Search PubMed⌕ Search

Biomedical subjects

M A Andrade

Publications and source records attributed to M A Andrade.

At least 37 records · Page 2Linked to original sources
PubMed1999

Immunohistochemical detection of parathyroid hormone-related protein in a cutaneous squamous cell carcinoma causing humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein is the main humoral factor implicated. In spite of the fact that normal keratinocytes produce parathyroid hormone-related protein, it is highly unusual for patients with squamous cell carcinomas of the skin to present with humoral hypercalcemia of malignancy. We present a well-documented case of cutaneous squamous cell carcinoma complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of high parathyroid hormone-related protein production by the tumoral cells.

Aged↗
PubMed1999

Position-specific annotation of protein function based on multiple homologs.

I present in this work an algorithm for deriving protein functional annotations which are position-specific. The input is based on the results of a sequence similarity search of the query sequence against a sequence database. Strings of words are extracted from the descriptions of the proteins, and the correlation between proteins having the same descriptors and the amino acid conservation is used to compute a score that indicates which descriptor is likely to describe better the function of each particular residue. Analysis of the score curves and comparison of different functions allows an easy detection of parts of the sequence associated to different function. Different levels of functional specificity can be compared, allowing to choose the one that suits better the function of the protein. Immediate applications of this algorithm are, support for (automated) methods of protein functional annotation, and database coherence check.

Algorithms↗
PubMed1999

Automatic extraction of biological information from scientific text: protein-protein interactions.

We describe the basic design of a system for automatic detection of protein-protein interactions extracted from scientific abstracts. By restricting the problem domain and imposing a number of strong assumptions which include pre-specified protein names and a limited set of verbs that represent actions, we show that it is possible to perform accurate information extraction. The performance of the system is evaluated with different cases of real-world interaction networks, including the Drosophila cell cycle control. The results obtained computationally are in good agreement with current biological knowledge and demonstrate the feasibility of developing a fully automated system able to describe networks of protein interactions with sufficient accuracy.

Algorithms↗
PubMed1998

Updated catalogue of homologues to human disease-related proteins in the yeast genome.

The recent availability of the full Saccharomyces cerevisiae genome offers a perfect opportunity for revising the number of homologues to human disease-related proteins. We carried out automatic analysis of the complete S. cerevisiae genome and of the set of human disease-related proteins as identified in the SwissProt sequence data base. We identified 285 yeast proteins similar to 155 human disease-related proteins, including 239 possible cases of human-yeast direct functional equivalence (orthology). Of these, 40 cases are suggested as new, previously undiscovered relationships. Four of them are particularly interesting, since the yeast sequence is the most phylogenetically distant member of the protein family, including proteins related to diseases such as phenylketonuria, lupus erythematosus, Norum and fish eye disease and Wiskott-Aldrich syndrome.

Amino Acid Sequence↗
PubMed1998

Adaptation of protein surfaces to subcellular location.

In vivo, proteins occur in widely different physio-chemical environments, and, from in vitro studies, we know that protein structure can be very sensitive to environment. However, theoretical studies of protein structure have tended to ignore this complexity. In this paper, we have approached this problem by grouping proteins by their subcellular location and looking at structural properties that are characteristic to each location. We hypothesize that, throughout evolution, each subcellular location has maintained a characteristic physio-chemical environment, and that proteins in each location have adapted to these environments. If so, we would expect that protein structures from different locations will show characteristic differences, particularly at the surface, which is directly exposed to the environment. To test this hypothesis, we have examined all eukaryotic proteins with known three-dimensional structure and for which the subcellular location is known to be either nuclear, cytoplasmic, or extracellular. In agreement with previous studies, we find that the total amino acid composition carries a signal that identifies the subcellular location. This signal was due almost entirely to the surface residues. The surface residue signal was often strong enough to accurately predict subcellular location, given only a knowledge of which residues are at the protein surface. The results suggest how the accuracy of prediction of location from sequence can be improved. We concluded that protein surfaces show adaptation to their subcellular location. The nature of these adaptations suggests several principles that proteins may have used in adapting to particular physio-chemical environments; these principles may be useful for protein design.

Amino Acids↗
PubMed1998

Computational space reduction and parallelization of a new clustering approach for large groups of sequences.

MOTIVATION: The explosive growth of the biological sequences databases stimulated by genome projects has modified the framework of several applications in the biological sequence analysis area. In most cases, this new scenario is characterized by studies on large sets of sequences, suggesting the need for effective and automatic methods for their clustering. A more effective clustering of the database could be followed by the application of common family analysis schemes to the groups so formed. RESULTS: In this work, we present a new strategy to reduce the computational cost associated with the clustering of large sets of sequences which are expected to contain several families. The strategy is based on the grouping of the sequences into families by using a dynamic threshold on a pairwise sequence similarity criterion. Routine clustering of large data sets can now be done very efficiently. The method developed here achieves a computational space reduction of about an order of magnitude over more traditional ones of all-versus-all comparisons. The outcome of this approach produces family groupings that reproduce closely already accepted biological results. Our work includes a parallel implementation for distributed memory multiprocessors with a dynamic scheduling strategy for performance optimization. AVAILABILITY: By anonymous ftp at ftp.ac.uma.es (/pub/ots/pCluster directory), or from our Web site http://www.cnb. uam.es/www/software/software_index.html CONTACT: ots@ac.uma.es

Algorithms↗
PubMed1998

Automatic extraction of keywords from scientific text: application to the knowledge domain of protein families.

MOTIVATION: Annotation of the biological function of different protein sequences is a time-consuming process currently performed by human experts. Genome analysis tools encounter great difficulty in performing this task. Database curators, developers of genome analysis tools and biologists in general could benefit from access to tools able to suggest functional annotations and facilitate access to functional information. APPROACH: We present here the first prototype of a system for the automatic annotation of protein function. The system is triggered by collections of s related to a given protein, and it is able to extract biological information directly from scientific literature, i.e. MEDLINE abstracts. Relevant keywords are selected by their relative accumulation in comparison with a domain-specific background distribution. Simultaneously, the most representative sentences and MEDLINE abstracts are selected and presented to the end-user. Evolutionary information is considered as a predominant characteristic in the domain of protein function. Our system consequently extracts domain-specific information from the analysis of a set of protein families. RESULTS: The system has been tested with different protein families, of which three examples are discussed in detail here: 'ataxia-telangiectasia associated protein', 'ran GTPase' and 'carbonic anhydrase'. We found generally good correlation between the amount of information provided to the system and the quality of the annotations. Finally, the current limitations and future developments of the system are discussed. AVAILABILITY: The current system can be considered as a prototype system. As such, it can be accessed as a server at http://columba.ebi.ac. uk:8765/andrade/abx. The system accepts text related to the protein or proteins to be evaluated (optimally, the result of a MEDLINE search by keyword) and the results are returned in the form of Web pages for keywords, sentences and s. SUPPLEMENTARY INFORMATION: Web pages containing full information on the examples mentioned in the text are available at: http://www.cnb.uam.es/ approximately cnbprot/keywords/ CONTACT: valencia@cnb.uam.es

Abstracting and Indexing↗
PubMed1998

Growth hormone (GH) response to GH-releasing peptide-6 in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion.

In type 1 diabetes mellitus (DM 1), high GH basal levels and exaggerated GH responses to several stimuli, including GHRH, have been described. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release, both in vitro and in vivo. The aim of this study was to evaluate the effects of GHRP-6 alone or in combination with GHRH on GH secretion in DM 1. Six type 1 diabetic males and six age-, sex-, and body mass index-matched control volunteers were studied. Each subject received GHRH (100 microg iv), GHRP-6 (90 microg iv), and GHRH plus GHRP-6 on three separate days. GH peak values were higher in DM 1 patients than in control volunteers, after GHRH (52.2+/-9.8 vs. 19.3+/-6.0 microg/L; P = 0.016), GHRP-6 (66.2+/-9.6 vs. 39.9+/-6.3 microg/L; P = 0.05), and GHRH plus GHRP-6 (81.8+/-4.4 vs. 53.7+/-8.2 microg/L; P = 0.01). An additive GH response to combined administration of these two peptides was observed in diabetic patients. Serum insulin-like growth factor (IGF)-1 levels were diminished in DM 1, with respect to normal subjects (145.2+/-21.5 vs. 269.7+/-42.0 microg/L; P = 0.01), whereas IGF-binding protein-3 levels were not significantly different between DM-1 and controls. In summary, GHRP-6 is a potent stimulus for GH secretion in DM 1. The combined administration of GHRP-6 plus GHRH constitutes the most powerful stimulus for GH secretion in DM 1. These patients exhibit a greater GH secretory capacity than normal subjects, probably caused by a diminished tone in the IGF-1 sustained negative feedback control exerted upon somatotroph responsiveness.

Adult↗
PubMed1998

Acute otitis media in children with bronchiolitis.

OBJECTIVE: We investigated the prevalence and the etiology of acute otitis media (AOM) in children with bronchiolitis to determine whether AOM in such children is due entirely or mainly to respiratory syncytial virus (RSV), in which case routine antimicrobial treatment would not be appropriate. METHODS: The study group consisted of children aged 2 to 24 months with bronchiolitis. In patients with AOM at entry, nasal washings for RSV enzyme-linked immunosorbent assay were obtained, and Gram-stained smear, bacterial culture, and reverse transcriptase polymerase chain reaction to detect the presence of RSV were performed on middle-ear aspirates. Patients without AOM were reevaluated at 48 to 72 hours, 8 to 10 days, and 18 to 22 days. RESULTS: Forty-two children with bronchiolitis were enrolled. Sixty-two percent had AOM at entry or developed AOM within 10 days. An additional 24% had or eventually developed otitis media with effusion. Only 14% remained free of both AOM and otitis media with effusion throughout the 3-week observation period. All patients with AOM had 1 or more bacterial pathogens isolated from one or both middle-ear aspirates. Of 33 middle-ear aspirates, Streptococcus pneumoniae was isolated in 15, Haemophilus influenzae in 8, Moraxella catarrhalis in 8, and Staphylococcus aureus in 2. Two middle-ear aspirates yielded 2 pathogens each; 2 aspirates had no growth. RSV was identified in 17 (71%) of 24 patients with AOM. CONCLUSION: Bacterial AOM is a complication in most children with bronchiolitis. Accordingly, in patients with bronchiolitis and associated AOM, antimicrobial treatment is indicated.

Acute Disease↗
PubMed1997

DNA sequencing and analysis of 130 kb from yeast chromosome XV.

We have determined the nucleotide sequence of 129,524 bases of yeast (Saccharomyces cerevisiae) chromosome XV. Sequence analysis revealed the presence of 59 non-overlapping open reading frames (ORFs) of length > 300 bp, three tRNA genes, four delta elements and one Ty-element. Among the 21 previously known yeast genes (36% of all ORFs in this fragment) were nucleoporin (NUP1), ras protein (RAS1), RNA polymerase III (RPC1) and elongation factor 2 (EF2). Further, 31 ORFs (53% of the total) were found to be homologous to known protein or DNA sequences, or sequence patterns. For seven ORFs (11% of the total) no homology was found. Among the most interesting protein identification in this DNA fragment are an inositol polyphosphatase, the second gene of this type found in yeast (homologous to the human OCRL gene involved in Lowe's syndrome), a new ADP ribosylation factor of the arf6 subfamily, the first protein containing three C2 domains, and an ORF similar to a Bacillus subtilis cell-cycle related protein. For each ORF detailed sequence analysis was carried out, with a full consideration of its biological function and pointing out key regions of interest for further functional analysis.

ADP-Ribosylation Factors↗
PubMed1997

Characterization of new proteins found by analysis of short open reading frames from the full yeast genome.

We have analysed short open reading frames (between 150 and 300 base pairs long) of the yeast genome (Saccharomyces cerevisiae) with a two-step strategy. The first step selects a candidate set of open reading frames from the DNA sequence based on statistical evaluation of DNA and protein sequence properties. The second step filters the candidate set by selecting open reading frames with high similarity to other known sequences (from any organism). As a result, we report ten new predicted proteins not present in the current sequence databases. These include a new alcohol dehydrogenase, a protein probably related to the cell cycle, as well as a homolog of the prokaryotic ribosomal protein L36 likely to be a mitochondrial ribosomal protein coded in the nuclear genome. We conclude that the analysis of short open reading frames leads to biologically interesting discoveries, even though the quantitative yield of new proteins is relatively low.

Alcohol Dehydrogenase↗
PubMed1997

Classification of protein families and detection of the determinant residues with an improved self-organizing map.

Using a SOM (self-organizing map) we can classify sequences within a protein family into subgroups that generally correspond to biological subcategories. These maps tend to show sequence similarity as proximity in the map. Combining maps generated at different levels of resolution, the structure of relations in protein families can be captured that could not otherwise be represented in a single map. The underlying representation of maps enables us to retrieve characteristic sequence patterns for individual subgroups of sequences. Such patterns tend to correspond to functionally important regions. We present a modified SOM algorithm that includes a convergence test that dynamically controls the learning parameters to adapt them to the learning set instead of being fixed and externally optimized by trial and error. Given the variability of protein family size and distribution, the addition of this features is necessary. The method is successfully tested with a number of families. The rab family of small GTPases is used to illustrate the performance of the method.

Algorithms↗
PubMed1997

Bioinformatics: from genome data to biological knowledge.

Recently, molecular biologists have sequenced about a dozen bacterial genomes and the first eukaryotic genome. We can now obtain answers to detailed questions about the complete set of genes of an organism. Bioinformatics methods are increasingly used for attaching biological knowledge to long lists of genes, assigning genes to biological pathways, comparing the gene sets of different species, identifying specificity factors, and describing sets of highly conserved proteins common to all domains of life. Substantial progress has recently been made in the availability of primary and added-value databases, in the development of algorithms and of network information services for genome analysis. The pharmaceutical industry has greatly benefited from the accumulation of sequence data through the identification of targets and candidates for the development of drugs, vaccines, diagnostic markers and therapeutic proteins.

Databases, Factual↗
PubMed1997

Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage.

UNLABELLED: It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index. IN CONCLUSION: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.

Adolescent↗
PubMed1997

Automatic annotation for biological sequences by extraction of keywords from MEDLINE abstracts. Development of a prototype system.

We have developed a prototype for the automatic annotation of functional characteristics in protein families. The system is able to extract biological information directly from scientific literature in the form of MEDLINE abstracts. The criterion for selecting relevant keywords is the difference between their frequency in the abstracts associated with the protein family under study and its frequency in other unrelated protein families. The concept of functional information associated to protein families is the key feature of our system and gathers evolutionary information into the problem of functional annotation of biological sequences. The system has been tested in two different scenarios: first, a large set of protein families with a small number of abstract per family and second, selected protein families with large number of abstracts attached to each one. In both cases the performances are compared with annotations provided by human experts showing a clear relation between the amount of information provided to the system and the quality of the annotations. The automatic annotations are in many cases of similar quality to the ones contained in current data bases. The possibilities and difficulties to be encountered during the development of a full system for automatic annotation are discussed.

Abstracting and Indexing↗
PubMed1996

Structural study of the development of ocularity domains using a neural network model.

We present a model for the development of ocularity domains in the visual cortex of mammals during the embryonic stage. We model the thalamo-cortical pathway with a self-organising neural network with two source layers, each of them serving different retinae, and one target layer, where the connections end. The connectivity between the source layers and the target layer is driven by Hebbian learning. In both the source layers and the target layer we assume excitatory lateral signal diffusion between proximal neurons that causes them to be correlated. According to the developmental state being modelled, we do not consider either correlation or anti-correlation between the signals originated in neurons of different retinae. The basic assumptions made are proved to be sufficient to attain a distribution of connections arranged in ocularity domains. The dependence of the geometry of the ocularity domains on the parameters of the model is analysed and a correlation between the width of the signal diffusion and the extent of the domains is found. The generality of the assumptions made allows an easy translation of the model to explain the development of other elements of the sensory nervous system.

Animals↗