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Mesangial cell hypercellularity and iron accumulation in the kidney associated with administration of a sickle hemoglobin modulator in CD-1 mice. CD-1小鼠肾系膜细胞高细胞化和铁积累与镰状血红蛋白调节剂的施用有关。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-23 DOI: 10.1177/03009858241306400
Shambhunath Choudhary, Catherine Picut, Sarah R Vargas, Diana Otis, Timothy M Coskran, David Karanian, Jamie K DaSilva, Christopher Houle, Laurence O Whiteley

The kidney plays an important role in iron homeostasis and mesangial cells (MCs) are phagocytic cells important for glomerular homeostasis. Sickle hemoglobin (HbS) modulators are promising clinical candidates for treatment of sickle cell disease. Although they prevent disease pathophysiology of HbS polymerization and red blood cell (RBC) sickling by increasing hemoglobin oxygen affinity, higher oxygen affinity can also cause transient tissue hypoxia with compensatory increases in erythropoiesis and subsequent increases in RBC turnover. CD-1 mice treated with an HbS modulator for 2 weeks developed higher RBC mass, increased erythropoiesis, and, by 1 month, deposition of intracellular pigments in renal tubular and parietal epithelium. In addition, in mice treated for 26 weeks, pigment was observed in MCs, which was accompanied by glomerular cell aggregates (MC hypercellularity) and tubulo-interstitial inflammation. The pigment was confirmed by Perl's iron staining and transmission electron microscopy (TEM) to be iron-containing proteins. Glomerular cell aggregates were confirmed to be MCs by TEM, and Ki-67 immunolabeling suggested that MC hypercellularity was due to proliferation. Collectively, these findings, along with iron-containing proteins in livers and spleens, suggested that iron overload secondary to increased RBC turnover led to increased renal iron reabsorption. While both MC hypercellularity and tubulo-interstitial inflammation were thought to be responses to long-term accumulation of iron, the former was considered a homeostatic response to eliminate iron, and maintain glomerular structure and function, while the latter was more consistent with an iron-catalyzed oxidative stress response. To our knowledge, this is the first report of MC hypercellularity in a preclinical toxicity study.

肾脏在铁稳态中起重要作用,系膜细胞(MCs)是肾小球稳态中重要的吞噬细胞。镰状血红蛋白(HbS)调节剂是治疗镰状细胞病的有希望的临床候选药物。虽然它们通过增加血红蛋白氧亲和力来预防HbS聚合和红细胞(RBC)镰状细胞的疾病病理生理,但更高的氧亲和力也会引起短暂的组织缺氧,伴有红细胞生成的代偿性增加和随后的红细胞周转增加。用HbS调节剂治疗CD-1小鼠2周后,红细胞数量增加,红细胞生成增加,1个月后,肾小管和壁上皮细胞内色素沉积。此外,在小鼠治疗26周后,在MCs中观察到色素,并伴有肾小球细胞聚集(MC高细胞性)和小管间质炎症。该色素经珀尔氏铁染色和透射电镜(TEM)证实为含铁蛋白。透射电镜证实肾小球细胞聚集体为MCs, Ki-67免疫标记提示MCs高细胞化是由增殖引起的。总的来说,这些发现以及肝脏和脾脏中的含铁蛋白表明,继发于红细胞周转增加的铁过载导致肾铁重吸收增加。虽然MC高细胞性和小管间质性炎症都被认为是对铁的长期积累的反应,但前者被认为是一种消除铁、维持肾小球结构和功能的稳态反应,而后者更符合铁催化的氧化应激反应。据我们所知,这是临床前毒性研究中首次报道MC高细胞性。
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引用次数: 0
Response to "Letters or not, here we come! A communal perspective on credentials needed for a productive career in veterinary pathology". 对 "不管有没有文凭,我们都来了!兽医病理学领域富有成效的职业生涯所需证书的共同视角"。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-18 DOI: 10.1177/03009858241306413
Grant Maxie
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引用次数: 0
Three novel neoplasms in Nancy Ma's owl monkeys (Aotus nancymaae). 南希·马鸮猴的三种新肿瘤。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-18 DOI: 10.1177/03009858241300549
Rebecca L Bacon, Carolyn L Hodo, Stephanie J Buchl, Martha E Hensel

Neoplasms are only sporadically reported in New World primates and rarely in owl monkeys (Aotus spp.), specifically. Previous reports of neoplasms in owl monkeys are primarily restricted to lymphoma induced by Herpesvirus saimiri infection, although other tumors in the central nervous, genitourinary, gastrointestinal, and endocrine systems have been sporadically reported. Herein, we describe 3 previously unreported neoplasms in owl monkeys (Aotus nancymaae) including a pericardial mesothelioma in a 6-year-old male, a nephroblastoma in a 2-year-old male, and a cervical neoplasm with characteristics of an epithelioid trophoblastic tumor in a 4-year-old female, all occurring in the same closed breeding colony at a research facility in central Texas. Reporting of spontaneously occurring neoplasms in research colony populations is important for identifying potential animal models of human diseases and for improving colony management and species health.

肿瘤仅在新大陆灵长类动物中偶有报道,在鸮猴(Aotus spp.)中很少报道。尽管在中枢神经系统、泌尿生殖系统、胃肠道和内分泌系统中也有零星的肿瘤报道,但先前关于猫头鹰猴肿瘤的报道主要局限于猴疱疹病毒感染引起的淋巴瘤。在本文中,我们描述了3例以前未报道的猫头鹰猴肿瘤,包括一例6岁雄性的心包间皮瘤,一例2岁雄性的肾母细胞瘤,以及一例4岁雌性的具有上皮样滋养细胞肿瘤特征的宫颈肿瘤,所有这些肿瘤都发生在德克萨斯州中部一个研究机构的同一封闭繁殖群体中。在研究群体中报告自发发生的肿瘤对于确定人类疾病的潜在动物模型以及改善群体管理和物种健康具有重要意义。
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引用次数: 0
Neurology and comparative medicine influenced my career in neuropathology. 神经病学和比较医学影响了我的神经病理学生涯。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-18 DOI: 10.1177/03009858241303677
Brian A Summers
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引用次数: 0
Response to: Certifying "day one ready" pathologists: are we accomplishing our goals? 回应:认证 "第一天就绪 "的病理学家:我们的目标实现了吗?
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-16 DOI: 10.1177/03009858241303204
Lauri Diehl, Jerry Ritchey, Rachel Reams, Amy Durham, Tony Alves, Kevin Esch, Nicky Parry, Paige Carmichael, Tara Arndt, Alicia Olivier, Ryan Jennings, Shelley Burton
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引用次数: 0
Certifying "day one ready" pathologists: Are we accomplishing our goals? 认证“第一天准备就绪”的病理学家:我们是否完成了我们的目标?
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-16 DOI: 10.1177/03009858241302843
Mark R Ackermann, Dalen W Agnew, Linden E Craig, Taryn A Donovan, Jey W Koehler, Ingeborg M Langohr, Christiane V Löhr, Richard Luong, Emily Meseck, Patricia Pesavento, Brian F Porter, Simon L Priestnall, Daniel R Rissi, Duncan S Russell, Davis Seelig, Mee-Ja M Sula, Charles Wiedmeyer, Bruce H Williams, Andrew D Miller
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引用次数: 0
Infarctive encephalopathy in zoo-housed gibbons in North America. 北美动物园饲养的长臂猿的脑梗塞性脑病。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-12 DOI: 10.1177/03009858241302844
Mei Aoki Schultz, Josephine B Rose, Katherine Olstad, Johnny R Cross, Kali A Holder, Katharine L Hope, Beth Richards, Andrew D Miller

Progressive neurologic signs without a known underlying etiology have been observed in managed gibbon populations housed at institutions in North America. In 2018, the Gibbon Species Survival Plan initiated a veterinary survey to evaluate clinical histories among gibbons displaying neurologic signs. The clinical results of this survey as well as the results of a centralized histologic review of brain samples from 5 species of managed gibbons displaying neurologic signs are outlined here. Reported neurologic deficits in gibbons surveyed included tremors (12/12, 100%), ataxia/incoordination (11/12, 92%), fine motor skill deficits (11/12, 92%), weakness (10/12, 83%), and mentation deficits (7/12, 58%). Gross lesions were not identified in the brain. However, in affected animals, histology revealed infarctive lesions in the cerebrocortical (14/15, 93% of animals) and cerebellar (10/15, 67% of animals) gray/white matter. Lesions were absent in the thalamus, mesencephalon, and brainstem. Lesions were typified by areas of parenchymal loss, perivascular foamy macrophage accumulation, and extensive gliosis dominated by gemistocytic astrocytes. In all affected animals, vessels located in the center of the lesions had increased tortuosity with loss of medial distinction, variable medial hyperplasia, and multifocal medial vacuolation that was accentuated by Masson's trichrome staining. Thrombotic lesions were not identified, and amyloid was not identified by Congo red staining. Ionized calcium-binding adaptor molecule 1 (IBA1) immunohistochemistry revealed extensive macrophage infiltration, even in areas in which lesions were not identified on histologic examination. This study reveals a pattern of small-vessel disease among gibbons displaying neurologic signs, and the resulting clinical syndrome is here termed "gibbon infarctive encephalopathy."

进行性神经症状没有已知的潜在病因已观察到管理长臂猿种群安置在机构在北美。2018年,长臂猿物种生存计划启动了一项兽医调查,以评估出现神经症状的长臂猿的临床病史。本次调查的临床结果以及对5种显示神经系统症状的管理长臂猿脑样本的集中组织学检查结果在此概述。报告的长臂猿神经功能缺陷包括震颤(12/12,100%)、共济失调/不协调(11/12,92%)、精细运动技能缺陷(11/12,92%)、虚弱(10/12,83%)和精神缺陷(7/12,58%)。脑部未发现明显病变。然而,在受影响的动物中,组织学显示脑皮质(14/15,93%的动物)和小脑(10/15,67%的动物)灰质/白质有梗死灶。丘脑、中脑和脑干未见病变。病变的典型表现为实质丧失、血管周围泡沫状巨噬细胞积聚和以星形胶质细胞为主的广泛胶质瘤。在所有受影响的动物中,位于病变中心的血管扭曲度增加,内侧区分丧失,可变的内侧增生和多灶内侧空泡化,Masson三色染色强化了这一点。未发现血栓性病变,刚果红染色未发现淀粉样蛋白。离子钙结合接头分子1 (IBA1)免疫组织化学显示广泛的巨噬细胞浸润,甚至在组织学检查未发现病变的区域。本研究揭示了长臂猿表现出神经系统体征的小血管疾病模式,由此产生的临床综合征在这里被称为“长臂猿梗死性脑病”。
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引用次数: 0
High mortality associated with avian reoviral hepatitis in young quail (Colinus virginianus). 幼鹌鹑(Colinus virginianus)与禽呼肠孤病毒肝炎相关的高死亡率。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-12 DOI: 10.1177/03009858241302842
Panchan Sitthicharoenchai, Jianqiang Zhang, Liying Tian, Judith Stasko, Amro Hashish, Cheng-Shun Hsueh, Yuko Sato, Benjamin Hause, Mohamed El-Gazzar

High mortality in bobwhite quail chicks (Colinus virginianus) (35%-85%) was reported from a grower flock in Iowa during July and August of 2022. Two diagnostic submissions of dead, 3-day-old quail chicks were received. Postmortem examination revealed multifocal, pinpoint, pale tan foci in the liver of all birds. Histologic examination revealed moderate to severe, acute, multifocal, random necrotizing hepatitis with multinucleated cells and dystrophic mineralization. Metagenomic sequencing of liver detected orthoreovirus. A high level of avian reovirus (ARV) RNA was identified by real-time reverse transcriptase-PCR. ARV was successfully isolated from liver and lung on the Leghorn male hepatoma cell line. In addition, electron microscopy revealed orthoreovirus viral particles and virus factories in the formalin-fixed livers and viral-infected cell culture. This case highlights ARV as a potential cause of hepatitis in quail chicks and should be considered in the differential diagnosis.

据报道,2022年7月至8月,在爱荷华州的一个养殖群中,山鹑雏鸟(Colinus virginianus)的死亡率很高(35%-85%)。收到两份死亡的3日龄鹌鹑雏鸟的诊断报告。死后检查发现所有鸟类肝脏有多灶性、针状、浅褐色灶。组织学检查显示中度至重度急性多灶性随机坏死性肝炎伴多核细胞及营养不良矿化。肝检出正呼肠孤病毒的宏基因组测序。实时逆转录- pcr技术鉴定出高水平禽呼肠孤病毒(ARV) RNA。成功地从Leghorn雄性肝癌细胞株的肝和肺中分离到ARV。此外,电子显微镜还发现在福尔马林固定的肝脏和病毒感染的细胞培养物中存在正呼肠孤病毒颗粒和病毒工厂。本病例强调ARV是鹌鹑雏鸟肝炎的潜在病因,应在鉴别诊断中予以考虑。
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引用次数: 0
Colocalization of hedgehog arterivirus 1 (HhAV-1) and histologic lesions in the European hedgehog (Erinaceus europaeus) with neurological disease. 刺猬动脉病毒1 (HhAV-1)在神经系统疾病欧洲刺猬(Erinaceus europaeus)中的共定位和组织学病变
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-12 DOI: 10.1177/03009858241300553
Fabian Z X Lean, Mark F Stidworthy, Akbar Dastjerdi, Tim Partridge, Stephen Smith, Julie Gough, Alejandro Núñez, Becki Lawson, Katharina Seilern-Macpherson

The European hedgehog (Erinaceus europaeus) is a protected species of conservation concern in the UK. In recent years, there have been multiple incidents of fatal encephalitis in captive hedgehogs in wildlife rescue centers associated with the molecular detection of a hedgehog arterivirus (HhAV-1). However, it remains unclear whether the virus is the causative agent of the central nervous system (CNS) lesions. In a retrospective investigation using postmortem material from 7 captive hedgehogs with neurological disease, and a single hedgehog with previously identified meningoencephalitis, histologic examination was conducted in tandem with viral RNA in situ hybridization (ISH) to appraise tissue distribution of HhAV-1 and the colocalization with histologic lesions. ISH revealed multicellular tropism of HhAV-1 involving monocyte-macrophage and vascular endothelial cells, with viral RNA detected in multiple organs, likely due to endotheliotropism and viremia. In the CNS, encephalomyelitis was mild whilst viral RNA was abundant and widely distributed, particularly in the microglial population and localized to areas with glial nodules. Splenic lymphoid depletion was generally mild but was moderate to severe in 2 septicemic animals. Brain samples from 13 control hedgehogs, found dead in the wild due to predation/trauma, were also screened for HhAV-1, of which 8 tested positive by real-time reverse transcription polymerase chain reaction (RT-PCR) with a low viral load. No CNS lesions or ISH labeling was observed in 2 of these control hedgehogs that could be examined histologically. Combined, these findings indicate that HhAV-1 infections in captive hedgehogs in English wildlife rescue centers may be associated with histopathologic alterations and clinical neurological disease.

欧洲刺猬(Erinaceus europaeus)是英国受保护的物种。近年来,野生动物救援中心圈养刺猬发生多起与刺猬动脉病毒(HhAV-1)分子检测相关的致死性脑炎。然而,尚不清楚该病毒是否是中枢神经系统(CNS)病变的病原体。在一项回顾性研究中,研究人员使用了7只患有神经系统疾病的圈养刺猬和1只先前确诊为脑膜脑炎的刺猬的死后材料,并结合病毒RNA原位杂交(ISH)进行了组织学检查,以评估HhAV-1的组织分布和与组织学病变的共定位。ISH显示HhAV-1具有多细胞性,涉及单核-巨噬细胞和血管内皮细胞,在多个器官中检测到病毒RNA,可能是由于嗜内皮性和病毒血症。在中枢神经系统,脑脊髓炎是轻微的,而病毒RNA丰富且广泛分布,特别是在小胶质细胞群中,并局限于胶质结节区域。脾淋巴细胞耗竭一般为轻度,2只败血症动物为中度至重度。对13只因捕食/创伤在野外死亡的对照组刺猬的脑样本进行了HhAV-1筛查,其中8只通过低病毒载量的实时逆转录聚合酶链反应(RT-PCR)检测呈阳性。其中2只对照刺猬未见CNS病变或ISH标记,可进行组织学检查。综上所述,这些发现表明,在英国野生动物救援中心圈养的刺猬中,HhAV-1感染可能与组织病理学改变和临床神经系统疾病有关。
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引用次数: 0
Tumor-infiltrating lymphocytes vary in different canine soft tissue sarcoma histological types. 不同犬软组织肉瘤组织学类型的肿瘤浸润淋巴细胞不同。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-12-09 DOI: 10.1177/03009858241300556
Giancarlo Avallone, Elena Brigandì, Chiara Tugnoli, Antonella Rigillo, Barbara Bacci, Paola Roccabianca

Soft tissue sarcomas (STSs) are conventionally viewed as poorly immunogenic tumors; however, some human STSs have recently been reported to elicit an immune response, thus representing potential candidates for immunotherapy. Data regarding immune cell infiltrates in canine STSs are limited and reported without tumor-type stratification. The aim of this study was to retrospectively assess tumor-infiltrating lymphocytes (TILs) in canine STSs of 5 different histotypes. Eighty-seven canine STSs were collected: 22 perivascular wall tumors (PWTs), 19 liposarcomas, 17 fibrosarcomas, 16 myxosarcomas, and 13 leiomyosarcomas. The tumors were graded and immunolabeled for CD3, CD20, and FoxP3, and slides were scanned. T-cell, B-cell, Treg, and total TIL densities were quantified with QuPath software and expressed as cells/mm2. The B/T-cells ratio and Treg/T-cell proportions were calculated. Total TIL densities were higher in PWTs and myxosarcomas (median = 225 and 303, respectively). PWTs had higher T-cell density but lower Treg proportion (median = 152 and 7.6% respectively). Myxosarcomas had higher Treg densities and B/T-cell ratios (median = 24.4 and 1.57, respectively). No association with grade was found among STSs as a group. In myxosarcomas, higher grade was significantly associated with higher total TILs, and CD20+ and FoxP3+ cell densities (p < .05). The results suggest that PWTs and myxosarcomas may represent the most immunogenic STS types. Myxosarcomas elicit a B-cell and Treg-rich immune response; PWTs stimulate a T-cell-rich and Treg-poor reaction. The immune system response may contribute to the more aggressive behavior of myxosarcomas and the more indolent course of PWTs.

软组织肉瘤(STSs)通常被认为是免疫原性差的肿瘤;然而,最近有报道称,一些人类性传播感染引起免疫反应,因此代表了免疫治疗的潜在候选者。关于犬STSs免疫细胞浸润的数据有限,并且没有肿瘤类型分层的报道。本研究的目的是回顾性评估5种不同组织型犬STSs的肿瘤浸润淋巴细胞(til)。共收集犬STSs 87例,其中血管周围壁瘤22例,脂肪肉瘤19例,纤维肉瘤17例,黏液肉瘤16例,平滑肌肉瘤13例。肿瘤分级并免疫标记CD3、CD20和FoxP3,扫描载玻片。使用QuPath软件定量t细胞、b细胞、Treg和总TIL密度,并以细胞/mm2表示。计算B/ t细胞比例和Treg/ t细胞比例。总TIL密度在PWTs和黏液肉瘤中较高(中位数分别为225和303)。PWTs的t细胞密度较高,Treg比例较低(中位数分别为152和7.6%)。黏液肉瘤具有较高的Treg密度和B/ t细胞比值(中位数分别为24.4和1.57)。作为一个群体,STSs与年级没有关联。黏液肉瘤中,分级越高,总TILs、CD20+和FoxP3+细胞密度越高(p < 0.05)。结果表明,PWTs和黏液肉瘤可能是最具免疫原性的STS类型。黏液肉瘤引起b细胞和富含treg的免疫反应;pwt刺激t细胞丰富和treg贫乏的反应。免疫系统反应可能导致黏液肉瘤更具侵袭性的行为和PWTs更惰性的病程。
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引用次数: 0
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Veterinary Pathology
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