Search PubMed⌕ Search

Biomedical subjects

Carlos Santos

Publications and source records attributed to Carlos Santos.

11 recordsLinked to original sources

Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together.

Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org.

Databases, Protein↗

SAGA: a subgraph matching tool for biological graphs.

MOTIVATION: With the rapid increase in the availability of biological graph datasets, there is a growing need for effective and efficient graph querying methods. Due to the noisy and incomplete characteristics of these datasets, exact graph matching methods have limited use and approximate graph matching methods are required. Unfortunately, existing graph matching methods are too restrictive as they only allow exact or near exact graph matching. This paper presents a novel approximate graph matching technique called SAGA. This technique employs a flexible model for computing graph similarity, which allows for node gaps, node mismatches and graph structural differences. SAGA employs an indexing technique that allows it to efficiently evaluate queries even against large graph datasets. RESULTS: SAGA has been used to query biological pathways and literature datasets, which has revealed interesting similarities between distinct pathways that cannot be found by existing methods. These matches associate seemingly unrelated biological processes, connect studies in different sub-areas of biomedical research and thus pose hypotheses for new discoveries. SAGA is also orders of magnitude faster than existing methods. AVAILABILITY: SAGA can be accessed freely via the web at http://www.eecs.umich.edu/saga. Binaries are also freely available at this website.

Algorithms↗

Comparison of type-specific human papillomavirus data from self and clinician directed sampling.

OBJECTIVE(S): To compare the type-specific human papillomavirus (HPV) recovery from physician and patient-collected samples. METHODS: Three hundred thirty-four (334) women attending colposcopy clinics in three countries were enrolled in this cross-sectional study. Cervicovaginal samples were collected by patients and physicians and processed with polymerase chain reaction and reverse line blot genotyping. McNemar's Chi-squared tests and Kappa statistics were utilized to determine statistical associations between physician- versus patient-collected samples. RESULTS: Oncogenic HPV infection was identified in 23.2% of patient-collected specimens compared to 34.9% of physician-collected specimens. Physician sampling detected significantly more infections with type 16 and 52 than did self-sampling and significantly more oncogenic HPV infection overall. For non-oncogenic HPV detection, there was no statistical difference between physician- and patient-collected samples. CONCLUSION(S): Patient sampling for HPV using a single vaginal brush does not identify all oncogenic HPV subtypes.

Colposcopy↗

Wnt pathway curation using automated natural language processing: combining statistical methods with partial and full parse for knowledge extraction.

MOTIVATION: Wnt signaling is a very active area of research with highly relevant publications appearing at a rate of more than one per day. Building and maintaining databases describing signal transduction networks is a time-consuming and demanding task that requires careful literature analysis and extensive domain-specific knowledge. For instance, more than 50 factors involved in Wnt signal transduction have been identified as of late 2003. In this work we describe a natural language processing (NLP) system that is able to identify references to biological interaction networks in free text and automatically assembles a protein association and interaction map. RESULTS: A 'gold standard' set of names and assertions was derived by manual scanning of the Wnt genes website (http://www.stanford.edu/~rnusse/wntwindow.html) including 53 interactions involved in Wnt signaling. This system was used to analyze a corpus of peer-reviewed articles related to Wnt signaling including 3369 Pubmed and 1230 full text papers. Names for key Wnt-pathway associated proteins and biological entities are identified using a chi-squared analysis of noun phrases over-represented in the Wnt literature as compared to the general signal transduction literature. Interestingly, we identified several instances where generic terms were used on the website when more specific terms occur in the literature, and one typographic error on the Wnt canonical pathway. Using the named entity list and performing an exhaustive assertion extraction of the corpus, 34 of the 53 interactions in the 'gold standard' Wnt signaling set were successfully identified (64% recall). In addition, the automated extraction found several interactions involving key Wnt-related molecules which were missing or different from those in the canonical diagram, and these were confirmed by manual review of the text. These results suggest that a combination of NLP techniques for information extraction can form a useful first-pass tool for assisting human annotation and maintenance of signal pathway databases. AVAILABILITY: The pipeline software components are freely available on request to the authors. CONTACT: dstates@umich.edu SUPPLEMENTARY INFORMATION: http://stateslab.bioinformatics.med.umich.edu/software.html.

Animals↗

Cross-sectional study of patient- and physician-collected cervical cytology and human papillomavirus.

OBJECTIVE: To compare the performance of patient- and physician-obtained cytology and human papillomavirus (HPV) testing for the detection of high-grade cervical intraepithelial neoplasia. METHODS: A cross-sectional study was performed involving 334 women seen at three colposcopy clinics (Tucson, Arizona; Hermosillo, Mexico; and Lima, Peru). All women used a cytobrush to self-collect specimens for cervical cytology and HPV testing. Subjects subsequently underwent physician collection for cytology and HPV, followed by a complete colposcopic evaluation with directed biopsy. Cytology was processed using thin-layer technology, and HPV was determined using the polymerase chain reaction technique. Test performance characteristics were determined using the histopathologic diagnosis as the reference standard and designating high-grade cervical intraepithelial neoplasia as clinically significant disease for the purpose of the analysis. RESULTS: The sensitivity of patient-collected cytology was significantly lower (55.0%) and specificity was significantly better (84.1%) than those of physician-directed sampling (85.2% and 73.4%, respectively). Patient-collected HPV had significantly lower sensitivity (49.0%) than physician sampling (82.2%), although specificity did not significantly differ. CONCLUSION: Patient collection is a feasible although inferior alternative to physician-collected cervical cytology and HPV testing.

Adolescent↗

Multiple sclerosis vs acute disseminated encephalomyelitis in childhood.

The initial presenting clinical and laboratory findings of either acute disseminated encephalomyelitis or the first attack of multiple sclerosis in the pediatric population were compared and contrasted. A retrospective review of the medical records was conducted of all children younger than 17 years who presented with either the diagnosis of acute disseminated encephalomyelitis or multiple sclerosis between 1987 and 2001. Seventeen cases of clinically definite multiple sclerosis (seven female, mean age 12.4 +/- 4.5 years) and seven cases of acute disseminated encephalomyelitis (three female; mean age 8.7 +/- 3.8 years) were reviewed. Systemic and nonfocal neurologic symptoms were more commonly evident in acute disseminated encephalomyelitis than in multiple sclerosis: fever (43% vs 6%), headache (57% vs 24%), fatigue (71% vs 29%), vomiting (57% vs 0%), and encephalopathy (71% vs 6%). In multiple sclerosis patients, T(2)-weighted white matter magnetic resonance imaging lesions were more commonly located in the corpus callosum (64% vs 17%) and the periventricular area (91% vs 50%) compared with those in patients with acute disseminated encephalomyelitis. These results suggest that acute disseminated encephalomyelitis and multiple sclerosis can be differentiated to some degree according to clinical and radiologic data at initial presentation, which is important because the long-term prognosis for childhood multiple sclerosis appears to be less favorable.

Adolescent↗

Non-cytotoxic gamma-delta peripheral T-cell lymphoma affecting the mandibular and parotidal lymph nodes and the skin.

In contrast to the majority of alphabeta peripheral T cell lymphomas (PTCL), which usually originate in lymph nodes and do not express NK-associated molecules, most gammadelta PTCL express a cytotoxic phenotype and originate at extranodal sites. We report a case of a patient with a gamma-delta PTCL who presented with large mandibular and parotidal lymphadenopathy and skin lesions. CD3(+)/TCR-Vdelta1 (+) lymphoma cells did not express the cell surface (CD11b, CD11c, CD16, CD56 and CD57) and cytoplasmic granule molecules (Perforin and Granzyme B) that usually characterize the cytotoxic T-cells, a phenotype that fulfils the criteria for diagnosis of a rare non-cytotoxic variant of a gammadelta T-cell lymphoma. "In situ" hybridization for Epstein-Barr virus-encoded RNA and latent membrane protein-1 gave negative results. The disease had an aggressive course and was resistant to chemotherapy and the patient died 4 months after diagnosis.

Antigens, Neoplasm↗

Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells.

Epidemiologic studies suggest that the consumption of red wine may lower the risk of cardiovascular disease. The cardioprotective effect of red wine has been attributed to the polyphenols present in red wine, particularly resveratrol (a stilbene, with estrogen-like activity), and the flavonoids, catechin, epicatechin, quercetin and phenolic acids such as gallic acid. At present, very little is known about the mechanisms by which red wine phenolic compounds benefit the cardiovascular system. Therefore, the aim of this study was to elucidate whether red wine polyphenolics reduce lipoprotein production and clearance by the liver. Cultured HepG2 cells were incubated in the presence of dealcoholized red wine, alcohol-containing red wine and atorvastatin for 24 h. The apolipoprotien B100 (apoB100) protein (marker of hepatic lipoproteins) was quantified on Western blots with an anti-apoB100 antibody and the enhanced chemiluminescence detection system. Apolipoprotein B100 levels in the cells and that secreted into the media were significantly reduced by 50% in liver cells incubated with alcohol-stripped red wine compared with control cells. This effect of dealcoholized red wine on apoB100 production in HepG2 cells was similar to the effect of atorvastatin. Apo B100 production was significantly attenuated by 30% in cells incubated with alcoholized red wine, suggesting that the alcohol was masking the effect of red wine polyphenolics. Apo B100 production was significantly attenuated by 45% with the polyphenolic compounds resveratrol and quercertin. In addition, dealcoholized and alcoholized red wine and atorvastatin significantly increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA and LDL receptor binding activity relative to controls. Dealcoholized red wine also increased LDL receptor gene expression. Collectively, this study suggests that red wine polyphenolics regulate major pathways involved in lipoprotein metabolism.

Apolipoprotein B-100↗

Cancer in first degree relatives of Latin American women with cervical cancer. A pilot study.

BACKGROUND: Cervical cancer is the most frequent cancer of women in Latin America, being strongly associated with infection by certain human papillomavirus (HPV) types. Familial cancer clustering can be due to interactions between infectious agents and host genes. MATERIALS AND METHODS: A cancer-related family history of first degree relatives was elicited in 335 women with invasive cervical cancer (probands) and in 335 women without cancer (controls) in Honduras, Peru and Uruguay, and the frequency of reported familial cancers among the relatives was compared between proband and control relatives. RESULTS: The mean age at the time of interview was 49.8 years for the probands and 50.1 years for the controls (NS). 3852 proband relatives had 114 primary cancers of the following major localisations: 22 uterus, 16 lung, 12 stomach and 64 others. 3333 control relatives had 101 primary cancers of the following major localizations: 18 uterus, 13 stomach, 12 breast, 11 intestinal, 10 lung and 37 others. The frequency of all cancer diagnosis among proband relatives was similar to the frequency among control relatives (odds ratio= 1.01; 95% confidence interval: 0.69-1.47). Nine haemolymphatic malignancies were reported among proband relatives versus 2 in control relatives (odds ratio=3.46; 95% confidence interval: 0.74-16.29). CONCLUSION: All cancer combined did not appear to be more frequent in first degree relatives of women with cervical cancer diagnosis, but haemolymphatic malignancies, a minor part of the cancer burden, may be overrepresented in relatives of women with cervical cancer, pointing to a pathogenic role of familial e.g. hereditary, immunosuppression.

Case-Control Studies↗