RESUMEN
BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (nâ=â126); cohort 2, 92-97% (nâ=â121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, pâ=â0.38), ROP (4% vs. 3%, pâ=â0.49), or PH (2% vs. 4%, pâ=â0.44). CONCLUSION: An oxygen saturation target of 92-97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94-98%.
Asunto(s)
Displasia Broncopulmonar , Hipertensión Pulmonar , Displasia Broncopulmonar/epidemiología , Edad Gestacional , Humanos , Hipertensión Pulmonar/epidemiología , Lactante , Recién Nacido , Recien Nacido Prematuro , Saturación de Oxígeno , Estudios RetrospectivosRESUMEN
The objective of this study was to evaluate, using three different genotype density panels, the accuracy of imputation from lower- to higher-density genotypes in dairy and beef cattle. High-density genotypes consisting of 777,962 single-nucleotide polymorphisms (SNP) were available on 3122 animals comprised of 269, 196, 710, 234, 719, 730 and 264 Angus, Belgian Blue, Charolais, Hereford, Holstein-Friesian, Limousin and Simmental bulls, respectively. Three different genotype densities were generated: low density (LD; 6501 autosomal SNPs), medium density (50K; 47,770 autosomal SNPs) and high density (HD; 735,151 autosomal SNPs). Imputation from lower- to higher-density genotype platforms was undertaken within and across breeds exploiting population-wide linkage disequilibrium. The mean allele concordance rate per breed from LD to HD when undertaken using a single breed or multiple breed reference population varied from 0.956 to 0.974 and from 0.947 to 0.967, respectively. The mean allele concordance rate per breed from 50K to HD when undertaken using a single breed or multiple breed reference population varied from 0.987 to 0.994 and from 0.987 to 0.993, respectively. The accuracy of imputation was generally greater when the reference population was solely comprised of the breed to be imputed compared to when the reference population comprised of multiple breeds, although the impact was less when imputing from 50K to HD compared to imputing from LD.
Asunto(s)
Bovinos/genética , Industria Lechera , Genotipo , Carne , Animales , Cruzamiento , Frecuencia de los Genes , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Especificidad de la Especie , Estadística como AsuntoRESUMEN
The objective of this study was to quantify the accuracy of imputing the genotype of parents using information on the genotype of their progeny and a family-based and population-based imputation algorithm. Two separate data sets were used, one containing both dairy and beef animals (n=3122) with high-density genotypes (735 151 single nucleotide polymorphisms (SNPs)) and the other containing just dairy animals (n=5489) with medium-density genotypes (51 602 SNPs). Imputation accuracy of three different genotype density panels were evaluated representing low (i.e. 6501 SNPs), medium and high density. The full genotypes of sires with genotyped half-sib progeny were masked and subsequently imputed. Genotyped half-sib progeny group sizes were altered from 4 up to 12 and the impact on imputation accuracy was quantified. Up to 157 and 258 sires were used to test the accuracy of imputation in the dairy plus beef data set and the dairy-only data set, respectively. The efficiency and accuracy of imputation was quantified as the proportion of genotypes that could not be imputed, and as both the genotype concordance rate and allele concordance rate. The median proportion of genotypes per animal that could not be imputed in the imputation process decreased as the number of genotyped half-sib progeny increased; values for the medium-density panel ranged from a median of 0.015 with a half-sib progeny group size of 4 to a median of 0.0014 to 0.0015 with a half-sib progeny group size of 8. The accuracy of imputation across different paternal half-sib progeny group sizes was similar in both data sets. Concordance rates increased considerably as the number of genotyped half-sib progeny increased from four (mean animal allele concordance rate of 0.94 in both data sets for the medium-density genotype panel) to five (mean animal allele concordance rate of 0.96 in both data sets for the medium-density genotype panel) after which it was relatively stable up to a half-sib progeny group size of eight. In the data set with dairy-only animals, sufficient sires with paternal half-sib progeny groups up to 12 were available and the within-animal mean genotype concordance rates continued to increase up to this group size. The accuracy of imputation was worst for the low-density genotypes, especially with smaller half-sib progeny group sizes but the difference in imputation accuracy between density panels diminished as progeny group size increased; the difference between high and medium-density genotype panels was relatively small across all half-sib progeny group sizes. Where biological material or genotypes are not available on individual animals, at least five progeny can be genotyped (on either a medium or high-density genotyping platform) and the parental alleles imputed with, on average, ⩾96% accuracy.
Asunto(s)
Algoritmos , Bovinos/genética , Genotipo , Polimorfismo de Nucleótido Simple , Alelos , Crianza de Animales Domésticos , Animales , Cruzamiento , Bovinos/fisiología , Industria Lechera , Femenino , Masculino , CarneRESUMEN
The objective was to analyze the proteomic composition of uterine flushes collected from beef heifers on day 7 after insemination. Estrus was synchronized in crossbred beef heifers by using a protocol with a controlled intravaginal drug releasing device. Heifers detected in standing estrus (within 24-48 h after removal of controlled intravaginal drug releasing device) were inseminated (estrus = day 0) with frozen-thawed semen from a single ejaculate of a bull with proven fertility. Heifers from which an embryo was recovered (after slaughter on day 7) were classified as either having a viable embryo (morula/blastocyst stage) or a degenerate embryo (arrested at the 2- to 16-cell stage). The overall recovery rate (viable and degenerate combined) was 64%. Global liquid chromatography coupled to tandem mass spectrometry proteomic analysis of the histotroph collected identified 40 high-confidence proteins present on day 7; 26 proteins in the viable group, 10 in the degenerate group, and 4 shared between both groups. Five proteins (platelet-activating factor acetylhydrolase IB subunit γ [PAFAH1B3], tubulin α-1D chain, tubulin ß-4A chain, cytochrome C, and dihydropyrimidinase-related protein-2) were unique or more abundant in the histotroph collected from animals with a viable embryo, and 1 protein (S100-A4) was more abundant in the histotroph collected from animals with a degenerate embryo. Of interest, PAFAH1B3, detected only in histotroph from the group yielding viable embryos, belongs to the group of platelet-activating factors that are known to be important for the development of the pre-implantation embryo in other species. To our knowledge this is the first report of PAFAH1B3 in relation to bovine early embryonic development.
Asunto(s)
Bovinos/metabolismo , Desarrollo Embrionario/fisiología , Útero/metabolismo , Animales , Cromatografía Liquida/veterinaria , Femenino , Ontología de Genes , Embarazo , Progesterona/sangre , Proteómica/métodos , Espectrometría de Masa por Ionización de Electrospray/veterinariaRESUMEN
Pregnancy per insemination is a major determinant of reproductive efficiency in cattle and is affected by concentrations of progesterone (P4) during early pregnancy. The relationship between pregnancy per artificial insemination (P/AI) and early luteal concentrations of P4, and repeatability of concentrations of P4 was examined on d 4, 5, 6, and 7 (day of standing estrus=d 0) in 118 Holstein Friesian heifers following 2 rounds of AI to 1 high-fertility sire. Repeatability estimates (R(e)) for P/AI were established following 4 rounds of AI. We found a linear and quadratic relationship between P/AI and concentrations of P4 on d 4 to 7 after estrus, as well as a linear and quadratic relationship between P/AI and the change in concentration of P4 from d 4 to 7 and from d 5 to 7. Optimum concentrations of P4 to maximize probability of P/AI were 2.5, 4.0, 5.0, 5.2, and 3.5 ng/mL for d 4, 5, 6, and 7, and the change from d 4 to 7, respectively. Repeatability of P/AI following 4 rounds of AI was low (R(e)=0.07). Repeatability estimates for concentrations of P4 from cycle to cycle indicated low repeatability between d 4 (R(e)=0.05) and 7 (R(e)=0.20). These data indicated the importance of P4 in the early luteal phase for pregnancy survival, but also demonstrated that high concentrations of P4 on these days have a deleterious effect on embryo viability. Early luteal (d 4 to 5) concentrations of P4 were a reasonable predictor of concentrations on d 7 and could be used as a diagnostic tool to identify animals at risk of subsequent embryo loss.
Asunto(s)
Mantenimiento del Cuerpo Lúteo/fisiología , Inseminación Artificial/veterinaria , Progesterona/fisiología , Animales , Bovinos , Cuerpo Lúteo/fisiología , Detección del Estro/métodos , Sincronización del Estro/métodos , Sincronización del Estro/fisiología , Femenino , Inseminación Artificial/fisiología , Embarazo , Progesterona/sangreRESUMEN
The somatotrophic axis consisting of pituitary-derived growth hormone and circulating insulin-like growth factor 1 has been well established as key regulators of animal health, metabolism, lactation, fertility, body composition and growth rate. The aim of this study was to simultaneously quantify the associations between SNPs in candidate genes of the somatotrophic axis (i.e., IGF-1, GH1 and GHR) with performance traits in Holstein-Friesian (HF) dairy cattle. Both novel SNPs identified previously by this group alongside other published SNPs within these genes were analysed for associations with performance in dairy cattle. Multiple regression analyses regressing genetic merit of up to 848 HF sires on novel SNPs (n = 76) and published SNPs (n = 33) were undertaken using weighted animal mixed linear models. Twenty-three SNPs were significantly associated with at least one of 18 traits analysed and involved in milk production, udder health, fertility and growth. Eight traits including milk fat composition, carcass conformation, stature, chest width, body depth, rump width, carcass and cull cow weight were independently associated with SNPs in two genes. Furthermore, for several traits including milk fat yield, somatic cell count, survival and carcass fat, SNPs in all three genes were independently associated with performance. Milk fat yield and carcass fat showed the highest number of independent associations across all three genes with five SNPs associated with both traits. The cumulative effects of the favourable alleles of all five SNPs across GH1, GHR and IGF-1 result in an increase of 5.9 kg and 28.6 units of milk fat and carcass fat, respectively. Cow survival was associated with a single SNP in each of the three genes with a cumulative allele effect of 1.5%. Independent effects of polymorphisms in GH1, GHR and IGF-1 reinforce the central role of the somatotrophic axis on animal development and performance.
Asunto(s)
Tamaño Corporal/genética , Bovinos/genética , Industria Lechera , Glándulas Mamarias Animales/metabolismo , Leche/metabolismo , Polimorfismo de Nucleótido Simple , Somatotrofos/metabolismo , Alelos , Animales , Secuencia de Bases , Bovinos/anatomía & histología , Bovinos/metabolismo , Femenino , Hormona del Crecimiento/genética , Salud , Análisis de SupervivenciaRESUMEN
The regulation of the bioavailability of insulin-like growth factors (IGFs) is critical for normal mammalian growth and development. The imprinted insulin-like growth factor 2 receptor gene (IGF2R) encodes a transmembrane protein receptor that acts to sequester and degrade excess circulating insulin-like growth factor 2 (IGF-II) - a potent foetal mitogen - and is considered an important inhibitor of growth. Consequently, IGF2R may serve as a candidate gene underlying important growth- and body-related quantitative traits in domestic mammalian livestock. In this study, we have quantified genotype-phenotype associations between three previously validated intronic bovine IGF2R single nucleotide polymorphisms (SNPs) (IGF2R:g.64614T>C, IGF2R:g.65037T>C and IGF2R:g.86262C>T) and a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. Notably, all three polymorphisms analysed were associated (P ≤ 0.05) with at least one of a number of performance traits related to animal body size: angularity, body depth, chest width, rump width, and animal stature. In addition, the C-to-T transition at the IGF2R:g.65037T>C polymorphism was positively associated with cow carcass weight and angularity. Correction for multiple testing resulted in the retention of two genotype-phenotype associations (animal stature and rump width). None of the SNPs analysed were associated with any of the milk traits examined. Analysis of pairwise r(2) measures of linkage disequilibrium between all three assayed SNPs ranged between 0.41 and 0.79, suggesting that some of the observed SNP associations with performance may be independent. To our knowledge, this is one of the first studies demonstrating associations between IGF2R polymorphisms and growth- and body-related traits in cattle. These results also support the increasing body of evidence that imprinted genes harbour polymorphisms that contribute to heritable variation in phenotypic traits in domestic livestock species.
Asunto(s)
Tamaño Corporal , Bovinos/genética , Impresión Genómica , Polimorfismo de Nucleótido Simple , Receptor IGF Tipo 2/genética , Animales , Femenino , MasculinoRESUMEN
The somatotrophic axis (GH-IGF) is a key regulator of animal growth and development, affecting performance traits that include milk production, growth rate, body composition, and fertility. The aim of this study was to quantify the association of previously identified SNPs in bovine growth hormone (GH1) and insulin-like growth factor 1 (IGF-1) genes with direct performance trait measurements of lactation and fertility in Holstein-Friesian lactating dairy cows. Sixteen SNPs in both IGF-1 and GH1 were genotyped across 610 cows and association analyses were carried out with traits of economic importance including calving interval, pregnancy rate to first service and 305-day milk production, using animal linear mixed models accounting for additive genetic effects. Two IGF-1 SNPs, IGF1i1 and IGF1i2, were significantly associated with body condition score at calving, while a single IGF-1 SNP, IGF1i3, was significantly associated with milk production, including milk yield (means ± SEM; 751.3 ± 262.0 kg), fat yield (21.3 ± 10.2 kg) and protein yield (16.5 ± 8.0 kg) per lactation. Only one GH1 SNP, GH33, was significantly associated with milk protein yield in the second lactation (allele substitution effect of 9.8 ± 5.0 kg). Several GH1 SNPs were significantly associated with fertility, including GH32, GH35 and GH38 with calving to third parity (22.4 ± 11.3 days) (GH32 and GH38 only), pregnancy rate to first service (0.1%) and overall pregnancy rate (0.05%). The results of this study demonstrate the effects of variants of the somatotrophic axis on milk production and fertility traits in commercial dairy cattle.
Asunto(s)
Composición Corporal/genética , Bovinos/genética , Fertilidad/genética , Hormona del Crecimiento/genética , Factor I del Crecimiento Similar a la Insulina/genética , Lactancia/genética , Animales , Bovinos/fisiología , Femenino , Genotipo , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
Enormous progress has been made in the selection of animals, including cattle, for specific traits using traditional quantitative genetics approaches. Nevertheless, considerable variation in phenotypes remains unexplained, and therefore represents potential additional gain for animal production. In addition, the paradigm shift in new disciplines now being applied to animal breeding represents a powerful opportunity to prise open the 'black box' underlying the response to selection and fully understand the genetic architecture controlling the traits of interest. A move away from traditional approaches of animal breeding toward systems approaches using integrative analysis of data from the 'omic' disciplines represents a multitude of exciting opportunities for animal breeding going forward as well as providing alternatives for overcoming some of the limitations of traditional approaches such as the expressed phenotype being an imperfect predictor of the individual's true genetic merit, or the phenotype being only expressed in one gender or late in the lifetime of an animal. This review aims to discuss these opportunities from the perspective of their potential application and contribution to cattle breeding. Harnessing the potential of this paradigm shift also poses some new challenges for animal scientists - and they will also be discussed.
RESUMEN
Growth hormone, produced in the anterior pituitary gland, stimulates the release of insulin-like growth factor-I from the liver and is of critical importance in the control of nutrient utilization and partitioning for lactogenesis, fertility, growth, and development in cattle. The aim of this study was to discover novel polymorphisms in the bovine growth hormone gene (GH1) and to quantify their association with performance using estimates of genetic merit on 848 Holstein-Friesian AI (artificial insemination) dairy sires. Associations with previously reported polymorphisms in the bovine GH1 gene were also undertaken. A total of 38 novel single nucleotide polymorphisms (SNP) were identified across a panel of 22 beef and dairy cattle by sequence analysis of the 5' promoter, intronic, exonic, and 3' regulatory regions, encompassing approximately 7 kb of the GH1 gene. Following multiple regression analysis on all SNP, associations were identified between 11 SNP (2 novel and 9 previously identified) and milk fat and protein yield, milk composition, somatic cell score, survival, body condition score, and body size. The G allele of a previously identified SNP in exon 5 at position 2141 of the GH1 sequence, resulting in a nonsynonymous substitution, was associated with decreased milk protein yield. The C allele of a novel SNP, GH32, was associated with inferior carcass conformation. In addition, the T allele of a previously characterized SNP, GH35, was associated with decreased survival. Both GH24 (novel) and GH35 were independently associated with somatic cell count, and 3 SNP, GH21, 2291, and GH35, were independently associated with body depth. Furthermore, 2 SNP, GH24 and GH63, were independently associated with carcass fat. Results of this study further demonstrate the multifaceted influences of GH1 on milk production, fertility, and growth-related traits in cattle.
Asunto(s)
Composición Corporal/genética , Bovinos/fisiología , Fertilidad/genética , Hormona del Crecimiento/genética , Lactancia/genética , Polimorfismo de Nucleótido Simple/genética , Animales , Bovinos/genética , Recuento de Células/veterinaria , Grasas de la Dieta/análisis , Femenino , Masculino , Leche/química , Leche/citología , Leche/metabolismo , Proteínas de la Leche/análisisRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) has been linked to mutations in genes encoding two members of the transforming growth factor-beta family, BMPR2 and ALK1, the latter of which is also associated with hereditary haemorrhagic telangiectasia (HHT). Relatively little is known about the genetics of childhood PAH, or about the clinical features of PAH in young patients with an ALK1 mutation. METHODS AND RESULTS: Three individuals diagnosed with PAH at 4, 16 and 17 years of age were found on subsequent genetic screening to have non-synonymous mutations of ALK1. All probands met criteria for HHT, although two presented with PAH before HHT was diagnosed. Extended family history revealed relatives with HHT in all three kindreds, a presumptive family history of PAH in two, one with multiple family members dying from PAH at young ages. All three patients in this series had systemic or suprasystemic right ventricular pressure and significantly elevated pulmonary vascular resistance, initially not responsive to oxygen and/or inhaled nitric oxide. All patients had pulmonary arteriovenous malformations and systemic arterial desaturation. CONCLUSION: This report highlights ALK1 mutations associated with a variable PAH phenotype, including pulmonary arteriovenous malformations and severe PAH presenting early in life. Echocardiographic screening for elevated right ventricular pressure may be indicated in patients with HHT, particularly those with an identified ALK1 mutation. Clinical features or a family history of HHT should be elicited in children and adolescents with idiopathic PAH; ALK1 screening may be appropriate when such features are present.
Asunto(s)
Receptores de Activinas Tipo II/genética , Predisposición Genética a la Enfermedad/genética , Hipertensión Pulmonar/genética , Telangiectasia Hemorrágica Hereditaria/genética , Adolescente , Preescolar , Análisis Mutacional de ADN , Pruebas Genéticas , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Linaje , Telangiectasia Hemorrágica Hereditaria/complicacionesRESUMEN
BACKGROUND: The molecular basis of idiopathic dilated cardiomyopathy, a primary myocardial disorder that results in reduced contractile function, is largely unknown. Some cases of familial dilated cardiomyopathy are caused by mutations in cardiac cytoskeletal proteins; this finding implicates defects in contractile-force transmission as one mechanism underlying this disorder. To elucidate this important cause of heart failure, we investigated other genetic causes of dilated cardiomyopathy. METHODS: Clinical evaluations were performed in 21 kindreds with familial dilated cardiomyopathy. A genome-wide linkage study prompted a search of the genes encoding beta-myosin heavy chain, troponin T, troponin I, and alpha-tropomyosin for disease-causing mutations. RESULTS: A genetic locus for mutations associated with dilated cardiomyopathy was identified at chromosome 14q11.2-13 (maximal lod score, 5.11; theta=0), where the gene for cardiac beta-myosin heavy chain is encoded. Analyses of this and other genes for sarcomere proteins identified disease-causing dominant mutations in four kindreds. Cardiac beta-myosin heavy-chain missense mutations (Ser532Pro and Phe764Leu) and a deletion in cardiac troponin T (deltaLys210) caused early-onset ventricular dilatation (average age at diagnosis, 24 years) and diminished contractile function and frequently resulted in heart failure. Affected persons had neither antecedent cardiac hypertrophy (average maximal left-ventricular-wall thickness, 8.5 mm) nor histopathological findings characteristic of hypertrophy. CONCLUSION: Mutations in sarcomere protein genes account for approximately 10 percent of cases of familial dilated cardiomyopathy and are particularly prevalent in families with early-onset ventricular dilatation and dysfunction. Because distinct mutations in sarcomere proteins cause either dilated or hypertrophic cardiomyopathy, the effects of mutant sarcomere proteins on muscle mechanics must trigger two different series of events that remodel the heart.
Asunto(s)
Cardiomiopatía Dilatada/genética , Cadenas Pesadas de Miosina/genética , Sarcómeros/genética , Troponina T/genética , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/patología , Niño , Preescolar , Mapeo Cromosómico , Cromosomas Humanos Par 14 , Femenino , Genes Dominantes , Humanos , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Missense , Contracción Miocárdica/genética , Contracción Miocárdica/fisiología , Miocardio/patología , Miosina Tipo IIB no Muscular , Linaje , Sarcómeros/fisiología , UltrasonografíaAsunto(s)
Toxinas Botulínicas/uso terapéutico , Distonía/tratamiento farmacológico , Músculo Masetero , Músculo Temporal , Adulto , Femenino , Humanos , Maloclusión Clase II de Angle/etiología , Maloclusión Clase II de Angle/cirugía , Mandíbula/cirugía , Ferulas Oclusales/efectos adversos , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/terapiaRESUMEN
Multidrug resistant Mycobacterium tuberculosis (MDR-MTB) infection has not been recognized as a serious problem in patients with human immunodeficiency virus (HIV) infection. Multidrug resistance (MDR) has appeared in our medical center in 24 out of 72 patients between January 1990 and May 1991 compared to 8 out of 132 patients within the period from 1982 to 1987 (relative risk 5.50 with 95 percent confidence interval 2.61 to 11.61). We describe 19 patients with MDR in MTB (isoniazid and at least one additional first line drug), who had serologic evidence of HIV infection, 13 of whom were diagnosed with acquired immunodeficiency syndrome (AIDS). The MTB cultures from 10 out of 19 patients with MDR were resistant to three or more drugs. Fifteen patients died although 9 out of these 15 had received at least a four-drug regimen for a mean time of seven weeks (range 2 to 12). This increase in MDR was seen in ten homosexuals and nine intravenous drug users. This rapid appearance of MDR-MTB strains is worrisome. New strategies for empiric therapy of such patients while awaiting sensitivity data are needed.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antituberculosos/uso terapéutico , Seropositividad para VIH/complicaciones , Mycobacterium tuberculosis/efectos de los fármacos , Infecciones Oportunistas/complicaciones , Tuberculosis Pulmonar/complicaciones , Adulto , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Humanos , Masculino , Infecciones Oportunistas/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
We have used exons 2 and 3 of the rat alpha-tropomyosin gene to analyze the basis of mutually exclusive exon selection. The basis of the strict mutually exclusive behavior of this exon pair is enforced by the proximity of the exon 3 branchpoint to the 5' splice site of exon 2. With the exception of smooth muscle cells, exon 3 rather than exon 2 is incorporated into mRNA in all cell types. We show here, using both in vivo and in vitro cell-free systems, that this alternative exon selection is a consequence of general principles that govern 3' splice site selection. In the absence of exon 3, exon 2 is utilized efficiently in all cells. Selection of exon 3 is therefore the default result of a competition between exons 2 and 3 for the flanking constitutive splice sites. The basis of this competition is the relative strength of the polypyrimidine tract/branchpoint elements of the two exons. The major determinant of this splice site strength is the pyrimidine content adjacent to the branchpoint, and this involves no other sequence specificity. The branchpoint elements play an important but secondary role. The functional strengths of the different polypyrimidine tract/branchpoint combinations, as determined in cis competition assays, showed a perfect correlation with their binding affinities to a spliceosome component that interacts with the pre-mRNA in an ATP-independent manner. Selection of exon 3 in most cell types therefore reflects the preferential interaction of these splice site elements with constitutive splicing factors early in spliceosome assembly. The aspects of splice site selection analyzed here are likely to be of general applicability to constitutive and alternative pre-mRNA splicing.
Asunto(s)
Exones , Genes , Empalme del ARN , Tropomiosina/genética , Animales , Secuencia de Bases , Sistema Libre de Células , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Pirimidinas , Ratas , Mapeo Restrictivo , Transcripción GenéticaRESUMEN
A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver strain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A repeated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of hypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Hipotiroidismo/complicaciones , Neumonía por Pneumocystis/complicaciones , Glándula Tiroides/microbiología , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Neumonía por Pneumocystis/diagnósticoRESUMEN
Extrapulmonary Pneumocystis carinii infection is a rare occurrence in patients with AIDS. Pleural involvement has been demonstrated in only one case, and this occurred after pneumothorax. This is a case report of pleural pneumocystosis in a patient with AIDS who did not have a pneumothorax.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Micosis/complicaciones , Enfermedades Pleurales/complicaciones , Pneumocystis , Adulto , Humanos , Masculino , Derrame Pleural/complicacionesRESUMEN
Inflamed and retractable mucosal margins around dental implants present unique problems in treatment. A rationale and technique for free gingival grafting around single or multiple implant abutments and two clinical examples are presented here.
Asunto(s)
Implantación Dental Endoósea , Encía/trasplante , Pilares Dentales , Implantación Dental Endoósea/efectos adversos , Implantes Dentales , Humanos , Mucosa Bucal/cirugía , Oseointegración , Enfermedades Periodontales/etiología , Enfermedades Periodontales/prevención & controlRESUMEN
From the Cincinnati Sportsmedicine and Orthopaedic Center and The Deaconess Hospital, Cincinnati, OH. Research Funded by the Cincinnati Sportsmedicine Research and Education Foundation and the United States Olympic Committee. The purpose of this study was to develop a physiological profile of the elite soccer athlete. Protocols were developed to assess flexibility, knee ligament translation, body composition, anaerobic power, lower extremity functional performance, and muscle strength. Eighty-three male U.S. National Team players provided data for this study. Different protocols were used over the years the data was gathered. Each area was tested, using a subset of the total group. The physiological profile of the elite soccer player was compiled from results in each area tested. The players were flexible, on the whole, although 17% of the players demonstrated hamstring tightness. All but one player tested had less than 2.5 mm anterior/posterior (A/P) knee ligament translation. The average body fat was 9.5%, and all athletes performed normally on the function tests. The mean power output on Wingate testing was 8.1 Watts per kilogram body weight. The average hamstring-to-quadricep torque ratio (H/Q) at 60 degrees /sec was 56% (right) and 56.6% (left), and at 450 degrees /sec, was 67.1% and 70.1 %. Identification and measurement of these key physiological qualities for the elite soccer athlete will provide standards and a baseline for trainers, coaches, players, and future investigators. J Orthop Sports Phys Ther 1990;12(4):147-152.
RESUMEN
PURPOSE: Hickman catheters are frequently used as convenient long-term venous access in patients with acquired immunodeficiency syndrome (AIDS). These patients seem to be at increased risk for bacterial infections of intravenous devices. The aim of our study was to determine the frequency of Hickman catheter infection in patients with AIDS as compared with that in other patients. PATIENTS AND METHODS: We analyzed the records of 69 patients who underwent 71 consecutive Hickman catheter placements during a one-year study period. RESULTS: Forty-six Hickman catheters were inserted in 44 patients with AIDS, and 25 Hickman catheters were placed in 25 other patients. There were 18 infections: 16 occurred in patients with AIDS, and two developed in the control group (p less than 0.05). The 16 infections in AIDS were as follows: five exit site, five septicemias, two tunnel, one septic phlebitis, and three probable Hickman catheter-related. Staphylococcus aureus was responsible for 14 cases (87%); Staphylococcus epidermidis was responsible for four cases (25%). Mean onset of infection was 32 days, but seven patients were diagnosed in the first eight days after Hickman catheter insertion. Fever occurred in all patients with early infection, leukopenia was present only in three; infusion of parenteral nutrition did not increase the risk. Two early infections were fatal. The rate of Hickman catheter infection in patients with AIDS was 0.47 per 100 catheter days, as compared with 0.09 in the control group. CONCLUSION: Our findings underscore the need for using Hickman catheters only when absolutely indicated in patients with AIDS, since the risk of serious infectious complications appears to be high.