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A Little Help From the Follicles: Understanding the Germinal Center Response to Human Immunodeficiency Virus 1 Infection and Prophylactic Vaccines. 卵泡的一点帮助:了解人类免疫缺陷病毒1型感染和预防性疫苗的生殖中心反应。
Q3 Medicine Pub Date : 2017-03-30 eCollection Date: 2017-01-01 DOI: 10.1177/1179555717695548
Ebony N Gary, Michele A Kutzler

Human immunodeficiency virus 1 (HIV-1) is the causative agent of AIDS. There are currently more than 35 million people living with HIV infection worldwide, and more than 2 million new infections occur each year. The global pandemic caused by HIV-1 is the subject of numerous research projects, with the development of a prophylactic vaccine and a therapeutic cure being the ultimate goals. The classic paradigms of vaccinology have proven incapable of producing a viable vaccine due to the complexity of the virus' replication cycle, its genetic diversity, and a lack of understanding of the immune correlates of protection. Here, we briefly discuss recent vaccine approaches and the immune correlates of protection from HIV-1 infection with a focus on the role of the germinal center as a reservoir of replication-competent virus and its role in the development of broadly neutralizing antibodies in response to vaccination.

人类免疫缺陷病毒1型(HIV-1)是艾滋病的病原体。目前,全世界有3500多万艾滋病毒感染者,每年新增感染人数超过200万。HIV-1引起的全球大流行是许多研究项目的主题,最终目标是开发预防性疫苗和治疗性疗法。由于病毒复制周期的复杂性、遗传多样性以及对保护的免疫相关性缺乏了解,疫苗学的经典范式已被证明无法生产出可行的疫苗。在这里,我们简要讨论了最近的疫苗方法和保护免受HIV-1感染的免疫相关性,重点讨论了生发中心作为复制能力病毒库的作用及其在疫苗接种后产生广泛中和抗体中的作用。
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引用次数: 1
cAMP Signaling Enhances HIV-1 Long Terminal Repeat (LTR)-directed Transcription and Viral Replication in Bone Marrow Progenitor Cells. cAMP 信号增强骨髓祖细胞中 HIV-1 长末端重复 (LTR) 引导的转录和病毒复制。
Q3 Medicine Pub Date : 2017-03-10 eCollection Date: 2017-01-01 DOI: 10.1177/1179555717694535
Anupam Banerjee, Luna Li, Vanessa Pirrone, Fred C Krebs, Brian Wigdahl, Michael R Nonnemacher

CD34+ hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter activity. Studies also implicated the protein kinase A (PKA) pathway and the downstream transcription factor CREB-1 in interfacing with cAMP response elements located in the CXCR4 and viral promoter. These observations suggest that the cAMP signaling pathway may serve as a regulator of CXCR4 levels and concomitantly of HIV-1 replication in bone marrow (BM) progenitor cells.

CD34+ 造血祖细胞已被证明易受 HIV-1 感染,这可能是由于 HIV-1 进入的核心受体 CXCR4 的低水平表达所致。鉴于这些观察结果,我们在细胞系模型(TF-1)中探讨了福斯可林对细胞表面 CXCR4 表达的影响。福斯可林通过腺苷酸环化酶(AC)使细胞内环磷酸腺苷(cAMP)升高,导致 CXCR4 转录上调,同时增加了利用 CXCR4 的 HIV-1 株 IIIB 的复制。瞬时表达分析也表明,CXCR4、CCR5 和 CXCR4/CCR5-utilizing HIV-1(分别为 LAI、YU2 和 89.6)启动子活性增加。研究还表明,蛋白激酶 A(PKA)通路和下游转录因子 CREB-1 与位于 CXCR4 和病毒启动子中的 cAMP 反应元件相互作用。这些观察结果表明,cAMP 信号通路可能是 CXCR4 水平的调节器,同时也是骨髓(BM)祖细胞中 HIV-1 复制的调节器。
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引用次数: 0
Hanging Fatalities in Central Bangkok, Thailand: A 13-Year Retrospective Study. 泰国曼谷中部的上吊死亡率:一项13年的回顾性研究。
Q3 Medicine Pub Date : 2017-02-23 eCollection Date: 2017-01-01 DOI: 10.1177/1179555717692545
Nattapong Tulapunt, Swarin Phanchan, Vichan Peonim

Hanging is violent asphyxial death. The objective of this study is to assess the data of hanging cases. A descriptive-retrospective study was conducted. We studied 244 hanging cases autopsied in Forensic Division, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, between January 2001 and December 2013. The study included 197 men (80.7%) and 47 women (19.2%). Their age ranged from 14 to 93 years. Most of these cases were incomplete hanging (83.6%). Features of hanging victims, such as tongue protrusion; congestion of face; petechial hemorrhage of face, conjunctiva, and internal organs; and neck injuries, significantly correlated with complete hanging. The predominant occupation of hanging victims was in the service industry (63.1%). Suicides usually occurred in private homes or apartments (84.8%). A suicide note was found in 6.1% of cases. The most common ligature material used was nylon rope, found in 61.1% of cases. The most underlying diseases of the victims in hanging cases were tuberculosis and human immunodeficiency virus infection, 9 cases each. Blood ethanol levels of 29 cases (11.8%) were detected to be higher than 150 mg%. Methamphetamine and benzodiazepine were detected in 5.3% and 3.3% of cases, respectively. This study provides comprehensive baseline data of hanging cases in central Bangkok.

上吊是暴力窒息死亡。本研究的目的是评估上吊案件的数据。采用描述性回顾性研究。我们研究了2001年1月至2013年12月期间在泰国曼谷玛希隆大学医学院Ramathibodi医院病理学系法医部尸检的244例上吊病例。该研究包括197名男性(80.7%)和47名女性(19.2%)。他们的年龄从14岁到93岁不等。不完全上吊占绝大多数(83.6%)。上吊受害者的特征,比如舌头突出;面部充血;面部、结膜及内脏点状出血;颈部损伤,与完全上吊明显相关。绞刑受害者的主要职业是服务业(63.1%)。自杀通常发生在私人住宅或公寓(84.8%)。在6.1%的案件中发现了遗书。最常用的结扎材料是尼龙绳,占61.1%。绞刑案件中受害者的主要疾病是肺结核和人类免疫缺陷病毒感染,各有9例。29例(11.8%)血乙醇浓度高于150mg %。甲基苯丙胺和苯二氮卓的检出率分别为5.3%和3.3%。本研究提供了曼谷市中心上吊案件的综合基线数据。
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引用次数: 12
Primary Melanotic Paraganglioma of Thyroid Gland: Report of a Rare Case With Clinicopathologic and Immunohistochemical Analysis and a Literature Review. 原发性甲状腺黑色素副神经节瘤:罕见临床病理及免疫组化分析1例并文献复习。
Q3 Medicine Pub Date : 2017-02-22 eCollection Date: 2017-01-01 DOI: 10.1177/1179555716684670
Yan-Jun Dong, Zhi-Wen Zhang, Zhen Wang, Xin-Ying Wang, Zhi-Zhen Tian, Xiang-Sheng Zhang

Background: Pigmented paraganglioma is a special type of paraganglioma, and it is rare in the thyroid.

Case presentation: We report a case of a 41-year-old woman who had complained of a mass in the thyroid gland. Histology revealed tumor cells arranged in a nest-like or organoid pattern, separated by delicate fibrovascular septa. Two distinct components were observed. In the first, which constituted the majority of the tumor cells, no pigments were observed. In the second, a few cells with pigment showed intercellular substance, but the structure was unclear. Using immunohistochemistry, cells in the first component were confirmed to be diffuse strong positive for synaptophysin, but negative for chromogranin A, pan-cytokeratin, calcitonin, and thyroglobulin. About 1% of tumor cells were stained by Ki-67. In the margins of the tumor, a few cells were observed to be positive for HMB-45 and Melan A after bleaching by oxalic acid. The stromal cells were positive for S-100. Using electron microscopy, a few cells containing many round melanin bodies with greater electron density granules of nonuniform size were observed. The diagnosis of primary melanotic paraganglioma of the thyroid gland was made.

Conclusion: Primary melanotic paraganglioma of the thyroid gland is a rare, low malignant potential tumor. To the best of our knowledge, this is the first case described.

背景:色素副神经节瘤是一种特殊类型的副神经节瘤,在甲状腺少见。病例介绍:我们报告一例41岁的妇女谁曾抱怨肿块在甲状腺。组织学显示肿瘤细胞呈巢状或类器官排列,由精细的纤维血管间隔隔开。观察到两种不同的成分。在占肿瘤细胞大多数的第一组中,未观察到色素。二是少量有色素的细胞可见细胞间物质,但结构不清楚。免疫组织化学证实,第一种成分的细胞突触素呈弥漫性强阳性,而嗜铬粒蛋白A、泛细胞角蛋白、降钙素和甲状腺球蛋白呈阴性。约1%的肿瘤细胞被Ki-67染色。肿瘤边缘部分细胞经草酸漂白后,HMB-45和黑色素a呈阳性。基质细胞S-100阳性。电镜观察到少数细胞含有许多圆形黑色素体,电子密度较大,大小不均匀。诊断为原发性甲状腺黑色素副神经节瘤。结论:原发性甲状腺黑色素副神经节瘤是一种罕见的低度恶性肿瘤。据我们所知,这是第一例被描述的病例。
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引用次数: 4
Phyllodes Tumor in a Lactating Breast. 哺乳期乳腺叶状瘤。
Q3 Medicine Pub Date : 2016-04-06 eCollection Date: 2016-01-01 DOI: 10.4137/CPath.S38476
Sudha S Murthy, K V V N Raju, Haripreetha G Nair

Phyllodes tumor is attributed to a small fraction of primary tumors of the breast. Such tumors occur rarely in pregnancy and lactation. We report a case of a 25-year-old lactating mother presenting with a lump in the left breast. Core needle biopsy was opined as phyllodes tumor with lactational changes, and subsequent wide local excision confirmed the diagnosis of benign phyllodes tumor with lactational changes. The characteristic gross and microscopic findings of a well-circumscribed lesion with leaf-like fibroepithelial growth pattern and typical nonuniform or diffuse stromal proliferation with periductal accentuation even in the absence of mitotic figures can help clinch the diagnosis. Benign phyllodes is known for its recurrence and requires wide excision and close follow-up. It is vital to identify these lesions even on limited biopsies as therapeutic options differ. This case is presented for its rarity and the diagnostic challenge it poses in limited biopsy.

叶状瘤被认为是乳腺原发肿瘤的一小部分。这种肿瘤很少发生在妊娠期和哺乳期。我们报告一个25岁的哺乳期母亲在左乳房出现肿块的病例。核心穿刺活检认为是乳腺变化的叶状瘤,随后广泛局部切除证实为乳腺变化的良性叶状瘤。典型的大体和显微镜检查结果显示,病灶边界清晰,叶状纤维上皮生长模式,典型的不均匀或弥漫性间质增生伴导管周围强化,即使没有有丝分裂象,也有助于确定诊断。良性叶状瘤以其复发而闻名,需要广泛切除和密切随访。即使在有限的活组织检查中识别这些病变也是至关重要的,因为治疗方案不同。本病例因其罕见性和在有限活检中提出的诊断挑战而被提出。
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引用次数: 9
A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses 以实性甲状腺及颈侧肿物为表现之第三/第四鳃袋异常1例
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.4137/CPath.S31734
Magda H. A. Nasreldin, E. Ibrahim, Somaia A. Saad El-Din
Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations.
鳃囊性异常可由第一、第二或第三/第四鳃弓的残余引起。鳃裂囊相关结构见于甲状腺内的实细胞窝、有或无相关淋巴成分的上皮囊肿、胸腺和/或甲状旁腺组织,异位软骨的形式较少见。我们报告一个罕见的病例左侧实性甲状腺肿大附近的两个颈部结节,在一个七岁的女性临床诊断提示恶性甲状腺肿瘤转移到颈部淋巴结。组织病理学检查显示其与第三/第四鳃囊性异常(由成熟软骨、胸腺和甲状旁腺组织组成)具有临床和放射相关性。
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引用次数: 1
Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells 抗原提呈细胞衍生的外泌体对免疫反应的调节
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.4137/CPath.S39925
Botros B. Shenoda, Seena K. Ajit
Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages.
外泌体介导的信号在介导炎症反应中是重要的。为了在受体细胞中发挥其生物学或病理生理功能,外泌体递送多种生物大分子,包括长、短编码和非编码rna、蛋白质和脂质。抗原呈递细胞分泌的外泌体可以通过减弱或刺激免疫反应而获得治疗益处。外泌体在携带和呈递功能性主要组织相容性肽复合物以调节抗原特异性T细胞反应中起着至关重要的作用。树突状细胞外泌体可以激活T细胞和B细胞,并在癌症治疗中探索其免疫刺激特性。巨噬细胞和树突状细胞衍生的外泌体的免疫抑制特性可以减轻几种炎症疾病动物模型的炎症。本文综述了外泌体在减轻炎症或增强免疫应答中的保护作用,重点介绍了来自dc和巨噬细胞的外泌体的研究。
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引用次数: 65
Cytopathological Diagnosis of an Unusual Cause of Malignant Hydrocele 恶性鞘膜积液罕见病因的细胞病理学诊断
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.4137/CPath.S40517
Ankur Jain, A. Khadwal, G. Prakash, N. Gupta, S. Varma, P. Malhotra
Testicular involvement in a case of acute lymphoblastic leukemia (ALL) is well reported, but occurrence of “isolated” malignant hydrocele is extremely uncommon. We herein report a case of a 22-year-old man who presented to our hematology clinic with fever and easy fatiguability of 2 weeks' duration. Examination revealed pallor, cervical lymphadenopathy, and bilateral scrotal swellings. He was diagnosed as a case of Philadelphia-positive ALL (B-cell type) based on peripheral smear, bone marrow examination, and flow cytometry of the marrow aspirate. Ultrasonography of scrotum revealed bilateral hydrocele with normal testes. Cytopathological analysis of the hydrocele fluid showed the presence of lymphoblasts. The patient was treated with modified BFM-90 protocol along with imatinib mesylate (600 mg/day). He achieved complete remission with a minimal residual disease of <0.001% at the end of induction therapy. However, the hydrocele persisted and a repeat cytological examination of the aspirate did not reveal any lymphoblasts. The patient was treated with consolidation (high-dose methotrexate), bilateral testicular irradiation, and re-induction following which the hydrocele disappeared. The patient is currently on maintenance phase of BFM-90 protocol and is alive at one year of follow-up. Contiguous spread from the subclinical testicular involvement is hypothesized as the mechanism for development of hydrocele in the current case. The role of cytopathology in the early diagnosis of testicular involvement in ALL is emphasized here.
急性淋巴细胞白血病(ALL)累及睾丸的病例报道较多,但“孤立性”恶性鞘膜积液的发生极为罕见。我们在此报告一例22岁的男子谁提出了我们的血液诊所发烧和容易疲劳的2周的时间。检查发现面色苍白,颈部淋巴结肿大,双侧阴囊肿胀。根据外周血涂片、骨髓检查和骨髓穿刺流式细胞术诊断为费城阳性ALL (b细胞型)病例。阴囊超声检查显示双侧阴囊积液,睾丸正常。鞘膜积液的细胞病理学分析显示淋巴母细胞的存在。患者采用改良BFM-90方案联合甲磺酸伊马替尼(600mg /天)治疗。在诱导治疗结束时,他的病情完全缓解,残余疾病<0.001%。然而,鞘膜积液持续存在,反复细胞学检查未发现任何淋巴细胞。患者接受巩固治疗(大剂量甲氨蝶呤),双侧睾丸照射,再诱导后,积液消失。患者目前处于BFM-90方案的维持阶段,随访1年存活。从亚临床睾丸受累的连续扩散被假设为本病例鞘膜积液发展的机制。细胞病理学在ALL累及睾丸的早期诊断中的作用在这里被强调。
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引用次数: 2
Diagnostic Implication and Clinical Relevance of Ancillary Techniques in Clinical Pathology Practice 辅助技术在临床病理实践中的诊断意义和临床意义
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.4137/CPath.S32784
J. Makki
Hematoxylin-eosin-stained slide preparation is one of the most durable techniques in medicine history, which has remained unchanged since implemented. It allows an accurate microscopic diagnosis of the vast majority of tissue samples. In many circumstances, this technique cannot answer all the questions posed at the initial diagnostic level. The pathologist has always been looking for additional ancillary techniques to answer pending questions. In our daily histopathology practice, we referred to those techniques as special stains, but nowadays, they are more than stains and are collectively called ancillary tests. They include a wide range of techniques starting from histochemical stains and ending in one or more advanced techniques, such as immunohistochemistry, immunofluorescence, molecular studies, cytogenetic studies, electron microscopy, flow cytometry, and polymerase chain reaction.
苏木精-伊红染色载玻片制备是医学史上最持久的技术之一,自实施以来一直保持不变。它允许对绝大多数组织样本进行准确的显微诊断。在许多情况下,这种技术不能回答在初始诊断水平上提出的所有问题。病理学家一直在寻找额外的辅助技术来回答悬而未决的问题。在我们的日常组织病理学实践中,我们将这些技术称为特殊染色,但现在,它们不仅仅是染色,而是统称为辅助测试。它们包括广泛的技术,从组织化学染色开始,到一种或多种先进技术,如免疫组织化学、免疫荧光、分子研究、细胞遗传学研究、电子显微镜、流式细胞术和聚合酶链反应。
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引用次数: 21
IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity IDO2:炎症自身免疫的致病介质
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.4137/CPath.S39930
Lauren M F Merlo, L. Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.
吲哚胺2,3-双加氧酶2 (IDO2)是研究较好的色氨酸分解酶IDO1的同源物,是一种免疫调节分子,对包括癌症和自身免疫在内的多种疾病具有潜在的作用。在这里,我们回顾了已知的IDO2与免疫功能之间的直接联系,特别是与自身免疫性炎症疾病(如类风湿关节炎和狼疮)的关系。越来越多的证据表明,IDO2作为自身免疫的促炎介质,具有与IDO1不同的功能表型。IDO2在抗原呈递细胞中表达,包括B细胞和树突状细胞,但在多种模型系统中,IDO2通过在B细胞中特异性地调节T细胞帮助来影响自身免疫背景下的炎症反应。鉴于IDO2的表达可导致炎症反应加剧,IDO2应被视为自身免疫性疾病的潜在治疗靶点。
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引用次数: 38
期刊
Clinical Medicine Insights- Pathology
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