhance the diagnostic efficiency of endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA) during surgery. By utilizing the CUNet3+ network model, cell clusters, including cancer cell clusters, can be accurately segmented in ROSE-stained pathological sections. The model demonstrated high accuracy, with an F1-score of 0.9604, recall of 0.9609, precision of 0.9654, and accuracy of 0.9834 on the internal testing data set. It also achieved an area under the receiver-operating characteristic curve of 0.9972 for cancer identification. The proposed algorithm saved time for on-site diagnosis, improved EBUS-TBNA efficiency, and outperformed classical segmentation algorithms in accurately identifying lung cancer cell clusters in ROSE-stained images. It effectively reduced over-segmentation, decreased network parameters, and enhanced computational efficiency, making it suitable for real-time patient evaluation during surgical procedures.</p></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Pages 1712-1723"},"PeriodicalIF":4.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Macrophage Extracellular Traps Suppress Particulate Matter–Induced Airway Inflammation","authors":"","doi":"10.1016/j.ajpath.2024.05.008","DOIUrl":"10.1016/j.ajpath.2024.05.008","url":null,"abstract":"<div><p>Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. The current study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both <em>in vitro</em> and <em>in vivo</em>. This effect was dependent on peptidylarginine deiminase type 4 (PAD4)–mediated histone citrullination. Additionally, reactive oxygen species were involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.</p></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Pages 1622-1635"},"PeriodicalIF":4.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bifidobacterium bifidum Strain BB1 Inhibits Tumor Necrosis Factor-α–Induced Increase in Intestinal Epithelial Tight Junction Permeability via Toll-Like Receptor-2/Toll-Like Receptor-6 Receptor Complex–Dependent Stimulation of Peroxisome Proliferator-Activated Receptor γ and Suppression of NF-κB p65","authors":"","doi":"10.1016/j.ajpath.2024.05.012","DOIUrl":"10.1016/j.ajpath.2024.05.012","url":null,"abstract":"<div><p><em>Bifidobacterium bifidum</em> strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α–induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α–induced increase in intestinal TJ permeability by interfering with TNF-α–induced enterocyte NF-κB p50/p65 and myosin light chain kinase (<em>MLCK</em>) gene activation. The BB1 protective effect against the TNF-α–induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α–induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, <em>MLCK</em> gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α–induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α–induced increase in intestinal epithelial TJ permeability via a PPAR-γ–dependent inhibition of NF-κB p50/p65 and <em>MLCK</em> gene activation.</p></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Pages 1664-1683"},"PeriodicalIF":4.7,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002116/pdfft?md5=7b46cac98828e94354d34b70fe195cd8&pid=1-s2.0-S0002944024002116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141400602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Local Tetanus Begins with a Neuromuscular Junction Paralysis around the Site of Tetanus Neurotoxin Release due to Cleavage of the Vesicle-Associated Membrane Protein","authors":"","doi":"10.1016/j.ajpath.2024.05.009","DOIUrl":"10.1016/j.ajpath.2024.05.009","url":null,"abstract":"<div><p>Local tetanus develops when limited amounts of tetanus neurotoxin (TeNT) are released by <em>Clostridium tetani</em> generated from spores inside a necrotic wound. Within days, a spastic paralysis restricted to the muscles of the affected anatomical area develops. This paralysis follows the retrograde transport of TeNT inside the axons of motoneurons and its uptake by inhibitory interneurons with cleavage of a vesicle-associated membrane protein required for neurotransmitter release. Consequently, incontrollable excitation of motoneurons causes contractures of innervated muscles and leads to local spastic paralysis. Here, the initial events occurring close to the site of TeNT release were investigated in a mouse model of local tetanus. A peripheral flaccid paralysis was found to occur, before or concurrent to the spastic paralysis. At variance from the confined TeNT proteolytic activity taking place within motor neuron terminals, central protein cleavage was detected within inhibitory interneurons controlling motor neuron efferents innervating muscle groups distant from the site of TeNT release. These results indicate peripheral activity of TeNT in tetanus and explains why the spastic paralysis observed in local tetanus, although confined to single limbs, generally affects multiple muscles. The initial TeNT neuroparalytic activity can be detected by measuring the compound muscle action potential, providing a very early diagnosis and therapy, thus preventing the ensuing life-threatening generalized tetanus.</p></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Pages 1752-1763"},"PeriodicalIF":4.7,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}