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1.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371956

RESUMO

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5-20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1ß and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Linhagem Celular , Sobrevivência Celular , Colágeno/análise , Citocinas/genética , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Derme/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Epiderme/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunomodulação , Tecido Linfoide/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Triterpenos Pentacíclicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Invest Ophthalmol Vis Sci ; 62(10): 27, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34427624

RESUMO

Purpose: We aimed to evaluate activation of conjunctiva-associated lymphoid tissue (CALT) in patients with keratitis using in vivo confocal microscopy (IVCM) and conjunctival impression cytology (CIC). Methods: In addition to anterior segment photography and corneal fluorescein staining, IVCM revealed the palpebral conjunctiva in all subjects, and CIC and immunofluorescence staining were performed. Results: Diffuse lymphoid tissue cell density in the eyes of patients with keratitis was significantly greater compared with healthy volunteers (P < 0.001). Similar trends were found in perifollicular lymphocyte density (P < 0.001), follicular density (P = 0.029), follicular center reflection intensity (P = 0.011), and follicular area (P < 0.001). Immunofluorescence staining showed that the proportions of CD4+ (61.7% ± 8.0% vs. 17.3% ± 10.2%, respectively, P < 0.001) and CD8+ (46.9% ± 10.0% vs. 19.6% ± 11.5%, respectively, P < 0.001) cells in patients with keratitis was greater compared with healthy volunteers. Interestingly, we also observed changes in the contralateral eye in subjects with keratitis. Conclusions: Our research suggests that CALT, as an ocular immune structure, is activated and plays an important role in the pathogenesis of keratitis. This has been overlooked previously. CALT is also active in the contralateral eye of subjects with keratitis.


Assuntos
Túnica Conjuntiva/patologia , Córnea/patologia , Infecções Oculares Bacterianas/patologia , Imunidade Celular , Ceratite/patologia , Tecido Linfoide/patologia , Adulto , Túnica Conjuntiva/imunologia , Córnea/metabolismo , Infecções Oculares Bacterianas/imunologia , Infecções Oculares Bacterianas/metabolismo , Feminino , Humanos , Ceratite/imunologia , Ceratite/metabolismo , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
J Radiol Case Rep ; 15(3): 19-28, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34267867

RESUMO

We present the case of a 79-year-old male, who was initially treated for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the right eyelid, and later for disease relapse in the stomach. During follow up, he was noted to have developed left arm nodules just medial to the proximal biceps muscle, which were found to be multiply enlarged lymph nodes on subsequent ultrasound imaging. Excisional biopsy of these nodes revealed MALT lymphoma. He was initially referred for consideration of radiation, but a restaging F-18 fluorodeoxyglucose positron emission tomography integrated with computed tomography (F-18 FDG PET/CT) further identified a focus of suspicious uptake in left calf, which was later also biopsy proven to be MALT lymphoma. His disease was upstaged as the result of this later finding, and the overall recommendation for treatment changed to favor systemic treatment with Rituximab.


Assuntos
Tecido Linfoide/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Membrana Mucosa/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Fluordesoxiglucose F18 , Humanos , Tecido Linfoide/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Masculino , Membrana Mucosa/diagnóstico por imagem , Estadiamento de Neoplasias , Conduta Expectante
4.
Rev Neurol ; 72(11): 397-406, 2021 06 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34042168

RESUMO

INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.


Assuntos
COVID-19/epidemiologia , Esclerose Múltipla , Biomarcadores , Sistema Nervoso Central/diagnóstico por imagem , Comorbidade , Exposição Ambiental , Epigênese Genética , Europa (Continente) , Substância Cinzenta/patologia , Humanos , Estilo de Vida , Subpopulações de Linfócitos/imunologia , Tecido Linfoide/patologia , Meninges/patologia , Microbiota , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Esclerose Múltipla/microbiologia , Esclerose Múltipla/patologia , Neuroglia/patologia , Neurologia/tendências , Neurônios/patologia , Remielinização
5.
Surg Pathol Clin ; 14(1): 75-96, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33526225

RESUMO

Lymphoepithelial carcinoma of salivary glands (LECSG) is an uncommon neoplasm. This article summarizes the findings of 438 cases in a review of the literature. Concurrent lymphoepithelial lesions may suggest a primary tumor. The tumor shows a nonkeratinizing carcinoma intimately associated with a rich lymphohistiocytic infiltrate, destroying adjacent salivary gland tissue. Irrespective of race or ethnicity, the tumors usually express Epstein-Barr virus, with Epstein-Barr virus encoded small RNA (EBER) and/or latent membrane protein-1 (LMP-1), although a subset does not. There is an overall good prognosis of about 80% at 5 years.


Assuntos
Carcinoma/patologia , Tecido Linfoide/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Carcinoma/virologia , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Hibridização In Situ , Incidência , Tecido Linfoide/virologia , Neoplasias Nasofaríngeas/diagnóstico , Reação em Cadeia da Polimerase , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/virologia
6.
Commun Biol ; 4(1): 27, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398113

RESUMO

Lassa virus (LASV) is endemic in West Africa and induces a viral hemorrhagic fever (VHF) with up to 30% lethality among clinical cases. The mechanisms involved in control of Lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. We used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease. After initial replication at the inoculation site, LASV reached the secondary lymphoid organs. LASV did not spread further in nonfatal disease and was rapidly controlled by balanced innate and T-cell responses. Systemic viral dissemination occurred during severe disease. Massive replication, a cytokine/chemokine storm, defective T-cell responses, and multiorgan failure were observed. Clinical, biological, immunological, and transcriptomic parameters resembled those observed during septic-shock syndrome, suggesting that similar pathogenesis is induced during Lassa fever. The outcome appears to be determined early, as differentially expressed genes in PBMCs were associated with fatal and non-fatal Lassa fever outcome very early after infection. These results provide a full characterization and important insights into Lassa fever pathogenesis and could help to develop early diagnostic tools.


Assuntos
Modelos Animais de Doenças , Febre Lassa/imunologia , Febre Lassa/virologia , Macaca fascicularis , Imunidade Adaptativa , Animais , Biomarcadores/metabolismo , Feminino , Imunidade Inata , Febre Lassa/sangue , Febre Lassa/patologia , Pulmão/patologia , Tecido Linfoide/patologia , Masculino , Transcriptoma
7.
Am J Surg Pathol ; 45(6): 841-853, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399339

RESUMO

We prospectively studied our institutional experience of bladder extranodal marginal zone (mucosa-associated lymphoid tissue [MALT]) lymphoma including bladder biopsies in which the possibility of MALT lymphoma was considered. We identified a subset of cases primary to the urinary bladder, presenting with prominent plasma cell infiltrates and symptoms mimicking bladder pain syndrome/interstitial cystitis. These proliferations were designated for this study as "monotypic plasma cell proliferation of uncertain clinical significance" (MPCP-US), as the features were insufficient for diagnosis of MALT lymphoma. We identified 33 patients, consisting of 22 cases of MPCP-US (6 of which were associated with amyloid deposition) and 11 cases of MALT lymphoma. MPCP-US was more prevalent in men (73%), a mass lesion was not identified at cystoscopy, and only 1 case had an accompanying urinary tract infection (4.5%). Histologically, MPCP-US presented as monotypic plasma cells arranged in a superficial band-like distribution in the lamina propria, predominantly kappa restricted (68%) and IgA+ or IgM+ (64% and 23%, respectively) and without a histologic mass of atypical B cells or plasma cells, not diagnostic for established MALT lymphoma or plasmacytoma. Secondary involvement of the bladder by other lymphoproliferative disorders was excluded and there was no evidence of progressive disease. MALT lymphomas are presented for comparison and our analysis demonstrated that MPCP-US represent a different clinicopathologic entity compared with classic MALT lymphoma. We present the first series of cases of MPCP-US. The recognition of this entity is fundamental to the development of management protocols to relieve intractable symptoms mimicking bladder pain syndrome/interstitial cystitis in these patients.


Assuntos
Proliferação de Células , Cistite Intersticial/patologia , Tecido Linfoide/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Plasmócitos/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Tecido Linfoide/química , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/genética , Masculino , Pessoa de Meia-Idade , Plasmócitos/química , Valor Preditivo dos Testes , Estudos Prospectivos , Bexiga Urinária/química , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/genética
8.
Cells ; 10(2)2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33498711

RESUMO

In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. In the present review, we summarize available evidence and recent updates on immune infiltrates in BC, focusing on current clinical applications, potential clinical implications and major unresolved issues.


Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunidade , Linfócitos/imunologia , Tecido Linfoide/patologia , Microambiente Tumoral/imunologia
9.
Int J Biol Macromol ; 171: 448-456, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33421472

RESUMO

To investigate the effects of Hericium erinaceus polysaccharide (HEP) on immunity in Muscovy duck reovirus (MDRV)-infected ducklings and explore its mechanism of action, an MDRV contact-infection model was established. Then, we investigated the influence of HEP on morphology of main immune organs in MDRV-infected ducklings by HE staining, while antioxidant capacity (T-AOC, MDA), serum protein levels (TP, ALB, GLO), complement levels (C3, C4) and antibody levels (IgA, IgM, IgG) were detected. Apoptotic indexes (apoptosisi rate and FAS-L) were also quantified by TUNEL method and immunohistochemical staining. Meanwhile, FADD and CytC (apoptosis-related genes), were tested by quantitative RT-PCR. Results showed that HEP could reduce the injuries of immune organs caused by MDRV. Additionally, HEP markedly diminished MDA (p < 0.01), while significantly increased T-AOC, TP, ALB, GLO, C3, C4, IgA, IgM and IgG (p < 0.01 or p < 0.05). Then, HEP shifted apoptosis time to an early MDRV-infected stage and reduced apoptosis at later MDRV-infected stage. This was associated with changes of FADD and CytC. Collectively, our data suggested that HEP could reduce the immunesuppression by many ways, such as decreasing organs' injuries, improving antioxidant capacity, serum proteins levels, antibody levels and complement levels, while diminish the apoptosis by lowering the FADD and CytC.


Assuntos
Patos/virologia , Hericium/química , Sistema Imunitário/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Doenças das Aves Domésticas/tratamento farmacológico , Infecções por Reoviridae/veterinária , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos Antivirais/sangue , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas/análise , Citocromos c/análise , Avaliação Pré-Clínica de Medicamentos , Proteína de Domínio de Morte Associada a Fas/análise , Linfócitos/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Oxirredução , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia , Distribuição Aleatória , Infecções por Reoviridae/tratamento farmacológico , Infecções por Reoviridae/imunologia , Infecções por Reoviridae/virologia
10.
Am J Clin Pathol ; 155(1): 97-105, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32915191

RESUMO

OBJECTIVES: Diagnosis of mycobacterial infections poses significant challenges in anatomic pathology. We recently described the use of antimycobacteria immunohistochemistry (IHC) as a sensitive, efficient diagnostic tool and now report the clinical performance of this assay among general, noninfectious disease pathology-trained anatomic pathologists. METHODS: Over a 2-year period, all cases were retrospectively identified in which mycobacterial IHC was performed during routine diagnostic workup. RESULTS: From October 2017 to September 2019, mycobacterial IHC was evaluated for 267 cases, resulting in 58 (22%) positive stains. Compared with culture and molecular results, the sensitivity and specificity of IHC were 52% and 80%, respectively. IHC performed significantly better than acid-fast bacilli (AFB) staining (Ziehl-Neelsen) (P < .0001; sensitivity 21%, specificity 92%) but similarly to modified AFB staining (mAFB; Fite-Faraco) (P = .9; sensitivity 61%, specificity 84%). In cases with discordant IHC and mAFB staining, there were no differences in rates of culture or polymerase chain reaction-confirmed positivity. CONCLUSIONS: Mycobacterial IHC was well adopted with superior clinical performance to AFB and comparable performance to mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections and suggests its potential role as a rapid screening test for molecular testing.


Assuntos
Imuno-Histoquímica , Infecções por Mycobacterium/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Tecido Linfoide/microbiologia , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Pele/microbiologia , Pele/patologia , Adulto Jovem
11.
Int Immunopharmacol ; 90: 107242, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307514

RESUMO

Colonic patches, the counterparts of Peyer's patches in the small intestine, are dynamically regulated lymphoid tissues in the colon that have an important role in defensing against microbial infections. Berberine is an isoquinoline alkaloid extracted from medicinal herbs including Rhizoma coptidis and has long been used for the treatment of infectious gastroenteritis, but its impact on the colonic lymphoid tissues (such as colonic patches) is unknown. In this study, we aimed to investigate whether berberine had any influences on the colonic patches in mice with bacterial infection. The results showed that oral berberine administration in bacterial infected mice substantially enhanced the hypertrophy of colonic patches, which usually possessed the features of two large B-cell follicles with a separate T-cell area. Moreover, the colonic patches displayed follicular dendritic cell networks within the B-cell follicles, indicative of mature colonic patches containing germinal centers. Concomitant with enlarged colonic patches, the cultured colon of infected mice treated with berberine secreted significantly higher levels of interleukin-1ß (IL-1ß), IL-6, TNF-α, and CCL-2, while NLRP3 inhibitor MMC950 or knockout of NLRP3 gene abrogated berberine-induced hypertrophy of colonic patches, suggesting the involvement of the NLRP3 signaling pathway in this process. Functionally, oral administration of berberine ameliorated liver inflammation and improved formed feces in the colon. Altogether, these results indicated that berberine was able to augment the hypertrophy of colonic patches in mice with bacterial infection probably through enhancing local inflammatory responses in the colon.


Assuntos
Infecções Bacterianas/patologia , Berberina/uso terapêutico , Colo/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Doenças Peritoneais/patologia , Animais , Linfócitos B/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Colo/crescimento & desenvolvimento , Colo/patologia , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Feminino , Gastroenterite/tratamento farmacológico , Tecido Linfoide/crescimento & desenvolvimento , Tecido Linfoide/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Doenças Peritoneais/tratamento farmacológico , Doenças Peritoneais/metabolismo , Linfócitos T/efeitos dos fármacos
12.
Microsc Microanal ; 27(1): 187-200, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33345760

RESUMO

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels "LVs"), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.


Assuntos
Diabetes Mellitus Experimental/patologia , Células Endoteliais , Pulmão/patologia , Tecido Linfoide/patologia , Mediastino/patologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Camundongos , Estreptozocina
13.
Dokl Biochem Biophys ; 494(1): 231-234, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33119823

RESUMO

The aim of this work was to study the effect of proton pencil beam scanning in the Bragg peak in the dose range of 0.1-1.5 Gy on the induction of cytogenetic damage in the bone marrow, reactive oxygen species (ROS) production in whole blood, and the state of lymphoid organs after total body irradiation of mice. Irradiation was carried out in the Prometeus proton synchrotron (Protvino) in the Bragg peak with proton energy at the output of 90-116 MeV. It was found that, under irradiation of mice in the range of low and medium doses of proton pencil beam scanning in the Bragg peak, the relative biological effectiveness (RBE) according to the criterion of cytogenetic changes was 1.15. In addition, it was found that the pathophysiological effect on the lymphoid organs and the production of ROS by blood cells were different as compared with the effect of X-rays.


Assuntos
Medula Óssea/efeitos da radiação , Tecido Linfoide/efeitos da radiação , Terapia com Prótons/métodos , Espécies Reativas de Oxigênio/metabolismo , Irradiação Corporal Total/métodos , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Masculino , Camundongos , Terapia com Prótons/efeitos adversos , Doses de Radiação , Eficiência Biológica Relativa , Irradiação Corporal Total/efeitos adversos
14.
Chest ; 158(3): e117-e121, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32892887

RESUMO

CASE PRESENTATION: A 77-year-old woman was referred to our interstitial lung disease unit. She presented with a history of progressive dyspnea on exertion and nonproductive, persistent cough over the previous year. She was diagnosed with Sjogren syndrome two years ago by a rheumatologist. In the context of Sjogren syndrome, she reported chronic xerostomia and xerophthalmia for the last 5 years. Her history was also notable for the presence of arterial hypertension and hypothyroidism. She denied the presence of shortness of breath, chest pain, arthralgia, muscle weakness, weight loss, night sweats, and fatigue. She reported exposure to house mold. There was no family history of respiratory diseases. The patient never smoked and denied alcohol consumption, illicit drug use, or any occupational exposures.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Síndrome de Sjogren/complicações , Idoso , Biópsia , Brônquios/patologia , Tosse/diagnóstico , Diagnóstico Diferencial , Diagnóstico por Imagem , Progressão da Doença , Dispneia/diagnóstico , Feminino , Humanos , Tecido Linfoide/patologia
15.
Arterioscler Thromb Vasc Biol ; 40(11): 2598-2604, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32907369

RESUMO

OBJECTIVE: NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis. Approach and Results: We found that feeding Ldlr-/- mice a Western diet substantially increased Nr4a1 expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated Ldlr-/- mice with complete B- or specific MZB-cell deletion of Nr4a1. Complete B-cell deletion of Nr4a1 led to increased atherosclerosis, which was accompanied by increased T follicular helper cell-germinal center axis response, as well as increased serum total cholesterol and triglycerides levels. Interestingly, specific MZB-cell deletion of Nr4a1 increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. Nr4a1-/- MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response. CONCLUSIONS: Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells.


Assuntos
Aorta/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Linfócitos B/metabolismo , Deleção de Genes , Tecido Linfoide/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/deficiência , Animais , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/patologia , Linfócitos B/patologia , Modelos Animais de Doenças , Progressão da Doença , Tecido Linfoide/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Placa Aterosclerótica , Receptores de LDL/deficiência , Receptores de LDL/genética , Transdução de Sinais
16.
Curr Top Microbiol Immunol ; 426: 119-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483659

RESUMO

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects the joints, with inflammation of the synovial membrane, characterized by hyperplasia, neo-angiogenesis, and immune cell infiltration that drives local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous. In particular, in about 40% of patients with RA, synovitis is characterized by a dense lymphocytic infiltrate that can acquire the features of fully functional tertiary lymphoid organs (TLO). These structures amplify autoimmunity and inflammation locally associated with worse prognosis and potential implications for treatment response. Here, we will review the current knowledge on TLO in RA, with a focus on their pathogenetic and clinical relevance.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Tecido Linfoide/patologia , Autoimunidade , Humanos , Tecido Linfoide/imunologia , Neovascularização Patológica , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia
17.
Anat Rec (Hoboken) ; 303(11): 2766-2773, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32445535

RESUMO

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM.


Assuntos
Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Ozônio/toxicidade , Pyroglyphidae/imunologia , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Pulmão/imunologia , Pulmão/patologia , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Macaca mulatta
18.
Cytopathology ; 31(3): 193-207, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32259367

RESUMO

Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour-like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic-like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra-salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.


Assuntos
Adenolinfoma/diagnóstico , Adenolinfoma/patologia , Adenoma/diagnóstico , Adenoma/patologia , Humanos , Linfócitos/patologia , Tecido Linfoide/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia
19.
Vet Dermatol ; 31(4): 309-e77, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32249482

RESUMO

BACKGROUND: Cutaneous vascular malformations (CVM) represent a spectrum of human diseases identified at birth or in paediatric patients and classified according to the type of vessel affected. Confusing classification in human medicine has led to misdiagnoses and frequent nomenclature revision. Cutaneous lymphatic malformations (CLM) are reported sporadically in humans. OBJECTIVE: To describe the clinicopathological findings of superficial dermal cutaneous lymphatic malformations (SDCLM) in two cats. ANIMALS: Two unrelated adult domestic short hair cats. METHODS: The two cats were evaluated clinically and with a dermoscope for recurrent swelling and presence of vesicles oozing serosanguineous fluid affecting the right and left hind foot, respectively, since birth. Skin biopsy specimens were collected for histopathological and immunohistochemical evaluation and electron microscopy. RESULTS: A CVM was suspected based on the age of onset, clinical signs, results of diagnostic imaging and histopathological findings. Dermoscopy was used to describe the alterations of the skin surface. The involvement of the lymphatic vessels was confirmed using immunohistochemical findings and electron microscopy. CONCLUSION AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first description of the clinical, dermoscopic, histopathological and ultrastructural characteristics of SDCLM in cats resembling the human counterpart. SDCLMs are rare conditions and appropriate histopathological and immunohistochemical confirmation is required to avoid misdiagnosis and mistreatment.


Assuntos
Doenças do Gato/patologia , Dermoscopia/veterinária , Tecido Linfoide/patologia , Malformações Vasculares/veterinária , Animais , Biópsia , Gatos , Masculino , Pele/patologia , Malformações Vasculares/patologia
20.
J Virol ; 94(11)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32213610

RESUMO

Ebola virus (EBOV) continues to pose a significant threat to human health, as evidenced by the 2013-2016 epidemic in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. EBOV causes hemorrhagic fever, organ damage, and shock culminating in death, with case fatality rates as high as 90%. This high lethality combined with the paucity of licensed medical countermeasures makes EBOV a critical human pathogen. Although EBOV infection results in significant damage to the liver and the adrenal glands, little is known about the molecular signatures of injury in these organs. Moreover, while changes in peripheral blood cells are becoming increasingly understood, the host responses within organs and lymphoid tissues remain poorly characterized. To address this knowledge gap, we tracked longitudinal transcriptional changes in tissues collected from EBOV-Makona-infected cynomolgus macaques. Following infection, both liver and adrenal glands exhibited significant and early downregulation of genes involved in metabolism, coagulation, hormone synthesis, and angiogenesis; upregulated genes were associated with inflammation. Analysis of lymphoid tissues showed early upregulation of genes that play a role in innate immunity and inflammation and downregulation of genes associated with cell cycle and adaptive immunity. Moreover, transient activation of innate immune responses and downregulation of humoral immune responses in lymphoid tissues were confirmed with flow cytometry. Together, these data suggest that the liver, adrenal gland, and lymphatic organs are important sites of EBOV infection and that dysregulating the function of these vital organs contributes to the development of Ebola virus disease.IMPORTANCE Ebola virus (EBOV) remains a high-priority pathogen since it continues to cause outbreaks with high case fatality rates. Although it is well established that EBOV results in severe organ damage, our understanding of tissue injury in the liver, adrenal glands, and lymphoid tissues remains limited. We begin to address this knowledge gap by conducting longitudinal gene expression studies in these tissues, which were collected from EBOV-infected cynomolgus macaques. We report robust and early gene expression changes within these tissues, indicating they are primary sites of EBOV infection. Furthermore, genes involved in metabolism, coagulation, and adaptive immunity were downregulated, while inflammation-related genes were upregulated. These results indicate significant tissue damage consistent with the development of hemorrhagic fever and lymphopenia. Our study provides novel insight into EBOV-host interactions and elucidates how host responses within the liver, adrenal glands, and lymphoid tissues contribute to EBOV pathogenesis.


Assuntos
Glândulas Suprarrenais , Ebolavirus , Regulação Viral da Expressão Gênica/imunologia , Doença pelo Vírus Ebola , Fígado , Tecido Linfoide , Doenças dos Macacos , Transcrição Genética/imunologia , Glândulas Suprarrenais/imunologia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/virologia , Animais , Ebolavirus/imunologia , Ebolavirus/metabolismo , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/metabolismo , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/veterinária , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Macaca fascicularis , Masculino , Doenças dos Macacos/imunologia , Doenças dos Macacos/metabolismo , Doenças dos Macacos/patologia , Doenças dos Macacos/virologia
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