115 research outputs found
Tympanic paragangliomas: case reports
Glomus tumors, also called paragangliomas, originate from nonchromaffin cells. The tumor is typically vascular and grows from capillary and pre-capillary vessels in-between epithelial cells. It is worth mentioning that the most common symptoms are pulsating tinnitus and hearing loss. Imaging studies (CT and MRI) are necessary for diagnosis. This paper shows five patients seen at the Hospital between 1995 and 2001 presenting glomus tympanicum. Women were most commonly affected, and the age ranged from 48 to 60 years (mean age of 50 years). The most common complaints were pulsating tinnitus and hearing loss. All patients were treated surgically.Os tumores glômicos, também chamados de paragangliomas, são formados por células não cromafins. O tumor é tipicamente vascular formado por vasos capilares e pré-capilares, interposto por células epiteliais. Para a sua abordagem inicial, deve-se ressaltar que os sintomas mais comumentes encontrados são o zumbido pulsátil e hipoacusia. A investigação através de imagem (tomografia computadorizada e ressonância magnética) se faz necessária. Apresentaremos neste trabalho 5 pacientes portadores de paragangliomas timpânicos atendidos no Hospital (de 1995 a 2001). O sexo predominante foi o feminino, a idade variou de 48 a 60 anos, com média de 50 anos. A queixa predominante foi o zumbido pulsátil e a hipoacusia. A conduta foi cirúrgica em todos os casos.Hospital Paulista de OtorrinolaringologiaUNIFESP-EPMUNIFESP, EPMSciEL
Osteoma of external acoustic meato: report of nine cases and literature review
The osteoma of external acoustic meatus corresponds to an abnormal and benign bony growth, that is developed under the skin of the auditory canal and that can cause total or partial obstruction of the external acoustic meatus. STUDY DESIGN: Serie study. MATERIAL AND METHOD: We reported in this study nine cases of osteoma of external acoustic meatus. The patients' ages varied between 23 and 70 years old, being the average age 40,6 years. These patients were 5 of the feminine sex and 4 were of the masculine sex. RESULTS: The more common symptoms were hipoacusia, caused by the partial or total obstruction of the canal, appealing external otitis and also the accumulation of cerumen deep in the external auditory canal with difficult removal. CONCLUSION: We recommended in the presented cases surgical treatment, which had good evolution, with no recidivism.Osteoma de meato acústico externo corresponde a um crescimento ósseo anormal e benigno, que se desenvolve abaixo da pele do conduto e pode causar obstrução total ou parcial do meato acústico externo. FORMA DE ESTUDO: Estudo de série. MATERIAL E MÉTODO: Apresentamos neste estudo nove casos de osteoma de meato acústico externo. A idade dos pacientes variou de 23 anos (idade mínima) e 70 anos (idade máxima), sendo a média 40,6 anos. Desses nove pacientes, 5 eram do sexo feminino e 4 eram do sexo masculino. RESULTADO: Os sintomas mais comuns foram: hipoacusia, causada pela obstrução parcial ou total do conduto, otites externas recorrentes e também impactação de cerume de difícil remoção. CONCLUSÃO: A conduta nos casos apresentados foi cirúrgica, com boa evolução, não ocorrendo recidivas.UNIFESP-EPMHospital Paulista de OtorrinolaringologiaUNIFESP, EPMSciEL
Dynamic and cell-specific DACH1 expression in human neocortical and striatal development
DACH1 is the human homolog of the Drosophila dachshund gene, which is involved in the development of the eye, nervous system, and limbs in the fly. Here, we systematically investigate DACH1 expression patterns during human neurodevelopment, from 5 to 21 postconceptional weeks. By immunodetection analysis, we found that DACH1 is highly expressed in the proliferating neuroprogenitors of the developing cortical ventricular and subventricular regions, while it is absent in the more differentiated cortical plate. Single-cell global transcriptional analysis revealed that DACH1 is specifically enriched in neuroepithelial and ventricular radial glia cells of the developing human neocortex. Moreover, we describe a previously unreported DACH1 expression in the human striatum, in particular in the striatal medium spiny neurons. This finding qualifies DACH1 as a new striatal projection neuron marker, together with PPP1R1B, BCL11B, and EBF1. We finally compared DACH1 expression profile in human and mouse forebrain, where we observed spatio-temporal similarities in its expression pattern thus providing a precise developmental description of DACH1 in the 2 mammalian species
Classical Swine Fever Virus p7 Protein Interacts with Host Protein CAMLG and Regulates Calcium Permeability at the Endoplasmic Reticulum
We have previously shown that Classical Swine Fever Virus (CSFV) p7 is an essential nonstructural protein with a viroporin activity, a critical function in the progression of virus infection. We also identified p7 domains and amino acid residues critical for pore formation. Here, we describe how p7 specifically interacts with host protein CAMLG, an integral ER transmembrane protein involved in intracellular calcium release regulation and signal response generation. Detection of interaction as well as the identification of p7 areas mediating interaction with CAMLG was performed by yeast two-hybrid. p7-CAMLG interaction was further confirmed by confocal microscopy in eukaryotic cells, co-expressing both proteins. Mutant forms of p7 having substituted native residues identified as mediating interaction with CAMLG showed a decreased co-localization compared with the native forms of p7. Furthermore, it is shown that native p7, but not the mutated forms of p7 that fail to interact with CAMLG, efficiently mediates calcium permeability in the ER. Interestingly, viruses harboring some of those mutated forms of p7 have been previously shown to have a significantly decreased virulence in swine.ARS/USDA-University of Connecticut SCA# 58-1940-1-190 and ARS/USDA-University of the Basque Country NACA#8064-32000-056-18S
Resource Concentration Modulates the Fate of Dissimilated Nitrogen in a Dual-Pathway Actinobacterium
Respiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO3−) ratio. Here we find that Intrasporangium calvum C5, a novel dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under low C concentrations, even at low C:NO3− ratios. This finding is in conflict with the paradigm that high C:NO3− ratios promote ammonification and low C:NO3− ratios promote denitrification. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that limitation for C and N is a major evolutionary selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological importance for microbial activity as evidenced by higher growth rates when I. calvum grows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-free conditions. Genomic analysis of I. calvum further reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that enzyme modules, NrfAH and NirK, are not constitutively expressed but rather induced by nitrite production via NarG. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered when resource concentrations are low, thereby decreasing catalytic activity of upstream electron transport steps (i.e., the bc1 complex) needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs
ASSESSING THE NUTRITIONAL CONDITION OF PREGNANT WOMEN IN THE CITY OF SANTO ANDRÉ THROUGH ROSSO’S GRAPH
A falta de vigilancia da condição nutricional da gestante durante o exame pré-natal tem dificultado intervenções adequadas no sentido de prevenir a ocorrência do baixo peso ao nascimento (BP). Foram avaliadas, prospectivamente, 95 gestantes de baixo nível sócio-econômico do Município de Santo André, para realização de exame pré-natal, utilizando-se a curva de Rosso para sua classificação nutricional. O percentual de mãe com baixo peso foi de 36,8%. As mães com mais de duas gestações apresentaram maior ocorrência de sobrepeso ou obesidade e as com menos de duas gestações, percentual significativamente maior de baixo peso. A anemia também se associou de maneira significativa às gestantes de baixo peso. O presente trabalho ressalta a importancia da implantação de instrumento na rede básica de saúde para controlar o ganho de peso da gestante, bem como da vigilancia de outros fatores de risco no intuito de reduzir os elevados percentuais de recém-nascidos com BP.The lack of monitoring ofthenutritional condition of pregnamtwomen during theprenatal exammat^lon has made it difficult for interventions aimir g at the prevention of low weight at birth (BP). 45 pregnmt women of low socio-economic levei registered m the posts of the FOUNDATION for ASSISTANCE to INFANCY (FAISA - Santo André, São Paulo) were evaluated, for accomplishment of prenatal exammation, using Rosso’s Graph for its nutritional classification. The achieved percentage of pregnantwomenwi^th low weightwas 36,8%. Mo^therswi^thmore thamtwo ges^tations and wi^th less than two presented greater occurrence of overweight obesi^ty amd low weight, respectively. Higher percentage of amemia in the pregmant women with low weight was verified. Therefore, it is evident that this instrument should be implemented as routine in ^the prenatal examinabon
Resource Concentration Modulates the Fate of Dissimilated Nitrogen in a Dual-Pathway Actinobacterium
Respiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO_3^−) ratio. Here we find that Intrasporangium calvum C5, a novel dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under low C concentrations, even at low C:NO_3^− ratios. This finding is in conflict with the paradigm that high C:NO_3^− ratios promote ammonification and low C:NO_3^− ratios promote denitrification. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that limitation for C and N is a major evolutionary selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological importance for microbial activity as evidenced by higher growth rates when I. calvum grows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-free conditions. Genomic analysis of I. calvumfurther reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that enzyme modules, NrfAH and NirK, are not constitutively expressed but rather induced by nitrite production via NarG. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered when resource concentrations are low, thereby decreasing catalytic activity of upstream electron transport steps (i.e., the bc1 complex) needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs
Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease
Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition
Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation
Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations in autophagy. However, the consequences of impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation as well as post-mortem material from patients with Huntington’s disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNA-induced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together, these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation but also directly contributes to global alterations of intracellular post-transcriptional networks
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