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1.
World J Urol ; 39(3): 943-951, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32436072

RESUMO

PURPOSE: To improve outcome prediction of extracorporeal shock wave lithotripsy (SWL) by development of a model based on easily available clinical and radiographical predictors and suitable for daily clinical use. MATERIALS AND METHODS: We evaluated predictive factors for SWL success in 517 consecutive patients suffering from urinary calculi who underwent SWL between 2010 and 2018. Analyses included descriptive statistics, receiver operating characteristic statistics and logistic regression. Predictive value was improved by combining parameters using model selection and recursive partitioning. RESULTS: Of the 517 patients, 310 (60.0%) had a successful SWL. Best individual predictor of SWL success was mean attenuation (MAV), with an area under the curve (AUC) of 0.668, and an optimal cutpoint (OC) of 987.5 HU. The best multivariable model, including MAV, stone size, skin to stone distance (SSD), presence of an indwelling stent, and four interaction effects, yielded an AUC of 0.736. Recursive partitioning would categorize patients into three outcome groups with high (76.9%), intermediate (41%) and low (10%) success probability. High probability of SWL success (76.9%) was found for patients with a stone with MAV ≤ 987 HU or with MAV > 987 HU but stone size ≤ 11 mm and SSD (45°) ≤ 88 mm. CONCLUSION: A model based on four established predictors, and provided as an Excel®-Tool, can clearly improve prediction of SWL success. In addition, patients can be classified into three defined outcome groups based on simple cutpoint combinations. Both tools improve informed decision-making in daily clinical practice and might reduce failure rates.


Assuntos
Litotripsia , Cálculos Urinários/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Rev Chil Pediatr ; 85(2): 174-82, 2014 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-25697205

RESUMO

INTRODUCTION: To determine the epidemiological profile of pediatric consultations treated at the emergency department (ED) is essential for planning processes of medical care and to guide education programs and research. OBJECTIVES: To describe the characteristics of the child population and the main reasons for consultation (RFC) seen in a pediatric emergency service. PATIENTS AND METHOD: A retrospective, descriptive clinical study was conducted regarding the visits to the Children's Emergency Service of an academic hospital in Santiago, for a period of twelve months. RFC were analyzed by age group, severity, seasonality, disposition and frequency of recurrent visits. RESULTS: 24,531 pediatric consultations were evaluated, 51.9% were male (n=12,720). The age of the patients ranged between one day old and 15 years, with a median age of 36.5 months. 1.5% of patients were newborns (NB), 17.6% were infants (n=4,326), 51.9% were preschoolers (n=12,725) and 29% were school children (n=7,118). Major RFC were fever (n=6,643, 28.2%), gastrointestinal symptoms (n=5,606, 23.8%) and respiratory symptoms (n=5,018, 21.3%), which did not differ significantly according to gender. Most patients (95.5%) were sent to their homes. The risk of hospitalization was more elevated in NB and in those with jaundice (OR=7.20, 95% CI 3.12 to 16.6), neurological symptoms (OR=6.90, 95% CI 4.60 -10.4) and poisoning (OR=6.45, 95% CI 2.82 to 14.7). About 4% were repeat visits, especially in the NB group. CONCLUSIONS: The epidemiological profile of pediatric consultations seen at the ED was similar to that described in previous studies. However, a lower rate of hospitalization was found even though the patients had similar risk profile.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Pacientes Ambulatoriais/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Chile , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
3.
Br J Cancer ; 109(7): 1895-8, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24002589

RESUMO

BACKGROUND: A hormonal aetiology is one explanation for the lower incidence of myeloid leukaemia in women compared with men. METHODS: In this population-based case-control study, we evaluated associations between exogenous hormone use and reproductive history and myeloid leukaemia, overall and by disease subtype. RESULTS: We observed a suggestive association between oral contraceptive use and acute myeloid leukaemia (odds ratio=0.55, 95% confidence interval=0.32-0.96). Hormone replacement therapy and reproductive factors were not associated with risk. CONCLUSION: Despite the biological plausibility for a role of oestrogen in leukaemogenesis, other aetiologic factors are likely to explain the differing incidence rates in males and females.


Assuntos
Anticoncepcionais Orais/efeitos adversos , Estrogênios/efeitos adversos , Terapia de Reposição Hormonal , Leucemia Mieloide/etiologia , História Reprodutiva , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Fatores de Risco , Adulto Jovem
4.
Cell Mol Life Sci ; 68(24): 4079-90, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21553234

RESUMO

Human organic cation transporter 2 (hOCT2) is involved in the transport of endogenous and exogenous organic cations mainly in cells of the kidney and the brain. Here, we focus on the regulation of hOCT2 by direct protein-protein interaction. Screening within a mating-based split-ubiquitin-yeast-two-hybrid system (mBSUS) revealed the lysosomal-associated protein transmembrane 4 alpha (LAPTM4A) as a potential interacting protein. Interaction of LAPTM4A and hOCT2 was confirmed by pulldown assays, FRET microscopy analysis and immunofluorescence microscopy. Functionally, overexpression of LAPTM4A significantly decreased ASP(+) uptake in HEK293 cells stably transfected with hOCT2, suggesting a negative regulation of hOCT2-mediated transport. Furthermore, overexpression of LAPTM4A leads to a significantly decreased hOCT2 plasma membrane expression in surface biotinylation experiments. In addition, significant expression of LAPTM4A in human kidney was demonstrated by immunoblotting and immunofluorescence.In this work, LAPTM4A has been identified as interaction partner of hOCT2. LAPTM4A regulates the function of hOCT2 by influencing its trafficking to/from the cell membrane and processing it via the intracellular sorting machinery.


Assuntos
Endocitose/fisiologia , Proteínas de Membrana Transportadoras/fisiologia , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transporte Biológico , Endossomos/metabolismo , Transferência Ressonante de Energia de Fluorescência , Células HEK293 , Humanos , Túbulos Renais Proximais/metabolismo , Lisossomos/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/fisiologia , Transportador 2 de Cátion Orgânico , Mapeamento de Interação de Proteínas , RNA Mensageiro/metabolismo
5.
Rev Chilena Infectol ; 28(5): 416-22, 2011 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-22051617

RESUMO

INTRODUCTION: Kawasaki disease (KD) is a serious disease in children due to its potential complications and sequelae if not promptly and adequately managed. OBJECTIVES: To describe clinical and epidemiological characteristics of children hospitalized due to KD at a tertiary care center and identify risk factors for poor outcome. PATIENTS AND METHODS: Retrospective and descriptive study of 32 medical records of patients hospitalized with diagnosis of KD at a tertiary care center of Santiago, Chile between February 1999 and May 2007. RESULTS: The annual frequency was of 5 cases, mainly boys and during spring. The median age at diagnosis was 1.5 years and 87.5% of the children were younger than 5 years. Typical presentation prevailed in all ages (68,7%). Coronary artery affection, including dilatation or aneurisms, occurred in 21.9% of the cases, with aneurysms in 3 cases. All patients were treated with aspirin and intravenous immunoglobulin (IVIG); 4 patients required a second dose. No deaths were reported. The identified risk factors for poor outcome were age older than 5 years and hypoalbuminemia. CONCLUSIONS: KD is an infrequent disease that mainly occurs in children younger than 5 years and with a typical presentation. There are risk factors associated with poor outcome.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Aspirina/uso terapêutico , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Estações do Ano , Índice de Gravidade de Doença , População Urbana
6.
Rev Chilena Infectol ; 28(6): 504-11, 2011 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-22286672

RESUMO

BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus found in children with acute respiratory tract infections (ARTI). OBJECTIVES: To describe the epidemiological and clinical profile of children < 5 years old consulting for ARTI, comparing cases of HBoV monoinfection and coinfection with other known respiratory viruses. Furthermore, we aimed to estimate the prevalence of viral shedding in asymptomatic children and perform phylogenetic analysis. PATIENTS AND METHODS: We investigated the presence of HBoV in nasopharyngeal secretions from children consulting for AlRTI and among asymptomatic controls, between 2007 and 2008, by polymerase chain reaction. RESULTS: HBoV was detected in 79 (21.8%) of 362 nasopharyngeal swabs obtained from children with ARTI. In 60/79 (76%), coinfection with other respiratory viruses was confirmed. Most common symptoms were cough, fever and rhinorrhea. Children infected only with HBoV showed significantly lower frequencies of respiratory distress, oxygen requirements and hospital admission than those with coinfection. HBoV was detected in 6/16 (37.5%) samples from asymptomatic children. The phylogenetic analysis of viruses from Chilean patients revealed that circulating HBoV was closely related to original strains. CONCLUSIONS: HBoV was found either in symptomatic and asymptomatic children. The severity of the disease was greater when HBoV was associated to other respiratory viruses.


Assuntos
Bocavirus Humano/genética , Infecções por Parvoviridae/virologia , Infecções Respiratórias/virologia , Doença Aguda , Pré-Escolar , Chile/epidemiologia , Métodos Epidemiológicos , Feminino , Bocavirus Humano/isolamento & purificação , Humanos , Lactente , Masculino , Nasofaringe/virologia , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Reação em Cadeia da Polimerase , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Estações do Ano
7.
Pathologe ; 31 Suppl 2: 193-8, 2010 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-20812013

RESUMO

Stimulation of the TNF receptors CD30 and CD95 exerts opposite effects. Crosstalk of both receptors is unknown. We aimed to reveal regulatory mechanisms of CD30-induced effects on CD95 signaling of cALCL cell lines. "CD30/CD95 crosstalk analysis" was performed in cALCL cell lines by comparison of CD30 or CD95 stimulation and CD30/CD95 costimulation. Receptor expression and induction of apoptosis was investigated by flow cytometry. mRNA expression of CD30-inducible genes (cFLIP, TRAF1, cIAP2, and A20) was compared by semiquantitative reverse transcription (RT-RQ-) PCR in stimulated and unstimulated cells. Protein expression of IκBα, p100/p52, caspase-8, caspase-3, and cFLIP was analyzed by immunoblotting. A lentiviral-based shRNA-mediated approach was used to inhibit cFLIP expression. CD30/CD95 crosstalk experiments revealed that CD30 ligation leads to NFκB-mediated cFLIP upregulation in cALCL cells, which in turn enhanced resistance to CD95-mediated apoptosis. This effect is based on the CD30-induced upregulation of cFLIP. Knockdown of cFLIP restores sensitivity to CD95-mediated apoptosis. We conclude that the anti-apoptotic function of CD30 antibodies should be kept in mind if CD30 antibody-based therapeutic concepts for ALCL lymphoma are considered.


Assuntos
Apoptose/genética , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Antígeno Ki-1/genética , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/patologia , Receptor Cross-Talk , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Receptor fas/genética , Linhagem Celular Tumoral , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/patologia , Regulação para Cima/genética
8.
Neuron ; 21(6): 1315-25, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9883725

RESUMO

Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin 1 (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.


Assuntos
Anormalidades Múltiplas/genética , Encefalopatias/genética , Encéfalo/patologia , Córtex Cerebral/fisiopatologia , Ventrículos Cerebrais , Coristoma/genética , Proteínas Contráteis/genética , Proteínas dos Microfilamentos/genética , Neurônios/fisiologia , Envelhecimento , Animais , Encéfalo/anormalidades , Encéfalo/anatomia & histologia , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Córtex Cerebral/anormalidades , Córtex Cerebral/patologia , Ventrículos Cerebrais/anormalidades , Ventrículos Cerebrais/patologia , Coristoma/fisiopatologia , Mapeamento Cromossômico , Desenvolvimento Embrionário e Fetal , Epilepsia/genética , Feminino , Morte Fetal , Filaminas , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Neurônios/patologia , Linhagem , Fenótipo , Caracteres Sexuais , Cromossomo X
9.
Cancer Genet ; 226-227: 30-35, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30005852

RESUMO

Acute lymphoblastic leukemia (ALL) represents the most common childhood malignancy. Although survival for pediatric B-ALL has approached 90%, variability in outcome among and within cytogenetically defined subgroups persists. While G-banding and fluorescence in situ hybridization (FISH) have been used to characterize leukemic clones, there is added value of chromosomal microarray and next generation sequencing in screening genome-wide for copy number aberrations, copy neutral loss of heterozygosity and nucleotide variations. Evaluation of novel genetic aberrations can provide information about the biologic mechanisms of cytogenetically defined subgroups associated with poor prognosis, explain heterogeneity in patient outcome and identify novel targets for therapeutic intervention. The high risk B-ALL intrachromosomal amplification of chromosome 21, (iAMP21), subtype is characterized by amplification of a region of chromosome 21 that typically encompasses the RUNX1 gene and is associated with poor prognosis. Analysis of chromosomal microarray and FISH data revealed that deletions of SH2B3, encoding a negative regulator of multiple tyrosine kinase and cytokine signaling pathways, are enriched among leukemias harboring iAMP21. Enrichment of SH2B3 aberrations in the iAMP21 subtype may indicate that loss of SH2B3 contributes to disease progression and raises the possibility that these leukemias may be sensitive to tyrosine kinase inhibitors.


Assuntos
Cromossomos Humanos Par 21/genética , Amplificação de Genes , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Proteínas/genética , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Bandeamento Cromossômico/métodos , Hibridização Genômica Comparativa , Citogenética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
10.
Virchows Arch ; 472(4): 557-565, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29374318

RESUMO

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.


Assuntos
Biomarcadores Tumorais/genética , DNA de Neoplasias/análise , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias/genética , Humanos , Patologia Molecular/métodos , Patologia Molecular/normas , Reprodutibilidade dos Testes , Pesquisa Translacional Biomédica/métodos
11.
J Clin Invest ; 102(3): 532-7, 1998 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-9691090

RESUMO

During each reproductive cycle, a preovulatory surge of gonadotropins induces meiotic maturation of the oocyte in the preovulatory follicle followed by ovulation. Although gonadotropins stimulate cAMP production in somatic cells of the follicle, a decrease in intra-oocyte cAMP levels is required for resumption of meiosis in oocytes. Based on the observed compartmentalization of the cAMP-degrading enzyme, phosphodiesterase, in follicular somatic and germ cells, inhibitors of phosphodiesterase 3 were used to block meiosis in ovulating oocytes in rodents. By this strategy, we demonstrated that fertilization and pregnancy could be prevented without disturbing follicle rupture and normal estrous cyclicity. In contrast to conventional contraceptive pills that disrupt ovarian steroidogenesis and reproductive cycles, the present strategy achieves effective contraception by selective blockage of oocyte maturation and development without alterations in ovulation and reproductive cyclicity.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Anticoncepcionais Femininos/farmacologia , AMP Cíclico/fisiologia , Estro/efeitos dos fármacos , Meiose/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Sistemas do Segundo Mensageiro/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3 , Feminino , Fertilização/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipoxantina/farmacologia , Isoenzimas/antagonistas & inibidores , Menotropinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Milrinona , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Indução da Ovulação , Gravidez , Purinonas/farmacologia , Piridazinas/farmacologia , Piridonas/farmacologia , Pirrolidinonas/farmacologia , Quinolonas/farmacologia , Ratos , Ratos Sprague-Dawley , Rolipram , Especificidade por Substrato , Tiofenos/farmacologia
12.
Nat Biotechnol ; 15(7): 663-7, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9219270

RESUMO

Glycoprotein hormones are noncovalent heterodimers comprised of a common alpha subunit and a hormone-specific beta subunit. Secretion and biologic action of these hormones are dependent on the formation of the heterodimer. The human LH beta subunit is unique among the other beta subunits in that it assembles inefficiently with the alpha subunit. To bypass this rate-limiting step, we constructed the LH single chains where the carboxy terminus of beta was fused to the amino terminus of alpha subunit through a linker. Compared to the human LH heterodimer, the extent of secretion was greater for the tethers although the rate was dependent on the nature of the linker. The LH single chains were biologically active even though there was loss of recognition by a LH-specific monoclonal antibody. This suggests that receptor binding of the single chains is not impaired by changes in the heterodimeric configuration resulting from tethering the subunits. In addition, single chains exhibited a remarkably greater in vitro stability than the heterodimer, implying that these analogs will be useful as diagnostic reagents and that their purification will be facilitated.


Assuntos
Hormônio Luteinizante/análogos & derivados , Animais , Sequência de Bases , Biotecnologia , Células CHO , Cricetinae , Primers do DNA/genética , Desenho de Fármacos , Estabilidade de Medicamentos , Humanos , Técnicas In Vitro , Hormônio Luteinizante/genética , Hormônio Luteinizante/farmacologia , Conformação Proteica , Engenharia de Proteínas , Receptores do LH/metabolismo , Transfecção
13.
Rev Chilena Infectol ; 24(1): 33-9, 2007 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-17369968

RESUMO

UNLABELLED: Fever is a frequent symptom of consultation in Pediatric Emergency Department. OBJECTIVES: to describe causes of acute fever of unknown origin (FUO) in infants under 36 months of age, the utility of requested tests and pediatrician decisions. PATIENTS AND METHODS: 309 cards of children under 36 months who consulted at Emergency Department for acute FUO were reviewed. RESULTS: 64 % were classified with well clinical condition. Most frequent causes were: probable viral respiratory infections (72%), urinary tract infection (7.4%), pneumonia (2.9%), bacteremia (1.9%), and bacterial meningitis (1.3%). Streptococcus pneumoniae was the most frequent agent isolated from blood cultures. Tests of best utility were: urine analysis and urine culture. Leukocytes count < 15.000/mm(3) and PCR < 4.0 mg/dl had a negative predictive value of 96 %. Nine point seven percent of the patients were hospitalized, while 14.2% received antibiotic treatment at home. CONCLUSIONS: We suggest to perform urine analysis and culture as the initial study for children with acute FUO and well clinical condition.


Assuntos
Infecções Bacterianas/complicações , Febre de Causa Desconhecida/etiologia , Doença Aguda , Algoritmos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Pré-Escolar , Serviço Hospitalar de Emergência , Febre de Causa Desconhecida/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
14.
Chem Commun (Camb) ; 53(94): 12601-12607, 2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-29139496

RESUMO

The 2017 Faraday Discussion on Complex Molecular Surfaces and Interfaces brought together theoreticians and experimentalists from both physical and chemical backgrounds to discuss the relevant applied and fundamental research topics within the broader field of chemical surface analysis and characterization. Main discussion topics from the meeting included the importance of "disordered" two-dimensional (2D) molecular structures and the utility of kinetically trapped states. An emerging need for new experimental tools to address dynamics and kinetic pathways involved in self-assembled systems, as well as the future prospects and current limitations of in silico studies were also discussed. The following article provides a brief overview of the work presented and the challenges discussed during the meeting.

15.
AJNR Am J Neuroradiol ; 27(9): 1817-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17032848

RESUMO

We present an unusual case of a complete first branchial cleft fistula communicating between the external auditory canal and the skin near the angle of the mandible. CT and fluoroscopic fistulography were used to establish the presence and course of the tract and to assist in surgical planning. The embryology and classification of first branchial cleft anomalies are discussed, with emphasis on the impact of imaging.


Assuntos
Região Branquial/anormalidades , Fístula Cutânea/diagnóstico por imagem , Meato Acústico Externo/anormalidades , Meato Acústico Externo/diagnóstico por imagem , Otopatias/congênito , Otopatias/diagnóstico por imagem , Fístula/congênito , Fístula/diagnóstico por imagem , Fluoroscopia , Tomografia Computadorizada por Raios X , Região Branquial/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Diatrizoato , Diatrizoato de Meglumina , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade
16.
Cancer Res ; 61(13): 5268-74, 2001 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-11431369

RESUMO

The acquisition of genetic abnormalities in human B-lineage acute lymphoblastic leukemia (ALL) culminates in the clonal expansion of bone marrow (BM)-derived leukemic blasts. However, the response of leukemic cells to signals transduced by the BM microenvironment is not completely understood. The present study describes a new human B-lineage ALL cell line designated BLIN-4 (B LINeage-4). BLIN-4 cells respond to multiple cytokines/human BM stromal cell-derived molecules. One subline (BLIN-4E) undergoes cell death in the absence of BM stromal cells or cytokines and slowly proliferates on human BM stromal cells supplemented with interleukin (IL)-7 + FLT3-ligand. Another subline (BLIN-4L) slowly proliferates in the absence of cytokines and BM stromal cells and shows robust proliferation on BM stromal cells supplemented with IL-7 + FLT3-ligand. Although human BM stromal cells are comparable with IL-7 + FLT3-ligand in supporting proliferation of BLIN-4L cells, neutralizing antibody experiments demonstrate that BLIN-4L expansion on BM stromal cells is IL-7/FLT3-ligand independent. BLIN-4L could also respond to human thymic stromal lymphopoietin. BLIN-4E and BLIN-4L have the identical immunoglobulin heavy chain rearrangement and a CD10(+)/CD19(+)/CD20(-)/CD22(+)/CD40(+)/mu heavy chain(-) phenotype. The original BM leukemic blasts harbored a ring chromosome 4 with a low percentage of cells also having either trisomy 8 or trisomy 18. The BLIN-4 sublines maintained the ring chromosome 4, but the trisomy 8 and trisomy 18 segregated into BLIN-4E and BLIN-4L, respectively. Thus, the BLIN-4 sublines exhibit biological characteristics consistent with a potential evolution in B-lineage ALL involving subclones with decreasing requirements on the BM microenvironment.


Assuntos
Células da Medula Óssea/citologia , Linfoma de Burkitt/patologia , Citocinas/farmacologia , Células Tumorais Cultivadas , Adolescente , Células da Medula Óssea/metabolismo , Linfoma de Burkitt/genética , Divisão Celular/efeitos dos fármacos , Linhagem da Célula , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Meios de Cultivo Condicionados , Feminino , Humanos , Interleucina-7/farmacologia , Proteínas de Membrana/farmacologia , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Receptores de Interleucina-7/biossíntese , Células Estromais/metabolismo , Tirosina Quinase 3 Semelhante a fms , Linfopoietina do Estroma do Timo
17.
Br J Pharmacol ; 173(4): 778-89, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26013851

RESUMO

BACKGROUND AND PURPOSE: NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction. EXPERIMENTAL APPROACH: Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3 , stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA. KEY RESULTS: Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells. CONCLUSIONS AND IMPLICATIONS: We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.


Assuntos
Anti-Inflamatórios/farmacologia , Células Epiteliais/efeitos dos fármacos , Giberelinas/farmacologia , Inflamação/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Pseudomonas aeruginosa/química , RNA Mensageiro/metabolismo , Mucosa Respiratória/metabolismo , Relação Estrutura-Atividade
18.
Biochim Biophys Acta ; 1268(1): 88-96, 1995 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-7626667

RESUMO

The purpose of the present work was to study the acute regulation of glucose uptake in cultured cardiac endothelial cells (CEC). Two types of potential stimuli were considered: (1) agents that are known to acutely stimulate glucose transport (i.e., within minutes) in fat and muscle tissues and (2) agents that influence endothelial cell function. Among the former agents, neither insulin, nor catecholamines (adrenaline, dopamine, phenylephrine), nor serotonin affected the rate of glucose transport in CEC, while SH-group reagents (phenylarsine oxide, diamide or menadione) were inhibitory. Among the factors of the second group that were tested (heparin, ADP, histamine, bradykinin), histamine was found to stimulate glucose transport in CEC by 10-50%. This effect was concentration-dependent (with an EC50 value approximately equal to 12 microM) and reached a maximum within 5 min upon histamine addition. This stimulation of glucose transport was suppressed by pyrilamine (100 nM), a specific H1-receptor antagonist, but not by cimetidine (100 microM), a H2-selective antagonist. Northern blot and Western blot analysis of CEC extracts revealed the presence of the ubiquitous glucose transporter isoform GLUT1 mRNA and protein, but not of the 'insulin-regulatable' isoform GLUT4. In conclusion, this is the first report on an acute stimulation of glucose transport in cardiac endothelial cells, in particular, and in an insulin-unresponsive cell type, in general. The effect of histamine is most likely mediated by H1-receptors and cannot be accounted for by a recruitment of GLUT4.


Assuntos
Endotélio Vascular/metabolismo , Glucose/metabolismo , Histamina/farmacologia , Proteínas Musculares , Difosfato de Adenosina/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Cimetidina/farmacologia , Vasos Coronários/citologia , Desoxiglucose/metabolismo , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 4 , Insulina/farmacologia , Masculino , Proteínas de Transporte de Monossacarídeos/biossíntese , Pirilamina/farmacologia , RNA Mensageiro/biossíntese , Ratos , Compostos de Sulfidrila
19.
Diabetes ; 36(1): 20-6, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3792663

RESUMO

The counterregulatory hormone responses to hypoglycemia and a non-glucose stimulus, exercise, were evaluated in 18 subjects with type I diabetes and in 9 normal controls. Subjects with diabetes had no overt neuropathy, with R-R variations and postural plasma norepinephrine increments that were similar to those of controls. The diabetic subjects exhibited normal increments in plasma growth hormone (GH), norepinephrine, and cortisol but blunted or absent responses in plasma epinephrine and glucagon when hypoglycemia was severe (less than 40 mg/dl). During a 60-min clamped reduction in plasma glucose at approximately 65 mg/dl, plasma GH and epinephrine increased 6- to 15-fold in controls but 2- to 4-fold in diabetics (P less than .05). However, when subjects were exercised at this plasma glucose level (50 W for 10 min), plasma epinephrine and GH in diabetics rose markedly by 150-400% to attain the peaks reached by the controls. Plasma norepinephrine and cortisol increased to similar levels in both groups, and plasma glucagon was not significantly changed. We conclude that epinephrine and GH secretion in response to hypoglycemia are reduced in type I diabetes but that these defects are stimulus specific because the responses to exercise are not reduced.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Epinefrina/fisiologia , Hormônio do Crescimento/fisiologia , Adulto , Glicemia/análise , Epinefrina/sangue , Hormônio do Crescimento/sangue , Humanos , Hipoglicemia/fisiopatologia , Esforço Físico
20.
J Orthop Res ; 23(4): 743-9, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16022985

RESUMO

Common image-based diagnostic techniques used to detect ankle ligament injuries or the effects of those injuries (e.g., mechanical instability) include magnetic resonance imaging (MRI) and stress radiography. Each of these techniques has limitations. The interpretation of the results obtained through stress radiography, a two-dimensional technique, is highly controversial. MRI can facilitate visualization of soft tissue, but three-dimensional visualization of the full length of the ligaments or detecting partial ligament damage is difficult. This work is part of a long-term study aimed at improving the diagnostic ability of MRI by utilizing it not only to visualize the ligaments but also to detect the mechanical instability produced at the ankle and subtalar joints due to ligament damage. The goal of the present study was to evaluate the ability of a previously developed technique called 3D stress MRI (sMRI) to detect in vitro the effect of damage to the lateral collateral ligaments and the stabilizing effect produced by two common surgical reconstruction techniques. MRI data were collected from eight cadaver limbs in a MR compatible ankle-loading device in neutral, inversion, and anterior drawer. Each specimen was tested intact, after cutting the anterior talo-fibular ligament followed by the calcaneo-fibular ligament and after applying two reconstructions. Ligament injuries produced significant changes in the response of the ankle and subtalar joints to load as detected by the 3D stress MRI technique. Both surgical procedures restored mechanical stability to the joints but they differed in the amount and type of stabilization achieved. We concluded that 3D sMRI can extend the diagnostic power of MRI from the current practice of slice-by-slice visualization to the assessment of mechanical function, the compromise in this function due to injury, and the effects of surgery.


Assuntos
Traumatismos do Tornozelo/patologia , Traumatismos do Tornozelo/cirurgia , Ligamentos Laterais do Tornozelo/patologia , Ligamentos Laterais do Tornozelo/cirurgia , Imageamento por Ressonância Magnética/métodos , Procedimentos de Cirurgia Plástica , Idoso , Idoso de 80 Anos ou mais , Traumatismos do Tornozelo/fisiopatologia , Articulação do Tornozelo/patologia , Articulação do Tornozelo/fisiopatologia , Articulação do Tornozelo/cirurgia , Cadáver , Humanos , Imageamento Tridimensional , Técnicas In Vitro , Ligamentos Laterais do Tornozelo/fisiopatologia , Estresse Mecânico , Suporte de Carga
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