Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 157
Filtrar
1.
Acta Gastroenterol Belg ; 87(1): 7-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38431785

RESUMO

Background and study aims: Peroral endoscopic myotomy (POEM) is the preferred technique for the treatment of esophageal motility disorders and is less invasive than surgery. This study was performed to compare two university centers in the practice of POEM, in terms of efficacy and adverse events, for the treatment of esophageal motility disorder. Patients and methods: Retrospective comparative study of patients undergoing a POEM between September 2020 and December 2022 from the University Hospital of Liège (Belgium) and Besançon (France). The clinical success was defined by an Eckardt score ≤ 3 after the procedure. Results: Fifty-five patients were included. In both centers, 87,3% of the patients had achalasia (mostly type II), and 12,7% had another esophageal motility disorder. The use of antibiotic prophylaxis was systematic in Liège center but not in Besançon center (100% and 9.1% respectively). The mean value of the post-operative Eckardt score was 1.55± 2.48 in both center with 93.2% of patients with a score ≤ 3 (92% in Besançon and 94.74% in Liège). The rate of adverse event was generally low. There were two minor adverse events more frequent in Liège, clinical capnomediastinum and pain at day one, but they were managed with conservative treatment. Only 7.3% of the total patients had an infectious phenomenon that did not correlate with the use of antibiotic prophylaxis. Conclusion: The post-operative Eckardt score and the adverse event rate were comparable between the university centers. This study confirmed that POEM is a safe and effective technique. It also showed that using an antibiotic prophylaxis does not influence the development of infectious adverse events.


Assuntos
Acalasia Esofágica , Transtornos da Motilidade Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Humanos , Estudos Retrospectivos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Resultado do Tratamento , Miotomia/efeitos adversos , Miotomia/métodos , Acalasia Esofágica/cirurgia , Esofagoscopia/efeitos adversos , Esofagoscopia/métodos
2.
J Transl Autoimmun ; 7: 100207, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37577138

RESUMO

Background: Psoriatic arthritis (PsA), an immune-mediated chronic inflammatory skin and joint disease, affects approximately 0.27% of the adult population, and 20% of patients with psoriasis. Up to 10% of psoriasis patients are estimated for having undiagnosed PsA. Early diagnosis and treatment can prevent irreversible joint damage, disability and deformity. Questionnaires for screening to identify undiagnosed PsA patients require patient and physician involvement. Objective: To evaluate a proprietary machine learning tool (PredictAI™) developed for identification of undiagnosed PsA patients 1-4 years prior to the first time that they were suspected of having PsA (reference event). Methods: This retrospective study analyzed data of the adult population from Maccabi Healthcare Service between 2008 and 2020. We created 2 cohorts: The general adult population ("GP Cohort") including patients with and without psoriasis and the Psoriasis cohort ("PsO Cohort") including psoriasis patients only. Each cohort was divided into two non-overlapping train and test sets. The PredictAI™ model was trained and evaluated with 3 years of data predating the reference event by at least one year. Receiver operating characteristic (ROC) analysis was used to investigate the performance of the model, built using gradient boosted trees, at different specificity levels. Results: Overall, 2096 patients met the criteria for PsA. Undiagnosed PsA patients in the PsO cohort were identified with a specificity of 90% one and four years before the reference event, with a sensitivity of 51% and 38%, and a PPV of 36.1% and 29.6%, respectively. In the GP cohort and with a specificity of 99% and for the same time windows, the model achieved a sensitivity of 43% and 32% and a PPV of 10.6% and 8.1%, respectively. Conclusions: The presented machine learning tool may aid in the early identification of undiagnosed PsA patients, and thereby promote earlier intervention and improve patient outcomes.

3.
Tech Coloproctol ; 25(7): 849-855, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33978860

RESUMO

BACKGROUND: Fecal incontinence is a multifactorial problem and its etiology is complex. Various therapies are available and different success rates have been described. The aim of this study was to assess the effectiveness and safety of non-dynamic graciloplasty in patients with passive fecal incontinence. METHODS: We retrospectively studied charts of patients with fecal incontinence treated with graciloplasty at our institution from November 2015 until June 2018. Patients were included according to the following criteria: (1) presence of predominantly passive fecal incontinence and (2) presence of a lax perineal body. Primary outcome was the effectiveness, defined as a significant reduction or absence of the complaints of passive fecal incontinence at 3, 6 and 12 months after surgery. Second, we studied the safety of the procedure evaluating the complications within 30 days after surgery. RESULTS: Thirty-one patients met the inclusion criteria. Twenty-six of them, in addition to passive incontinence as the main symptom, had some degree of fecal urgency. The median age at the first visit to the outpatient clinic was 64.0 years (IQR 52-68). Most patients were female (n = 29, 94%). At 3 months after graciloplasty, 71% (22 of 31) of patients were successfully treated for their passive fecal incontinence. At 6 months, the success rate of the graciloplasty increased to 77%. At 12 months among the patients who were still seen in the clinic, the success rate was 58% (18/31). Two patients cancelled follow-up visits after 3 months, because of failure to control symptoms in 1 case. After 6 months, 9 patients were given the choice to do telephone follow-up only. Of these 11 patients without in-person follow-up, 10 were contacted 1 year after surgery and in 7 of them, the graciloplasty was effective in controlling their passive fecal incontinence for an overall success rate of 80% (25/31). Of the 26 patients with mixed passive and urge incontinence, 6 (23%) still complained of urge incontinence at 1 year. Of these patients with persistent urge incontinence, 6 underwent sacral nerve stimulation which was successful in 4. Two serious complications occurred within 30 days. A rectal perforation requiring temporary colostomy and a recto-vaginal fistula which was successfully repaired. CONCLUSION: Non-dynamic graciloplasty is an effective treatment for passive fecal incontinence. Differentiation based on subtypes of fecal incontinence might be important for a pattern-specific approach to treatment. More research is necessary to determine the right indications for more invasive treatments of fecal incontinence.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Terapia por Estimulação Elétrica , Incontinência Fecal , Doenças Retais , Canal Anal/cirurgia , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Feminino , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
World J Surg ; 44(10): 3199-3206, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32794035

RESUMO

INTRODUCTION: Since the outbreak of COVID-19, measures were taken to protect healthcare staff from infection, to prevent infection of patients admitted to the hospital and to distribute PPE according to need. To assure the proper protection without overuse of limited supply of these equipments, screening of patients before surgical or diagnostic procedure was implemented. This study evaluates the results of this screening. METHOD: All patients screened for COVID-19 before procedure warranting either general, locoregional anaesthesia or sedation were included. Screening included a symptom questionnaire by phone, PCR and HRCT chest testing. Surgical or procedural details were registered together with actions taken based on screening results. RESULTS: Three hundred ninety-eight screenings were performed on 386 patients. The symptom questionnaire was completed in 72% of screenings. In 371 screenings, PCR testing was performed and negative. HRCT chest found 18 cases where COVID-19 could not be excluded, with negative PCR testing. Three patients had their surgery postponed due to inconclusive screening, and additional measures were taken in three other patients. There were incidental findings in 14% of HRCT chest scans. DISCUSSION: Pre-operative screening will differentiate if PPE is needed for procedures and which patients can safely have elective surgery during this COVID-19 pandemic and in the times to come. HRCT chest has no additional value in the pre-operative screening of asymptomatic patients. Screening can be performed with a symptom questionnaire, and additional screening with PCR testing in high-risk patient groups should be considered.


Assuntos
Infecções Assintomáticas , Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Testes Diagnósticos de Rotina , Procedimentos Cirúrgicos Eletivos , Programas de Rastreamento/métodos , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Feminino , Humanos , Controle de Infecções/instrumentação , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , SARS-CoV-2 , Adulto Jovem
6.
United European Gastroenterol J ; 7(1): 60-68, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30788117

RESUMO

Background: Success and event rates of endoscopic ultrasound (EUS)-guided biliary drainage vary with techniques, and results from different studies remain inconsistent. Objective: We conducted a proportion meta-analysis to evaluate the efficacy and safety of EUS-guided biliary drainage and compare the outcomes of current procedures. Methods: We searched MEDLINE, Embase, Cochrane and Web of knowledge to identify studies reporting technical success, clinical success and complication rates of EUS-guided biliary drainage techniques to estimate their clinical and technical efficacy and safety. Results: We identified 17 studies including a total of 686 patients. The overall clinical success and technical success rates were respectively 84% confidence interval (CI) 95% (80-88) and 96% CI 95% (93-98) for hepaticogastrostomy, and respectively 87% CI 95% (82-91) and 95% CI 95 (91-97) for choledochoduodenostomy. Reported adverse event rates were significantly higher (p = 0.01) for hepaticogastrostomy (29% CI 95% (24-34)) compared to choledochoduodenostomy (20% CI 95% (16-25)). Compared with hepaticogastrostomy, the pooled odds ratio for the complication rate of choledochoduodenostomy was 2.01 (1.25; 3.24) (p = 0.0042), suggesting that choledochoduodenostomy might be safer than hepaticogastrostomy. Conclusion: The available literature suggests choledochoduodenostomy may be a safer approach compared to hepaticogastrostomy. Randomized controlled trials with sufficiently large cohorts are needed to compare techniques and confirm these findings.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Drenagem , Cirurgia Assistida por Computador , Ultrassonografia de Intervenção , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocostomia/métodos , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Stents , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/métodos
7.
Eur J Trauma Emerg Surg ; 44(1): 71-77, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28271148

RESUMO

PURPOSE: Few studies compare management and outcomes of obstructive colonic cancer, depending on the tumor site. We aim to evaluate the differences in patient characteristics, tumor characteristics, and outcomes of emergency surgery for obstructive right-sided versus left-sided colonic cancers. METHODS: Between 2000 and 2009, 71 consecutive patients had an emergency colectomy following strict and clear definition of obstruction in a single institution. We retrospectively analyzed pre, per, and postoperative data that were prospectively collected. RESULTS: There were 31 and 40 patients in the right and left group, respectively. Patients aged over 80 were more frequent in the right group (p = 0.03). At operation, ileocecal valve was less often competent in the right group (p = 0.03). The one-stage strategy was more frequent in the right group (p = 0.008). Patients in the right group had a higher rate of nodes invasion (p = 0.04). One- and two-year mortality rate in the right group had a tendency to be higher. CONCLUSIONS: Patients presenting with a right obstructive colonic cancer are older, have a more advanced locoregional disease, and are more often treated in a one-stage strategy than patients with a left obstructive tumor.


Assuntos
Colectomia , Neoplasias Colorretais/complicações , Medicina de Emergência , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Linfonodos/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Colectomia/mortalidade , Neoplasias Colorretais/mortalidade , Comorbidade , Feminino , Humanos , Obstrução Intestinal/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
8.
Allergy ; 72(11): 1686-1693, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28376268

RESUMO

BACKGROUND: Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of patients with atopic dermatitis (AD) carry the high-affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. OBJECTIVES: We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro-generated LC. METHODS: Epidermal cells from healthy skin were analyzed for their expression of AhR and AhRR. LC generated from CD34+ hematopoietic stem cells (CD34LC) were treated with the UV photoproduct and AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). Cell surface receptors, transcription factors, and the tolerogenic tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) were analyzed using flow cytometry and quantitative PCR. RESULTS: Epidermal LC and CD34LC express AhR and AhRR. AhR was also found in keratinocytes, which lack AhRR. AhR activation of LC by FICZ caused downregulation of FcεRI in CD34LC without affecting their maturation. AhR-mediated regulation of FcεRI did not involve any known transcription factors related to this receptor. Furthermore, we could show upregulation of IDO mediated by AhR engagement. CONCLUSIONS: Our study shows that AhR activation by FICZ reduces FcεRI and upregulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Dermatite Atópica/imunologia , Retroalimentação Fisiológica/fisiologia , Inflamação/imunologia , Células de Langerhans/metabolismo , Receptores de Hidrocarboneto Arílico/fisiologia , Adulto , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de IgE/metabolismo , Proteínas Repressoras/metabolismo
9.
Colloids Surf B Biointerfaces ; 143: 7-14, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26998862

RESUMO

Stable, non-agglomerated TiO2 nanoparticle (NP) dispersions are a crucial requirement for an accurate NP dosing in in vitro and in vivo experiments. In this study self-synthesised TiO2 NPs were stabilised in three different cell culture media (DMEM, RPMI, BEGM) with the help of stabilising agents. Cell culture tested stabilisers (bovine serum albumin, fetal bovine serum) were compared to non-tested commercial products which are commonly utilized in the cement industry (Melflux(®) 4930 F, Melpers(®) 4343, Sika(®) ViscoCrete(®)-10110178). For a quantitative evaluation and comparison of the degree of stabilisation, a sedimentation study using UV absorbance spectroscopy was carried out and the agglomerate size was measured via dynamic light scattering. The cytotoxicity of the novel surfactants and stabilised NPs was examined in a head and neck squamous cell carcinoma-derived FaDu cell line and in human mesenchymal stem cells. We successfully stabilised TiO2 NPs with Melflux(®) 4930 F in each cell culture medium, achieving perfect stability over at least one day and agglomerate sizes of less than 100nm, while the cytotoxicity of the NPs was not affected.


Assuntos
Ácidos Carboxílicos/química , Éteres/química , Nanopartículas Metálicas/química , Titânio/química , Animais , Ácidos Carboxílicos/farmacologia , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/química , Éteres/farmacologia , Floculação/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Polimerização , Cultura Primária de Células , Soroalbumina Bovina/química , Soluções , Tensoativos/química , Titânio/farmacologia
11.
Int J Stroke ; 9(4): 394-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24898282

RESUMO

BACKGROUND AND PURPOSE: The study aims to compare lipid profiles among ischemic stroke patients in a predominantly Caribbean-Hispanic population in Miami and a Mestizo Hispanic population in Mexico City. METHODS: We analyzed ischemic stroke Hispanic patients with complete baseline fasting lipid profile enrolled contemporaneously in the prospective registries of two tertiary care teaching hospitals in Mexico City and Miami. Demographic characteristics, risk factors, medications, ischemic stroke subtype, and first fasting lipid profile were compared. Vascular risk factor definitions were standardized. Multiple linear regression analysis was performed to compare lipid fractions. RESULTS: A total of 324 patients from Mexico and 236 from Miami were analyzed. Mexicans were significantly younger (58 · 1 vs. 67 · 4 years), had a lower frequency of hypertension (53 · 4% vs. 79 · 7%), and lower body mass index (27 vs. 28 · 5). There was a trend toward greater prevalence of diabetes in Mexicans (31 · 5 vs. 24 · 6%, P = 0 · 07). Statin use at the time of ischemic stroke was more common in Miami Hispanics (18 · 6 vs. 9 · 4%). Mexicans had lower total cholesterol levels (169 · 9 ± 46 · 1 vs. 179 · 9 ± 48 · 4 mg/dl), lower low-density lipoprotein (92 · 3 ± 37 · 1 vs. 108 · 2 ± 40 · 8 mg/dl), and higher triglyceride levels (166 · 9 ± 123 · 9 vs. 149 · 2 ± 115 · 2 mg/dl). These differences remained significant after adjusting for age, gender, hypertension, diabetes, body mass index, smoking, ischemic stroke subtype, and statin use. CONCLUSION: We found significant differences in lipid fractions in Hispanic ischemic stroke patients, with lower total cholesterol and low-density lipoprotein, and higher triglyceride levels in Mexicans. These findings highlight the heterogeneity of dyslipidemia among the Hispanic race-ethnic group and may lead to different secondary prevention strategies.


Assuntos
Isquemia/epidemiologia , Transtornos do Metabolismo dos Lipídeos/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hispânico ou Latino , Hospitais de Ensino/estatística & dados numéricos , Humanos , Isquemia/complicações , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
12.
Allergy ; 68(7): 890-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23742057

RESUMO

BACKGROUND: A unique type of CD11c(pos) dendritic cells (DC) is abundant in inflamed tissue, for example, in chronic inflammatory skin diseases. Due to their remarkable production of tumor necrosis factor (TNF)-α and inducible NO synthase (iNOS), these cells have been referred to as TNF and iNOS-producing DC (Tip-DC). While Tip-DC have been mainly characterized in murine models of infection, functional data about their human counterpart are lacking. OBJECTIVES: We sought to generate human Tip-DC in vitro und thus provide a new model for the investigation of their phenotype and function. METHODS: We generated human Tip-DC from monocytic precursor cells of healthy individuals, atopic and psoriatic patients using human serum. Resting and stimulated cells were analyzed by flow cytometry, real-time PCR, and by ELISA. INOS activity was measured by fluorometric detection of NO. RESULTS: Tip-DC closely resembled their in vivo counterparts by expressing CD11c, CD86, and CD40 while lacking CD1a, CD1c, or CD207/Langerin. Bacterial stimulation of Tip-DC from healthy donors, atopic dermatitis, or psoriasis patients resulted in a similar increase in iNOS activity and TNF-α production. In kinetic experiments, TNF-α, a putative activator of Tip-DC, could not induce NOS2. Upon bacterial stimulation, TNFA, IL6, IL12B, and IL23A mRNA appeared in a first wave, while IL12A and NOS2 mRNA were up-regulated later on but not blocked by anti-TNF-α agents, implying a biphasic pro-inflammatory response. CONCLUSIONS: We developed a new model for the study of human Tip-DC and provide the first evidence of their pro-inflammatory capacity.


Assuntos
Citocinas/metabolismo , Células Dendríticas/imunologia , Óxido Nítrico Sintase Tipo II/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Animais , Células Cultivadas , Citocinas/imunologia , Células Dendríticas/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/fisiopatologia , Citometria de Fluxo , Humanos , Camundongos , Monócitos/imunologia , Monócitos/metabolismo , Óxido Nítrico Sintase Tipo II/imunologia , Psoríase/imunologia , Psoríase/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/imunologia
13.
Leukemia ; 27(12): 2301-10, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23508117

RESUMO

Fms-like tyrosine kinase-3 is a commonly mutated gene in acute myeloid leukemia, with about one-third of patients carrying an internal-tandem duplication of the juxtamembrane domain in the receptor (FLT3-ITD). FLT3-ITD exhibits altered signaling quality, including aberrant activation of STAT5. To identify genes affecting FLT3-ITD-mediated STAT5 signaling, we performed an esiRNA-based RNAi screen utilizing a STAT5-driven reporter assay. Knockdowns that caused reduced FLT3-ITD-mediated STAT5 signaling were enriched for genes encoding proteins involved in protein secretion and intracellular protein transport, indicating that modulation of protein transport processes could potentially be used to reduce constitutive STAT5 signaling in FLT3-ITD-positive cells. The relevance of KDELR1, a component involved in the Golgi-ER retrograde transport, was further analyzed. In FLT3-ITD-expressing leukemic MV4-11 cells, downregulation of KDELR1 resulted in reduced STAT5 activation, proliferation and colony-forming capacity. Stable shRNA-mediated depletion of KDELR1 in FLT3-ITD-expressing 32D cells likewise resulted in reduced STAT5 signaling and cell proliferation. Importantly, these cells also showed a reduced capacity to generate a leukemia-like disease in syngeneic C3H/HeJ mice. Together our data suggest intracellular protein transport as a potential target for FLT3-ITD driven leukemias, with KDELR1 emerging as a positive modulator of oncogenic FLT3-ITD activity.


Assuntos
Genoma , Proteínas/fisiologia , Interferência de RNA , Transdução de Sinais/fisiologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Animais , Sequência de Bases , Primers do DNA , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT5/metabolismo
14.
Allergy ; 68(5): 621-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23534406

RESUMO

BACKGROUND: Epidermal Langerhans cells (LC) expressing the high-affinity receptor for IgE (FcεRI) play a key role in atopic dermatitis (AD). AD skin is highly colonized with Staphylococcus aureus (S.a.), which are sensed by Toll-like receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of FcεRI on LC. OBJECTIVES: To study a putative impact of TLR2 signaling on FcεRI, we analyzed FcεRI and known transcription factors of the receptor after ligand binding to TLR2. METHODS: We generated LC from CD34(+) progenitors in vitro (CD34LC) expressing FcεRI and TLR2 as well as its partners TLR1 and TLR6. The expression of FcεRI and known transcription factors of the receptor was analyzed on the protein and RNA level by flow cytometry, Western blotting, and real-time PCR. RESULTS: For CD34LC from 123 donors, we observed a high heterogeneity in FcεRI surface expression correlating with mRNA level of its α-chain. Stimulation of TLR1/2 or TLR2/6 dramatically down-regulated FcεRI on protein and mRNA level of both α- and γ-chain. Further analysis of putative transcription factors for FCER1A revealed the lack of GATA1 in CD34LC, weak expression of ELF1 and YY1, and high expression of PU.1. While ELF1 and YY1 appeared to be little affected by TLR2 engagement, PU.1 was significantly down-regulated. CONCLUSIONS: Taken together, our findings show that in human, LC ligation of TLR2 by S.a.-derived products down-regulates FcεRI and its transcription factor PU.1, thus suggesting that FcεRI is controlled by PU.1 in these cells.


Assuntos
Células de Langerhans/metabolismo , Proteínas Proto-Oncogênicas/genética , Receptores de IgE/genética , Receptor 2 Toll-Like/metabolismo , Transativadores/genética , Antígenos CD34/metabolismo , Células Cultivadas , Expressão Gênica , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Humanos , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Receptores de IgE/metabolismo , Receptor 1 Toll-Like/genética , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Receptor 6 Toll-Like/genética , Receptor 6 Toll-Like/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Z Gastroenterol ; 51(2): 213-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23417367

RESUMO

A 71-year-old woman suffering from mild anemia with an hemoglobin level of 10.7 g/dL (normal ≥ 12 g/dL) was referred to our unit for further endoscopic evaluation. Upper gastrointestinal endoscopy revealed no abnormal findings. Colonoscopy detected a smoothly lined, thin and worm-like polyp measuring 6 cm in length with minor erosions on its surface. It was located in the left transverse colon. Microscopic examination of the resected specimen disclosed the very rare case of a colonic polypoid cavernous hemangioma. Recurrent latent bleeding from this lesion could be responsible for the observed mild anemia in this patient. A review of the literature and suggestions for endoscopic treatment are given.


Assuntos
Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemangioma Cavernoso/diagnóstico , Idoso , Anemia Ferropriva/etiologia , Anemia Ferropriva/patologia , Neoplasias do Colo/cirurgia , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia , Diagnóstico Diferencial , Feminino , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/cirurgia , Hemangioma Cavernoso/patologia , Hemangioma Cavernoso/cirurgia , Humanos
16.
Mucosal Immunol ; 6(1): 136-45, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22763408

RESUMO

The molecular mechanisms that restore intestinal epithelial homeostasis during colitis are incompletely understood. Here, we report that during intestinal inflammation, multiple inflammatory cytokines promote the activity of a master regulator of cell proliferation and apoptosis, serine/threonine kinase CK2. Enhanced mucosal CK2 protein expression and activity were observed in animal models of chronic colitis, particularly within intestinal epithelial cells (IECs). The in vitro treatment of intestinal epithelial cell lines with cytokines resulted in increased CK2 expression and nuclear translocation of its catalytic α subunit. Similarly, nuclear translocation of CK2α was a prominent feature observed in colonic crypts from individuals with ulcerative colitis and Crohn's disease. Further in vitro studies revealed that CK2 activity promotes epithelial restitution, and protects normal IECs from cytokine-induced apoptosis. These observations identify CK2 as a key regulator of homeostatic properties of the intestinal epithelium that serves to promote wound healing, in part through inhibition of apoptosis under conditions of inflammation.


Assuntos
Caseína Quinase II/metabolismo , Colite/imunologia , Colite/metabolismo , Homeostase/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Animais , Apoptose/genética , Caseína Quinase II/genética , Caspases/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Proliferação de Células , Colite/induzido quimicamente , Colite/genética , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Camundongos , Transporte Proteico , Ratos , Cicatrização , beta Catenina/metabolismo
17.
PLoS Pathog ; 8(9): e1002889, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23028307

RESUMO

CD8(+) T-cell responses against latent viruses can cover considerable portions of the CD8(+) T-cell compartment for many decades, yet their initiation and maintenance remains poorly characterized in humans. A key question is whether the clonal repertoire that is raised during the initial antiviral response can be maintained over these long periods. To investigate this we combined next-generation sequencing of the T-cell receptor repertoire with tetramer-sorting to identify, quantify and longitudinally follow virus-specific clones within the CD8(+) T-cell compartment. Using this approach we studied primary infections of human cytomegalovirus (hCMV) and Epstein Barr virus (EBV) in renal transplant recipients. For both viruses we found that nearly all virus-specific CD8(+) T-cell clones that appeared during the early phase of infection were maintained at high frequencies during the 5-year follow-up and hardly any new anti-viral clones appeared. Both in transplant recipients and in healthy carriers the clones specific for these latent viruses were highly dominant within the CD8(+) T-cell receptor Vß repertoire. These findings suggest that the initial antiviral response in humans is maintained in a stable fashion without signs of contraction or changes of the clonal repertoire.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Receptores de Antígenos de Linfócitos T/genética , Antígenos Virais/imunologia , Citomegalovirus/genética , Herpesvirus Humano 4/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Transplante de Rim/imunologia , Pessoa de Meia-Idade , Fatores de Tempo , Latência Viral , Adulto Jovem
18.
Z Geburtshilfe Neonatol ; 216(2): 77-81, 2012 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-22517048

RESUMO

Smoking during pregnancy is a major risk factor for intrauterine growth retardation. The aim of the Thuringian SGA - (small-for-gestational-age) - study was to evaluate the effects of maternal smoking during pregnancy on birth weight and length as well as postnatal growth dynamics and catch-up growth.Between 1992 and 2002 in all 2 447 liveborn children were assessed with birth weight (GG) <10th percentile and/or birth length (GL) <- 2.0 SDS. A questionnaire was sent to 383 parents of severe SGA children (GG and/or GL <- 2.5 SDS) to report weight and height of the children actually. 108 reports could analysed (mean age 8.0±3.4 years of life).The number of SGA babies in regard to all liveborn children decreased from 14.1% to 9.4% between 1992 and 2002. 14% of SGA babies were born preterm. The mean nicotine abuse was 2 cigarettes per day (range 0-40). 17.6% of the mothers of SGA babies were smoking, whereas in severe SGA 26.9% of smokers was recorded. There is a inverse correlation of nicotine abuse with birth weight (r=- 0.09; p<0.01) or birth length (r=- 0.08; p<0.01). Catch-up growth did not exist in 30.6% of the severe growth restricted children. The risk for short stature in later life was doubled in SGA children.Nicotine abuse during pregnancy is a risk factor for an SGA baby and could have long-lasting effects on growth dynamics during childhood with a lack of catch-up growth.


Assuntos
Anormalidades Craniofaciais/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Peso ao Nascer , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Gravidez , Medição de Risco , Fatores de Risco , Adulto Jovem
19.
Nat Commun ; 2: 600, 2011 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-22186896

RESUMO

Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-γ-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.


Assuntos
Adenocarcinoma/imunologia , Anticorpos Neutralizantes/uso terapêutico , Fatores de Transcrição Forkhead/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Pulmonares/imunologia , Pulmão/imunologia , Proteínas com Domínio T/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Administração Intranasal , Adulto , Idoso , Animais , Anticorpos Neutralizantes/administração & dosagem , Antígenos CD/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Vigilância Imunológica , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/imunologia , Linfócitos T Reguladores/imunologia
20.
Endoscopy ; 43(8): 664-70, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21623560

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technique for "en bloc" resection of superficial tumors of the gastrointestinal tract. In France, experience with this technique is still limited. We wanted to assess the development of ESD in France, with special attention to short term outcomes. PATIENTS AND METHODS: Members of the Société Française d'Endoscopie Digestive (SFED) who declared performing ESD reported their cases prospectively on a voluntary basis. Demographic, clinical, and technical data, and the results of immediate complications were collected. Case reports were completed prospectively by each investigator before pooled analysis. RESULTS: A total of 188 consecutive case reports were collected from 16 centers. The median case mix per center was 6 patients (range 1-43). The lesion sites treated by ESD were the stomach (n = 75), esophagus (n = 27), duodenum (n = 1), cecum (n = 2), right colon (n = 3), transverse colon (n = 5), sigmoid (n = 3), and rectum (n = 72). The median size of the lesions was 26 mm (range 2-150 mm). En bloc resection was achieved in 77.1% of cases, with complete R0 resection in 72.9%. Histopathology results showed high grade dysplasia or superficial cancer in 71.2%. The median duration of ESD was 105 minutes (range 20-450 minutes). The short term morbidity was 29.2% including 34 cases of perforation (18.1%), and 21 hemorrhages (11.2%) during the 24 hours following ESD, 89% of which were managed conservatively or endoscopically. CONCLUSION: In this early experience, the feasibility of ESD appeared to be good but R0 resection and complication rates did not match those reported by Japanese authors and must be improved by an extended practice.


Assuntos
Dissecação/métodos , Endoscopia Gastrointestinal/métodos , Mucosa Gástrica/cirurgia , Neoplasias Gastrointestinais/cirurgia , Mucosa Intestinal/cirurgia , Perfuração Intestinal/etiologia , Hemorragia Pós-Operatória/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Dissecação/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , França , Neoplasias Gastrointestinais/patologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA