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1.
Nat Commun ; 12(1): 1009, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579927

RESUMO

Self-reactive CD8+ T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we characterize the transcriptional and epigenetic landscape of self-reactive CD8+ T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8+ T cells emerging from acute viral infection. We find that autoimmune CD8+ T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling. This self-reactive CD8+ T cell fate depends on the transcriptional regulation by the DNA-binding HMG-box protein TOX which remodels more than 400 genomic regions including loci such as Tcf7, which is central to stemness of CD8+ T cells. Continuous exposure to CNS self-antigen sustains TOX levels in self-reactive CD8+ T cells, whereas genetic ablation of TOX in CD8+ T cells results in shortened persistence of self-reactive CD8+ T cells in the inflamed CNS. Our study establishes and characterizes the genetic differentiation program enabling chronic T cell-driven immunopathology in CNS autoimmunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Sistema Nervoso Central/metabolismo , Montagem e Desmontagem da Cromatina , Animais , Autoimunidade/imunologia , Feminino , Regulação da Expressão Gênica , Memória Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
2.
Commun Biol ; 3(1): 720, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247183

RESUMO

Immunotherapies targeting the PD-1/PD-L1 axis are now a mainstay in the clinical management of multiple cancer types, however, many tumors still fail to respond. CCL2 is highly expressed in various cancer types and has been shown to be associated with poor prognosis. Inhibition or blockade of the CCL2/CCR2 signaling axis has thus been an area of interest for cancer therapy. Here we show across multiple murine tumor and metastasis models that CCR2 antagonism in combination with anti-PD-1 therapy leads to sensitization and enhanced tumor response over anti-PD-1 monotherapy. We show that enhanced treatment response correlates with enhanced CD8+ T cell recruitment and activation and a concomitant decrease in CD4+ regulatory T cell. These results provide strong preclinical rationale for further clinical exploration of combining CCR2 antagonism with PD-1/PD-L1-directed immunotherapies across multiple tumor types especially given the availability of small molecule CCR2 inhibitors and antibodies.

3.
J Clin Transl Sci ; 4(1): 73, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32257414

RESUMO

[This corrects the article DOI: 10.1017/cts.2019.4.].

5.
J Clin Transl Sci ; 3(2-3): 105-112, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31660233

RESUMO

Introduction: Core facilities play crucial roles in carrying out the academic research mission by making available to researchers advanced technologies, facilities, or expertise that are unfeasible for most investigators to obtain on their own. To facilitate translational science through support of core services, the University of California, Los Angeles Clinical and Translational Science Institute (UCLA CTSI) created a Core Voucher program. The underlying premise is that by actively promoting interplay between researchers and core facilities, a dynamic feedback loop could be established that could enhance both groups, the productivity of the former and the relevance of the latter. Our primary goal was to give translational investigators what they need to pursue their immediate projects at hand. Methods: To implement this system across four noncontiguous campuses, open-source web-accessible software applications were created that were scalable and could efficiently administer investigator submissions and subsequent reviews in a multicampus fashion. Results: In the past five years, we have processed over 1400 applications submitted by over 750 individual faculty members across both clinical and nonclinical departments. In total, 1926 core requests were made in conjunction with 1467 submitted proposals. The top 10 most popular cores accounted for 50% of all requests, and the top half of the most popular cores accounted for 90% of all requests. Conclusion: Tracking investigator demand provides a unique window into what are the high- and low-priority core services that best support translational research.

6.
Nature ; 571(7764): 211-218, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31207603

RESUMO

Exhausted CD8+ T (Tex) cells in chronic infections and cancer have limited effector function, high co-expression of inhibitory receptors and extensive transcriptional changes compared with effector (Teff) or memory (Tmem) CD8+ T cells. Tex cells are important clinical targets of checkpoint blockade and other immunotherapies. Epigenetically, Tex cells are a distinct immune subset, with a unique chromatin landscape compared with Teff and Tmem cells. However, the mechanisms that govern the transcriptional and epigenetic development of Tex cells remain unknown. Here we identify the HMG-box transcription factor TOX as a central regulator of Tex cells in mice. TOX is largely dispensable for the formation of Teff and Tmem cells, but it is critical for exhaustion: in the absence of TOX, Tex cells do not form. TOX is induced by calcineurin and NFAT2, and operates in a feed-forward loop in which it becomes calcineurin-independent and sustained in Tex cells. Robust expression of TOX therefore results in commitment to Tex cells by translating persistent stimulation into a distinct Tex cell transcriptional and epigenetic developmental program.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Epistasia Genética , Proteínas de Homeodomínio/metabolismo , Transcrição Genética , Animais , Calcineurina/metabolismo , Sinalização do Cálcio , Retroalimentação Fisiológica , Feminino , Regulação da Expressão Gênica/imunologia , Genótipo , Memória Imunológica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Evasão Tumoral
7.
Nature ; 571(7764): 270-274, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31207604

RESUMO

Tumour-specific CD8 T cell dysfunction is a differentiation state that is distinct from the functional effector or memory T cell states1-6. Here we identify the nuclear factor TOX as a crucial regulator of the differentiation of tumour-specific T (TST) cells. We show that TOX is highly expressed in dysfunctional TST cells from tumours and in exhausted T cells during chronic viral infection. Expression of TOX is driven by chronic T cell receptor stimulation and NFAT activation. Ectopic expression of TOX in effector T cells in vitro induced a transcriptional program associated with T cell exhaustion. Conversely, deletion of Tox in TST cells in tumours abrogated the exhaustion program: Tox-deleted TST cells did not upregulate genes for inhibitory receptors (such as Pdcd1, Entpd1, Havcr2, Cd244 and Tigit), the chromatin of which remained largely inaccessible, and retained high expression of transcription factors such as TCF-1. Despite their normal, 'non-exhausted' immunophenotype, Tox-deleted TST cells remained dysfunctional, which suggests that the regulation of expression of inhibitory receptors is uncoupled from the loss of effector function. Notably, although Tox-deleted CD8 T cells differentiated normally to effector and memory states in response to acute infection, Tox-deleted TST cells failed to persist in tumours. We hypothesize that the TOX-induced exhaustion program serves to prevent the overstimulation of T cells and activation-induced cell death in settings of chronic antigen stimulation such as cancer.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Diferenciação Celular/imunologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias/imunologia , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/deficiência , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Homeodomínio/genética , Humanos , Memória Imunológica , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Camundongos , Neoplasias/patologia , Fenótipo , Receptores de Antígenos de Linfócitos T/imunologia , Transcrição Genética
9.
Nat Commun ; 9(1): 2878, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-30038333

RESUMO

The soft tissues of many fossil vertebrates preserve evidence of melanosomes-micron-scale organelles that inform on integumentary coloration and communication strategies. In extant vertebrates, however, melanosomes also occur in internal tissues. Hence, fossil melanosomes may not derive solely from the integument and its appendages. Here, by analyzing extant and fossil frogs, we show that non-integumentary melanosomes have high fossilization potential, vastly outnumber those from the skin, and potentially dominate the melanosome films preserved in some fossil vertebrates. Our decay experiments show that non-integumentary melanosomes usually remain in situ provided that carcasses are undisturbed. Micron-scale study of fossils, however, demonstrates that non-integumentary melanosomes can redistribute through parts of the body if carcasses are disturbed by currents. Collectively, these data indicate that fossil melanosomes do not always relate to integumentary coloration. Integumentary and non-integumentary melanosomes can be discriminated using melanosome geometry and distribution. This is essential to accurate reconstructions of the integumentary colours of fossil vertebrates.


Assuntos
Anuros/fisiologia , Cor , Fósseis , Melanossomas/metabolismo , Xenopus/fisiologia , Animais , Evolução Biológica , Plumas , Iguanas/fisiologia , Melaninas/química , Pigmentação , Pele/metabolismo , Vertebrados , Xenopus laevis
10.
Immunity ; 48(5): 937-950.e8, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29768177

RESUMO

Infections are thought to trigger CD8+ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in CTLs during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection. TOX repressed the activity of several transcription factors (including Id2, TCF-1, and Notch) that are known to drive CTL differentiation. TOX also reduced immune checkpoint sensitivity by restraining the expression of the inhibitory checkpoint receptor CD244 on the surface of CTLs, leading to increased CTL-mediated damage in the CNS. Our results identify TOX as a transcriptional regulator of tissue-destructive CTLs in autoimmunity, offering a potential mechanistic link to microbial triggers.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Proteínas de Homeodomínio/imunologia , Coriomeningite Linfocítica/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Adulto , Idoso , Animais , Autoimunidade/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Linfócitos T Citotóxicos/imunologia
11.
J Exp Med ; 215(1): 249-262, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29183988

RESUMO

Early innate lymphoid progenitors (EILPs) have recently been identified in mouse adult bone marrow as a multipotential progenitor population specified toward innate lymphoid cell (ILC) lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic approaches collectively establish EILPs as an intermediate progenitor between ALPs and ILCps. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.


Assuntos
Diferenciação Celular , Imunidade Inata , Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/metabolismo , Animais , Biomarcadores , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Citocinas/metabolismo , Fator de Transcrição GATA3/metabolismo , Perfilação da Expressão Gênica , Imunofenotipagem , Subpopulações de Linfócitos/citologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Células Progenitoras Linfoides/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Fenótipo
12.
Nat Commun ; 8(1): 1900, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196657

RESUMO

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show induction of a molecularly distinct subset of activated lung ILC2, termed ILC210. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC210 are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC210. In vivo, IL-2 enhances ILC210 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC210 population contracts after cessation of stimulation in vivo, with maintenance of a subset that can be recalled by restimulation, analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population.


Assuntos
Imunidade Inata , Linfócitos/imunologia , Animais , Células Cultivadas , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Pulmão/citologia , Pulmão/imunologia , Ativação Linfocitária , Linfócitos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th2/imunologia
13.
J Eukaryot Microbiol ; 64(3): 407-411, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28337822

RESUMO

Universal taxonomic frameworks have been critical tools to structure the fields of botany, zoology, mycology, and bacteriology as well as their large research communities. Animals, plants, and fungi have relatively solid, stable morpho-taxonomies built over the last three centuries, while bacteria have been classified for the last three decades under a coherent molecular taxonomic framework. By contrast, no such common language exists for microbial eukaryotes, even though environmental '-omics' surveys suggest that protists make up most of the organismal and genetic complexity of our planet's ecosystems! With the current deluge of eukaryotic meta-omics data, we urgently need to build up a universal eukaryotic taxonomy bridging the protist -omics age to the fragile, centuries-old body of classical knowledge that has effectively linked protist taxa to morphological, physiological, and ecological information. UniEuk is an open, inclusive, community-based and expert-driven international initiative to build a flexible, adaptive universal taxonomic framework for eukaryotes. It unites three complementary modules, EukRef, EukBank, and EukMap, which use phylogenetic markers, environmental metabarcoding surveys, and expert knowledge to inform the taxonomic framework. The UniEuk taxonomy is directly implemented in the European Nucleotide Archive at EMBL-EBI, ensuring its broad use and long-term preservation as a reference taxonomy for eukaryotes.


Assuntos
Classificação , Eucariotos/classificação , Animais , Bactérias/classificação , Biodiversidade , Bases de Dados de Ácidos Nucleicos , Ecossistema , Meio Ambiente , Eucariotos/citologia , Eucariotos/genética , Eucariotos/fisiologia , Células Eucarióticas , Fungos/classificação , Filogenia
14.
Nat Rev Microbiol ; 15(1): 6-20, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27867198

RESUMO

Protists, which are single-celled eukaryotes, critically influence the ecology and chemistry of marine ecosystems, but genome-based studies of these organisms have lagged behind those of other microorganisms. However, recent transcriptomic studies of cultured species, complemented by meta-omics analyses of natural communities, have increased the amount of genetic information available for poorly represented branches on the tree of eukaryotic life. This information is providing insights into the adaptations and interactions between protists and other microorganisms and macroorganisms, but many of the genes sequenced show no similarity to sequences currently available in public databases. A better understanding of these newly discovered genes will lead to a deeper appreciation of the functional diversity and metabolic processes in the ocean. In this Review, we summarize recent developments in our understanding of the ecology, physiology and evolution of protists, derived from transcriptomic studies of cultured strains and natural communities, and discuss how these novel large-scale genetic datasets will be used in the future.


Assuntos
Organismos Aquáticos/fisiologia , Metabolismo Energético/fisiologia , Eucariotos/fisiologia , Transcriptoma/genética , Organismos Aquáticos/genética , Evolução Biológica , Ecossistema , Eucariotos/genética
15.
Bio Protoc ; 6(6)2016 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-27239483

RESUMO

Subtypes of innate lymphoid cells (ILC), defined based on their cytokine secretion profiles and transcription factor expression, are important for host protection from pathogens and maintaining tissue homeostasis. ILCs develop from common lymphoid progenitors (CLP) in the bone marrow. Using the methods described here, we have previously shown that loss of the transcriptional regulator TOX (Thymocyte-selection associated HMG-box protein) leads to specific changes in ILC development and differentiation. Here, we describe how to obtain ILCs from in vivo isolated CLP grown in vitro.

16.
Mediators Inflamm ; 2015: 243868, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26556952

RESUMO

TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.


Assuntos
Proteínas de Grupo de Alta Mobilidade/fisiologia , Imunidade Inata , Linfócitos/imunologia , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Linhagem da Célula , Humanos , Células Matadoras Naturais/imunologia
18.
Nat Immunol ; 16(6): 599-608, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25915732

RESUMO

Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.


Assuntos
Proteínas de Homeodomínio/metabolismo , Células Matadoras Naturais/fisiologia , Subpopulações de Linfócitos/fisiologia , Células Progenitoras Linfoides/fisiologia , Receptores Notch/metabolismo , Animais , Células da Medula Óssea/fisiologia , Diferenciação Celular/genética , Linhagem da Célula/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Feminino , Proteínas de Homeodomínio/genética , Imunidade Inata/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores Notch/genética , Transcriptoma
19.
BMC Cancer ; 15: 22, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25632947

RESUMO

BACKGROUND: A breast cancer susceptibility locus has been mapped to the gene encoding TOX3. Little is known regarding the expression pattern or biological role of TOX3 in breast cancer or in the mammary gland. Here we analyzed TOX3 expression in murine and human mammary glands and in molecular subtypes of breast cancer, and assessed its ability to alter the biology of breast cancer cells. METHODS: We used a cell sorting strategy, followed by quantitative real-time PCR, to study TOX3 gene expression in the mouse mammary gland. To study the expression of this nuclear protein in human mammary glands and breast tumors, we generated a rabbit monoclonal antibody specific for human TOX3. In vitro studies were performed on MCF7, BT474 and MDA-MB-231 cell lines to study the effects of TOX3 modulation on gene expression in the context of breast cancer cells. RESULTS: We found TOX3 expression in estrogen receptor-positive mammary epithelial cells, including progenitor cells. A subset of breast tumors also highly expresses TOX3, with poor outcome associated with high expression of TOX3 in luminal B breast cancers. We also demonstrate the ability of TOX3 to alter gene expression in MCF7 luminal breast cancer cells, including cancer relevant genes TFF1 and CXCR4. Knockdown of TOX3 in a luminal B breast cancer cell line that highly expresses TOX3 is associated with slower growth. Surprisingly, TOX3 is also shown to regulate TFF1 in an estrogen-independent and tamoxifen-insensitive manner. CONCLUSIONS: These results demonstrate that high expression of this protein likely plays a crucial role in breast cancer progression. This is in sharp contrast to previous studies that indicated breast cancer susceptibility is associated with lower expression of TOX3. Together, these results suggest two different roles for TOX3, one in the initiation of breast cancer, potentially related to expression of TOX3 in mammary epithelial cell progenitors, and another role for this nuclear protein in the progression of cancer. In addition, these results can begin to shed light on the reported association of TOX3 expression and breast cancer metastasis to the bone, and point to TOX3 as a novel regulator of estrogen receptor-mediated gene expression.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/genética , Animais , Proteínas Reguladoras de Apoptose , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Ligantes , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Camundongos , Prognóstico , Receptores de Progesterona/metabolismo , Transativadores
20.
J Pediatr Urol ; 9(1): 51-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22177779

RESUMO

OBJECTIVE: The objective of this study was to evaluate risk factors for new contralateral vesicoureteral reflux (NCVUR) and to investigate whether assessment of the non-refluxing contralateral ureter (NRCU) by hydrodistention and selective treatment can reduce the incidence of NCVUR. MATERIALS AND METHODS: From 2001 to 2007, 339 of 841 patients (40%) were treated for unilateral VUR by endoscopic injection. While in the first 267 patients the NRCU was only assessed by hydrodistention but not injected (observation group), NRCUs of the subsequent 72 patients were prophylactically treated if deemed at high risk for NCVUR (H2 or H3) (prophylaxis group). RESULTS: NCVUR occurred in 30 of 267 patients (11.2%) whose NRCUs were observed. No statistically significant risk factors for NCVUR were found in this group. In the subsequent 72 patients, whose H2 and H3 ureters were selectively injected (N = 56), no cases of NCVUR were seen. CONCLUSIONS: Prophylactic endoscopic treatment of NRCU H2 and H3 ureters successfully prevented the occurrence of NCVUR.


Assuntos
Dextranos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Ureter , Refluxo Vesicoureteral/tratamento farmacológico , Refluxo Vesicoureteral/prevenção & controle , Adolescente , Criança , Pré-Escolar , Endoscopia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Injeções Intralesionais/métodos , Masculino , Fatores de Risco , Prevenção Secundária , Resultado do Tratamento , Refluxo Vesicoureteral/epidemiologia
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