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The aim of this study is to describe oral health knowledge, behaviors, and beliefs of Latino parents with children under the ages of 6 years and to conduct a needs assessment with Latino families to better understand the challenges in maintaining oral health for their children. The investigator collaborated with a community serving the organization to recruit Latino primary caregivers for focus groups interviews and 30 primary caregivers were recruited. The focus groups data was transcribed and analyzed using a grounded theory approach using QDA Miner software. Findings from the focus groups demonstrate that the primary caregivers described barriers in maintaining oral health for their children including cultural barriers, child's temperament, lack of time, and easy access to high-risk foods. All participants said that they wanted to receive information on the oral health of their children; they wanted the dentist or the hygienist to demonstrate oral hygiene practices and explain to them the reasons for oral health behaviors. Although the primary caregivers recognized some factors related to caries development, their knowledge was limited in depth. Culturally appropriate oral health education is required for this population, which could lead to more adherent oral health behavior and a higher sense of self-efficacy in Latino parents.
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OBJECTIVES: The aim of this study was to identify new prognostic factors in metastatic renal cell carcinoma (RCC) based on the analysis of precisely defined metastatic tissue. METHODS: Expression profiling was done on 26 snap-frozen samples of clear-cell RCC metastases with complete follow-up (up to 116 months) using laser microdissection and oligonucleotide microarrays (Affymetrix). A prognosis-associated gene signature was determined using the semi-supervised principal components analysis method. Validation was performed with quantitative RT-PCR on samples of normal renal tissue (n = 6), RCC primary tumor (n = 57), and RCC metastases (n = 59). Immunohistochemistry (IHC) was done to localize HNF-1B. RESULTS: Analysis of expression data revealed a three-gene signature consisting of HNF-1B, KIAA1919, and SYDE1, which discriminated well between 2 prognosis groups (P < .05), independently of the TNMG classification. Expression of HNF-1B was analyzed in detail. HNF-1B mRNA expression correlated with malignant transformation and progression (normal renal tissue > primary tumor > metastasis; P < .0001). There was a significant correlation between high HNF-1B mRNA expression in primary tumor and better prognosis (P < .05). IHC showed a specific nuclear HNF-1B staining confined to the tumor cells of the primary tumors and of the metastases. CONCLUSIONS: The level of HNF-1B mRNA expression significantly decreases with tumor progression, and patients with high HNF-1B mRNA levels have a significantly better prognosis. HNF-1B might be a useful prognostic factor for metastatic RCC and also a potential therapeutic target in the future.
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Carcinoma de Células Renales/secundario , Regulación hacia Abajo , Factor Nuclear 1-beta del Hepatocito/fisiología , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Factor Nuclear 1-beta del Hepatocito/biosíntesis , Factor Nuclear 1-beta del Hepatocito/genética , Humanos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: The inflammatory enzyme indoleamine 2,3-dioxygenase (IDO) participates in immune tolerance and tumor immune escape processes by degradation of the essential amino acid tryptophan and formation of toxic catabolites. Here, we analyzed the role of IDO in tumor growth and disease progression in patients with clear cell renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Expression of IDO mRNA was analyzed by quantitative reverse transcription-PCR in 55 primary and 52 metastatic RCC, along with 32 normal kidneys. Western blot and immunohistochemistry analyses were used to semiquantitatively determine IDO proteins in a subset of tumor samples, in RCC cell lines, and microvessel endothelial cells. IDO expression was correlated with expression of the proliferation marker Ki67 in tumor cells and survival of patients with tumor. RESULTS: More than 75% of the clear cell RCC in comparison to normal kidney contained elevated levels of IDO mRNA, which correlated with their IDO protein content. Low IDO mRNA levels in primary tumors represented an unfavorable independent prognostic factor (hazard ratio, 3.8; P = 0.016). Unexpectedly, immunohistochemical analyses revealed that IDO is nearly exclusively expressed in endothelial cells of newly formed blood vessels and is virtually absent from tumor cells, although RCC cells could principally synthesize IDO as shown by in vitro stimulation with IFN-gamma. A highly significant inverse correlation between the density of IDO-positive microvessels and the content of proliferating Ki67-positive tumor cells in primary and metastatic clear cell RCC was found (P = 0.004). CONCLUSIONS: IDO in endothelial cells might limit the influx of tryptophan from the blood to the tumor or generate tumor-toxic metabolites, thus restricting tumor growth and contributing to survival.
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Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/enzimología , Células Endoteliales/enzimología , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/enzimología , Anciano , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Células Endoteliales/patología , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interferón gamma/farmacología , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neovascularización Patológica/enzimología , Neovascularización Patológica/patología , Pronóstico , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Estudios Retrospectivos , Triptófano/metabolismoRESUMEN
BACKGROUND: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mutations are typically located within epidermal growth factor-like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk. OBJECTIVES: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. DESIGN: Screening for NOTCH3 mutations was performed in 125 unrelated German CADASIL patients with biopsy-proven disease by direct sequencing of exons coding for epidermal growth factor-like repeats. Results were compared with those of previously published studies. RESULTS: We detected 54 distinct mutations (117 missense mutations and 3 in-frame deletions) in 120 (96.0%) of the 125 patients. Of the mutations, 58.3% were located in exon 4 and 85.8% in exons 2 through 6. In 5 patients (4.0%), no mutation was identified. CONCLUSIONS: Almost 90% of mutations could be detected within a few exons (exons 2-6). Thus, genetic testing should initially be focused on these exons, with some variation depending on the population in whom it is being performed. Yet, genetic testing for CADASIL is associated with a nameable proportion of false-negative results. Cases with a high index of clinical suspicion should be investigated by skin biopsy if genetic testing is negative.
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CADASIL/genética , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular/genética , Biopsia , Análisis Mutacional de ADN , Exones , Pruebas Genéticas , Humanos , Receptor Notch3 , Receptores NotchAsunto(s)
Proteínas de Unión al ADN/genética , Enfermedad de Parkinson/genética , Mutación Puntual , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Dopamina/metabolismo , Exones , Salud de la Familia , Humanos , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. OBJECTIVE: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. METHODS: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. RESULTS: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. CONCLUSION: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma.
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Ácido Aminolevulínico , Neoplasias de los Bronquios/diagnóstico , Fluorescencia , Fármacos Fotosensibilizantes , Protoporfirinas , Análisis de Varianza , Bronquios/citología , Carcinoma de Pulmón de Células no Pequeñas/patología , Técnicas de Cocultivo , Células Epiteliales/fisiología , Humanos , Cinética , Neoplasias Pulmonares , Microscopía Fluorescente , Técnicas de Cultivo de Órganos , Sensibilidad y Especificidad , Análisis EspectralRESUMEN
Mutations in the gene for epsilon-sarcoglycan (SGCE) have been found to cause myoclonus-dystonia syndrome. We now report clinical and genetic findings in nine additional European families with myoclonus-dystonia syndrome. The clinical presentation in 24 affecteds was homogeneous with myoclonus predominantly of neck and upper limbs in 23 of them and dystonia, presenting as cervical dystonia and/or writer's cramp, in 13 cases. Six novel and one previously known heterozygous SGCE mutations were identified. SGCE deficiency seems to be the common pathogenetic mechanism in myoclonus-dystonia syndrome.