Effect of growth-promoting 17ß estradiol, 19 nortestosterone and dexamethasone on circulating levels of nine potential biomarker candidates in veal calves

The use of screening methods based on the detection of biological effects of growth promoters is a promising approach to assist residue monitoring. To reveal useful effects on protein metabolism, male and female veal calves at 10 weeks of age were treated thrice with a combination of 25 mg 17ß-estradiol 3-benzoate and 150 mg 19-nortestosterone decanoate with 2 weeks intervals and finally once with 4 mg dexamethasone. Hormone-treated calves showed a significant accelerated growth rate over 6 weeks. Plasma samples of treated and control calves were analysed for immunoreactive inhibin (ir-inhibin), osteocalcin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), IGFBP-3, luteinzing hormone (LH), follicle-stimulating hormone (FSH) and prolactin using immunoaffinity assays. Hormone treatment did not affect levels of IGF-1, IGFBP-2, IGFBP-3, LH, FSH and prolactin. The concentration of circulating ir-inhibin decreased, however, significantly (P < 0.05) in bull calves upon administration of the sex steroids, whereas it remained unchanged in the female animals. Dexamethasone treatment decreased significantly (P < 0.05) circulating levels of osteocalcin in both female and male animals. Ir-inhibin and osteocalcin were, therefore, considered as candidates for a protein biomarker-based screening assay for detection of abuse of estrogens, androgens and/or glucocorticoids in cattle fattening, which is being developed in the framework of EU research project BioCop

Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Objectives: We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).
Background: Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.
Methods: The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.
Results: A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of <2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups.
Conclusions: The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

Mutation altering the miR-184 seed region causes keratoconus with cataract

MicroRNAs (miRNAs) bind to complementary sequences within the 3? untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract, by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3? UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue-specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs may aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.

Sense of coherence and psychiatric morbidity: a 19-year register-based prospective study

Background Most prospective studies on the relationship between sense of coherence (SOC) and mental health have been conducted using subjective health indicators and short-term follow-ups. The objective of this prospective occupational cohort study was to examine whether a strong sense of coherence is a protective factor against psychiatric disorders over a long period of time.

Comparison of two polyclonal antibodies for the detection of 19-nortestosterone in bovine bile by ELISA

19-Nortestosterone (beta-NT) is banned for use as a growth promoter in food animals within the European Union. For regulatory control purposes, urine and bile samples are routinely screened by immunoassay. The aim of the present study was to compare the ability of two immunoassays, using two rabbit polyclonal antibodies raised against two different NT derivatives, to detect NT residues in bovine bile. One antiserum cross-reacted with both alpha-NT and beta-NT (alpha/beta-NT), whereas the other was specific for alpha-NT. Bile samples from 266 slaughtered cattle were deconjugated and analyzed using both antibodies, with all screening positives (>2 ng ml(-1)) confirmed by high resolution gas chromatography mass spectrometry. The alpha/beta-NT and alpha-NT antibody-based ELISAs screened 39 and 44 samples positive, respectively, with NT confirmed in 22 and 39, respectively. The alpha/beta-NT antibody-based ELISA produced a false-negative rate of 44% compared to 0% for the alpha-NT antibody-based ELISA. Supplementary investigations concluded that a matrix effect was a major cause of the marked differences in false-negative rates. This result underlines the necessity to validate immunoassays in the sample matrix.

Observation of high transient gain in the germanium x-ray laser at 19.6 nm

The transient-excitation pumping scheme, in which a picosecond duration pulse rapidly heats the plasma preformed by a low-intensity nanosecond pulse, was used to pump the Ne-like germanium, J = 0-1 transition at 19.6 nm. A small-signal gain coefficient of 30 cm(-1) was measured for targets less than or equal to 5 mm long. (C) 1998 Optical Society of America.

A study to optimise the temporal drive pulse structure for efficient XUV lasing on the J=0-1, 19.6 nm line of Ge XXIII

Short pulses of 100 ps FWHM duration at 1.06 mu m wavelength are used as the pump source for driving the J = 0-1, 19.6 nm, Ne-like germanium X-ray laser. Different combinations of short pulses are investigated and quantitatively compared. Configurations investigated include a single pulse, double pulses at 400 ps and 800 ps separation, single pulses with prepulses and double pulses with prepulses. Data are presented in the form of integrated energy measurements, and supported by modelling. The most efficient short pulse configurations are shown to be orders of magnitude more effective than pumping with nanosecond duration pulses. (C) 1997 Elsevier Science B.V.

Saturated output of a Ge XXIII x-ray laser at 19.6 nm

We report on measurements of the saturated single frequency output of a Ge XXIII x-ray laser on the J=0-->1 transition at 19.6 nm from a refraction compensating double target driven by 150 J of energy from 75-ps Nd-glass laser pulses. The 19.6-nm line completely dominated the laser output. The output energy was measured to be 0.9 mJ in a beam of 6.6x30 mrad(2) divergence, corresponding to a conversion efficiency of 6 x 10(-6).

Using low and high prepulses to enhance the J=0-1 transition at 19.6 nm in the Ne-like germanium XUV laser

We report a study of the effect of prepulses on XUV lasing of Ne-like germanium for an irradiation geometry where approximate to 20 mm long germanium slab targets were irradiated at approximate to 1.6 x 10(13) W cm(-2) using approximate to 0.7 ns (1.06 mu m) pulses from the VULCAN glass laser. Prepulses were generated at fractional power levels of approximate to 2 x 10(-4) (low) and approximate to 2 x 10(-2) (high) and arrived on target 5 and 3.2 ns respectively in advance of the main heating pulse, For both the low and high prepulses the output of the 3p-3s, J = 0-1, line at 19.6 nm was enhanced such that the peak radiant density (J/st) for this line became greater than that for the normally stronger J = 2-1 lines at 23.2 and 23.6 nm. The J = 0-1 line, whose FWHM duration was reduced from approximate to 450 ps to approximate to 100 ps, delivered approximate to 6 x more power (W) than the average for the combined J = 2-1 lines, whose FWHM duration was approximate to 500 ps for both levels of prepulse, The higher prepulse was more effective, yielding approximate to 2 x more radiant density and approximate to 7 x more power on both the J = 0-1 and J = 2-1 transitions compared to the low prepulse case, The most dramatic observation overall was the approximate to 40 x increase of power in the J = 0-1 line for the high prepulse (approximate to 2%) case compared with the zero prepulse case. These observations, coupled with measurements of beam divergence and beam deviation through refractive bending, as well as general agreement with modelling, lead us to conclude that, for germanium, the main influence of the prepulse is (a) to increase the energy absorbed from the main pulse, (b) to increase the volume of the gain zone and (c) to relax the plasma density gradients, particularly in the J = 0-1 gain zone.