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1.
Chirurg ; 90(12): 957-965, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31691141

RESUMO

The lymphatic system of the lungs is complex. To maintain an effective gas exchange there is a need for a dense lymphatic network. The alveolae have no lymphatic vessels. There is no segment-specific lymph drainage. For both lungs there are fixed bronchopulmonary lymph nodes but the number and size of the lymph nodes are variable. There are seven mediastinal lymph node chains that vary in extent, each of which acts as an independent functional unit. The accurate assessment of the nodal status needs a simple reproducible nodal map. The division into compartments or zones makes this easier. Mediastinal lymph node metastases without involvement of bronchopulmonary lymph nodes are possible. The development mechanism of this skip metastasizing is multifactorial.


Assuntos
Neoplasias Pulmonares , Linfonodos/anatomia & histologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/fisiologia , Metástase Linfática , Sistema Linfático/anatomia & histologia , Mediastino/anatomia & histologia , Estadiamento de Neoplasias
2.
Nat Commun ; 10(1): 4594, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597914

RESUMO

Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO+-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.


Assuntos
Linfonodos/fisiologia , Vasos Linfáticos/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Coluna Vertebral/fisiologia , Ducto Torácico/fisiologia , Animais , Processamento de Imagem Assistida por Computador/métodos , Linfonodos/anatomia & histologia , Vasos Linfáticos/anatomia & histologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Confocal , Microscopia de Fluorescência , Traumatismos da Medula Espinal/patologia , Coluna Vertebral/anatomia & histologia , Ducto Torácico/anatomia & histologia
3.
Bull Exp Biol Med ; 167(2): 194-197, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31243683

RESUMO

We studied age-associated changes in contractile activity of isolated cervical and mesenteric lymph nodes in rats. In young and middle-aged rats, no significant changes in contractile activity of lymph nodes were revealed. In old rats, the amplitude of spontaneous contractions of lymph nodes was lower and their rate was higher than in young and middle-aged animals; the sensitivity of lymph nodes to vasoactive agents was reduced and the threshold of the response was higher in old rats.


Assuntos
Linfonodos/fisiologia , Contração Muscular/fisiologia , Miócitos de Músculo Liso/fisiologia , Acetilcolina/farmacologia , Animais , Histamina/farmacologia , Linfonodos/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Ratos
4.
Dokl Biol Sci ; 484(1): 10-12, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31016496

RESUMO

Endothelium-dependent relaxation mechanisms have been studied in phenylephrine-precontracted capsules of bovine mesenteric lymph nodes studied in vitro. Tetraethylammonium chloride and TRAM-34 in a solution with L-NAME and Indomethacin, which suppress the production NO and prostacyclin of endothelium, increased the tone of the lymph nodes. We believe that in bovine mesenteric lymph nodes, the dilation mechanism is mediated by hyperpolarization of the endothelium, which is associated with activation of large- and intermedium conductance Ca2+-activated potassium channels.


Assuntos
Endotélio/fisiologia , Linfonodos/fisiologia , Potenciais da Membrana , Animais , Bovinos , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Epoprostenol/metabolismo , Indometacina/farmacologia , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Masculino , Mesentério , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Pirazóis/farmacologia
5.
Immunol Rev ; 289(1): 62-83, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977201

RESUMO

Secondary lymphoid organs like lymph nodes (LNs) are the main inductive sites for adaptive immune responses. Lymphocytes are constantly entering LNs, scanning the environment for their cognate antigen and get replenished by incoming cells after a certain period of time. As only a minor percentage of lymphocytes recognizes cognate antigen, this mechanism of permanent recirculation ensures fast and effective immune responses when necessary. Thus, homing, positioning, and activation as well as egress require precise regulation within LNs. In this review we discuss the mediators, including chemokines, cytokines, growth factors, and others that are involved in the formation of the LN anlage and subsequent functional organization of LNs. We highlight very recent findings in the fields of LN development, steady-state migration in LNs, and the intranodal processes during an adaptive immune response.


Assuntos
Quimiocinas/metabolismo , Linfonodos/fisiologia , Linfócitos/imunologia , Imunidade Adaptativa , Animais , Movimento Celular , Citocinas/metabolismo , Humanos , Ativação Linfocitária , Organogênese
6.
Acta Pharmacol Sin ; 40(9): 1168-1183, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30858476

RESUMO

Understanding the dynamics of the immune response following late myocardial reperfusion is critical for the development of immunomodulatory therapy for myocardial infarction (MI). Cyclosporine A (CSA) possesses multiple therapeutic applications for MI, but its effects on the inflammation caused by acute MI are not clear. This study aimed to determine the dynamics of the immune response following myocardial ischemia/reperfusion (I/R) and the effects of CSA in a mouse model of prolonged myocardial ischemia designated to represent the human condition of late reperfusion. Adult C57BL/6 mice were subjected to 90 min of closed-chest myocardial I/R, which induced severe myocardial injury and excessive inflammation in the heart. Multicomponent analysis of the immune response caused by prolonged I/R revealed that the peak of cytokines/chemokines in the systemic circulation was synchronized with the maximal influx of neutrophils and T-cells in the heart 1 day after MI. The peak of cytokine/chemokine secretion in the infarcted heart coincided with the maximal macrophage and natural killer cell infiltration on day 3 after MI. The cellular composition of the mediastinal lymph nodes changed similarly to that of the infarcted hearts. CSA (10 mg/kg/day) given after prolonged I/R impaired heart function, enlarged the resulting scar, and reduced heart vascularization. It did not change the content of immune cells in hearts exposed to prolonged I/R, but the levels of MCP-1 and MIP-1α (hearts) and IL-12 (hearts and serum) were significantly reduced in the CSA-treated group in comparison to the untreated group, indicating alterations in immune cell function. Our findings provide new knowledge necessary for the development of immunomodulatory therapy targeting the immune response after prolonged myocardial ischemia/reperfusion.


Assuntos
Ciclosporina/farmacologia , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Quimiocinas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Células Matadoras Naturais/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Neutrófilos/metabolismo , Linfócitos T/metabolismo , Fatores de Tempo , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia
7.
J Dairy Sci ; 102(4): 3452-3468, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30799109

RESUMO

Inconsistent evidence of inflammatory immune cell infiltrates in adipose tissues with extensive triglyceride mobilization raises the possibility that regulatory or anti-inflammatory immune cell populations reside within the mesenteric adipose tissue (MAT) and mesenteric lymph nodes (MLN). These resident immune cell populations may be involved in attenuating the inflammatory response. We explored the immune cell population of MAT and MLN collected from lean, lactating Holstein cows without apparent disease in an abattoir (n = 42). Lean cows had a body condition score of 2.6 ± 0.1 (mean ± SD) with a greater frequency of adipocyte area occurring in small rather than large adipocytes. Cells were labeled with monoclonal antibodies specific to bovine leukocyte antigens for enumeration by flow cytometry. Within both lymph node and adipose tissues, relatively large subpopulations of cells expressed the ß2 integrins CD11b and CD11c, class II major histocompatibility antigens (MHCII), and the SIIRP-1α receptor (CD172a) typical of dendritic cells and macrophages. Macrophage/dendritic cell heterogeneity was marked by ß2 integrin expression alone or in conjunction with CD172a or MHCII across subpopulations from both tissues; CD209, the DC-SIGN c-type lectin receptor of dendritic cells, was not detected by fluorescence-activated cell sorting in either tissue. Lymphocytes comprised 74.1 ± 3.7% and 13.7 ± 3.7% of the MLN and MAT cell populations, respectively, and CD3+CD4+ lymphocytes accounted for 49.8 ± 9.9% of the MLN and 6.13 ± 1.23% of the MAT cells. Fox P3+ regulatory lymphocytes comprised 15.3 ± 1.1% and 6.73 ± 0.52% of the MLN and MAT cells, whereas γδ+ lymphocytes accounted for 6.65 ± 0.74% and 3.91 ± 0.43% of the MLN and MAT cells, respectively. Subpopulations of CD3+CD8+ cytotoxic T cells and CD3+CD11c+ innate lymphocytes were present in MLN but not MAT. These results show that subpopulations of resident tissue macrophages, dendritic cells, T helper lymphocytes, regulatory T lymphocytes (Tregs), and γδ lymphocytes reside in mesenteric lymph nodes and adipose tissues. Balance in the innate and adaptive immune functions embedded in these tissues could support metabolic health.


Assuntos
Tecido Adiposo/citologia , Células Dendríticas , Linfonodos/fisiologia , Linfócitos T Reguladores , Tecido Adiposo/fisiologia , Animais , Peso Corporal , Bovinos , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/metabolismo , Lactação , Mesentério , Camundongos
8.
Brain Pathol ; 29(2): 176-192, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30192999

RESUMO

The imbalance between production and clearance of amyloid-beta (Aß) is a key step in the onset and development of Alzheimer's disease (AD). Therefore, reducing Aß accumulation in the brain is a promising therapeutic strategy for AD. The recently discovered glymphatic system and meningeal lymphatic vasculature have been shown to be critical for the elimination of interstitial waste products, especially Aß, from the brain. In the present study, ligation of deep cervical lymph nodes was performed to block drainage of this system and explore the consequences on Aß-related pathophysiology. Five-month-old APP/PS1 mice and their wild-type littermates received deep cervical lymphatic node ligation. One month later, behavioral testing and pathological analysis were conducted. Results demonstrated that ligation of dcLNs exacerbated AD-like phenotypes of APP/PS1 mice, showing more severe brain Aß accumulation, neuroinflammation, synaptic protein loss, impaired polarization of aquaporin-4 and deficits in cognitive and exploratory behaviors. These results suggest that brain lymphatic clearance malfunction is one of the deteriorating factors in the progression of AD, and restoring its function is a potential therapeutic target against AD.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Linfonodos/fisiologia , Sistema Linfático/fisiologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Aquaporina 4/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Progressão da Doença , Hipocampo/metabolismo , Humanos , Linfonodos/metabolismo , Linfonodos/cirurgia , Sistema Linfático/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Amiloide/patologia , Córtex Pré-Frontal/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-30488802

RESUMO

BACKGROUND: Secondary lymphoid organs (SLO) are distributed in many districts of the body and, especially, lymph nodes, spleen and gut-associated lymphoid tissue are the main cellular sites. On the other hand, tertiary lymphoid organs (TLO) are formed in response to inflammatory, infectious, autoimmune and neoplastic events. Developmental Studies: In the present review, emphasis will be placed on the developmental differences of SLO and TLO between small intestine and colon and on the role played by various chemokines and cell receptors. Undoubtedly, microbiota is indispensable for the formation of SLO and its absence leads to their poor formation, thus indicating its strict interaction with immune and non immune host cells. Furthermore, food antigens (for example, tryptophan derivatives, flavonoids and byphenils) bind the aryl hydrocarbon receptor on innate lymphoid cells (ILCs), thus promoting the development of postnatal lymphoid tissues. Also retinoic acid, a metabolite of vitamin A, contributes to SLO development during embryogenesis. Vitamin A deficiency seems to account for reduction of ILCs and scarce formation of solitary lymphoid tissue. Translational Studies: The role of lymphoid organs with special reference to intestinal TLO in the course of experimental and human disease will also be discussed. Future Perspectives: Finally, a new methodology, the so-called "gut-in-a dish", which has facilitated the in vitro interaction study between microbe and intestinal immune cells, will be described.


Assuntos
Antígenos/fisiologia , Alimentos , Linfócitos/fisiologia , Tecido Linfoide/crescimento & desenvolvimento , Microbiota/fisiologia , Animais , Hipersensibilidade Alimentar/imunologia , Humanos , Mucosa Intestinal/imunologia , Linfonodos/crescimento & desenvolvimento , Linfonodos/fisiologia , Tecido Linfoide/imunologia , Tecido Linfoide/fisiologia , Microbiota/imunologia
10.
J Pathol ; 247(5): 662-671, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30584795

RESUMO

Recent advances have provided evidence for the involvement of neutrophils in both innate and adaptive immunity, robustly challenging the old dogma that neutrophils are short-lived prototypical innate immune cells solely involved in acute responses to microbes and exerting collateral tissue damage. There is now ample evidence showing that neutrophils can migrate into different compartments of the lymphoid system where they contribute to the orchestration of the activation and/or suppression of lymphocyte effector functions in homeostasis and during chronic inflammation, such as autoimmune disorders and cancer. In support of this notion, neutrophils can generate a wide range of cytokines and other mediators capable of regulating the survival, proliferation and functions of both T and B cells. In addition, neutrophils can directly engage with lymphocytes and promote antigen presentation. Furthermore, there is emerging evidence of the existence of distinct and diverse neutrophil phenotypes with immunomodulatory functions that characterise different pathological conditions, including chronic and autoimmune inflammatory conditions. The aim of this review is to discuss the mechanisms implicated in neutrophil trafficking into the lymphoid system and to provide an overview of the immuno-regulatory functions of neutrophils in health and disease in the context of adaptive immunity. Copyright © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Linfonodos/fisiologia , Neoplasias/imunologia , Neutrófilos/fisiologia , Animais , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Humanos , Fenótipo
11.
Immunobiology ; 224(1): 133-141, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30348458

RESUMO

The present study was undertaken to investigate whether or not chronic stress effect and its reversibility on lymphoid organs is duration dependent. Male rats were exposed to restraint (1 h) followed by a gap of 4 h to forced swimming exercise (15 min) daily for 2, 4 and 8 weeks. After each exposure period, rats were allowed to recover for 6 weeks. Stress exposure resulted in duration dependent decreases in weight of thymus and axillary lymph nodes, lymphocyte counts of spleen, thymus and axillary lymph nodes and number of islets of white pulp of spleen and increases in apoptotic index of splenocytes, thymocytes and lymphocytes of axillary lymph nodes. All the parameters of lymphoid organs studied showed significant alterations in 2 weeks of stress exposure indicated their sensitivity to stress effects in short term exposure and thymus was the most sensitive organ among all. The alterations in all the parameters of spleen and majority of parameters of thymus and axillary lymph nodes returned to control level in recovery group rats of 2 and 4 weeks exposure but not in that of 8 weeks exposure. The present study for the first time reveal that severity of stress effects on lymphoid organs increases with increasing duration of exposure and shorter the exposure period faster the recovery. In addition, an in vitro study showed that corticosterone caused apoptosis of thymocytes, splenocytes and lymphocytes of axillary lymph nodes in dose dependent manner. Thus corticosterone induced death of cells of lymphoid organs under stress is the major cause of involution of lymphoid organs.


Assuntos
Linfonodos/fisiologia , Linfócitos/fisiologia , Tecido Linfoide/fisiologia , Estresse Fisiológico/imunologia , Timócitos/fisiologia , Timo/fisiologia , Animais , Apoptose , Células Cultivadas , Doença Crônica , Corticosterona/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Endogâmicos , Restrição Física
12.
Microsurgery ; 39(3): 247-254, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30508286

RESUMO

PURPOSE: Vascularized lymph node transfer is becoming more common in the treatment of lymphedema, but suitable small animal models for research are lacking. Here, we evaluated the feasibility of pedicled vascularized inguinal lymph node transfer in mice. METHODS: Twenty-five mice were used in the study. An inguinal lymph node-bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node. Indocyanine green (ICG) angiography was used to confirm vascularity of the flap. ICG lymphography was performed to evaluate lymphatic flow at 3 and 4 weeks postoperatively. Patent blue dye was injected into the ipsilateral hind paw to observe staining of the transferred lymph node at 4 weeks postoperatively. All transferred lymph nodes were then harvested and histologically evaluated by hematoxylin and eosin staining. RESULTS: In 16 of the 25 mice, ICG lymphography showed reconnection between the transferred lymph node and the afferent lymphatic vessels, as confirmed by patent blue staining. Histologically, these transferred lymph nodes with afferent lymphatic reconnection significantly regressed in size (0.37 ± 0.24 mm2 ) and showed clear follicle formation, whereas those without afferent lymphatic reconnection showed less size regression (1.31 ± 1.17 mm2 ); the cell population was too dense to allow identification of follicles. CONCLUSIONS: We established a mouse model of vascularized lymph node transfer with predictable afferent lymphatic reconnection. Both the vascularization and reconnection might be necessary for functional regeneration of the transferred lymph node.


Assuntos
Aloenxertos Compostos/transplante , Linfonodos/irrigação sanguínea , Linfonodos/fisiologia , Linfedema/cirurgia , Regeneração , Retalhos Cirúrgicos/irrigação sanguínea , Angiografia , Animais , Modelos Animais de Doenças , Dissecação , Artérias Epigástricas , Estudos de Viabilidade , Membro Posterior/diagnóstico por imagem , Canal Inguinal , Linfonodos/anatomia & histologia , Linfonodos/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/fisiologia , Linfografia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Artéria Poplítea , Dados Preliminares
13.
Sci Rep ; 8(1): 15073, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305678

RESUMO

The present study investigated the clinical impact of neck lymph node (LN) metastasis in locally advanced inoperable thoracic esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy (CCRT) with a curative intent. There were 404 ESCC patients enrolled, including 35 patients with neck LN metastasis and 369 patients without such metastasis. Through the propensity score matching method, 35 patients of the 369 patients without neck LN metastasis were matched to the 35 patients with neck LN metastasis. Progression-free survival (PFS) and overall survival (OS) were found to be significantly worse in the neck LN metastasis group compared to the full non-neck LN metastasis group (9.8 months versus 5.9 months, P < 0.001, and 18.2 months versus 9.7 months, P = 0.001) and the matched non-neck LN metastasis group (9.9 months versus 5.9 months, P = 0.006, and 19.4 months versus 9.7 months, P = 0.007). In order to determine the difference between neck LN and supraclavicular LN metastasis, seventy patients with supraclavicular LN metastasis were also selected from the 369 patients without neck LN metastasis for comparison. Subsequently, when compared to the ESCC patients with supraclavicular LN metastasis, significantly worse PFS (8.5 months versus 5.9 months, P = 0.026) and OS (17.2 months versus 9.7 months, P = 0.047) were still found in the ESCC patients with neck LN metastasis. Our study indicates that neck LN metastasis is an independent poor prognostic factor for locally advanced inoperable thoracic ESCC patients who have undergone CCRT.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/fisiologia , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
14.
BMC Bioinformatics ; 19(Suppl 7): 200, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-30066642

RESUMO

BACKGROUND: The aim of this article is to analyze the effect on biochemical recurrence and on overall survival of removing an extensive number of pelvic lymph nodes during prostate cancer surgery. The lack of evidence from randomized clinical trials to address this specific question has hampered the ability to determine the true effect of the number of nodes removed. RESULTS: Our analysis is based on a large observational study, and this can lead unadjusted estimates to be very sensitive to confounding bias due to the different prognosis of individuals. We assess the effect of the number of lymph nodes removed by means of an Inverse Probability Weighting adjustment based on a Poisson regression model, and by a Doubly-robust adjustment. CONCLUSIONS: Our findings suggest that a large number of nodes removed is associated with a significant improvement in time to biochemical recurrence. However, it appears to have no impact on overall survival.


Assuntos
Excisão de Linfonodo , Linfonodos/fisiologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Análise de Regressão , Análise de Sobrevida , Fatores de Tempo
15.
Elife ; 72018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30066671

RESUMO

Understanding cellular processes occurring in vivo on time scales of days to weeks requires repeatedly interrogating the same tissue without perturbing homeostasis. We describe a novel setup for longitudinal intravital imaging of murine peripheral lymph nodes (LNs). The formation and evolution of single germinal centers (GCs) was visualized over days to weeks. Naïve B cells encounter antigen and form primary foci, which subsequently seed GCs. These experience widely varying rates of homogenizing selection, even within closely confined spatial proximity. The fluidity of GCs is greater than previously observed with large shifts in clonality over short time scales; and loss of GCs is a rare, observable event. The observation of contemporaneous, congruent shifts in clonal composition between GCs within the same animal suggests inter-GC trafficking of memory B cells. This tool refines approaches to resolving immune dynamics in peripheral LNs with high temporospatial resolution and minimal perturbation of homeostasis.


Assuntos
Linfócitos B/imunologia , Evolução Clonal , Seleção Clonal Mediada por Antígeno/imunologia , Centro Germinativo/citologia , Linfonodos/citologia , Animais , Linfócitos B/citologia , Linfócitos B/fisiologia , Movimento Celular , Células Cultivadas , Centro Germinativo/imunologia , Centro Germinativo/fisiologia , Linfonodos/imunologia , Linfonodos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Imagem com Lapso de Tempo
16.
Trends Immunol ; 39(10): 775-787, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30150089

RESUMO

Lymph nodes (LNs) are strategically positioned outposts of the immune system that underpin regional immune surveillance. The current model describing LN formation in mice is based on a two cell-type interaction scheme with lymphoid tissue inducer cells regulating the activation of mesenchymal lymphoid tissue organizer cells. We highlight here the key role of lymphatic endothelial cells during the initiation of LN formation. The involvement of lymphatic endothelial cells as an additional organizer cell type in LN organogenesis unveils multiple control levels that govern the generation of lymphoid organs. Moreover, the linkage between lymphangiogenic and lymphvasculogenic processes and guidance of the accumulation and activation of lymphoid tissue inducer cells in the embryo suggests that LN formation may be driven on demand by developing organ systems.


Assuntos
Células Endoteliais/imunologia , Linfonodos/fisiologia , Células-Tronco Mesenquimais/imunologia , Modelos Imunológicos , Organogênese/fisiologia , Animais , Diferenciação Celular , Humanos , Vigilância Imunológica , Camundongos
17.
Indian J Pathol Microbiol ; 61(3): 407-409, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30004067

RESUMO

Sclerosing pneumocytoma (SP) is an uncommon benign tumor, and metastasis of SP has been rarely reported. Here, we report the case of a 26-year-old woman with surgically confirmed SP. The tumor diameter was 40 mm, and metastasis to mediastinal and regional lymph nodes was observed. Immunohistochemically, both surface and round cells were positive for epithelial membrane antigen, thyroid transcription factor 1, and vimentin. Only surface cells expressed creatine kinase, carcinoembryonic antigen, napsin A, and cytokeratin 7, and only round cells expressed progesterone receptor. Ki-67 was detected in ~3% of cells, and the rate of weak positive p53 staining was 3%. Both cell types were negative for chromogranin A, synaptophysin, CD3, and CK20. Multiple metastases in a young SP patient are very rare, and potential mechanisms of metastasis may be related to epithelial-mesenchymal transformation.


Assuntos
Linfonodos/fisiologia , Hemangioma Esclerosante Pulmonar/complicações , Hemangioma Esclerosante Pulmonar/patologia , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/citologia , Metástase Linfática , Mucina-1/genética , Mucina-1/imunologia , Hemangioma Esclerosante Pulmonar/diagnóstico , Hemangioma Esclerosante Pulmonar/cirurgia , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/imunologia , Vimentina/genética , Vimentina/imunologia
18.
Invest Ophthalmol Vis Sci ; 59(7): 2699-2707, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860456

RESUMO

Purpose: To visualize and quantify lymphatic drainage of aqueous humor from the eye to cervical lymph nodes in the dynamic state. Methods: A near-infrared tracer was injected into the right eye anterior chamber of 10 mice under general anesthesia. Mice were imaged with photoacoustic tomography before and 20 minutes, 2, 4, and 6 hours after injection. Tracer signal intensity was measured in both eyes and right and left neck lymph nodes at every time point and signal intensity slopes were calculated. Slope differences between right and left eyes and right and left nodes were compared using paired t-test. Neck nodes were examined with fluorescence optical imaging and histologically for the presence of tracer. Results: Following right eye intracameral injection of tracer, an exponential decrease in tracer signal was observed from 20 minutes to 6 hours in all mice. Slope differences of the signal intensity between right and left eyes were significant (P < 0.001). Simultaneously, increasing tracer signal was observed in the right neck node from 20 minutes to 6 hours. Slope differences of the signal intensity between right and left neck nodes were significant (P = 0.0051). Ex vivo optical fluorescence imaging and histopathologic examination of neck nodes confirmed tracer presence within submandibular nodes. Conclusions: Active lymphatic drainage of aqueous from the eye to cervical lymph nodes was measured noninvasively by photoacoustic imaging of near-infrared nanoparticles. This unique in vivo assay may help to uncover novel drugs that target alternative outflow routes to lower IOP in glaucoma and may provide new insights into lymphatic drainage in eye health and disease.


Assuntos
Humor Aquoso/fisiologia , Linfonodos/fisiologia , Sistema Linfático/fisiologia , Modelos Animais , Nanopartículas/química , Técnicas Fotoacústicas , Animais , Drenagem , Feminino , Masculino , Camundongos
19.
Lung Cancer ; 121: 54-60, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29858028

RESUMO

OBJECTIVES: Genetic profiles of primary and metastatic lung tumor have been investigated by previous studies. However, whether they can be replaced by each other to guide treatment remains controversial. Moreover, it is unclear that whether genetic profiles of plasma can reflect genetic divergence between primary and metastatic lesions. MATERIALS AND METHODS: In this prospective study, we collected 35 pairs of matched primary tumor tissue, metastatic lymph nodes and plasma from treatment-naïve patients with advanced non-squamous non-small cell lung cancer (NSCLC) and applied to capture-based sequencing using a panel consisting 56 NSCLC-related genes to interrogate the heterogeneity and similarity among the 3 sites. RESULTS: We observed 62.0% (67/108) by-variant concordance rate among primary tumor, metastatic lymph nodes and plasma as well as 76.4% (81/106) by-variant concordance rate between primary tumor and metastatic lymph nodes. When the analysis restricted to driver genes, we achieved 60.9% (28/46) and 77.3% (34/44) concordance, respectively. Furthermore, there is no statistically significant difference in progression-free survival (PFS) of 17 patients who used matched targeted therapy between patients having 100% concordance rate between primary tumor and metastatic lymph nodes and patients having partially matched mutational profiles. CONCLUSION: Collectively, our study revealed a similar genetic profile shared between primary tumor and metastatic lymph nodes. The limited discordance observed can be partially reflected by plasma. Sequencing results obtained from either site can be utilized for providing treatment guidance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Neoplasias Pulmonares/genética , Linfonodos/fisiologia , Metástase Linfática/genética , Adulto , Idoso , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Transcriptoma
20.
Plast Reconstr Surg ; 142(3): 688-697, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29927833

RESUMO

BACKGROUND: Vascularized lymph node transfer is a promising surgical treatment for lymphedema. This study investigated the effect of ischemia on the lymphatic drainage efficiency of vascularized lymph node flaps and the critical ischemia time of lymph nodes. METHODS: Twenty-four lymph nodes containing groin flaps in 12 Sprague-Dawley rats were dissected. Clamping of the vascular pedicle was performed for 0, 1, 3, 5, 6, or 7 hours; then, each was allowed to reperfuse by means of the vascular pedicle for 1 hour. Perfusion and ischemic changes were assessed using indocyanine green lymphography; laser Doppler flowmetry; and histologic studies with associated lymphatic vessel endothelial hyaluronan receptor-1, CD68, 4',6-diamidino-2-phenylindole, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and glutathione assay stains. RESULTS: The mean latency period of the groin lymph node flaps was 247 ± 67, 83 ± 15, 72 ± 42, 30 ± 18, and 245 ± 85 seconds in the 0-, 1-, 3-, 5-, and 6-hour groups, respectively. Perfusion detected by laser Doppler was 85.2 ± 14.5, 87.2 ± 36.7, 129.8 ± 33.7, 140.4 ± 148.5, 156.1 ± 91.4, and 41.2 ± 34.8 perfusion units at ischemia times of 0, 1, 3, 5, 6, and 7 hours, respectively. Cell damage measured by glutathione was 46.8 ± 10.2, 67.7 ± 14.2, 62.8 ± 15.4, 126.6 ± 5.9, 259.0 ± 70.3, and 109.1 ± 27.5 at ischemia times of 0, 1, 3, 5, 6, and 7 hours, respectively. Histologically, as ischemia time increased, hemorrhage and congestion became more severe. CONCLUSIONS: The critical ischemia time of vascularized lymph nodes is 5 hours in the rodent animal model, verified by indocyanine green lymphatic fluid uptake, laser Doppler perfusion, and histologic assessments. Interestingly, lymphatic drainage and perfusion of vascularized lymph nodes were improved with an increased ischemia time before the critical 5 hours was reached.


Assuntos
Isquemia/fisiopatologia , Linfonodos/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Isquemia/etiologia , Fluxometria por Laser-Doppler , Linfonodos/diagnóstico por imagem , Linfonodos/fisiologia , Linfonodos/transplante , Linfedema/cirurgia , Linfografia , Masculino , Ratos , Ratos Sprague-Dawley , Retalhos Cirúrgicos/fisiologia , Retalhos Cirúrgicos/transplante , Fatores de Tempo
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