Biomedical subjects

Paulo B Paiva

Publications and source records attributed to Paulo B Paiva.

5 recordsLinked to original sources

PubMed2007

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model.

In the study of temporal lobe epilepsy (TLE) the characterization of genes expressed in the hippocampus is of central importance for understanding their roles in epileptogenic mechanisms. Although several large-scale studies on TLE gene expression have been reported, precise assignment of individual genes associated with this syndrome is still debatable. Here we investigated differentially expressed genes by comparison of mRNAs from normal and epileptic rat hippocampus in the pilocarpine model of epilepsy. For this we used a powerful EST sequencing methodology, ORESTES (Open Reading frame Expressed Sequence Tags), which generates sequence datasets enriched for mRNAs open reading frames (ORFs) rather than simple 5' and 3' ends of mRNAs. Analysis of our sequences shows that ORESTES readily enables the identification of epilepsy associated ORFs. PFAM analysis of protein motifs present in our ORESTES epilepsy database revealed diverse important protein family domains, such as cytoskeletal, cell signaling and protein kinase domains, which could be involved in processes underlying epileptogenesis. More importantly, we show that the expression of homer 1a, known to be coupled to mGluR and NMDA synaptic transmission, is associated with pilocarpine induced status epilepticus (SE). The combined use of the pilocarpine model of epilepsy with the ORESTES technique can significantly contribute to the identification of specific genes and proteins related to TLE. This is the first study applying a large-scale method for rapid shotgun sequencing directed to ORFs in epilepsy research.

Animals↗

PubMed2006

Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy.

OBJECTIVES: Laser-induced thermal therapy (LITT) for cancer is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, and so on) is directly applied into a tumor at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real- or "near" real-time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. The objective of this study is to report UCLA's experience using UTZ monitoring of Nd:YAG laser thermal ablation of malignant cervical adenopathy in a phase II study. STUDY DESIGN: The authors conducted a retrospective study of patients treated at a tertiary medical center. METHODS: Forty-seven patients with a total of 55 neck tumors were treated on an outpatient basis in the operating room using UTZ for image-guided laser interstitial thermal therapy. Laser energy was delivered through an SLT Nd:YAG laser powered at 30 W (power density: 2,200 J/cm). RESULTS: Eleven patients had a complete response ranging from 5.5 to 90 months (mean, 22.1 months). Based on the findings of this study, it was possible to show that proximity to the carotid artery was the most relevant factor in projecting patient survival. Patients' individual treatment analysis and final outcome are further discussed. CONCLUSIONS: LITT ablation of malignant cervical adenopathy was considered safe and feasible. No intraoperative complications occurred. Further development of this technique applying laser energy delivery to mathematical imaging models should lead to more effective tumor palliation as an alternative to surgery.

Adult↗

PubMed2004

A transcript finishing initiative for closing gaps in the human transcriptome.

We report the results of a transcript finishing initiative, undertaken for the purpose of identifying and characterizing novel human transcripts, in which RT-PCR was used to bridge gaps between paired EST clusters, mapped against the genomic sequence. Each pair of EST clusters selected for experimental validation was designated a transcript finishing unit (TFU). A total of 489 TFUs were selected for validation, and an overall efficiency of 43.1% was achieved. We generated a total of 59,975 bp of transcribed sequences organized into 432 exons, contributing to the definition of the structure of 211 human transcripts. The structure of several transcripts reported here was confirmed during the course of this project, through the generation of their corresponding full-length cDNA sequences. Nevertheless, for 21% of the validated TFUs, a full-length cDNA sequence is not yet available in public databases, and the structure of 69.2% of these TFUs was not correctly predicted by computer programs. The TF strategy provides a significant contribution to the definition of the complete catalog of human genes and transcripts, because it appears to be particularly useful for identification of low abundance transcripts expressed in a restricted set of tissues as well as for the delineation of gene boundaries and alternatively spliced isoforms.

Alternative Splicing↗

PubMed2003

Sequence analysis reveals how G protein-coupled receptors transduce the signal to the G protein.

Sequence entropy-variability plots based on alignments of very large numbers of sequences-can indicate the location in proteins of the main active site and modulator sites. In the previous article in this issue, we applied this observation to a series of well-studied proteins and concluded that it was possible to detect most of the residues with a known functional role. Here, we apply the method to rhodopsin-like G protein-coupled receptors. Our conclusion is that G protein binding is the main evolutionary constraint on these receptors, and that other ligands, such as agonists, act as modulators. The activation of the receptors can be described as a simple, two-step process, and the residues involved in signal transduction can be identified.

Amino Acid Sequence↗

PubMed2003

Identification of functionally conserved residues with the use of entropy-variability plots.

We introduce sequence entropy-variability plots as a method of analyzing families of protein sequences, and demonstrate this for three well-known sequence families: globins, ras-like proteins, and serine-proteases. The location of an aligned residue position in the entropy-variability plot correlates with structural characteristics, and with known facts about the roles of individual amino acids in the function of these proteins. The large numbers of known sequences in these families allowed us to introduce new filtering methods for variability patterns. The results are discussed in terms of a simple evolutionary model for functional proteins.

Algorithms↗