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At least 1,171 records · Page 65Linked to original sources
PubMed2002

Treatment of chronic hepatitis C: a systematic review.

This systematic review addressed 3 issues regarding current treatments for chronic hepatitis C: (1) efficacy and safety in treatment-naive patients; (2) efficacy and safety in selected subgroups of patients; and (3) effects on long-term clinical outcomes. Electronic databases were searched for articles from January 1996 to March 2002. Additional articles were identified by searching references in pertinent articles and recent journals and by questioning experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, or clinical outcome measures. For data collection, paired reviewers assessed the quality of each study and abstracted data. This systematic review found that the combination of high-dose peginterferon and ribavirin was more efficacious than standard interferon and ribavirin in persons infected with hepatitis C virus (HCV) genotype 1 (sustained virologic response [SVR] rate: 42% vs. 33%) and that ranges of SVR rates were higher with peginterferon than standard interferon monotherapy in naïve patients (10% to 39% vs. 3% to 19%). Reports were consistent in showing treatment with interferon and ribavirin was more efficacious than interferon monotherapy in treatment-naive persons and previous nonresponders and relapsers. Studies were moderately consistent in showing that treatment decreases the risk for hepatocellular carcinoma (HCC). The evidence on treatment in important subgroups was limited by a lack of randomized controlled trials. Thus, the combination of peginterferon and ribavirin was the most efficacious treatment in patients with HCV genotype 1. Long-term outcomes were improved in patients with hepatitis C who achieved an SVR with treatment.

Antiviral Agents↗
PubMed2004

GermOnline, a cross-species community knowledgebase on germ cell differentiation.

GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics.

Animals↗
PubMed2006

Intra- and interpopulation genotype reconstruction from tagging SNPs.

The optimal method to be used for tSNP selection, the applicability of a reference LD map to unassayed populations, and the scalability of these methods to genome-wide analysis, all remain subjects of debate. We propose novel, scalable matrix algorithms that address these issues and we evaluate them on genotypic data from 38 populations and four genomic regions (248 SNPs typed for approximately 2000 individuals). We also evaluate these algorithms on a second data set consisting of genotypes available from the HapMap database (1336 SNPs for four populations) over the same genomic regions. Furthermore, we test these methods in the setting of a real association study using a publicly available family data set. The algorithms we use for tSNP selection and unassayed SNP reconstruction do not require haplotype inference and they are, in principle, scalable even to genome-wide analysis. Moreover, they are greedy variants of recently developed matrix algorithms with provable performance guarantees. Using a small set of carefully selected tSNPs, we achieve very good reconstruction accuracy of "untyped" genotypes for most of the populations studied. Additionally, we demonstrate in a quantitative manner that the chosen tSNPs exhibit substantial transferability, both within and across different geographic regions. Finally, we show that reconstruction can be applied to retrieve significant SNP associations with disease, with important genotyping savings.

Algorithms↗
PubMed2005

Integrating genomic data to predict transcription factor binding.

Transcription factor binding sites (TFBS) in gene promoter regions are often predicted by using position specific scoring matrices (PSSMs), which summarize sequence patterns of experimentally determined TF binding sites. Although PSSMs are more reliable than simple consensus string matching in predicting a true binding site, they generally result in high numbers of false positive hits. This study attempts to reduce the number of false positive matches and generate new predictions by integrating various types of genomic data by two methods: a Bayesian allocation procedure, and support vector machine classification. Several methods will be explored to strengthen the prediction of a true TFBS in the Saccharomyces cerevisiae genome: binding site degeneracy, binding site conservation, phylogenetic profiling, TF binding site clustering, gene expression profiles, GO functional annotation, and k-mer counts in promoter regions. Binding site degeneracy (or redundancy) refers to the number of times a particular transcription factor's binding motif is discovered in the upstream region of a gene. Phylogenetic conservation takes into account the number of orthologous upstream regions in other genomes that contain a particular binding site. Phylogenetic profiling refers to the presence or absence of a gene across a large set of genomes. Binding site clusters are statistically significant clusters of TF binding sites detected by the algorithm ClusterBuster. Gene expression takes into account the idea that when the gene expression profiles of a transcription factor and a potential target gene are correlated, then it is more likely that the gene is a genuine target. Also, genes with highly correlated expression profiles are often regulated by the same TF(s). The GO annotation data takes advantage of the idea that common transcription targets often have related function. Finally, the distribution of the counts of all k-mers of length 4, 5, and 6 in gene's promoter region were examined as means to predict TF binding. In each case the data are compared to known true positives taken from ChIP-chip data, Transfac, and the Saccharomyces Genome Database. First, degeneracy, conservation, expression, and binding site clusters were examined independently and in combination via Bayesian allocation. Then, binding sites were predicted with a support vector machine (SVM) using all methods alone and in combination. The SVM works best when all genomic data are combined, but can also identify which methods contribute the most to accurate classification. On average, a support vector machine can classify binding sites with high sensitivity and an accuracy of almost 80%.

Algorithms↗
PubMed2000

TT virus (TTV) genotypes in native and non-native prostitutes of Irian Jaya, Indonesia: implication for non-occupational transmission.

We investigated prostitutes in Irian Jaya, an Indonesian territory of New Guinea, to know whether TT virus (TTV) is sexually transmitted and what genotypes of TTV exist there. An ORF2 region of the TTV genome was analyzed for 44 isolates from prostitutes (19 were Irian Jaya natives but 25 were immigrants from Java or other islands of Indonesia) and 26 isolates from women of child-bearing age in Surabaya as a control. The WX(7)HX(3)CX(1)CX(5)H motif sequence of the ORF2 was compared across the 70 Indonesian isolates with a reference of 47 Japanese isolates (filed in databases) and the prototype TTV isolate TA278. A total of 77 different sequences were generated from the comparison, but a phylogenetic analysis suggested that they could be divided into three categories: group A, group B and others (the third group was highly diverse). Interestingly, most of the Indonesian isolates belonged to group B (74%): this rate was considerably higher than that observed previously in Japanese isolates. Group B isolates were further compared for the N-terminal 95 amino acids of the ORF2, with a result that the natives of Irian Jaya had a different pattern of genotype distribution from other groups. In particular, 9 out of 19 isolates from the Irian Jaya-natives were co-classified under a distinct branch, to which none of the other Indonesian and Japanese isolates belonged. Our data indicate that TTV genotypes reflect the birth place of the infected prostitutes rather than their work environment, and thus suggest that an infection is more likely during the early period of life than through sexual transmission. In addition, the presence of an Irian Jaya-specific genotype is intriguing from an anthropological and viral evolutionary point of view, because Irian Jaya has been isolated from contact with other areas for a long time.

Adolescent↗
PubMed2004

Estimation of the number of authentic orphan genes in bacterial genomes.

Genome annotation produces a considerable number of putative proteins lacking sequence similarity to known proteins. These are referred to as "orphans." The proportion of orphan genes varies among genomes, and is independent of genome size. In the present study, we show that the proportion of orphan genes roughly correlates with the isolation index of organisms (IIO), an indicator introduced in the present study, which represents the degree of isolation of a given genome as measured by sequence similarity. However, there are outlier genomes with respect to the linear correlation, consisting of those genomes that may contain excess amounts of orphan genes. Comparisons of genome sequences among closely related strains revealed that some of the annotated genes are not conserved, suggesting that they are ORFs occurring by chance. Exclusion of these non-conserved ORFs within closely related genomes improved the correlation between the proportion of orphan genes and the IIO values. Assuming that the correlation holds in general, this relationship was used to estimate the number of "authentic" orphan genes in a genome. Using this definition of authentic orphan genes, the anomalies arising from over-assignments, e.g., the percentages of structural annotations, were corrected for 16 genomes, including those of five archaea.

Amino Acid Sequence↗
PubMed2006

Validation and functional annotation of expression-based clusters based on gene ontology.

BACKGROUND: The biological interpretation of large-scale gene expression data is one of the paramount challenges in current bioinformatics. In particular, placing the results in the context of other available functional genomics data, such as existing bio-ontologies, has already provided substantial improvement for detecting and categorizing genes of interest. One common approach is to look for functional annotations that are significantly enriched within a group or cluster of genes, as compared to a reference group. RESULTS: In this work, we suggest the information-theoretic concept of mutual information to investigate the relationship between groups of genes, as given by data-driven clustering, and their respective functional categories. Drawing upon related approaches (Gibbons and Roth, Genome Research 12:1574-1581, 2002), we seek to quantify to what extent individual attributes are sufficient to characterize a given group or cluster of genes. CONCLUSION: We show that the mutual information provides a systematic framework to assess the relationship between groups or clusters of genes and their functional annotations in a quantitative way. Within this framework, the mutual information allows us to address and incorporate several important issues, such as the interdependence of functional annotations and combinatorial combinations of attributes. It thus supplements and extends the conventional search for overrepresented attributes within a group or cluster of genes. In particular taking combinations of attributes into account, the mutual information opens the way to uncover specific functional descriptions of a group of genes or clustering result. All datasets and functional annotations used in this study are publicly available. All scripts used in the analysis are provided as additional files.

Algorithms↗
PubMed2002

Genes of the Pseudoviridae (Ty1/copia retrotransposons).

A comprehensive survey of the Pseudoviridae (Ty1/copia) retroelement family was conducted using the GenBank sequence database and completed genome sequences of several model organisms. Plant genomes were the most abundant sources of Pseudoviridae, with the Arabidopsis thaliana genome having 276 distinct elements. A reverse transcriptase amino acid sequence phylogeny indicated that the Pseudoviridae comprises highly divergent members. Coding sequences for a representative subset of elements were analyzed to identify conserved domains and differences that may underlie functional divergence. With the exception of some fungal elements (e.g., Ty1), most Pseudoviridae encode Gag and Pol on a single open reading frame. In addition to the nearly ubiquitous RNA-binding motif of nucleocapsid, three new conserved domains were identified in Gag. pol-encoded aspartic protease was similar to the retroviral enzyme and could be mapped onto the HIV-1 structure. Pol was highly conserved throughout the family. The greatest divergence among Pol sequences was seen in the C-terminus of integrase (IN). We defined a large motif (GKGY) after the IN catalytic domain that is unique to the Pseudoviridae. Additionally, the extreme C-terminus of IN is rich in simple sequence motifs. A distinct lineage of Pseudoviridae in plants have envlike genes. This lineage has undergone a large expansion of Gag characterized by an alpha-helix-rich domain containing coiled-coil motifs. In several elements, this domain is flanked on both sides by RNA-binding domains. We propose that this monophyletic lineage defines a new Pseudoviridae genus, herein referred to as the AGROVIRUS:

Amino Acid Sequence↗
PubMed2004

ISYMOD: a knowledge warehouse for the identification, assembly and analysis of bacterial integrated systems.

MOTIVATION: Complex biological functions emerge from interactions between proteins in stable supra-molecular assemblies and/or through transitory contacts. Most of the time protein partners of the assemblies are composed of one or several domains which exhibit different biochemical functions. Thus the study of cellular process requires the identification of different functional units and their integration in an interaction network; such complexes are referred to as integrated systems. In order to exploit with optimum efficiency the increased release of data, automated bioinformatics strategies are needed to identify, reconstruct and model such systems. For that purpose, we have developed a knowledge warehouse dedicated to the representation and acquisition of bacterial integrated systems involved in the exchange of the bacterial cell with its environment. RESULTS: ISYMOD is a knowledge warehouse that consistently integrates in the same environment the data and the methods used for their acquisition. This is achieved through the construction of (1) a domain knowledge base (DKB) devoted to the storage of the knowledge about the systems, their functional specificities, their partners and how they are related and (2) a methodological knowledge base (MKB) which depicts the task layout used to identify and reconstruct functional integrated systems. Instantiation of the DKB is obtained by solving the tasks of the MKB, whereas some tasks need instances of the DKB to be solved. AROM, an object-based knowledge representation system, has been used to design the DKB, and its task manager, AROMTasks, for developing the MKB. In this study two integrated systems, ABC transporters and two component systems, both involved in adaptation processes of a bacterial cell to its biotope, have been used to evaluate the feasibility of the approach.

ATP-Binding Cassette Transporters↗
PubMed1997

Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents.

In the present study, we report the characterization of the p53 tumor suppressor pathway in the 60 cell lines of the National Cancer Institute (NCI) anticancer drug screen, as well as correlations between the integrity of this pathway and the growth-inhibitory potency of 123 anticancer agents in this screen. Assessment of p53 status in these lines was achieved through complete p53 cDNA sequencing, measurement of basal p53 protein levels and functional assessment of (a) transcriptional activity of p53 cDNA from each line in a yeast assay, (b) gamma-ray-induced G1 phase cell cycle arrest, and (c) gamma-ray-induced expression of CIP1/WAF1, GADD45, and MDM2 mRNA. Our investigations revealed that p53 gene mutations were common in the NCI cell screen lines: 39 of 58 cell lines analyzed contained a mutant p53 sequence. cDNA derived from almost all of the mutant p53 cell lines failed to transcriptionally activate a reporter gene in yeast, and the majority of mutant p53 lines studied expressed elevated basal levels of the mutant p53 protein. In contrast to most of the wild-type p53-containing lines, cells containing mutant p53 sequence were also deficient in gamma-ray induction of CIP1/WAF1, GADD45, and MDM2 mRNA and the ability to arrest in G1 following gamma-irradiation. Taken together, these assessments provided indications of the integrity of the p53 pathway in the 60 cell lines of the NCI cell screen. These individual p53 assessments were subsequently used to probe a database of growth-inhibitory potency for 123 "standard agents," which included the majority of clinically approved anticancer drugs. These 123 agents have been tested against these lines on multiple occasions, and a proposed mechanism of drug action had previously been assigned to each agent. Our analysis revealed that cells with mutant p53 sequence tended to exhibit less growth inhibition in this screen than the wild-type p53 cell lines when treated with the majority of clinically used anticancer agents: including DNA cross-linking agents, antimetabolites, and topoisomerase I and II inhibitors. Similar correlations were uncovered when we probed this database using most of the other indices of p53 status we assessed in the lines. Interestingly, a class of agents that differed in this respect was the antimitotic agents. Growth-inhibitory activity of these agents tended, in this assay, to be independent of p53 status. Our characterization of the p53 pathway in the NCI cell screen lines should prove useful to researchers investigating fundamental aspects of p53 biology and pharmacology. This information also allows for the large-scale analysis of the more than 60,000 compounds tested against these lines for novel agents that might exploit defective p53 function as a means of preferential toxicity.

Antineoplastic Agents↗
PubMed2003

Protein expression levels of the Src activating protein AFAP are developmentally regulated in brain.

The Src family of nonreceptor tyrosine kinases plays an important role in modulating signals that affect growth cone extension, neuronal differentiation, and brain development. Recent reports indicate that the Src SH2/SH3 binding partner AFAP-110 has the capacity to modulate actin filament integrity as a cSrc activating protein and as an actin filament bundling protein. Both AFAP-110 and a brain specific isoform called AFAP-120 (collectively referred to as AFAP) exist at high levels in chick embryo brain. We sought to identify the localization of AFAP in mouse brain in order to identify its expression pattern and potential role as a cellular modulator of Src family kinase activity and actin filament integrity in the brain. In E16 mouse embryos, AFAP expression levels were very high and concentrated in the olfactory bulb, cortex, forebrain, cerebellum, and various peripheral sensory structures. In P3 mouse pups, overall expression was reduced compared to E16 embryos, and AFAP was found primarily in olfactory bulb, cortex, and cerebellum. AFAP expression levels were significantly reduced in adult mice, with high expression levels only detected in the olfactory bulb. Western blot analysis indicated that concentrated expression of AFAP correlates well with the AFAP-120 isoform, which appears to be a splice variant of AFAP-110. As the expression pattern of AFAP overlaps with the reported expression patterns of cSrc and Fyn, we hypothesize that AFAP is positioned to modulate signal transduction cascades that direct activation of these nonreceptor tyrosine kinases and concomitant cellular changes that occur in actin filaments during brain development.

Adaptor Proteins, Vesicular Transport↗
PubMed2003

Systematic review: peginterferon vs. standard interferon in the treatment of chronic hepatitis C.

BACKGROUND: Randomized controlled trials over the last decade have demonstrated incremental improvement in the treatment efficacy of chronic hepatitis C with combination interferon and ribavirin therapy when compared with interferon monotherapy. AIM: To perform a systematic review of clinical trials directly comparing interferon formulations to test the hypothesis that a true difference in terms of efficacy exists between standard interferon (with and without ribavirin) and peginterferon (with and without ribavirin). METHODS: A search of the on-line bibliographic databases MEDLINE and PUBMED was performed independently by two authors to identify all relevant articles. In addition, the reference sections of all relevant articles were manually searched to identify any missed articles. Quality was assessed using the Jadad scale, which is an accepted scale specific for randomized controlled trials. A priori, it was decided to include only articles with a Jadad score of three or higher in the final analysis. Data were abstracted on to pre-determined abstraction sheets. The inclusion of articles, the data abstracted and the methodological score differences were adjudicated by consensus with agreement of the authors performing the search. RESULTS: Seven citations of randomized controlled trials, comparing at least two different interferon formulations and evaluating the sustained virological response as a primary end-point, were identified. These relevant articles were abstracted, and five of the seven were found to have a Jadad score of three or higher and comprised the final set of citations reviewed. The studies consistently demonstrated that peginterferon monotherapy was superior to standard interferon, even in patients with advanced fibrosis. With regard to combination interferon therapy, only two high-quality articles compared peginterferon plus ribavirin with standard interferon plus ribavirin. Both studies demonstrated that the overall sustained virological response was statistically better with peginterferon plus ribavirin. CONCLUSIONS: On the basis of this systematic review, peginterferon-based regimens are superior to standard interferon-based regimens for the treatment of chronic hepatitis C.

Adult↗
PubMed2000

Prediction of genetic structure in eukaryotic DNA using reference point logistic regression and sequence alignment.

MOTIVATION: Current software tools are moderately effective in predicting genetic structure (exons, introns, intergenic regions, and complete genes) from raw DNA sequence data. Improvements in accuracy and speed are needed to deal with the increasing volume of data from large scale sequencing projects. RESULTS: We present a two-stage computer program to predict genetic structure in eukaryotic DNA. The first stage makes use of a novel statistical technique, called reference point logistic (RPL) regression, to calculate scores for potential functional sites. These site scores are combined with interval content, length, and state scores, via a Generalized Hidden Markov Model, to determine a combined score for each possible parse of a given DNA sequence into exons, introns, and intergenic regions. An optimal parse is found using a dynamic programming algorithm. In the second stage, protein sequence alignment methods are applied to improve the accuracy of the initial parse. Computation in the first stage of the program is very fast (1 s on a 360 MHz CPU for a 16 kb sequence) and its predictive accuracy typically matches or exceeds the best results reported for other methods (Sensitivity = 0.93 and Specificity = 0.93 for the Burset/Guigótest set). Computation in the second stage is slower, but the final predictions are more accurate (Sn = 0.97, Sp = 0.97). The program (called GRPL) can handle partial, single, and multi-gene sequences. The program is also capable of predicting the genetic structure of vertebrate, invertebrate, and plant DNA with nearly equal accuracy. Statistical techniques have also been introduced to model the effects of varying C+G content in a continuous manner and to control overfitting of parameters for smaller training sets. AVAILABILITY: An academic implementation of GRPL, compiled for SUN workstations, is available by anonymous ftp from snipe.pharmacy. ualberta.ca/pub. The training and test sets used in this work, together with supplementary material, can be found at the same location. A commercial implementation is available as a component of GeneTool (BioTools Inc., http://biotools.com).

Algorithms↗
PubMed1993

Nutrient intake of Dunedin women during pregnancy.

AIM: To assess the adequacy of dietary intake of women during the three trimesters of pregnancy. METHOD: Dietary intakes of 63 primiparous and 32 multiparous healthy pregnant Dunedin women were obtained by 3 day weighed records at about 12 weeks, 24 weeks, and 36 weeks of gestation. Energy and nutrient intakes were derived using the University of Otago food composition database. RESULTS: Mean energy and nutrient intakes differed remarkably little between primiparous and multiparous women; data were combined for analysis. Energy intakes at first and second trimesters were similar to that for non pregnant women in the National Heart Foundation 1977 survey but greater than in the LINZ 1989 survey. Energy and carbohydrate intakes had increased at third trimester; across the trimesters carbohydrate accounted for 44-46% energy intake, fat for 39% and protein for 15%. Protein intakes at the 10th centile were almost the same as the recommended low risk intake of 51 g/d set by WHO/FAO: No vitamin or mineral showed a trend in intake through the trimesters. Vitamin and mineral intakes were in general greater for the pregnant women than for nonpregnant women in both 1977 and 1989 studies. By comparison with recommended intakes for NZ, Australia, USA and UK, intakes for folate, vitamin B-6, iron and possibly zinc and thiamin were potentially inadequate. Over 10% were heavy smokers and 20% were light smokers; nutrient intakes were less for the smokers than for the nonsmokers, as were birth weights; energy intakes for smokers had not increased at the third trimester. CONCLUSION: An improvement in quality of diet is needed during pregnancy and in prenatal period; smoking should continue to be strongly discouraged.

Adult↗
PubMed2006

Active site structures and the redox properties of blue copper proteins: atomic resolution structure of azurin II and electronic structure calculations of azurin, plastocyanin and stellacyanin.

Understanding how the active site structures of blue copper proteins determine their redox properties is the central structure-function relationship question of this important class of protein, also referred to as cupredoxins. We here describe both experimental and computational studies of azurin, plastocyanin and stellacyanin designed to define more accurately the geometric structures of the active site of the reduced and oxidized species, and thus to understand how these structures determine the redox potentials of these proteins. To this end the crystal structure of reduced azurin II has been determined at an atomic resolution of 1.13 Angstrom and is presented here. Co-ordinates and structure factors have been deposited in the RCSB Protein Data Bank with accession codes 2ccw and r2ccwsf respectively. The improved accuracy provided by the atomic resolution for the metal stereochemistry are utilised in conjunction with the EXAFS data for theoretical calculations. Multilevel calculations involving density functional theory and molecular mechanical potentials are used to predict both the geometric and electronic structure of the active sites of azurin, plastocyanin and stellacyanin and to estimate the relative redox potentials of these three proteins. We have also compared the relative energies of the structures obtained from experiment at varying resolutions, and from the isolated and embedded cluster calculations. We find significant energy differences between low and high (atomic) resolution structures arising primarily due to inaccuracies in the Cu-ligand distances in the lower resolution structures, emphasising the importance of accurate, very high resolution structural information. QM/MM structures are only approximately 1 kcal mol(-1) lower in energy than the 1.13 Angstrom structure while the optimized gas phase structure is 13.0 kcal mol(-1) lower in energy.

Alcaligenes↗
PubMed2002

Computed tomography characteristics of advanced primary pulmonary lymphoepithelioma-like carcinoma.

Our objectives were to document CT features of advanced primary pulmonary lymphoepithelioma-like carcinoma (LELC) and to determine features that may assist differentiation from other non-small cell lung cancers (NSCLC). Imaging and clinical data of all patients with biopsy-proven pulmonary LELC ( n=12) were retrieved from a database of all NSCLC patients over a 2-year period. Twenty-five controls were recruited from other inoperable non-LELC NSCLC patients from the database. Pre-treatment CT scans of the thorax of both study and control patients were reviewed for lobe involved; tumour site, borders and size; and pleural, vascular or pulmonary involvement. Presence of lymphangitis carcinomatosis was noted. Lymph node metastasis was characterised as ipsilateral or contralateral enlarged (>1 cm) mediastinal or hilar nodes, or as peribronchovascular nodal spread. Differences between the two groups were tested using Mann-Whitney rank-sum test. The LELC tumours were significantly larger (45.67 vs 17.71 cm(2)) than controls and were closely associated with the mediastinum. There were more LELC tumours with well-defined borders ( p<0.001) and fewer with spiculated borders ( p<0001) than non-LELC tumours. There was increased peribronchovascular nodal spread ( p=0.01) and vascular encasement ( p=0.02) in LELC compared with non-LELC tumours. Advanced primary pulmonary LELC has distinct radiological features, and can appear as well-defined tumour closely associated with the mediastinum, with peribronchovascular spread and vascular encasement.

Adenocarcinoma↗
PubMed2004

Mucous membrane pemphigoid and pseudopemphigoid.

PURPOSE: To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid. DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred eighty consecutive patients referred for the evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001. METHODS: Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ. MAIN OUTCOME MEASURES: Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease. RESULTS: Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%). CONCLUSIONS: Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.

Adolescent↗
PubMed2002

Evolutionary dynamics of mammalian mRNA untranslated regions by comparative analysis of orthologous human, artiodactyl and rodent gene pairs.

Most evolutionary studies based on molecular data refer to the portion of genomes encoding for proteins. Today, however, more and more attention is paid to the so-called 'non-coding' regions, which constitute a notable portion of the metazoan nuclear genome. Among them, the untranslated regions of messenger RNAs (mRNA UTRs) are particularly important, as they are involved in the regulation of gene expression, controlling translation efficiency as well as mRNA localization and stability. Up to now, only few studies have focused on the analysis of the compositional and structural features of UTRs, or carried out to investigate quantitatively their evolutionary dynamics. For this reason we have carried out an inter-order study on the evolutionary rate of 5' and 3' UTRs with respect to the corresponding coding region in 93 triplets of orthologous genes (selected through a phylogenetic approach, for a total of 645 625 nt) belonging to Primates (Homo sapiens), Artiodactyla (Bos taurus) and Rodentia (Mus spp.). Our study, that considered only likely orthologous genes, has revealed interesting features on the evolution of these regions concerning nucleotide substitution rate and indels and repetitive element distribution. UTRs from different genes showed a remarkable heterogeneity in the evolutionary dynamics, with some homologous so highly divergent to prevent their alignment, and other rather conserved, at least in some regions, most divergent sequence pairs were excluded from our analysis. The comparison between the nucleotide substitution rates calculated for 5' and 3' UTRs with those calculated on synonymous coding position allowed us to verify and measure the existence of functional constraints acting upon the UTRs of different genes which have shown, in many cases, a positive selection driven evolutionary dynamics.

Animals↗