68 resultados para Weinberg, Steven: Unelmia viimeisestä teoriasta


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PURPOSE: To compare mechanical and ethanol epithelial removal with respect to myofibroblast development and haze formation after photorefractive keratectomy (PRK). METHODS: Seventeen rabbits underwent mechanical or ethanol debridement, and the opposite eye of each rabbit served as an unwounded control. In both groups, the epithelium was removed with a spatula and discarded. A -9.00-diopter PRK was performed in each eye. The level of haze in each cornea at 4 weeks was graded at the slit-lamp microscope according to the Fantes scale. Myofibroblast generation was detected with immunocytochemistry for alpha-smooth muscle actin (alpha-SMA) and cells were quantitatively analyzed. RESULTS: No difference was noted between the two groups in alpha-SMA + myofibroblasts 4 weeks after surgery (43.6 +/- 2.0/400X field and 45.7 +/- 4.8/400X field in ethanol and mechanical groups, respectively) (P=.10). A slight difference was noted but did not reach statistical significance with regard to stromal haze between ethanol and mechanical groups (2.0 +/- 0.5 and 2.3 +/- 0.4, respectively, P=.063). The ethanol and mechanical groups were statistically different when compared to controls regarding stromal haze and alpha-SMA+ cells (P <.0001 for all comparisons). CONCLUSIONS:No difference was noted in clinical haze or myofibroblast generation between corneas that had PRK with mechanical,or ethanol epithelial debridement. [J Refract Surg., 2008;24:923-927.]

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Interleukin (IL)-1 alpha and beta are important modulators of many functions of corneal epithelial and stromal cells that occur following injury to the cornea, including the influx of bone marrow-derived inflammatory cells into the stroma attracted by chemokines released from the stroma and epithelium. In this study, we examined the effect of topical soluble IL-1 receptor antagonist on bone marrow-derived cell influx following corneal epithelial scrape injury in a mouse model. C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1 receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20 mg/ml or vehicle for 24 h prior to immunocytochemical detection of marker CD11b-positive cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a marked effect in blocking cell influx. For example, in experiment 1, topical IL-1 receptor antagonist markedly reduced detectible CD11b-positive cells into the corneal stroma at 24 It after epithelial injury compared with the vehicle control (3.5 +/- 0.5 (standard error of the mean) cells/400x field and 13.9 +/- 1.2 cells/400x field, respectively, p < 0.01). A second experiment with a different observer performing cell counting had the same result. Thus, the data demonstrate conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b-positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor antagonist could be an effective adjuvant for clinical treatment of corneal conditions in which unwanted inflammation has a role in the pathophysiology of the disorder. (c) 2008 Elsevier Ltd. All rights reserved.

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Background: We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). Methods: We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Results: Parents of bipolar children reported lower levels of family cohesion (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.03 1) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Limitations: Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Conclusion: Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder. (C) 2007 Elsevier B.V. All rights reserved.

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Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J Physiol Heart Circ Physiol 300: H1914-H1922, 2011. First published March 4, 2011; doi:10.1152/ajpheart.01048.2010.-The coupling between arterial elastance (E(A); net afterload) and lea ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium. nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV): did not differ between old (70 +/- 8 yr. n = 15) and young (30 +/- 5 yr. n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 +/- 3.1 mmHg/ml) versus young (11.4 +/- 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 +/- 0.11) versus young (0.16 +/- 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

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GLUT is the major glucose transporter in mammalian cells. Single nucleotide polymorphisms (SNP) at GLUT1 promoter and regulatory regions have been associated to the risk of developing nephropathy in different type 1 and type 2 diabetic populations. It has been demonstrated that differences in allelic and genotypic frequencies of GLUT1 gene (SLC2A1) polymorphisms occur among different populations. Therefore, ethnic differences in distribution of GLUT1 gene polymorphisms may be an important factor in determining gene-disease association. In this study, we investigated the XbaIG > T and HaeIIIT > C polymorphisms in six different Brazilian populations: 102 individuals from Salvador population (Northern Brazil), 56 European descendants from Joinville (South Brazil), 85 Indians from Tiryi tribe (North Brazil) and 127 samples from Southern Brazil: 44 from European descendants, 42 from African descendants and 41 from Japanese descendants. Genotype frequencies from both sites did not differ significantly from those expected under the Hardy-Weinberg equilibrium. We verified that the allele frequencies of both polymorphisms were heterogeneous in these six Brazilian ethnic groups.

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Polymorphic variations of several genes associated with drugs and xenobiotic metabolism have been linked to the factors that predispose to the carcinogenesis process. As considerable interindividual and interethnic variation in metabolizing enzyme activity has been associated with polymorphic alleles, we evaluated the frequency of the polymorphisms of CYP2D6, EPHX1 and NQO1 genes in 361 Brazilian individuals separated by ethnicity (European and African ancestry), using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The allele frequencies of the variants *3 and *4 for the gene CYP2D6 were 0.04 and 0.14 for white subjects and 0.03 and 0.10 for black individuals, respectively. For the both variants of the gene EPHX1, we found higher allele frequencies among white individuals compared with mulatto subjects (0.62 vs 0.54 and 0.18 vs 0.14, respectively); however, these differences were not statistically significant (p = 0.39 and 0.56, respectively). For the NQO1 gene we observed a higher frequency of the homozygous genotype among black individuals (7.9%) compared with white subjects (6.3%) (p = 0.003). The genotype frequencies were within the Hardy-Weinberg equilibrium. We concluded that the allele frequencies of CYP2D6, EPHX1 and NQO1 gene polymorphisms in this Brazilian population showed ethnic variability when compared with those observed in other populations.

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Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

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To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

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The tibial plateau leveling osteotomy (TPLO) is a relatively new and innovative surgical treatment for the cranial cruciate ligament rupture in the canine species. The real intent of the procedure is to provide functional stability to the stifle joint by eliminating or neutralizing the cranial tibial thrust during weight bearing instead to restore the cranial cruciate ligament function. The proposal of this study is to report a review of the TPLO procedure, emphasizing procedure, surgical technique, post operative care and complications. The TPLO procedure consists in a radial osteotomy in the tibial plato and rotation of the caudal plateau in order to obtain a desired angle, After the leveling of the tibial plateau, a bone plate and screws are used to stabilize the osteotomy until bone is healed up. The complications that have been associated with the procedure include tibial tuberosity fracture and patellar tendon tendinosis. This procedure has become increasingly more popular for surgical treatment of cranial cruciate ligament injuries in large breed dog. The long term clinical results have not been completely elucidated yet. It has been showed that this technique doesn`t halt the degenerative joint disease.

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Rickettsia species antibodies have been detected in some cats but it is unknown whether infected cats develop clinical signs. The prevalence of Rickettsia species deoxyribonucleic acid (DNA) in blood from clinically ill cats has not been determined. The objective of this study was to determine if cats with fever (body temperature >= 102.5 degrees F [39.2 degrees C]) were more likely to have evidence of rickettsial infection than healthy, age-matched, control cats with a body temperature < 102.5 degrees F. Rickettsia species polymerase chain reaction (PCR) assays were performed to detect rickettsial DNA extracted from blood (71 paired samples), indirect immunofluorescence assays (IFA) were performed to detect serum antibodies against Rickettsia felis (90 paired samples) and Rickettsia rickettsii (91 paired samples), and the results between pairs were compared. All samples were negative for Rickettsia species DNA. More cats with fever were seropositive for R felis or R rickettsii than control cats, but results were not statistically significant. Results of this pilot study failed to show an association between Rickettsia species DNA or Rickettsia species antibodies and fever. (c) 2008 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

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The influence of the aspect ratio (building height/street canyon width) and the mean building height of cities on local energy fluxes and temperatures is studied by means of an Urban Canopy Model (UCM) coupled with a one-dimensional second-order turbulence closure model. The UCM presented is similar to the Town Energy Balance (TEB) model in most of its features but differs in a few important aspects. In particular, the street canyon walls are treated separately which leads to a different budget of radiation within the street canyon walls. The UCM has been calibrated using observations of incoming global and diffuse solar radiation, incoming long-wave radiation and air temperature at a site in So Paulo, Brazil. Sensitivity studies with various aspect ratios have been performed to assess their impact on urban temperatures and energy fluxes at the top of the canopy layer. In these simulations, it is assumed that the anthropogenic heat flux and latent heat fluxes are negligible. Results show that the simulated net radiation and sensible heat fluxes at the top of the canopy decrease and the stored heat increases as the aspect ratio increases. The simulated air temperature follows the behavior of the sensible heat flux. (C) 2010 Elsevier Ltd. All rights reserved.

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Tropical vegetation is a major source of global land surface evapotranspiration, and can thus play a major role in global hydrological cycles and global atmospheric circulation. Accurate prediction of tropical evapotranspiration is critical to our understanding of these processes under changing climate. We examined the controls on evapotranspiration in tropical vegetation at 21 pan-tropical eddy covariance sites, conducted a comprehensive and systematic evaluation of 13 evapotranspiration models at these sites, and assessed the ability to scale up model estimates of evapotranspiration for the test region of Amazonia. Net radiation was the strongest determinant of evapotranspiration (mean evaporative fraction was 0.72) and explained 87% of the variance in monthly evapotranspiration across the sites. Vapor pressure deficit was the strongest residual predictor (14%), followed by normalized difference vegetation index (9%), precipitation (6%) and wind speed (4%). The radiation-based evapotranspiration models performed best overall for three reasons: (1) the vegetation was largely decoupled from atmospheric turbulent transfer (calculated from X decoupling factor), especially at the wetter sites; (2) the resistance-based models were hindered by difficulty in consistently characterizing canopy (and stomatal) resistance in the highly diverse vegetation; (3) the temperature-based models inadequately captured the variability in tropical evapotranspiration. We evaluated the potential to predict regional evapotranspiration for one test region: Amazonia. We estimated an Amazonia-wide evapotranspiration of 1370 mm yr(-1), but this value is dependent on assumptions about energy balance closure for the tropical eddy covariance sites; a lower value (1096 mm yr(-1)) is considered in discussion on the use of flux data to validate and interpolate models.

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White-lipped peccaries, Tayassu pecari, are neotropical ungulates whose populations have been declining in numerous locations within their geographical distribution. Here we describe 16 microsatellite loci isolated from T. pecari and their cross-amplification in collared peccaries, Pecari tajacu. In 30 individuals of T. pecari, a total of 32 alleles were found in ten polymorphic loci, ranging from 2 to 8 alleles per locus with a mean of 3.2. The expected and observed heterozygosity ranged from 0.143 to 0.802 and from 0 to 0.704, respectively. Two loci deviated from Hardy-Weinberg equilibrium. In P. tajacu, nine loci were polymorphic with a mean of 3.2 alleles per locus. These molecular markers will be useful to study the genetic status of peccary populations and, consequently, to help their conservation.

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The bare-faced curassow (Crax fasciolata) is a large Neotropical bird that suffers anthropogenic pressure across much of its range. A captive population is maintained for conservation management, although there has been no genetic screening of stocks. Based on the six microsatellite markers developed for Crax globulosa, the genetic variability of C. fasciolata and possible differences between a wild and a captive population were investigated. Only three loci were polymorphic, with a total of 27 alleles. More than half of these alleles were private to the wild (n = 8) or captive (n = 7) populations. Significant deviations from Hardy-Weinberg equilibrium were restricted to the captive population. Despite the number of private alleles, genetic drift has probably promoted differentiation between populations. Our results indicate that wild C. fasciolata populations are genetically impoverished and structured, but species-specific microsatellite markers will be necessary for a more reliable assessment of the species` genetic diversity.

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This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.