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1.
Nat Genet ; 23(2): 203-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10508518

RESUMO

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.


Assuntos
Arabidopsis/genética , Marcadores Genéticos/genética , Genoma de Planta , Ascomicetos/crescimento & desenvolvimento , Mapeamento Cromossômico , DNA de Plantas/genética , Genes de Plantas/genética , Predisposição Genética para Doença , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo Genético
2.
Science ; 281(5380): 1194-7, 1998 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-9712584

RESUMO

As more genomes are sequenced, the identification and characterization of the causes of heritable variation within a species will be increasingly important. It is demonstrated that allelic variation in any two isolates of a species can be scanned, mapped, and scored directly and efficiently without allele-specific polymerase chain reaction, without creating new strains or constructs, and without knowing the specific nature of the variation. A total of 3714 biallelic markers, spaced about every 3.5 kilobases, were identified by analyzing the patterns obtained when total genomic DNA from two different strains of yeast was hybridized to high-density oligonucleotide arrays. The markers were then used to simultaneously map a multidrug-resistance locus and four other loci with high resolution (11 to 64 kilobases).


Assuntos
Mapeamento Cromossômico/métodos , Técnicas Genéticas , Variação Genética , Genoma Fúngico , Saccharomyces cerevisiae/genética , Alelos , Cicloeximida/farmacologia , Resistência Microbiana a Medicamentos/genética , Resistência a Múltiplos Medicamentos/genética , Deleção de Genes , Genes Fúngicos , Ligação Genética , Marcadores Genéticos , Genótipo , Hibridização de Ácido Nucleico , Fenótipo , Recombinação Genética
3.
Am J Cardiol ; 80(9): 1236-8, 1997 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9359563

RESUMO

This investigation finds that percent of predicted maximum oxygen consumption, an age- and gender-adjusted measurement of exercise, capacity, describes the degree of functional impairment in women more accurately than peak oxygen consumption. This evidence must be considered when cardiopulmonary metabolic parameters are used for prognostic stratification of women with heart failure.


Assuntos
Cardiomiopatia Dilatada/epidemiologia , Insuficiência Cardíaca/epidemiologia , Consumo de Oxigênio/fisiologia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Caracteres Sexuais , Fatores Sexuais , Fatores de Tempo
4.
J Am Soc Echocardiogr ; 10(6): 602-7, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9282349

RESUMO

BACKGROUND: Recent work has shown significant enhancement in myocardial contrast intensity with brief ultrasound pulsing gated to a discrete portion of the cardiac cycle over conventional 30 Hz imaging. We hypothesized that limiting ultrasound imaging to less than every cardiac cycle would further intensity the myocardial echo-contrast effect. We therefore sought to determine the best pulsing frequency for ultrasound imaging to achieve optimal myocardial perfusion after the intravenous administration of FSO69 using fundamental and second harmonic imaging. METHODS AND RESULTS: In 13 male mongrel dogs, myocardial contrast opacification was determined while varying the cardiac cycle-triggering frequency of ultrasound imaging after intravenous injections of FSO69. Resulting myocardial echo-contrast intensities with a cardiac cycle-triggering frequency of every beat during end-diastole were compared with those with a cardiac cycle-triggering frequency of every third and fifth beat. Myocardial opacification, measured by background-subtracted peak intensity and visual scoring, was significantly greater when ultrasound imaging was triggered to every third and fifth beats compared with every beat. These benefits were seen with imaging in both the fundamental and second harmonic modes. Optimal myocardial opacification with FSO69 was achieved with injections as low as 0.1 ml, a dose that produced significant acoustic shadowing in only 24% of the injections. The degree of myocardial opacification was not significantly affected when the images were acquired during end-systole or end-diastole. CONCLUSIONS: Electrocardiogram-gated ultrasound imaging to every third or fifth cardiac cycle greatly improves myocardial opacification compared with imaging each cardiac cycle. This benefit was increased twofold to threefold with the use of second harmonic imaging as compared with fundamental imaging.


Assuntos
Albuminas , Meios de Contraste , Ecocardiografia/métodos , Fluorocarbonos , Albuminas/administração & dosagem , Animais , Meios de Contraste/administração & dosagem , Cães , Eletrocardiografia , Fluorocarbonos/administração & dosagem , Injeções Intravenosas , Masculino , Contração Miocárdica
7.
Phys Rev Lett ; 91(8): 086802, 2003 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-14525266

RESUMO

Collective and single-particle spin-flip excitations of a two-dimensional electron gas in a semimagnetic Cd(1-x)Mn(x)Te quantum well are observed by resonant Raman scattering. Application of a magnetic field splits the spin subbands and a spin polarization is induced in the electron gas. Above 1 T the collective modes, which disperse with the in-plane wave vector, dominate the spectra. The local spin-density approximation provides a good description of our results and enables us to confirm that the energy of the low wave vector collective mode is given by the bare Zeeman energy.

8.
Am Heart J ; 135(4): 641-6, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9539480

RESUMO

BACKGROUND: Noninvasive estimation of pulmonary capillary wedge pressure (PCWP) with Doppler-derived mitral inflow pattern has been shown to correlate well with invasively measured PCWP; however, it has not yet been determined whether Doppler-derived mitral inflow pattern can be used to estimate PCWP accurately in heart transplant recipients. METHODS: To determine if mitral and pulmonary venous inflow data can be applied to calculate PCWP in heart transplant recipients, some-day echocardiograms and right heart catheterizations were reviewed and 83 echocardiograms with adequate mitral inflow patterns in 53 patients were studied. Twenty-eight studies that also had adequate pulmonary venous inflow patterns were selected for offline analysis. RESULTS: Using a previously published formula [PCWP = 17 + (5.3 x E/A) - (0.11 x IVRT)], where E/A is the ratio of early to late mitral inflow velocities and IVRT is the isovolumic relaxation time, we derived a calculated PCWP, the results of which compared poorly with the measured PCWP (r = 0.33; p = 0.002). Linear regression analysis of measured PCWP versus mitral inflow Doppler flow velocity parameters also revealed poor to modest correlation. Adding parameters derived from the pulmonary venous inflow patterns failed to improve this correlation. CONCLUSION: Doppler-derived estimation of PCWP with mitral and pulmonary venous inflow patterns cannot be used to reliably predict PCWP in heart transplant recipients.


Assuntos
Ecocardiografia Doppler , Transplante de Coração , Valva Mitral/fisiopatologia , Veias Pulmonares/fisiopatologia , Pressão Propulsora Pulmonar/fisiologia , Adolescente , Adulto , Idoso , Função do Átrio Direito , Biópsia , Velocidade do Fluxo Sanguíneo , Cateterismo Cardíaco , Débito Cardíaco , Criança , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Transplante de Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos
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