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At least 721 records · Page 40Linked to original sources
PubMed2006

Multiple-electrode radiofrequency ablation creates confluent areas of necrosis: in vivo porcine liver results.

PURPOSE: To prospectively evaluate, in vivo in pigs, an impedance-based multiple-electrode radiofrequency (RF) ablation system for creation of confluent areas of hepatic coagulation. MATERIALS AND METHODS: The study was preapproved by the institutional research animal care and use committee. A prototype multiple-electrode RF system that enables switching between three electrically independent electrodes at impedance spikes was created. Forty-two coagulation zones (18 with single, 12 with cluster, and 12 with multiple [three single electrodes spaced 2 cm apart] electrodes) were created at laparotomy in 15 female pigs. Half the ablations were performed for 12 minutes, and half were performed for 16 minutes. The coagulation zones were excised and sliced into approximately 3-mm sections for measurement. Analysis of variance and two-sample t tests (with Bonferroni correction, alpha = .0033) were used to assess for differences between groups. RESULTS: At 12 minutes, the mean multiple-electrode coagulation was significantly larger than the mean single-electrode coagulation (minimum diameter, 2.8 vs 1.6 cm; maximum diameter, 4.2 vs 2.0 cm; volume, 22.1 vs 6.7 cm(3); P < .0033 for all comparisons). The mean maximum diameter achieved at 12 minutes with multiple electrodes was significantly larger than that achieved with the cluster electrode (4.2 vs 2.9 cm, P = .02). At 16 minutes, the mean multiple-electrode coagulation (minimum diameter, 3.2 cm; maximum diameter, 4.2 cm; volume, 29.1 cm(3)) was significantly larger than the mean single-electrode (minimum diameter, 1.7 cm; maximum diameter, 2.2 cm; volume, 7.1 cm(3); P < .0033 for all comparisons) and cluster-electrode (minimum diameter: 2.3 cm, P = .007; maximum diameter: 3.2 cm, P = .005; volume: 13.1 cm(3), P = .001) coagulations. CONCLUSION: Compared with the single and cluster systems used as controls, the multiple-electrode RF ablation system enabled the creation of significantly larger coagulation zones.

Animals↗
PubMed2003

Characterization of the catalase-peroxidase KatG from Burkholderia pseudomallei by mass spectrometry.

The electron density maps of the catalase-peroxidase from Burkholderia pseudomallei (BpKatG) presented two unusual covalent modifications. A covalent structure linked the active site Trp111 with Tyr238 and Tyr238 with Met264, and the heme was modified, likely by a perhydroxy group added to the vinyl group on ring I. Mass spectrometry analysis of tryptic digests of BpKatG revealed a cluster of ions at m/z 6585, consistent with the fusion of three peptides through Trp111, Tyr238, and Met264, and a cluster at m/z approximately 4525, consistent with the fusion of two peptides linked through Trp111 and Tyr238. MS/MS analysis of the major ions at m/z 4524 and 4540 confirmed the expected sequence and suggested that the multiple ions in the cluster were the result of multiple oxidation events and transfer of CH3-S to the tyrosine. Neither cluster of ions at m/z 4525 or 6585 was present in the spectrum of a tryptic digest of the W111F variant of BpKatG. The spectrum of the tryptic digest of native BpKatG also contained a major ion for a peptide in which Met264 had been converted to homoserine, consistent with the covalent bond between Tyr238 and Met264 being susceptible to hydrolysis, including the loss of the CH3-S from the methionine. Analysis of the tryptic digests of hydroperoxidase I (KatG) from Escherichia coli provided direct evidence for the covalent linkage between Trp105 and Tyr226 and indirect evidence for a covalent linkage between Tyr226 and Met252. Tryptic peptide analysis and N-terminal sequencing revealed that the N-terminal residue of BpKatG is Ser22.

Amino Acid Sequence↗
PubMed2004

Food habits are related to glycemic control among people with type 2 diabetes mellitus.

OBJECTIVE: To investigate the food habits of people with type 2 diabetes and to identify those habits related to glycemic control. DESIGN: The purposive sampling plan targeted people (40 to 65 years old) living in two urban communities in the Southeastern United States with type 2 diabetes for >1 year (60% women, 50% African Americans and low-income individuals). In-depth interviews were used to identify food habits. Glycated hemoglobin (HbA(1c)) was measured to assess glycemic control. SUBJECTS: The final sample contained 89 participants (62% women, 48% African American, and 43% below 200% of the poverty level). STATISTICAL ANALYSES PERFORMED: Analysis of variance, principal component/factor analysis, cluster analysis, and multiple regression were used to relate food habits to glycemic control. RESULTS: A four-factor solution derived from 15 food habits explained 51.5% of the total variance in HbA(1c) values. High factor scores for three factors (Basic Eating Practices, Meal Planning, and Carbohydrate/Vegetable Strategies) and low factor scores for a fourth factor (Challenges of Dining Out) were related to lower HbA(1c) values. Based on similar patterns across the 15 food habits, participants were clustered into four groupings. The clusters differing on HbA(1c) (mean+/-standard deviation) were Healthful Eating Lifestyle (6.25+/-0.25), Disciplined Eating Approach (7.31+/-0.35), Limited Dietary Focus (8.28+/-0.33), and Poor Dietary Management (9.05+/-0.24). These groupings reflected different food habit factor profiles. CONCLUSIONS: Knowledge of the specific food habits of people with diabetes can offer a way to structure a meaningful dialog with clients about dietary self-management and guide the collaborative development of relevant dietary goals.

Adult↗
PubMed2006

A general approach for two-stage analysis of multilevel clustered non-Gaussian data.

In this article, we propose a two-stage approach to modeling multilevel clustered non-Gaussian data with sufficiently large numbers of continuous measures per cluster. Such data are common in biological and medical studies utilizing monitoring or image-processing equipment. We consider a general class of hierarchical models that generalizes the model in the global two-stage (GTS) method for nonlinear mixed effects models by using any square-root-n-consistent and asymptotically normal estimators from stage 1 as pseudodata in the stage 2 model, and by extending the stage 2 model to accommodate random effects from multiple levels of clustering. The second-stage model is a standard linear mixed effects model with normal random effects, but the cluster-specific distributions, conditional on random effects, can be non-Gaussian. This methodology provides a flexible framework for modeling not only a location parameter but also other characteristics of conditional distributions that may be of specific interest. For estimation of the population parameters, we propose a conditional restricted maximum likelihood (CREML) approach and establish the asymptotic properties of the CREML estimators. The proposed general approach is illustrated using quartiles as cluster-specific parameters estimated in the first stage, and applied to the data example from a collagen fibril development study. We demonstrate using simulations that in samples with small numbers of independent clusters, the CREML estimators may perform better than conditional maximum likelihood estimators, which are a direct extension of the estimators from the GTS method.

Animals↗
PubMed2004

Unexplained cancer clusters: common threads.

A number of identified cancer clusters have followed exposures to mixtures of chemicals. The causes for these cancers could not be attributed to any of the individual chemicals in the mixtures and up to now have remained unexplained. The author presents case studies showing that these previously unexplained cancer clusters have common characteristics. First, they can be attributed to exposures to mixtures that contain at least one lipophilic and one hydrophilic chemical, with octanol:water partition coefficients, K(ow), indicative of lipophilic or hydrophilic character. Second, the specific combinations of lipophiles and hydrophiles act as individual entities and produce cancers not associated with exposure to any of the individual chemicals contained in the mixtures. The cancers that follow these exposures can be in the form of single or multiple cancers per cluster.

Carcinogens↗
PubMed1983

Jejunal manometry patterns in health, partial intestinal obstruction, and pseudoobstruction.

The purpose of this study was to determine the utility of jejunal manometry in evaluating patients having partial small intestinal obstruction or the pseudoobstruction syndrome. We studied 10 healthy volunteers, 9 patients with documented mechanical obstruction, and 3 patients with chronic intestinal pseudoobstruction during fasting and for 2 h after a 650-kcal meal. Contractile activity, especially during phase 2, was extremely variable in all individuals studied. After the meal, the most striking finding in mechanical obstruction was the regular occurrence of clustered contractions. These were defined as 3-10 regular contractions, occurring 1 per 5 s, preceded and followed by at least 1 min of absent motor activity. The associated periods of quiescent motor activity may account for the unexpectedly reduced frequency and motility index in obstructed patients compared with normal subjects after the meal. Two different contractile patterns occurred in patients with pseudoobstruction. Before and after the meal, infrequent and low-amplitude contractions occurred in 2 patients, and multiple, aborally migrating, clustered contractions occurred in the other patient with pseudoobstruction. Manometric abnormalities occur in both mechanical obstruction and pseudoobstruction. However, the technique is probably not more sensitive than radiologic procedures, and the abnormalities that are detected by manometry are not specific. Some of the same motility changes occurred in both disorders.

Adult↗
PubMed2006

TomatEST database: in silico exploitation of EST data to explore expression patterns in tomato species.

TomatEST is a secondary database integrating expressed sequence tag (EST)/cDNA sequence information from different libraries of multiple tomato species. Redundant EST collections from each species are organized into clusters (gene indices). A cluster consists of one or multiple contigs. Multiple contigs in a cluster represent alternatively transcribed forms of a gene. The set of stand-alone EST sequences (singletons) and contigs, representing all the computationally defined 'Transcript Indices', are annotated according to similarity versus protein and RNA family databases. Sequence function description is integrated with the Gene Ontologies and the Enzyme Commission identifiers for a standard classification of gene products and for the mapping of the expressed sequences onto metabolic pathways. Information on the origin of the ESTs, on their structural features, on clusters and contigs, as well as on functional annotations are accessible via a user-friendly web interface. Specific facilities in the database allow Transcript Indices from a query be automatically classified in Enzyme classes and in metabolic pathways. The 'on the fly' mapping onto the metabolic maps is integrated in the analytical tools. The TomatEST database website is freely available at http://biosrv.cab.unina.it/tomatestdb.

Computational Biology↗
PubMed1999

Headache diagnosis.

Headache is an extremely common symptom in primary care practice. Despite the ubiquity of the pain, differential diagnosis of headache is not difficult, provided the clinician obtains a comprehensive history. A complete physical examination and specific testing may be required to rule out other underlying causes, but headache itself falls into 3 main classes that are readily identified. Migraine headache occurs most commonly in women, is of moderate to severe intensity, and is often accompanied by nausea and increased sensitivity to light and sound. Cluster headache describes multiple recurrent attacks of severe unilateral pain and occurs most frequently in men. Tension-type headache is the most common form, characterized by mild to moderate dull pain that is often brought on by stress and/or depression. Understanding the triggers and manifestations of these headache types is essential for effective management.

Cluster Headache↗
PubMed1991

Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence repeats.

The centromere-associated B' and B DNA sequence repeats of Schizosaccharomyces pombe chromosomes I and II have been found to contain clusters of tRNA genes. The centromere II region (cen2) includes at least 22 tRNA genes distributed among five copies of the B sequence repeat containing genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Val). Individual B repeats are variously associated with other tRNA genes, including those specifying tRNA(Lys), tRNA(Arg), and tRNA(Glu2). The centromere I region (cen1) contains at least six tRNA genes in two copies of the B' repeated element, including genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Glu3). Multiple tandemly arranged clusters of tRNA genes are presumably conserved due to restricted recombination frequencies in the centromere regions.

Base Sequence↗
PubMed2002

Pore-scale network model for three-phase flow in mixed-wet porous media.

We describe the development and application of a three-dimensional pore-scale network simulator for modeling capillary-dominated three-phase flow in porous media where the wettability varies from pore to pore, i.e., where each pore is allowed to have a different oil-water contact angle from a chosen distribution. Physical constraint equations for the remaining gas-oil and gas-water contact angles are implemented. In weakly wetted pores wetting films are absent, which reduces the continuity of the various phases in the network and increases the number of phase clusters that are disconnected from inlet or outlet. Mobilization of disconnected clusters requires incorporation of double and multiple displacement chains that involve a string of neighboring phase clusters, e.g., gas-->oil-->gas-->oil-->water. Furthermore, when multiple displacement chains cause disconnected clusters to reconnect to the outlet, the phase pressures at the outlet boundary are updated consistent with the pressures within the system. A number of benchmark simulations for systems with nonuniform wettability, mixed-wet with the larger pores oil-wet, are presented. The outcome of these simulations is presented as phase paths in saturation space and in the form of pore occupancy histograms and histograms of the length and type of displacement chains. Comparison of simulated saturation paths with those of an analytical capillary bundle model with the same wettability show good agreement where phase continuity is high and decreasing agreement as phase continuity in the network decreases. The saturation paths and occupancy and displacement statistics for a number of water-alternating-gas injection (WAG) simulations bring out the various features of the model, in particular, those related to the wettability. We find that multiple displacements do occur, mainly during higher-order WAG floods, although their effect on oil recovery seems limited. Variation of the outlet boundary pressure differences has an effect in certain regions of the saturation space that are defined by the analytical model.

Journal Article↗
PubMed2005

Simultaneous human papillomavirus 6 (HPV 6) -positive condyloma acuminatum, HPV 31-positive Bowen's disease, and non HPV-associated extramammary Paget's disease coexisting within an area presenting clinically as condyloma acuminatum.

An 83-year-old Japanese man presented with multiple verrucous papules clustering on a plaque located on the frontal aspect of the scrotum. Histologically, there were three distinct epithelial changes compatible with condyloma acuminatum, Bowen's disease, and extramammary Paget's disease (EMPD). By in situ hybridization, the zone of condyloma acuminatum was positive for HPV 6 and well demarcated from HPV 31-positive Bowen's disease. EMPD was negative for targeted HPV 6/11/16/18/31/33 probes. Immunohistochemically, Paget's cells expressing cytokeratin 7 were distributed as scattered single cells or clusters mainly in the lower part of the HPV 6/31-positive epithelium. To the best of our knowledge, this is the first reported case of the occurrence of condyloma acuminatum, Bowen's disease, and EMPD within the same lesion.

Aged, 80 and over↗
PubMed1996

A computer program for regression analysis of ordered categorical repeated measurements.

RMORD is an easy-to-use FORTRAN program for the analysis of clustered ordinal data using the method of Stram, Wei, and Ware. This method constitutes an extension of the proportional-odds model to the situation in which groups of responses are correlated. At each measurement occasion, a proportional-odds regression model is fit to the data by maximizing the occasion-specific likelihood function. The joint asymptotic distribution of the occasion-specific regression parameter estimators is obtained along with a consistent estimator of their asymptotic covariance matrix. RMORD may be used when ordinal measurements are obtained at a common set of observation times for multiple subjects or clusters. Both missing data and covariates which vary within clusters can be accommodated. The program can be run on microcomputers, workstations, and mainframe computers. Two examples illustrating the usage and features of RMORD are provided.

Age Distribution↗
PubMed2002

[Magnetoencephalographic localization of multiple seizure foci for surgical treatment of intractable frontal lobe epilepsy: confirmation with intra-operative electrocorticography].

A successfully treated case of intractable FLE, of which preoperative magnetoencephalography (MEG) provided multiple spike localization and intraoperative corticogram (ECoG) confirmed the resection area. A 22-year-old male patient, with a history of subdural abscess at the age of 14 years, had suffered frequent simple (SPSs) and complex partial seizures (CPSs) and falling attacks since the age of 16 years. Although he underwent corpus callosotomy at the age of 17 years, additional surgical treatment was considered because of intractable and more frequent SPSs and CPSs. Magnetic resonance (MR) imaging demonstrated diffuse lesions in the right frontal lobe. Although, both interictal and ictal electroencephalography (EEG) failed to show focal epileptogenic localization, interictal MEG localized several clusters over the multiple anatomical lesions in the right prefrontal and frontal opercular regions. The patient underwent right fronto-temporal craniotomy, and anterior frontal lobectomy, followed by lesionectomy of the premotor area based on the intraoperative ECoG findings. The ECoG localized frequent spike discharges over the right prefrontal, frontal operculum and premotor cortices, which showed good correspondence with the MEG findings. MEG can be a useful noninvasive method for presurgical evaluation of intractable FLE.

Adult↗
PubMedDate not supplied

Understanding human DNA sequence variation.

Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an "out of Africa" hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics.

Base Sequence↗
PubMed1998

Automated protein sequence database classification. II. Delineation Of domain boundaries from sequence similarities.

MOTIVATION: Decomposing each protein into modular domains is a basic prerequisite to classify accurately structural units in biological molecules. Boundaries between domains are indicated by two similar amino acid sequence segments located within the same protein (repeats) or within homologous proteins at notably different distances from their respective N- or C-termini. RESULTS: We have developed an automated method that combines such positional constraints derived from various detected pairwise sequence similarities to delineate the modular organization of proteins. The procedure has been applied to a non-redundant data set of 26 990 proteins whose sequences were taken from the PIR and SWISS-PROT databanks and shared <60% sequence identity amongst pairs. The resultant clustering, delineation and multiple alignment of 24 380 sequence fragments yielded a new database of 4364 domain families. Comparison of the domain collection with that of PRODOM indicates a clear improvement in the number and size of domain families, domain boundaries and multiple sequence alignments. The accuracy and sensitivity of the method are illustrated by results obtained for ankyrin-like repeats and EGF-like modules. AVAILABILITY: The resulting database, called DOMO, is available through the database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT: gracy@infobiogen.fr

Algorithms↗
PubMed2003

Cysteine residues in the C-terminal lobe of Src: their role in the suppression of the Src kinase.

To evaluate the function of cysteine residues of the Src kinase, we constructed a series of Src mutants in which some of cysteines were replaced to alanines. With these mutants, we studied the effect of SH-alkylating agents, N-[p-(2-benzimidazolyl)phenyl] maleimide (BIPM) and N-(9-acridinyl) maleimide (NAM), on their kinase activity. Of 10 cysteine residues scattered over v-Src, either a single mutation at Cys520 or multiple mutations at the four clustered cyteines, Cys483, Cys487, Cys496 and Cys498, yielded clear resistance to the treatment with 10 microM BIPM or 1 microM NAM. In contrast, other cysteines including those in the SH2 domain and those in the catalytic cleft of the kinase domain were dispensable for the inactivation by BIPM and NAM. Similarly, deletion of SH2 and SH3 did not confer the resistance to v-Src, suggesting the inactivation by the SH-alkylating agents is SH2/SH3-independent. Although Cys520-mutated v-Src was resistant to 1 microM NAM, it was inactivated by 5 microM NAM. However, combined mutation including all of Cys483, Cys487, Cys496, Cys498 and Cys520 yielded clear resistance to 5 microM NAM. Among these mutants, those with double mutations in the four clustered cysteines yielded a temperature sensitive phenotype in the transfected cells, whereas Cys520 did not, suggesting that Cys520 has, at least in part, a discrete function. In contrast to v-Src, c-Src, which lacks cysteine at position 520, was resistant to 1 microM NAM but sensitive to 5 microM NAM. While replacement of Phe520 of c-Src to cysteine made it sensitive to 1 microM NAM, double mutation in clustered cysteines again yielded resistance to 5 microM NAM. Taken together, our results strongly suggest that the multiple cysteine residues clustered at the end of the C-terminal lobe are critical for the inhibition by the SH-alkylating agents and, thereby, have an allosteric repressor effect on the catalytic activity of Src in a SH2-phosphoTyr527 independent manner.

Alkylating Agents↗
PubMed1992

Regulatory sequences clustered at the 5' end of the first intron of the human thymidylate synthase gene function in cooperation with the promoter region.

A human thymidylate synthase (TS) minigene containing 5'- and 3'-flanking sequences, all the exons, and only intron 1 showed a normal frequency of stable transformation when transfected into TS-negative mutant cells, whereas minigenes in which intron 1 was replaced by intron 2 or deleted in the above construct showed only a few percent of the above frequency. Introduction of intron 1 into the above intronless or intron 2 minigene restored the transforming activities regardless of its position and orientation. Deletion analysis revealed two positive and one negative regulatory sequences in the 5' end of intron 1, each of which seemed to bind specific proteins as shown by gel shift analysis. Intron 1 also stimulated expression of a TS promoter-CAT gene construct but not that of an SV40 promoter-CAT gene construct. These results indicate that the multiple regulatory sequences clustered in intron 1 stimulate TS gene expression in concert with the 5'-flanking sequences.

Gene Expression Regulation, Enzymologic↗