Predicting binding sites of hydrolase-inhibitor complexes by combining several methods

Background Protein-protein interactions play a critical role in protein function. Completion of many genomes is being followed rapidly by major efforts to identify interacting protein pairs experimentally in order to decipher the networks of interacting, coordinated-in-action proteins. Identification of protein-protein interaction sites and detection of specific amino acids that contribute to the specificity and the strength of protein interactions is an important problem with broad applications ranging from rational drug design to the analysis of metabolic and signal transduction networks. Results In order to increase the power of predictive methods for protein-protein interaction sites, we have developed a consensus methodology for combining four different methods. These approaches include: data mining using Support Vector Machines, threading through protein structures, prediction of conserved residues on the protein surface by analysis of phylogenetic trees, and the Conservatism of Conservatism method of Mirny and Shakhnovich. Results obtained on a dataset of hydrolase-inhibitor complexes demonstrate that the combination of all four methods yield improved predictions over the individual methods. Conclusions We developed a consensus method for predicting protein-protein interface residues by combining sequence and structure-based methods. The success of our consensus approach suggests that similar methodologies can be developed to improve prediction accuracies for other bioinformatic problems

Pseudotumor inflamatório do fígado: o imitador bom das neoplasias hepáticas

Resumo: O Pseudotumor Inflamatório do Fígado (PIF) é uma neoplasia benigna rara nos países ocidentais e a sua etiologia ainda não foi determinada. O seu diagnóstico é difícil, dada a ausência de clínica, alterações analíticas ou achados imagiológicos específicos, confundindo-se frequentemente com outras neoplasias hepáticas e levando à sua inadequada ressecção. O exame histológico é o gold standard para o seu diagnóstico. Não existe consenso sobre a terapêutica ideal a efetuar. O prognóstico é excelente verificando-se habitualmente resolução completa da lesão. Neste artigo, apresenta-se o caso de um PIF diagnosticado durante a investigação de uma massa hepática num homem com hábitos etílicos importantes mas sem estigmas de doença hepática crónica e com nível sérico de alfa-fetoproteina normal. Perante o resultado histológico de PIF e a evolução benigna que lhe está associada, manteve-se uma atitude expectante e houve resolução dos sintomas, normalização das análises e desaparecimento completo da lesão. Abstract: The Inflammatory Pseudotumor of the Liver is an uncommon benign tumor in occidental countries and its etiology remains unclear. Its diagnosis is difficult, because there are no specific symptoms, analytic abnormalities or radiologic findings, and is usually mistake with other hepatic tumors inducing its inadequate resection. The histological examination is the gold standard for the diagnosis of Inflammatory Pseudotumor of the Liver. There is no consensus about the ideal treatment. In the majority of cases, the prognosis is excellent with the complete resolution of the lesion. In this paper, it is reported one case of Inflammatory Pseudotumor of the Liver diagnosed during the investigation of a hepatic lesion in a man with history of alcohol abuse but without stigmata of chronic liver disease and with a normal serum alpha-fetoprotein level. Given the histological result of Inflammatory Pseudotumor of the Liver and benign associated with it, has remained a expectant attitude and there was resolution of symptoms, normalization of analysis and complete disappearance of the lesion

Inflammatory pseudotumor of the liver: A good imitator of hepatic neoplasms

O Pseudotumor Inflamatório do Fígado (PIF) é uma neoplasia benigna rara nos países ocidentais e a sua etiologia ainda não foi determinada. O seu diagnóstico é difícil, dada a ausência de clínica, alterações analíticas ou achados imagiológicos específicos, confundindo-se frequentemente com outras neoplasias hepáticas, o que leva à sua inadequada ressecção. O exame histológico é o gold standard para o seu diagnóstico. Não existe consenso sobre a terapêutica ideal a efetuar. O prognóstico é excelente verificando-se habitualmente resolução completa da lesão. Neste artigo, apresenta-se o caso de um PIF diagnosticado durante a investigação de uma massa hepática num homem com hábitos etílicos importantes mas sem estigmas de doença hepática crónica e com nível sérico de alfa-fetoproteina normal.The Inflammatory Pseudotumor of the Liver is an uncommon benign tumor in occidental countries and its etiology remains unclear. Its diagnosis is difficult, because there are no specific symptoms, analytic abnormalities or radiologic findings, and is usually mistaken with other hepatic tumors inducing its inadequate resection. The histological examination is the gold standard for the diagnosis of Inflammatory Pseudotumor of the Liver. There is no consensus about the ideal treatment. In the majority of cases, the prognosis is excellent with complete resolution of the lesion. We report the diagnostic and conservative management of a case of Inflammatory Pseudotumor of the Liver diagnosed during the investigation of a hepatic lesion in a man with history of alcohol abuse but without stigmata of chronic liver disease and normal serum alpha-fetoprotein level

Potential for Chlorine Gas–induced Injury in the Extrapulmonary Vasculature

Exposure to chlorine gas (Cl2) primarily causes injury to the lung and is characterized by inflammation and oxidative stress mediated by reactive chlorine species. Reducing lung injury and improving respiratory function are the principal therapeutic goals in treating individuals exposed to Cl2 gas. Less is known on the potential for Cl2 gas exposure to cause injury to extrapulmonary tissues and specifically to mediate endothelial dysfunction. This concept is forwarded in this article on the basis that (1) many irritant gases whose reactivity is limited to the lung have now been shown to have effects that promote endothelial dysfunction in the systemic vasculature, and as such lead to the acute and chronic cardiovascular disease events (e.g., myocardial infarctions and atherosclerosis); and (2) that endogenously produced reactive chlorine species are now considered to be central in the development of cardiovascular diseases. This article discusses these two areas with the view of providing a framework in which potential extrapulmonary toxic effects of Cl2 gas exposure may be considered

Cortical myoclonus in Huntington's disease.

We describe three patients with Huntington's disease, from two families, in whom myoclonus was the predominant clinical feature. The diagnosis was confirmed at autopsy in two cases and by DNA analysis in all three. These patients all presented before the age of 30 years and were the offspring of affected fathers. Neurophysiological studies documented generalised and multifocal action myoclonus of cortical origin that was strikingly stimulus sensitive, without enlargement of the cortical somatosensory evoked potential. The myoclonus improved with piracetam therapy in one patient and a combination of sodium valproate and clonazepam in the other two. Cortical reflex myoclonus is a rare but disabling component of the complex movement disorder of Huntington's disease, which may lead to substantial diagnostic difficulties

Predicting binding sites of hydrolase-inhibitor complexes by combining several methods

Background Protein-protein interactions play a critical role in protein function. Completion of many genomes is being followed rapidly by major efforts to identify interacting protein pairs experimentally in order to decipher the networks of interacting, coordinated-in-action proteins. Identification of protein-protein interaction sites and detection of specific amino acids that contribute to the specificity and the strength of protein interactions is an important problem with broad applications ranging from rational drug design to the analysis of metabolic and signal transduction networks. Results In order to increase the power of predictive methods for protein-protein interaction sites, we have developed a consensus methodology for combining four different methods. These approaches include: data mining using Support Vector Machines, threading through protein structures, prediction of conserved residues on the protein surface by analysis of phylogenetic trees, and the Conservatism of Conservatism method of Mirny and Shakhnovich. Results obtained on a dataset of hydrolase-inhibitor complexes demonstrate that the combination of all four methods yield improved predictions over the individual methods. Conclusions We developed a consensus method for predicting protein-protein interface residues by combining sequence and structure-based methods. The success of our consensus approach suggests that similar methodologies can be developed to improve prediction accuracies for other bioinformatic problems.This article is from BMC Bioinformatics 5 (2005): 205, doi: 10.1186/1471-2105-5-205. Posted with permission.</p