bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning and characterization of the bovine EGR4 gene and evaluation as candidate gene for bovine spinal dysmyelination
Authors: Nissen P. H. , Thomsen B. , Offenberg H. , Thomsen P. D. , Bendixen C. 
Published: December 2004

SummaryGenes of the early growth response (EGR) family encode transcription factors with a highly conserved DNA binding zinc finger domain, which regulate a variety of genes, e.g. late myelin genes. Here, the cloning, genomic structure and expression of the bovine orthologue of the EGR4 gene are reported. The gene consists of two exons and encodes a 482 amino acid protein with a Cys2His2 zinc finger structure. The predicted protein shares between 80 and 87% identity to mouse, rat and human EGR4 proteins and all four species share almost complete identity in the DNA‐binding domain. The bovine transcript is alternatively spliced by retaining intronic sequence, giving rise to two different mRNAs differing in three nucleotides and resulting in an extra alanine residue in the longer variant of the predicted protein. The gene was mapped by radiation hybrid (RH) mapping to markers on bovine chromosome 11. EGR4 transcripts were detected by reverse transcriptase polmerase chain reaction (RT‐PCR) in the frontal cortex and cerebellum, and a low expression level was also detected in the liver. The EGR4 gene was evaluated as a candidate gene for bovine spinal dysmyelination (BSD). Sequencing of the gene from a homozygous affected animal and a heterozygous carrier revealed a single base mutation that leads to an amino acid substitution at residue 322 in EGR4. Genotype analysis of this polymorphism in a pedigree segregating for BSD, as well as in a panel of different cattle breeds, and sequence analysis of the entire coding region suggested that the EGR4 is not the gene responsible for BSD. Furthermore, 87 animals of different cattle breeds were screened for single‐nucleotide polymorphisms (SNPs) resulting in the identification of two SNPs in EGR4.
Identification of quantitative trait loci for growth and carcass composition in cattle1
Authors: Casas E. , Keele J. W. , Shackelford S. D. , Koohmaraie M. , Stone R. T. 
Published: December 2004

SummaryA genomic screening to detect quantitative trait loci (QTL) affecting growth, carcass composition and meat quality traits was pursued. Two hundred nineteen microsatellite markers were genotyped on 176 of 620 (28%) progeny from a Brahman × Angus sire mated to mostly MARC III dams. Selective genotyping, based on retail product yield (%) and fat yield (%), was used to select individuals to be genotyped. Traits included in the study were birth weight (kg), hot carcass weight (kg), retail product yield, fat yield, marbling score (400 = slight00 and 500 = small00), USDA yield grade, and estimated kidney, heart and pelvic fat (%). The QTL were classified as significant when the expected number of false positives (ENFP) was less than 0.05 (F‐statistic greater than 17.3), and suggestive when the ENFP was <1 (F‐statistic between 10.2 and 17.3). A significant QTL (F = 19; ENFP = 0.02) was detected for marbling score at centimorgan (cM) 54 on chromosome 2. Suggestive QTL were detected for fat yield at 50 cM, for retail product yield at 53 cM, and for USDA yield grade at 63 cM on chromosome 1, for marbling score at 56 cM, for retail product yield at 70 cM, and for estimated kidney, heart and pelvic fat at 79 cM on chromosome 3, for marbling score at 44 cM, for hot carcass weight at 49 cM, and for estimated kidney, heart and pelvic fat at 62 cM on chromosome 16, and for fat yield at 35 cM on chromosome 17. Two suggestive QTL for birth weight were identified, one at 12 cM on chromosome 20 and the other at 56 cM on chromosome 21. An additional suggestive QTL was detected for retail product yield, for fat yield, and for USDA yield grade at 26 cM on chromosome 26. Results presented here represent the initial search for quantitative trait loci in this family. Validation of detected QTL in other populations will be necessary.
Genetic markers applied in regression tree prediction models
Authors: Hizer S. E. , Wright T. M. , Garcia D. K. 
Published: December 2004

SummaryClassification and regression tree (CART) modelling was used to determine infectious hypodermal and haematopoietic necrosis virus (IHHNV) resistance and susceptibility in Penaeus stylirostris. In a previous study, eight random amplified polymorphic DNA (RAPD) markers and viral load values using real‐time quantitative PCR were obtained and used as the training data set in order to create numerous regression tree models. Specifically, the genetic markers were used as categorical predictor variables and viral load values as the dependent response variable. To determine which model has the highest predictive accuracy for future samples, RAPD fingerprint data was generated from new Penaues stylirostris IHHNV resistant and susceptible individuals and used to test the regression models. The best performing tree was a four terminal node tree with three genetic markers as significant variables. Marker‐assisted breeding practices may benefit from the creation of regression tree models that apply genetic markers as predictive factors. To our knowledge this is the first study to use RAPD markers as predictors within a CART prediction model to determine viral susceptibility.
Mapping of bovine ovulation rate QTL; an analytical approach for three generation pedigrees
Authors: Arias J. , Kirkpatrick B. 
Published: December 2004

SummaryInterval mapping was conducted for ovulation rate quantitative trait loci (QTL) using data from two related families from the United States Department of Agriculture, US Meat Animal Research Center twinning cattle herd. Both families are extended, three generation pedigrees from which records of sons, daughters and granddaughters were analysed. Both a method of analysis and results from that analysis are reported herein. Results from one of the two families (839802) were previously reported, but reanalysis here including the second, related family (839803) and a revised statistical model lessens support for the previously reported QTL. Results from interval mapping provided evidence for QTL in regions corresponding to those previously suggested for chromosomes 7 (chromosome‐wise P < 0.05) and 19 (chromosome‐wise P < 0.01) in the 839802 family, although statistical significance was reduced. In contrast to the previous report, evidence for a chromosome 5 QTL in the same family was greatly reduced while support for a QTL on chromosome 10 increased (chromosome‐wise P < 0.01). Analysis of data from the related 839803 family failed to replicate evidence of QTL observed on either chromosome 7 or chromosome 19 in the 839802 family.
Detection and characterization of SNPs useful for identity control and parentage testing in major European dairy breeds
Authors: Werner F. A. O. , Durstewitz G. , Habermann F. A. , Thaller G. , Krämer W. , Kollers S. , Buitkamp J. , Georges M. , Brem G. , Mosner J. , Fries R. 
Published: December 2004

SummaryWe propose the use of single nucleotide polymorphisms (SNPs) instead of polymorphic microsatellite markers for individual identification and parentage control in cattle. To this end, we present an initial set of 37 SNP markers together with a gender‐specific SNP for identity control and parentage testing in the Holstein, Fleckvieh and Braunvieh breeds. To obtain suitable SNPs, a total of 91.13 kb of random genomic DNA was screened yielding 531 SNPs. These, and 43 previously identified SNPs, were subjected to the following selection criteria: (1) the frequency of the minor allele must be larger than 0.1 in at least two of the three examined breeds, and (2) markers should not be linked closely. Allele frequencies were estimated by analysing sequencing traces of pooled DNA or by genotyping individual DNA samples. The selected SNP loci were physically mapped by radiation hybrid mapping or by fluorescence in situ hybridization, and tested against the neutral mutation hypothesis. The presented marker set theoretically allows probabilities of identity less than 10−13 for individual verification and exclusion powers exceeding 99.99% for parentage testing.
Power of exclusion for parentage verification and probability of match for identity in American kennel club breeds using 17 canine microsatellite markers
Authors: DeNise S. , Johnston E. , Halverson J. , Marshall K. , Rosenfeld D. , McKenna S. , Sharp T. , Edwards J. 
Published: December 2004

SummaryDNA analysis of microsatellite markers has become a common tool for verifying parentage in breed registries and identifying individual animals that are linked to a database or owner. Panels of markers have been developed in canines, but their utility across and within a wide range of breeds has not been reported. The American Kennel Club (AKC) authorized a study to determine the power to exclude non‐parents and identify individuals using DNA genotypes of 17 microsatellite markers in two panels. Cheek swab samples were voluntarily collected at Parent Breed Club National Specialty dog shows and 9561 samples representing 108 breeds were collected, averaging 88.5 dogs per breed. The primary panel of 10 markers exceeded 99% power of exclusion for canine parentage verification of 61% of the breeds. In combination with the secondary panel of seven markers, 100% of the tested breeds exceeded 99% power of exclusion. The minimum probability match rate of the first panel was 3.6 × 10−5 averaged across breeds, and with the addition of the second panel, the probability match rate was 3.2 × 10−8; thus the probability of another random, unrelated dog with the same genotype is very low. The results of this analysis indicated that, on average, the primary panel meets the AKC's needs for routine parentage testing, but that a combination of 10–15 genetic markers from the two panels could yield a universal canine panel with enhanced processing efficiency, reliability and informativeness.
Development and linkage relationships for new microsatellite markers of the sea bass (Dicentrarchus labrax L.)
Authors: Chistiakov D. A. , Hellemans B. , Tsigenopoulos C. S. , Law A. S. , Bartley N. , Bertotto D. , Libertini A. , Kotoulas G. , Haley C. S. , Volckaert F. A. M. 
Published: December 2004

SummaryTwenty‐eight polymorphic microsatellites were isolated from the sea bass, Dicentrarchus labrax, using a microsatellite enrichment protocol and selective hybridization with oligonucleotide probes. Analysis for these markers and 11 recently described microsatellites of D. labrax found linkage between 26 loci and revealed eight linkage groups.
Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects
Authors: Spina E. , Avenoso A. , Campo G. M. , Scordo M. G. , Caputi A. P. , Perucca E. 
Published: December 2004

Aims The aim of the study was to characterize further the role of CYP3A4 in the metabolism of tricyclic antidepressants. Methods The effect of oral ketoconazole (200 mg day−1 for 14 days) on the kinetics of a single oral dose of imipramine (100 mg) and desipramine (100 mg) was evaluated in two groups of six healthy male subjects. Results Ketoconazole administration was associated with a decrease in imipramine apparent oral clearance (from 1.16±0.21 to 0.96±0.20 l h−1 kg−1, mean±s.d.; ‘of2\P<0.02), a prolongation in imipramine half‐life (from 16.7±3.3 to 19.2±5.4 h, ‘of2\P<0.05) and a decrease in area under the curve of metabolically derived desipramine (from 3507±1707 to 3180±1505 nmol l−1 h, P<0.05), whereas concentrations of 2‐hydroxy‐imipramine were unaffected. In the subjects given desipramine, no significant changes in desipramine and 2‐hydroxy‐desipramine kinetics were observed during ketoconazole treatment. Conclusions These findings indicate that ketoconazole, a relatively specific inhibitor of CYP3A4, inhibits the N‐demethylation of imipramine without affecting the 2‐hydroxylation of imipramine and desipramine. This interaction, confirms that CYP3A4 plays a role in the demethylation of tricyclic antidepressants.
Effects of frusemide and hypoxia on the pulmonary vascular bed in man
Authors: Kiely David G. , Cargill Robert I. , Lipworth Brian J. 
Published: December 2004

Aims Diuretic therapy is conventionally used to treat oedema in patients with hypoxic cor pulmonale. This condition is associated with activation of the renin angiotensin system (RAS) with elevated levels of angiotensin II (ANG II), a potent pulmonary pressor agent. We explored the hypothesis that RAS activation by diuretic therapy might therefore worsen hypoxic pulmonary vasoconstriction via the effects of ANG II on the pulmonary vascular bed. Methods Eight normal volunteers were studied on 2 separate days. They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic, by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85–90% adjusted for a further 20 min to achieve an SaO2 of 75–80%. Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure, cardiac output and hence pulmonary vascular resistance (PVR). Results Plasma renin activity (PRA) was significantly (P<0.01) increased after prior treatment with frusemide compared with placebo at all time points. Prior treatment with frusemide significantly (P<0.05) increased PVR compared with placebo at baseline: 185±17 vs 132±10 dyn s cm−5 at an SaO2 of 85–90%: 291±18 vs 229±16 dyn s cm−5 and at SaO2 of 75–80%: 356±12 vs 296±17 dyn s cm−5 respectively. However, the delta‐PVR response to hypoxaemia was not significantly altered by frusemide compared with placebo. In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not significantly alter systemic haemodynamic parameters either at baseline or during hypoxia.. Conclusions Thus, prior treatment with frusemide increased baseline pulmonary vascular resistance and significantly augmented the hypoxaemic pulmonary vascular response in additive fashion. It is hypothesised that this effect of frusemide may be due to RAS activation with ANG II mediated pulmonary vasoconstriction.
Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization
Authors: Robinson Robert T. C. E. , Harris Nigel D. , Ireland Robert H. , Lindholm Anders , Heller Simon R. 
Published: December 2004

Aims
Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.
Methods
A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4–6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter‐regulatory hormones.
Results
The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h−1 kg−1, IAsp mean ± s.d. 1.22 ± 0.32 l h−1 kg−1). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 ± 0.01 to 4.87 ± 0.48 nm, P < 0.001, IAsp, 0.24 ± 0.01 to 4.99 ± 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 ± 0.3 to 4.2 ± 0.2 mm, P < 0.001, IAsp, 4.2 ± 0.3 to 4.2 ± 0.3 mm, P < 0.001).
Conclusions
Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia‐induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.
The distribution and gender difference of CYP3A activity in Chinese subjects
Authors: Zhu Bing , Liu Zhao‐Qian , Chen Guo‐Lin , Chen Xiao‐Ping , Ou‐Yang Dong‐Sheng , Wang Lian‐Sheng , Huang Song‐Lin , Tan Zhi‐Rong , Zhou Hong‐Hao 
Published: December 2004

Aims
To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender‐related differences in CYP3A activity.
Methods
Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1′‐hydroxymidazolam:midazolam (1′‐OH‐MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1′‐OH‐MDZ and MDZ in plasma were measured by HPLC
Results
A 13‐fold variation of CYP3A activity (log1′‐OH‐MDZ:MDZ: range −0.949–0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov–Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: −0.36 vs−0.43, P < 0.05; 95% CI for difference: −0.127, −0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05).
Conclusions
A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle.
Systemic bioactivity of intranasal triamcinolone and mometasone in perennial allergic rhinitis
Authors: Lee Daniel K. C. , Robb Fiona M. , Sims Erika J. , Currie Graeme P. , McFarlane Lesley C. , Lipworth Brian J. 
Published: December 2004

Aims
To evaluate the systemic bioactivity of triamcinolone acetonide (TA) 220 µg or mometasone furoate (MF) 200 µg over 3 weeks in perennial allergic rhinitis.
Methods
Twenty‐seven patients received TA 220 µg or MF 200 µg once daily for 3 weeks with a 2 week placebo washout period prior to each randomized treatment. Measurements were made at baseline after each washout and after each randomized treatment, comprising overnight 10‐h urinary cortisol corrected for creatinine (OUCC), 08.00 h plasma cortisol and 08.00 h serum osteocalcin.
Results
There were no significant differences between baseline values prior to TA or MF, and for any outcome measures comparing randomized treatments to respective baseline values or comparing TA with MF. For OUCC compared with baseline, the geometric mean fold suppression (95% CI) was 1.02 (0.78, 1.33) for TA (2% decrease), 1.07 (0.80, 1.42) for MF (7% decrease), and 1.05 (0.79, 1.39) for TA vs MF (5% decrease).
Conclusions
Standard doses of TA or MF over 3 weeks showed no differences in systemic bioactivity markers compared with respective baseline values after placebo washout, and there were no differences between TA vs MF.
Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease
Authors: Singh S. D. , Whale C. , Houghton N. , Daley‐Yates P. , Kirby S. M. , Woodcock A. A. 
Published: December 2004

Aims  We have previously shown that the systemic exposure to inhaled fluticasone propionate (FP) is reduced in asthmatics compared with healthy subjects. We have now compared its pharmacokinetics in patients suffering from chronic obstructive pulmonary disease (COPD, n = 10) and matched healthy subjects (n = 13).Methods  A double‐blind, randomized, cross‐over study design was used. Plasma FP and serum cortisol were measured for 12 h after subjects received hydrofluoroalkane FP 1000 µg day−1 inhaled (via an MDI and spacer) for 7 days and following a single 1000‐µg intravenous dose.Results  The pharmacokinetics differed in the two groups. After inhalation, geometric least square means were significantly lower in the COPD group for the plasma AUC (1961 vs 2996 pg ml−1 h−1 for COPD and controls, respectively; P = 0.03) and the Cmax (235 vs 421 pg ml−1 for COPD and controls, respectively; P = 0.03). Suppression of serum cortisol concentration over 12 h was greater in healthy controls. Weighted mean serum cortisol concentration (nmol l−1) in healthy subjects and COPD was 93 and 170, respectively (P = 0.03). The intravenous pharmacokinetic parameters for FP were comparable in the two groups, resulting in similar suppression of serum cortisol.Conclusions  We conclude that the altered pharmacokinetics of inhaled fluticasone propionate in COPD caused less hypothalamic–pituitary–adrenal suppression than in healthy controls. This is further evidence that the systemic effects of inhaled corticosteroids should be assessed in patients and not healthy subjects.
Arylamine N‐acetyltransferase‐2 genotypes in the Thai population
Authors: Kukongviriyapan Veerapol , Prawan Auemduan , Tassaneyakul Wichittra , Aiemsa‐ard Jareerat , Warasiha Benjamart 
Published: December 2004

Aims
To determine the frequencies of the major arylamine‐ N‐acetyltransferase‐2 (NAT2) alleles in the Thai population.
Methods
DNA samples from 235 Thai individuals were analysed by polymerase chain reaction with restriction fragment length polymorphism assays.
Results
The frequency distribution of major NAT2 alleles, including NAT2*4, NAT2*5, NAT2*6 and NAT2*7 were 0.381 (95% CI 0.337, 0.426), 0.038 (0.023, 0.060), 0.326 (0.283, 0.370) and 0.204 (0.169, 0.244), respectively. When converted to phenotypes, the study population comprised 63.8% rapid acetylators and 36.2% slow acetylators.
Conclusions
The pattern of NAT2 alleles of Thais is similar to those of many Asian populations, although the frequency of NAT2*4 is significantly lower and NAT2*7 is higher than that of Oriental populations.