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1.
J Dairy Sci ; 104(9): 10020-10028, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34147222

RESUMEN

Compared with cow fertility, genetic analyses of bull fertility are limited and based on relatively few animals. The aim of the present study was to estimate genetic parameters for semen characteristics of Norwegian Red bulls at the artificial insemination (AI) center (Geno AI station, Stange, Norway) and to estimate genetic correlations between some of these traits and andrology traits measured at the performance test station. The data from the AI center consisted of records from 137,919 semen collections from 3,145 bulls with information on semen weight, sperm concentration, motility before and after cryopreservation, motility change during cryopreservation, and number of accepted straws made. Data from the performance test station included 12,522 observations from 3,219 bulls on semen volume, concentration, and motility (%) when fresh and after storing for 24 and 48 h. Genetic parameters were estimated using linear animal repeatability models that included fixed effects of year-month of observation, age of bull, interaction between semen collection number, and interval between collections for all traits and type of diluter for postcryopreservation traits. The random effects included test-day, permanent environmental, and additive genetic effects of the bull. Based on records from the AI center, we found that semen weight, sperm concentration, and number of straws were moderately heritable (0.18-0.20), whereas motility had a lower heritability (0.02-0.08). Heritability of motility (%) was higher after cryopreservation than before. Genetic correlations among the semen characteristics ranged from unfavorable (-0.35) to favorable (0.93), with standard errors ranging from 0.02 to 0.22. Among the most precise genetic correlation estimates, number of straws made from a batch correlated favorably with semen weight (0.62 ± 0.06) and sperm concentration (0.44 ± 0.08), whereas sperm concentration was negatively correlated with weight (-0.33 ± 0.09). The genetic correlation between motility (%) before and after cryopreservation was 0.64 ± 0.14, and motility change during cryopreservation had a strong favorable genetic correlation with motility after cryopreservation (-0.93 ± 0.02). The estimated genetic correlation (standard error) between the traits volume, concentration, and motility when fresh measured at the performance test station and their respective corresponding traits at the AI center were 0.83 (0.05), 0.78 (0.09), and 0.49 (0.31). The final product at the AI center (number of accepted straws) correlated genetically favorably with all semen characteristic traits recorded at the performance test station (ranging from 0.51 to 0.67). Our results show that the andrology testing done at the performance test station is a resource to identify the genetically best bulls for AI production.


Asunto(s)
Preservación de Semen , Semen , Animales , Bovinos/genética , Criopreservación/veterinaria , Femenino , Inseminación Artificial/veterinaria , Masculino , Análisis de Semen/veterinaria , Preservación de Semen/veterinaria , Motilidad Espermática/genética , Espermatozoides
2.
J Dairy Sci ; 103(7): 6311-6317, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32389477

RESUMEN

The aim of this study was to estimate genetic parameters for body weight (BW) at 150 d (Bw_150d), and 330 d (Bw_330d) of age and average daily weight gain (Dwg), and to estimate genetic correlations between these traits and semen characteristic traits: volume; concentration (Conc); motility in fresh, 24-h, and 48-h samples (Mot0h, Mot24h, Mot48h); and sperm defects. Data were collected at the performance test station of young Norwegian Red bulls from 2002 to 2012, before selection of bulls for artificial insemination. The weight and growth data consisted of observations for 3,209 bulls, and andrology information was available for up to 2,034 of these bulls. Genetic parameters were estimated using linear animal models. Models for BW and growth traits included the group and year the bull left the station and the pen they occupied during weighing (group-year-pen) and parity of their dam as fixed effects. Models for andrology traits had group-year, age in months (11 to 15), and the interaction between ejaculate number and days since previous collection included as fixed effects. Estimated heritability was 0.14 for Bw_150d, 0.26 for Bw_330d, and 0.34 for Dwg; the estimated genetic correlations among these traits were all favorable. Both BW traits correlated favorably with all the semen characteristic traits (0.20 to 0.76), whereas Dwg was favorably correlated with volume, Mot24h, Mot48h, and sperm defects, and unfavorably correlated with Conc (-0.25) and Mot0h (-0.53). Our results indicate that the genetic correlations between weight and growth traits and semen characteristics depend on the age of the bulls. Although most genetic correlations were favorable, selection for higher daily weight gain between 150 and 330 d might explain the slight negative genetic trends observed for semen characteristics in young Norwegian Red bulls.


Asunto(s)
Peso Corporal , Bovinos/fisiología , Semen , Aumento de Peso , Animales , Bovinos/genética , Bovinos/crecimiento & desarrollo , Femenino , Inseminación Artificial , Modelos Lineales , Masculino , Noruega , Paridad , Fenotipo , Embarazo , Selección Artificial , Motilidad Espermática , Espermatozoides
3.
J Dairy Sci ; 103(1): 545-555, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31668445

RESUMEN

The aim of this study was to estimate genetic parameters and genetic trends for male fertility in Norwegian Red bulls. We analyzed data on semen characteristics traits collected at the performance test station of young bulls from 1994 to 2016, in an andrology test used to ensure acceptable semen quality before being selected as an artificial insemination bull. Traits included were volume, concentration, and motility (percentage of moving sperm cells) in fresh samples and after storing for 24 and 48 h, and sperm defects. The data consisted of 14,972 ejaculates from 3,927 young (11-15 mo) Norwegian Red bulls. Genetic parameters were estimated using bivariate linear animal models that included age in months, group-year, and collection-group (main effect of the interaction between ejaculate number and interval between collections) as fixed effects, and test-day and additive genetic and permanent environment effect of the bull as random effects. Considerable genetic coefficients of variation were found for concentration and volume, with lower values for motility. Estimated heritabilities ranged from 0.02 and 0.03 (for sperm defects and motility in fresh samples) to 0.14 (volume and concentration measured on a continuous scale). All estimated genetic correlations were favorable, but the genetic correlations between volume and concentration and volume and sperm defects were not significantly different from zero. The genetic correlations between concentration and motility traits ranged from 0.53 to 0.83, and those between volume and the motility traits were between 0.24 and 0.57. All traits showed a slightly unfavorable genetic trend. Our results indicate that selection of bulls with better sperm quality is possible.


Asunto(s)
Bovinos/genética , Análisis de Semen/veterinaria , Semen , Animales , Inseminación Artificial/veterinaria , Masculino , Noruega , Motilidad Espermática , Espermatozoides
4.
J Anim Breed Genet ; 134(2): 144-151, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27488613

RESUMEN

The aim of this study was to evaluate the quality of the data provided from sheepdog trials in Norway, estimate heritabilities, repeatabilities and genetic correlations for the traits included in the trial and make recommendations on how sheepdog trials best can be utilized in the breeding of Border Collies in Norway. The analyses were based on test results from sheepdog trials carried out in Norway from 1993 to 2012. A total of 45 732 records from 3841 Border Collies were available, but after quality assurance only a third was left. The results demonstrated little information in the data. Heritabilities varied between 0.010 and 0.056 with standard errors ranging from 0.010 to 0.023, while repeatabilities ranged from 0.041 to 0.286. There is a need to assure the quality of data to improve the information in the test results. We recommend adding new traits based on the Herding Trait Characterization scheme evaluated in Sweden, and on traits from the predatory motor pattern, regarded as common for all dogs. These new traits may be scored across the elements that make up the current trial system, which should be kept in place to stimulate participation in the genetic evaluation scheme.


Asunto(s)
Cruzamiento , Perros/genética , Perros/fisiología , Animales , Perros/clasificación , Femenino , Masculino , Noruega , Linaje , Conducta Predatoria , Suecia
5.
Clin Exp Immunol ; 177(3): 712-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24773420

RESUMEN

Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.


Asunto(s)
Granulocitos , Leucaféresis , Monocitos , Sarcoidosis/terapia , Adulto , Líquido del Lavado Bronquioalveolar/citología , Femenino , Humanos , Leucaféresis/métodos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Radiografía , Sarcoidosis/diagnóstico por imagen , Sarcoidosis Pulmonar/diagnóstico por imagen , Sarcoidosis Pulmonar/terapia , Subgrupos de Linfocitos T/metabolismo , Resultado del Tratamiento
6.
J Anim Breed Genet ; 130(3): 170-7, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23679942

RESUMEN

The aim of this study was to examine how to apply optimal contribution selection (OCS) in the Norwegian and the North-Swedish cold-blooded trotter and give practical recommendations for the future. OCS was implemented using the software Gencont with overlapping generations and selected a few, but young sires, as these turn over the generations faster and thus is less related to the mare candidates. In addition, a number of Swedish sires were selected as they were less related to the selection candidates. We concluded that implementing OCS is feasible to select sires (there is no selection on mares), and we recommend the number of available sire candidates to be continuously updated because of amongst others deaths and geldings. In addition, only considering sire candidates with phenotype above average within a year class would allow selection candidates from many year classes to be included and circumvent current limitation on number of selection candidates in Gencont (approx. 3000). The results showed that mare candidates can well be those being mated the previous year. OCS will, dynamically, recruit young stallions and manage the culling or renewal of annual breeding permits for stallions that had been previously approved. For the annual mating proportion per sire, a constraint in accordance with the maximum that a sire can mate naturally is recommended.


Asunto(s)
Cruzamiento/métodos , Caballos , Animales , Estudios de Factibilidad , Endogamia , Noruega , Conducta Sexual Animal , Programas Informáticos , Suecia
7.
J Intern Med ; 272(5): 465-71, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22469005

RESUMEN

BACKGROUND: An increased percentage of CD4+ T cells is usually observed in bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis. In HLA-DRB1*03-positive patients, such T cells express the T-cell receptor (TCR) AV2S3+ gene segment. It is not known whether cells found in BALF reflect those in enlarged regional lymph nodes (LNs). Therefore, the aim of this study was to compare T-cell phenotypes in BALF, blood and mediastinal LNs. METHODS: Fifteen patients underwent clinical investigation including bronchoscopy with bronchoalveolar lavage. Blood samples were drawn, and endoscopic ultrasound-guided fine-needle aspiration of enlarged mediastinal LNs was performed via the oesophagus. T cells from all three compartments were analysed by flow cytometry for markers of activity, differentiation and T regulatory function. RESULTS: The CD4/CD8 ratio was significantly higher in BALF compared with regional LNs and was also significantly higher in LNs than in blood. The CD4+ T cells were recently activated and more differentiated in BALF than in blood and LNs. There was an accumulation of T regulatory cells (FOXP3+) in LNs and a correlation between high levels of FOXP3+ cells in BALF and in LNs. In HLA-DRB1*03-positive patients, TCR AV2S3+ CD4+ T cells were predominantly localized within BALF. CONCLUSIONS: The CD4+ T-cell phenotype in BALF indicates an active ongoing specific immune response primarily localized to the alveolar space.


Asunto(s)
Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD4-Positivos/inmunología , Ganglios Linfáticos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Sarcoidosis Pulmonar/inmunología , Adulto , Anciano , Antígenos/genética , Antígenos/inmunología , Broncoscopía/métodos , Estudios de Casos y Controles , Femenino , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/genética , Sarcoidosis Pulmonar/genética , Estadística como Asunto
8.
Vet Pathol ; 49(6): 950-62, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22461225

RESUMEN

Acute respiratory distress syndrome is a common complication in severe sepsis. In pigs, the lungs play an important role in clearing systemic bacterial infections due to pulmonary intravascular macrophages found specifically in pigs. However, this increases the exposure of the porcine lungs to pathogens and potential injury. The authors propose that increasing the concentration of the inoculum without changing the bacterial dose will lead to severe sepsis with pronounced pulmonary lesions. This could potentially create a risk of cytokine spillover to the circulation, leading to an increased systemic response. Eight Danish Landrace pigs, approximately 10 weeks old, were inoculated twice with a low or once with a high concentration of Staphylococcus aureus. Three pigs were sham-inoculated. The animals were grouped based on macro- and microscopic lung lesions. The mRNA expression of local pulmonary inflammatory markers was compared to protein levels of systemic inflammatory markers. The most severe pulmonary lesions were observed in animals receiving the high S. aureus concentration, indicating that severity of lesions is dependent on inoculum concentration rather than total numbers of bacteria. Furthermore, local mRNA expression of inflammatory cytokines appeared to be dependent on the magnitude and severity of tissue destruction, including the ability to confine the lesions. Increasing mRNA levels of serum amyloid A could be a confident marker of severity of pulmonary lesions. Since no correlation was observed between local and systemic levels of inflammatory cytokines, this finding could indicate an ability of the porcine lung to compartmentalize the local inflammatory response and thus restrict systemic contribution.


Asunto(s)
Citocinas/metabolismo , Síndrome de Dificultad Respiratoria/veterinaria , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus/fisiología , Enfermedades de los Porcinos/patología , Animales , Carga Bacteriana , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Femenino , Pulmón/metabolismo , Pulmón/microbiología , Pulmón/patología , Ganglios Linfáticos/patología , Macrófagos Alveolares/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/microbiología , Síndrome de Dificultad Respiratoria/patología , Sepsis , Índice de Severidad de la Enfermedad , Organismos Libres de Patógenos Específicos , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Sus scrofa , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/microbiología
9.
J Anim Breed Genet ; 129(2): 164-70, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22394238

RESUMEN

There have been several approaches to the estimation of breeding values of performance in trotters, and the objective of this study was to validate different alternatives for genetic evaluation of racing performance in the North Swedish and Norwegian cold-blooded trotters. The current bivariate approach with the traits racing status (RACE) and earnings (EARN) was compared with a threshold-linear animal model and the univariate alternative with the performance trait only. The models were compared based on cross-validation of standardized earnings, using mean-squared errors of prediction (MSEP) and the correlation between the phenotype (Y) and the estimated breeding value (EBV). Despite possible effects of selection, a rather high estimate of heritability of EARN was found in our univariate analysis. The genetic trend estimate for EARN was clearly higher in the bivariate specification than in the univariate model, as a consequence of the considerable size of estimated heritability of RACE and its high correlation with EARN (approximately 0.8). RACE is highly influenced by ancestry rather than the on-farm performance of the horse itself. Consequently, the use of RACE in the genetic analysis may inflate the genetic trend of EARN because of a double counting of pedigree information. Although, because of the higher predictive ability of the bivariate specification, the improved ranking of animals within a year-class and the inability to discriminate between models for genetic trend, we propose to base prediction of breeding values on the current bivariate model.


Asunto(s)
Caballos/genética , Condicionamiento Físico Animal , Animales , Femenino , Modelos Lineales , Masculino , Linaje , Deportes
10.
Anim Genet ; 42(5): 457-65, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21906097

RESUMEN

Mastitis is the most frequent and costly disease in dairy production and solutions leading to a reduction in the incidence of mastitis are highly demanded. Here a genome-wide association study was performed to identify polymorphisms affecting susceptibility to mastitis. Genotypes for 17 349 SNPs distributed across the 29 bovine autosomal chromosomes from a total of 2589 sires with 1 389 776 daughters with records on clinical mastitis were included in the analysis. Records of occurrence of clinical mastitis were divided into seven time periods in the first three lactations in order to identify quantitative trait loci affecting mastitis susceptibility in particular phases of lactation. The most convincing results from the association mapping were followed up and validated by a combined linkage disequilibrium and linkage analysis. The study revealed quantitative trait loci affecting occurrence of clinical mastitis in the periparturient period on chromosomes 2, 6 and 20 and a quantitative trait locus affecting occurrence of clinical mastitis in late lactation on chromosome 14. None of the quantitative trait loci for clinical mastitis detected in the study seemed to affect lactation average of somatic cell score. The SNPs highly associated with clinical mastitis lie near both the gene encoding interleukin 8 on chromosome 6 and the genes encoding the two interleukin 8 receptors on chromosome 2.


Asunto(s)
Estudio de Asociación del Genoma Completo , Mastitis Bovina/genética , Sitios de Carácter Cuantitativo , Animales , Bovinos , Cromosomas de los Mamíferos , Femenino , Predisposición Genética a la Enfermedad , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple
11.
Anim Genet ; 42(5): 466-74, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21906098

RESUMEN

Reproductive performance is a critical trait in dairy cattle. Poor reproductive performance leads to prolonged calving intervals, higher culling rates and extra expenses related to multiple inseminations, veterinary treatments and replacements. Genetic gain for improved reproduction through traditional selection is often slow because of low heritability and negative correlations with production traits. Detection of DNA markers associated with improved reproductive performance through genome-wide association studies could lead to genetic gain that is more balanced between fertility and production. Norwegian Red cattle are well suited for such studies, as very large numbers of detailed reproduction records are available. We conducted a genome-wide association study for non-return rate, fertility treatments and retained placenta using almost 1 million records on these traits and 17 343 genome-wide single-nucleotide polymorphisms. Genotyping costs were minimized by genotyping the sires of the cows recorded and by using daughter averages as phenotypes. The genotyped sires were assigned to either a discovery or a validation population. Associations were only considered to be validated if they were significant in both groups. Strong associations were found and validated on chromosomes 1, 5, 8, 9, 11 and 12. Several of these were highly supported by findings in other studies. The most important result was an association for non-return rate in heifers in a region of BTA12 where several associations for milk production traits have previously been found. Subsequent fine-mapping verified the presence of a quantitative trait loci (QTL) having opposing effects on non-return rate and milk production at 18 Mb. The other reproduction QTL did not have pleiotropic effects on milk production, and these are therefore of considerable interest for use in marker-assisted selection.


Asunto(s)
Bovinos/genética , Estudio de Asociación del Genoma Completo , Lactancia , Sitios de Carácter Cuantitativo , Reproducción , Animales , Bovinos/fisiología , Femenino , Masculino , Leche , Embarazo
12.
Pharmacogenomics J ; 10(6): 513-23, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20157331

RESUMEN

The dose of docetaxel is currently calculated based on body surface area and does not reflect the pharmacokinetic, metabolic potential or genetic background of the patients. The influence of genetic variation on the clearance of docetaxel was analysed in a two-stage analysis. In step one, 583 single-nucleotide polymorphisms (SNPs) in 203 genes were genotyped on samples from 24 patients with locally advanced non-small cell lung cancer. We found that many of the genes harbour several SNPs associated with clearance of docetaxel. Most notably these were four SNPs in EGF, three SNPs in PRDX4 and XPC, and two SNPs in GSTA4, TGFBR2, TNFAIP2, BCL2, DPYD and EGFR. The multiple SNPs per gene suggested the existence of common haplotypes associated with clearance. These were confirmed with detailed haplotype analysis. On the basis of analysis of variance (ANOVA), quantitative mutual information score (QMIS) and Kruskal-Wallis (KW) analysis SNPs significantly associated with clearance of docetaxel were confirmed for GSTA4, PRDX4, TGFBR2 and XPC and additional putative markers were found in CYP2C8, EPHX1, IGF2, IL1R2, MAPK7, NDUFB4, TGFBR3, TPMT (2 SNPs), (P<0.05 or borderline significant for all three methods, 14 SNPs in total). In step two, these 14 SNPs were genotyped in additional 9 samples and the results combined with the genotyping results from the first step. For 7 of the 14 SNPs, the results are still significant/borderline significant by all three methods: ANOVA, QMIS and KW analysis strengthening our hypothesis that they are associated with the clearance of docetaxel.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Especies Reactivas de Oxígeno/metabolismo , Taxoides/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel , Haplotipos , Humanos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Taxoides/metabolismo
13.
Acta Anaesthesiol Scand ; 54(4): 430-4, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19878101

RESUMEN

BACKGROUND: In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical-grade albumin influence the albumin-binding capacity for highly protein-bound drugs. However, the half-life of the stabilizers and the quantitative effect have been difficult to determine. METHOD: A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N-acetyl-DL-tryptophan, caprylate, and naproxen. RESULTS: The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N-acetyl-DL-tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N-acetyl-DL-tryptophan had a half-life of approximately 30 min. The half-life of caprylate was <15 min. CONCLUSION: A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free-fraction naproxen decreased together with the detectable levels of the stabilizers N-acetyl-DL-tryptophan and caprylate. N-acetyl-DL-tryptophan and caprylate have a short half-life in serum.


Asunto(s)
Albúminas/farmacología , Antiinflamatorios no Esteroideos/farmacocinética , Naproxeno/farmacocinética , Adulto , Albúminas/administración & dosificación , Caprilatos/farmacocinética , Estudios Cruzados , Femenino , Semivida , Humanos , Inmunohistoquímica , Indicadores y Reactivos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Excipientes Farmacéuticos , Resultado del Tratamiento , Triptófano/análogos & derivados , Triptófano/farmacocinética , Adulto Joven
14.
Anim Genet ; 41(3): 273-80, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19968646

RESUMEN

Dystocia and stillbirth are significant causes of female and neonatal death in many species and there is evidence for a genetic component to both traits. Identifying causal mutations affecting these traits through genome wide association studies could reveal the genetic pathways involved and will be a step towards targeted interventions. Norwegian Red cattle are an ideal model breed for such studies as very large numbers of records are available. We conducted a genome wide association study for direct and maternal effects of dystocia and stillbirth using almost 1 million records of these traits. Genotyping costs were minimized by genotyping the sires of the recorded cows, and using daughter averages as phenotypes. A dense marker map containing 17,343 single nucleotide polymorphisms covering all autosomal chromosomes was utilized. The genotyped sires were assigned to one of two groups in an attempt to ensure independence between the groups. Associations were only considered validated if they occurred in both groups. Strong associations were found and validated on chromosomes 4, 5, 6, 9, 12, 20, 22 and 28. The QTL region on chromosome 6 was refined using LDLA analysis. The results showed that this chromosome most probably contains two QTL for direct effect on dystocia and one for direct effect on stillbirth. Several candidate genes may be identified close to these QTL. Of these, a cluster of genes expected to affect bone and cartilage formation (i.e. SPP1, IBSP and MEPE) are of particular interest and we suggest that these genes are screened in candidate gene studies for dystocia and stillbirth in cattle as well as other species.


Asunto(s)
Enfermedades de los Bovinos/genética , Distocia/veterinaria , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Mortinato/veterinaria , Animales , Bovinos , Distocia/genética , Femenino , Polimorfismo de Nucleótido Simple , Embarazo
15.
Science ; 247(4944): 845-8, 1990 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-2406903

RESUMEN

A region in the human immunodeficiency virus (HIV) env message, with the potential to form a complex secondary structure (designated RRE), interacts with the rev protein (Rev). This interaction is believed to mediate export of HIV structural messenger RNAs from the nucleus to the cytoplasm. In this report the regions essential for Rev interaction with the RRE are further characterized and the functional significance of Rev-RRE interaction in vivo is examined. A single hairpin loop structure within the RRE was found to be a primary determinant for Rev binding in vitro and Rev response in vivo. Maintenance of secondary structure, rather than primary nucleotide sequence alone, appeared to be necessary for Rev-RNA interaction, which distinguishes it from the mechanism for cis-acting elements in DNA. Limited changes within the 200 nucleotides, which preserved the proper RRE conformational structure, were well tolerated for Rev binding and function. Thus, variation among the RRE elements present in the diverse HIV isolates would have little, if any, effect on Rev responsiveness.


Asunto(s)
Productos del Gen rev/metabolismo , VIH/genética , ARN Mensajero/genética , Transactivadores/metabolismo , Composición de Base , Secuencia de Bases , Deleción Cromosómica , Productos del Gen rev/genética , Genes rev , VIH/metabolismo , Datos de Secuencia Molecular , Mutación , Conformación de Ácido Nucleico , Plásmidos , Conformación Proteica , ARN Mensajero/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Productos del Gen rev del Virus de la Inmunodeficiencia Humana
16.
Science ; 285(5425): 260-3, 1999 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-10398604

RESUMEN

The tumor necrosis factor (TNF) superfamily of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. A member of the human TNF family, BLyS (B lymphocyte stimulator), was identified that induced B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes could be up-regulated by interferon-gamma. Soluble BLyS functioned as a potent B cell growth factor in costimulation assays. Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations. The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation.


Asunto(s)
Linfocitos B/inmunología , Activación de Linfocitos , Proteínas de la Membrana/fisiología , Monocitos/inmunología , Factor de Necrosis Tumoral alfa/fisiología , Secuencia de Aminoácidos , Animales , Factor Activador de Células B , Receptor del Factor Activador de Células B , Subgrupos de Linfocitos B/inmunología , Línea Celular , Células Cultivadas , Humanos , Inmunoglobulinas/sangre , Interferón gamma/farmacología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/farmacología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Receptores de Citocinas/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Proteínas Recombinantes/farmacología , Alineación de Secuencia , Especificidad de la Especie , Factor de Necrosis Tumoral alfa/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba
17.
Anim Genet ; 40(5): 701-12, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19466933

RESUMEN

Quantitative trait loci affecting clinical mastitis were detected and fine mapped to a narrow region on bovine chromosome 6 in the Norwegian Red cattle population. The region includes the casein gene cluster and several candidate genes thought to influence clinical mastitis. The most significant results were found for SNPs within the Mucin 7 gene. This gene encodes an antimicrobial peptide and constitutes part of the first line of defence for the mucosal immune system. Detection of long haplotypes extending several Mb may indicate that artificial selection has influenced the haplotype structures in the region. A search for selection sweeps supports this observation and coincides with association results found both by single SNP and haplotype analyses. Our analyses identified haplotypes carrying quantitative trait loci alleles associated with high protein yield and simultaneously fewer incidences of clinical mastitis. The fact that such haplotypes are found in relative high frequencies in Norwegian Red may reflect the combined breeding goal that is characterized by selection for both milk production and disease resistance. The identification of these haplotypes raises the possibility of overcoming the unfavourable genetic correlation between these traits through haplotype-assisted selection.


Asunto(s)
Mapeo Cromosómico/veterinaria , Mastitis Bovina/genética , Sitios de Carácter Cuantitativo/genética , Animales , Bovinos , Femenino , Marcadores Genéticos/genética , Haplotipos/genética , Desequilibrio de Ligamiento/genética , Mastitis Bovina/patología , Polimorfismo de Nucleótido Simple , Selección Genética
18.
J Pediatr Urol ; 15(4): 322-329, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31227314

RESUMEN

The investigation, management and follow-up of paediatric ureteropelvic junction obstruction is not standardized. The Young Pediatric Urology Committee of the European Society of Pediatric Urology interviewed five experts in the field on various aspects of management and compared this with published literature.


Asunto(s)
Manejo de la Enfermedad , Laparoscopía/métodos , Procedimientos de Cirugía Plástica/métodos , Obstrucción Ureteral/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Niño , Humanos , Pelvis Renal , Imagen por Resonancia Magnética , Ultrasonografía , Obstrucción Ureteral/diagnóstico
19.
Acta Anaesthesiol Scand ; 52(3): 406-12, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18269390

RESUMEN

BACKGROUND: In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs. METHODS: A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin. RESULTS: During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged. CONCLUSIONS: Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters.


Asunto(s)
Albúminas/metabolismo , Digitoxina/metabolismo , Naproxeno/metabolismo , Preparaciones Farmacéuticas/metabolismo , Warfarina/metabolismo , Adulto , Anciano , Albúminas/administración & dosificación , Femenino , Humanos , Derivados de Hidroxietil Almidón/administración & dosificación , Derivados de Hidroxietil Almidón/efectos adversos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Sustitutos del Plasma/administración & dosificación , Sustitutos del Plasma/efectos adversos , Unión Proteica , Procedimientos Quirúrgicos Operativos
20.
Anim Genet ; 39(2): 105-11, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18241301

RESUMEN

The extent and pattern of linkage disequilibrium (LD) between closely spaced markers contain information about population history, including past population size and selection history. Selection signatures can be identified by comparing the LD surrounding a putative selected allele at a locus to the putative non-selected allele. In livestock populations, locations of selection signatures identified in this way should be correlated with QTL affecting production traits, as the populations have been under strong artificial selection for these traits. We used a dense SNP map of bovine chromosome 6 to characterize the pattern of LD on this chromosome in Norwegian Red cattle, a breed which has been strongly selected for milk production. The pattern of LD was generally consistent with strong selection in regions containing QTL affecting milk production traits, including a strong selection signature in a region containing a mutation known to affect milk production. The results demonstrate that in livestock populations, the origin of selection signatures will often be QTL for livestock production traits, and illustrate the value of selection signatures in uncovering new mutations with potential effects on quantitative traits.


Asunto(s)
Bovinos/genética , Mapeo Cromosómico , Polimorfismo de Nucleótido Simple , Selección Genética , Animales , Simulación por Computador , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Desequilibrio de Ligamiento , Masculino , Modelos Genéticos , Noruega , Reproducción/genética
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