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At least 145 records · Page 8Linked to original sources
PubMed2005

Race modifies the association between breast carcinoma pathologic prognostic indicators and the positive status for HER-2/neu.

BACKGROUND: Inferences about the variations in the biology of breast carcinoma between African-Americans and Caucasians have been reported. The difference in the prevalence of positive HER-2/neu breast carcinoma was evaluated and the race-specific risk was assessed for positive HER-2/neu among a cohort of women diagnosed with their first primary breast carcinoma, given the accepted prognostic pathologic indicators for positive HER-2/neu status. METHODS: Demographic, clinical, and pathologic data were collected from existing databases. The status of HER-2/neu was considered positive if the immunohistochemistry score was 3+ or if the fluorescent in situ hybridization indicated a ratio greater than 2. Multivariable logistic regression was used to determine the race-specific risk for HER-2/neu positive breast carcinoma. RESULTS: The difference in the prevalence of HER-2/neu-positive status between African-American and Caucasian women was not statistically significant (P = 0.46). For Caucasian women the likelihood for positive HER-2/neu was statistically significant and increased almost linearly within each stage with nuclear grade dedifferentiation relative to the reference group, women with Stage 1, Grade 1 carcinomas. For African-American women, this risk was not significantly associated with stage, nuclear grade, their interaction term, or other pathologic prognostic indicators. CONCLUSIONS: The findings suggest that race modifies the association between the pathologic prognostic indicators of breast carcinoma and the likelihood of HER-2/neu-positive carcinoma. So far, clinical correlative studies of HER-2/neu have not included race as an independent variable. Concerns about the limited generalizability and the need for validation of the findings across racial lines have been expressed previously.

Black or African American↗
PubMedDate not supplied

Effects of the choice of age-adjustment method on maps of death rates.

Maps of morbidity or mortality rates, whether considered individually or as a layer in a geographic information system application, invite multiple comparisons of area rates. However, comparisons of rates across different populations require standardization of the age-specific rates to account for differences in population age structures. The indirect standardization method, or equivalently the standardized mortality ratio (SMR), has been recommended for small areas where age-specific rates can be quite variable. Although theoretically equivalent to directly adjusted rates under the assumption of independent age and area effects, indirect summary measures are not comparable across areas when this assumption is violated. We tested the validity of this assumption for the 10 most common causes of death in the United States during 1980-84 and examined the geographic clustering apparent when categorized death rates, adjusted by different methods, are presented as thematic maps. Although overall agreement between the methods was good (rank correlation coefficient > 82 per cent for each cause), when the adjusted rates were classified into quintiles 18 per cent of the states fell into different categories depending on the method of adjustment. Using an internal standard for the indirect method reduced this discrepancy to 4.9 per cent. However, both traditional chi-square tests and a generalized logistic spline model identified significant interactions between age and area for each cause of death, a violation of the assumption required for equivalence of the methods. Potential variation in geographic inferences is illustrated by maps of direct and indirect rates and an empirical Bayes posterior mean, which is a function of these traditionally adjusted rates. Based on these results, we recommend the direct age-adjustment method for rate maps.

Adolescent↗
PubMed2003

Multiple paternity in Rana dalmatina, a monogamous territorial breeding anuran.

Polyandry and sperm competition in anurans have rarely been documented. We investigated the genetic paternity inferred from allozyme variations in 650 tadpoles from four natural ponds in a territorial breeding anuran, Rana dalmatina. Multiple paternity was demonstrated, although R. dalmatina is regarded as a monogamous species. Polyandrous mating was not a common event, occurring only in 17.9% of clutches, with no significant differences among clutches. The proportions of tadpoles fathered by a second male did not significantly differ among ponds, showing that multipaternity was not restricted to a single site. Such a polyandry may result from synchronous multiple amplexus and should reduce the heterozygote deficit related to the breeding-pond fidelity usually exhibited by most anurans.

Animals↗
PubMed2005

Comparative analyses of genetic diversities within tomato and pepper collections detected by retrotransposon-based SSAP, AFLP and SSR.

The retrotransposon-based sequence-specific amplification polymorphism (SSAP) marker system was used to assess the genetic diversities of collections of tomato and pepper industrial lines. The utility of SSAP markers was compared to that of amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. On the basis of our results, SSAP is most informative of the three systems for studying genetic diversity in tomato and pepper, with a significant correlation of genetic relationships between different SSAP datasets and between SSAP, AFLP and SSR markers. SSAP showed about four- to ninefold more diversity than AFLP and had the highest number of polymorphic bands per assay ratio and the highest marker index. For tomato, SSAP is more suitable for inferring overall genetic variation and relationships, while SSR has the ability to detect specific genetic relationships. All three marker results for pepper showed general agreement with pepper types. Additionally, retrotransposon sequences isolated from one species can be used in related Solanaceae genera. These results suggest that different marker systems are suited for studying genetic diversity in different contexts depending on the group studied, where discordance between different marker systems can be very informative for understanding genetic relationships within the study group.

Capsicum↗
PubMed2004

A molecular analysis of the subgenus Transphlebotomus Artemiev, 1984 (Phlebotomus, Diptera, Psychodidae) inferred from ND4 mtDNA with new northern records of Phlebotomus mascittii Grassi, 1908.

A comparative molecular study was performed on the three species of Phlebotomine sandflies belonging to the subgenus Transphlebotomus Artemiev whose morphological differentiation is difficult. All three species have been suspected, but never proven, to be vectors of Leishmania infantum. The ND4 gene from mtDNA was sequenced from specimens of five populations of Phlebotomus mascittii Grassi from Belgium (the first records of Phlebotomine sandflies from this country), France, and Germany. Additionally, specimens from one population of Lebanese P. canaaniticus Adler and Theodor and of one population of Cypriot P. economidesi Leger, Depaquit and Ferte topotypes were examined. The results reveal the validity of the three taxa inferred from molecular variation and a molecular homogeneity shared by all of the populations of P. mascittii included into the present study. The epidemiological consequences are discussed.

Animals↗
PubMed1984

Interaction of alpha-thrombin and prethrombin 2, with phosphatidylserine-containing monolayers.

Prothrombin activation complex is located at a phospholipid surface on activated platelets. To see whether the thrombin domain of the molecule plays a role in the interaction with lipids, we investigated the direct interaction of human alpha-thrombin and its precursor prethrombin 2 with phospholipid monolayers of various compositions (PS/PC). Adsorption of the labeled proteins was determined by surface radioactivity measurements. Penetration of the proteins in the lipid layer was inferred from capacitance variation of the monolayer, measured by a.c. polarography. Disulfide bridges reduced at the electrode were determined by cyclic voltametry. In all the cases studied, although in different manners thrombin was found both to adsorb and penetrate the lipid layer, whereas prethrombin 2 did not penetrate pure phosphatidylcholine (PC). In the case of thrombin, but not of prethrombin 2, penetration is accompanied by S-S reduction which is maximum at 10 per cent of phosphatidylserine (PS). This indicates a different orientation for prethrombin 2 and thrombin in the lipid layer. This observation might be of importance for the comprehension of the architecture of the prothrombin activation complex and for the regulation of thrombin formation within the complex.

Enzyme Activation↗
PubMed1989

Interaction of human gamma-carboxyglutamic acid domainless prothrombin with phospholipids.

The conversion of prothrombin into thrombin occurs at the surface of stimulated platelets. In order to see the influence of gamma-carboxyglutamic acid in the interaction of prothrombin with phospholipid, we investigated the direct interaction of the peptide 1-41 and prothrombin (des 1-44) with phospholipid monolayers of various compositions. Adsorption of the labeled proteins was determined by surface radioactivity measurements. Penetration of the proteins into the lipid layers was inferred from capacitance variation of the monolayer, measured by a.c. polarography. Prothrombin (des 1-44) was found both to adsorb and to penetrate the lipid monolayers, in the presence and in the absence of Ca++. The effects are higher on 100% PS than on 25% PS. This protein was also found to increase the permeability of vesicles containing 25% PS to T1+ ions, in the presence and in the absence of Ca++. Comparison with prothrombin shows that Gla residues are clearly involved in the interaction at 25% PS; nevertheless, the peptide 1-41 does not penetrate. A model of interaction of prothrombin with phospholipid, including both adsorption of prothrombin by Gla residues and its penetration by another domain, is proposed.

1-Carboxyglutamic Acid↗
PubMed2004

Estimation of neurophysiological parameters from the waking EEG using a biophysical model of brain dynamics.

This paper presents the results from using electroencephalographic (EEG) data to estimate the values of key neurophysiological parameters using a detailed biophysical model of brain activity. The model incorporates spatial and temporal aspects of cortical function including axonal transmission delays, synapto-dendritic rates, range-dependent connectivities, excitatory and inhibitory neural populations, and intrathalamic, intracortical, corticocortical and corticothalamic pathways. Parameter estimates were obtained by fitting the model's theoretical spectrum to EEG spectra from each of 100 healthy human subjects. Statistical analysis was used to infer significant parameter variations occurring between eyes-closed and eyes-open states, and a correlation matrix was used to investigate links between the parameter variations and traditional measures of quantitative EEG (qEEG). Accurate fits to all experimental spectra were observed, and both inter-subject and between-state variability were accounted for by the variance in the fitted biophysical parameters, which were in turn consistent with known independent experimental and theoretical estimates. These values thus provide physiological information regarding the state. transitions (eyes-closed vs. eyes-open) and phenomena including cortical idling and alpha desynchronization. The parameters are also consistent with traditional qEEG, but are more informative, since they provide links to underlying physiological processes. To our knowledge, this is the first study where a detailed biophysical model of the brain is used to estimate neurophysiological parameters underlying the transitions in a broad range (0.25-50 Hz) of EEG spectra obtained from a large set of human data.

Awareness↗
PubMed2006

Optimising stable retroviral transduction of primary human synovial fibroblasts.

Fibroblast like synoviocytes are the main resident cells in normal joints and are known to play a major role in the pathogenesis of rheumatoid arthritis. Efficient gene targeting of fibroblast like synoviocytes (FLS) is a major goal of current ex vivo gene therapy approaches for the treatment of rheumatoid arthritis. However, there is a need to improve viral systems capable of delivering genes to human rheumatoid fibroblasts and attempts have been made to develop a protocol for high efficiency, reproducible gene transfer using a replication-defective retrovirus vector. The effects of different experimental conditions were examined as well as those related to cellular and viral features on the efficiency of transducing the retroviral-driven expression of enhanced green fluorescent protein (EGFP) to FLS harvested from patients with rheumatoid arthritis. The optimal method established involved a double round of infection by centrifugation with a resting period of 4h between rounds. This approach led to the transduction of 30-70% of FLS obtained from nine patients with rheumatoid arthritis. Consistent transduction efficiencies were achieved in repeat assays such that it could be inferred that the variations observed were attributable to the specific characteristics of each cell line. This simple protocol renders a consistent and reproducible efficiency of rheumatoid fibroblast transduction and makes stable gene targeting using non-replicating retrovirus derived vectors an affordable option for the treatment of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2004

Genetic differentiation of relictual populations of Alsophila spinulosa in southern China inferred from cpDNA trnL-F noncoding sequences.

The genetic differentiation and phylogeographical pattern of 11 relictual populations of Alsophila spinulosa distributed across Hainan, Guangdong, and Guangxi in southern China were inferred from sequence variations of trnL-F noncoding regions of chloroplast DNA (cpDNA). The length of trnL-F noncoding sequences varied from 863 to 940 bp. The A + T content was 62.23-63.36%. Sequences were neutral in terms of evolution (Tajima's criterion D=-0.62417, P>0.10 and Fu and Li's test D*=-1.45455, P>0.10; F*=-1.32798, P>0.10). Thirty-four haplotypes were identified based on nucleotide variation. Relatively high levels of haplotype diversity (h=0.929) and nucleotide diversity (Dij=0.022263) were detected in A. spinulosa, probably associated with its long evolutionary history which allowed the accumulation of genetic variation within lineages. Both the minimum spanning network and the strict consensus tree of the most parsimonious trees generated for haplotypes demonstrated that the investigated populations of A. spinulosa were subdivided into two geographical groups: Hainan and Guangdong-Guangxi. An analysis of molecular variance (AMOVA) indicated that most of the genetic variation (87.48%, P<0.001) was partitioned among regions. Spatial structure measurements revealed that population genetic structure was not related to geographical distance. This research suggests that blocked gene flow by Qiongzhou strait and an inbreeding system might result in the geographical subdivision between Hainan and Guangdong-Guangxi (F(ST)=0.92, Nm=0.09). Within each region, the "star like" pattern of phylogeography of haplotypes implied a population expansion process during evolutionary history. Gene genealogies together with coalescent theory were useful tools for uncovering the phylogeography of A. spinulosa.

China↗
PubMed2002

Tryptophan phosphorescence and pressure effects on protein structure.

After a brief introduction of the potentialities of Trp phosphorescence spectroscopy for probing the conformation and flexibility of protein structure, this presentation summarizes the effects of hydrostatic pressure (up to 3 kbar) on the native fold of monomeric and oligomeric proteins as inferred from the variation of the intrinsic phosphorescence lifetime and the oxygen and acrylamide bimolecular quenching rate constants of buried Trp residues. The pressure/temperature response of the globular fold and modulation of its dynamical structure is analyzed both in terms of a reduction of internal cavities and of hydration of the polypeptide. The implications of these findings for the thermodynamic stability of proteins and for the determination of subunit dissociation equilibria under high pressure conditions are also discussed.

Fluorescent Dyes↗
PubMedDate not supplied

Strong gradients for spatially resolved diffusion measurements.

A new multilayer approach to gradient coil design, which allows the production of very strong gradient coils with reasonable resistance and consequent power dissipation, has been developed. Using this approach we have designed and built a strong z-gradient coil that will accommodate vertically mounted samples contained in 5-mm nuclear magnetic resonance tubes. The coil has an efficiency of 1.73 Tm-1A-1, an inductance of 49 microH, and a resistance of 1.8 omega, with a homogeneous volume consisting of a central cylinder of 4.5-mm length and diameter. This coil has been used to monitor the diffusion of water in Nylon 6.6 at room temperature, during desorption. This system is difficult to monitor via nuclear magnetic resonance (NMR), because the diffusion coefficients are typically less than 10(-13) m2s-1, while the T2 relaxation time is less than 1 ms even when the sample is fully saturated. The resulting measurements show a strong concentration dependence of the T2 relaxation time and self-diffusion coefficient of the absorbed water. The measured concentration profiles are consistent with a Fickian diffusion process with a concentration-dependent diffusion coefficient. The measured self-diffusion values are in reasonable agreement with those inferred from the variation of the concentration profiles as a function of time, using the one-dimensional Fickian diffusion equation.

Absorption↗
PubMed2004

PCDD/F TEQ indicators and their mechanistic implications.

Stack gas samples from two incinerator facilities with different operating conditions were investigated to understand how indicators of toxic equivalency (TEQ) from among the 210 polychlorinated dibenzo-p-dioxin/furan (PCDD/F) isomers varied. This effort was motivated by the need to find more easily monitored indicator compound(s) of TEQ and to reconcile the varying indicator compounds reported in the literature. The measured isomer patterns were compared with those expected from known formation mechanisms to identify the dominant mechanism(s) and explain why certain compounds are relevant TEQ indicators. Despite differences in the facility types and operating conditions, a common pattern was found for the highly chlorinated (4Cl and higher) PCDDs/Fs. A combination of chlorination/dechlorination reactions as the dominant formation mechanism for PCDF was consistent with the observed isomer patterns, whereas condensation reactions of phenolic precursors appeared to be responsible for PCDD formation. PCDF isomers, ratherthan the PCDD isomers, were more closely related to the TEQ measure, likely because the chlorination mechanism favors 2,3,7,8-Cl-substitution more than the phenol condensation mechanism. Unlike highly chlorinated PCDD/F isomer patterns, less chlorinated PCDD/F patterns (especially, mono- and di-CDF) were sensitive to operating conditions and facility type. Competing formation mechanisms were inferred from the variation of observed isomer distribution patterns; this sensitivity resulted in relatively low correlations of these isomers with PCDD/F TEQ values. This suggests that any use of the low-chlorinated compounds as TEQ indicators for online monitoring processes are likely best suited for plant-specific, rather than universal, applications. In addition to many of the highly chlorinated (penta-CDF, hexa-, and heptaCDD/F) isomers being identified as strong TEQ indicators, 1 of 12 (8%), 5 of 17 (29%), and 5 of 28 (18%) of the separable tri-CDD, tri-CDF, and tetra-CDF isomers, respectively, were identified as strong (R2 > 0.7) TEQ indicators in both incinerators.

Air Pollutants↗
PubMed1996

From symmetry to asymmetry: phylogenetic patterns of asymmetry variation in animals and their evolutionary significance.

Phylogenetic analyses of asymmetry variation offer a powerful tool for exploring the interplay between ontogeny and evolution because (i) conspicuous asymmetries exist in many higher metazoans with widely varying modes of development, (ii) patterns of bilateral variation within species may identify genetically and environmentally triggered asymmetries, and (iii) asymmetries arising at different times during development may be more sensitive to internal cytoplasmic inhomogeneities compared to external environmental stimuli. Using four broadly comparable asymmetry states (symmetry, antisymmetry, dextral, and sinistral), and two stages at which asymmetry appears developmentally (larval and postlarval), I evaluated relations between ontogenetic and phylogenetic patterns of asymmetry variation. Among 140 inferred phylogenetic transitions between asymmetry states, recorded from 11 classes in five phyla, directional asymmetry (dextral or sinistral) evolved directly from symmetrical ancestors proportionally more frequently among larval asymmetries. In contrast, antisymmetry, either as an end state or as a transitional stage preceding directional asymmetry, was confined primarily to postlarval asymmetries. The ontogenetic origin of asymmetry thus significantly influences its subsequent evolution. Furthermore, because antisymmetry typically signals an environmentally triggered asymmetry, the phylogenetic transition from antisymmetry to directional asymmetry suggests that many cases of laterally fixed asymmetries evolved via genetic assimilation.

Animals↗
PubMed2000

Search for Transits of a Short-Period, Sub-Saturn Extrasolar Planet Orbiting HD 46375.

Precise brightness measurements of HD 46375 have been acquired with an automatic telescope to search for transits of its short-period, sub-Saturn extrasolar planet. Transits of the companion do not occur, indicating that the inclination of the orbit i is less than 83 degrees and sini is less than 0.992. This upper limit on sini still preserves the possibility that the mass of the planet is less than Saturn's. Analysis of the photometry for HD 46375 reveals no photometric variability larger than 0.0001+/-0.0002 mag at the orbital period of the planet. This effectively eliminates starspots and stellar pulsations as the cause of the radial velocity variations used to infer the planet's existence.

Journal Article↗
PubMed2006

Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection.

PURPOSE: Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community. EXPERIMENTAL DESIGN: We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses. RESULTS: This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory. CONCLUSIONS: We show the importance of accurate functional analysis before inferring any genetic variation. The quality of the p53 databases is essential in order to prevent erroneous analysis and/or conclusions. The availability of functional data from our new p53 web site (http://p53.free.fr and http://www.umd.be:2072/) will allow functional prescreening to identify potential artifactual data.

Databases, Factual↗
PubMed1990

A new aspect of the morphological transformation of Trypanosoma cruzi brought about by environmental variation.

The development of Trypanosoma cruzi has been described both in vertebrate and invertebrate hosts, and the morphological transformations of the parasite have been studied in both cell-free cultures and tissue cultures. The investigators who studied this topic have emphasized the fact that the morphogenesis of T. cruzi may be associated with a series of factors. In the present study, we noted that when bloodstream trypomastigotes leave a vertebrate host reaching the digestive tract of triatomines through the blood sucking action of these vectors, specific culture by blood plating or maintenance of blood in physiological saline at different temperatures shows a phenomenon of trypanosome joining, with intensive movement of internal organelles (nucleus and kinetoplast) and junction at the kinetoplast level. Different situations may occur after this phenomenon, such as flagellate separation, passage of kinetoplast content from one individual to another, transformation into rounded elements that approach the pairs of agglomerate, or the formation of spherical elements similar to cyst-like bodies. When observed by light or phase-contrast microscopy, these bodies appear to be static and show inner structures moving in circles or in disorderly manner. On the basis of the molecular studies carried out by other authors, who observed that not all proteins synthetized from DNA are of immediate usefulness in the cell, but need to undergo activation by the action of another protein or of environmental variation, we may infer that T. cruzi, under adverse conditions, i.e. a change in habitat, may undergo transformations, taking on different forms for the exchange of genetic information for adaptation to the environment and for possible continuity of the evolutionary cycle.

Animals↗
PubMed2001

[Reproducibility of measurement of ocular pulse amplitude and intraocular pressure using Smartlens].

BACKGROUND: SmartLens (ODC Ophthalmic Development Company AG, Zürich) is a contact lens tonometer, which allows continuous registration of intraocular pressure (IOP) and ocular pulse amplitude (OPA) and simultaneous ophthalmoscopy. The purpose of this study was to evaluate the intra- and interobserver variability and reliability of intraocular pressure and ocular pulse amplitude measurements using SmartLens. METHODS: To evaluate the intraobserver variability, intraocular pressure (IOP) and ocular pulse amplitude (OPA) were both measured 5 times in 10 healthy eyes by one observer. To evaluate the interobserver variability, intraocular pressure and ocular pulse amplitude were measured by 3 different observers in 10 healthy eyes. Data description is based on coefficients of variation (SD/mean in %), statistical inference on ANOVA-based reliability estimation. RESULTS: The coefficient of the intraobserver variation was 9.57% for the IOP and 14.5% for the OPA (SD IOP: +/- 1.64 mmHg, SD OPA: +/- 0.39 mmHg). The coefficient of the interobserver variation with 5 replicate measurements was 10.16% for the IOP and 14% for the OPA (SD IOP: +/- 1.83 mmHg, SD OPA: +/- 0.4 mmHg). The interobserver reliability was 87% for the IOP and 86% for the OPA. One of the three observers obtained significantly higher IOP and OPA values. CONCLUSIONS: SmartLens is a reasonably precise and reliable device for IOP as well as OPA measurements but the results were not found to be observer independent.

Analysis of Variance↗