580 research outputs found
Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals
In the present study, we investigated whether the negative feedback action
of glucocorticoids (GCs) on the hypothalamo-pituitary-adrenal (HPA) axis
changes with age. We performed a 1-mg dexamethasone (DEX) suppression test
in 216 healthy elderly individuals. To investigate individual variability
of feedback sensitivity in more detail, 2.5 yr later a 0.25-mg DEX
suppression test was carried out in 164 of the same individuals. We
investigated whether there was an effect of age or gender on both basal
and post-DEX cortisol levels, as well as on the concentration of DEX.
Furthermore, we examined whether the reactions to the two doses of DEX
differed, and whether indications for an intraperson stability of baseline
cortisol levels could be found. Neither the pre- nor the post-1-mg DEX
plasma cortisol concentrations showed a correlation with age, and there
were no differences between men and women. The same was true for the pre-
and post-0.25-mg DEX cortisol concentrations. In reaction to 1 mg DEX,
over 90% of the subjects investigated showed a cortisol suppression to
levels below 50 nmol/L. After the administration of 0.25 mg DEX, there was
a much wider range in post-DEX cortisol concentrations. After the
administration of 1 mg DEX, there was a significant correlation between
liver function parameters and plasma DEX concentrations in males, and
there was a correlation between body mass index and plasma DEX
concentration in females. Plasma DEX concentrations after the
administration of 1 mg and 0.25 mg DEX were closely correlated within
subjects (P < 0.001). There was an intraindividual stability of serum
cortisol levels determined at an interval of 2.5 yr. Furthermore, the
individuals with the highest baseline cortisol concentrations also had the
highest post-0.25-mg DEX cortisol concentrations, indicating a close
relationship between basal cortisol levels and the feedback sensitivity of
the HPA axis to a low dose of DEX. These observations suggest a genetic
influence on the set point of the HPA axis. Aging does not seem to lead to
a change in HPA activity as measured by early morning total cortisol
levels. Also, no changes in the sensitivity of the feedback system to DEX
were observed with age. DEX metabolism is influenced by liver function (in
males) and by body mass index (in females)
A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo
We investigated whether a polymorphism at nucleotide position 1220,
resulting in an asparagine-to-serine change at codon 363 in the
glucocorticoid receptor (GR) gene is associated with an altered
sensitivity to glucocorticoids. In a group of 216 elderly persons, 13
heterozygotes for the N363S polymorphism were identified by PCR/single
strand conformation polymorphism analysis. In 2 dexamethasone (DEX)
suppression tests (DSTs), using 1 and 0.25 mg DEX, the circulating
cortisol and insulin concentrations were compared between N363S carriers
and controls. In the 1-mg DST, there were no differences between N363S
carriers and controls, with respect to adrenal suppression, but there was
a significantly higher (P < 0.05) insulin response in N363S carriers. In
the 0.25-mg DST, a significantly larger (P < 0.05) cortisol suppression
and higher (P < 0.05) insulin response were seen in N363S carriers.
Comparison of blood pressure, body mass index (BMI), and bone mineral
density (BMD) between the N363S carriers and controls showed that N363S
carriers had a higher (P < 0.05) BMI but normal blood pressure. There was
an obvious trend towards lower age-, BMI-, and sex-adjusted BMD in the
lumbar spine in N363S carriers. GR characteristics measured in 41 controls
and 9 N363S carriers in peripheral mononuclear leucocytes showed no
differences between N363S carriers and controls, with respect to GR number
and ligand binding affinity. However, there was a trend towards greater
sensitivity to DEX in the carriers' lymphocytes, in a mitogen-induced cell
proliferation assay. In transfection assays, the capacity of the codon 363
variant to activate mouse mammary tumor virus promotor-mediated
transcription in COS-1 cells was unaltered, when compared with the
wild-type GR. We conclude that in 6.0% of our study population, a
polymorphism in codon 363 of the GR gene was found. Individuals carrying
this polymorphism seemed healthy at clinical examination but had a higher
sensitivity to exogenously administered glucocorticoids, with respect to
both cortisol suppression and insulin response. Life-long exposure to the
mutated allele may be accompanied by an increased BMI and a lowered BMD in
the lumbar spine but does not affect blood pressure
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults
Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P = 1.9×10−32) and in the IL1 gene family region of chromosome 2 for IL-1ra (rs6743376, P = 2.3×10−26). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7×10−19). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4
Measurement of branching fraction ratios and CP asymmetries in
We report results on the decay and its charge
conjugate using a data sample of 85.4 million pairs recorded at the
resonance with the Belle detector at the KEKB asymmetric
storage ring. Ratios of branching fractions of Cabibbo-suppressed
to Cabibbo-favored processes are determined to be , and where the indices 1 and 2 represent the CP=+1
and CP=1 eigenstates of the system, respectively. We
find the partial-rate charge asymmetries for to be
and .Comment: 10 pages, 3 figures, submitted to Physical Review
Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider
This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)
Search for Charmless Two-body Baryonic Decays of B Mesons
We report the results of a search for the rare baryonic decays , , and . The analysis
is based on a data set of events collected by the
Belle detector at the KEKB collider. No statistically significant
signals are found, and we set branching fraction upper limits , , and at the 90% confidence level.Comment: 6 pages, 4 figures and 1 table. Submitted to Phys. Rev. D Rapid
Communication
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Evidence for CP-Violating Asymmetries in B0->pi+pi- Decays and Constraints on the CKM Angle phi2
We present an improved measurement of CP-violating asymmetries in B0 -> pi+
pi- decays based on a 78 fb^-1 data sample collected at the Y(4S) resonance
with the Belle detector at the KEKB asymmetric-energy e+e- collider. We
reconstruct one neutral B meson as a B0 -> pi+ pi- CP eigenstate and identify
the flavor of the accompanying B meson from inclusive properties of its decay
products. We apply an unbinned maximum likelihood fit to the distribution of
the time intervals between the two B meson decay points. The fit yields the
CP-violating asymmetry amplitudes Apipi = +0.77+/-0.27(stat)+/-0.08(syst) and
Spipi = -1.23+/-0.41(stat)+0.08/-0.07(syst), where the statistical
uncertainties are determined from Monte Carlo pseudo-experiments. We obtain
confidence intervals for CP-violating asymmetry parameters Apipi and Spipi
based on a frequentist approach. We rule out the CP-conserving case,
Apipi=Spipi=0, at the 99.93% confidence level. We discuss how these results
constrain the value of the CKM angle phi2.Comment: 26 pages, 13 figures, submitted to Phys. Rev.
Azimuthal anisotropy of K0s and Lambda prduction at mid-rapidity from Au+Au collisions at root s = 130 GeV
We report STAR results on the azimuthal anisotropy parameter v2 for strange
particles K0S, L and Lbar at midrapidity in Au+Au collisions at sNN = 130 GeV
at RHIC. The value of v2 as a function of transverse momentum of the produced
particles pt and collision centrality is presented for both particles up to pt
3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2
measurement is compared with hydrodynamic model calculations. The physics
implications of the pt integrated v2 magnitude as a function of particle mass
are also discussed.Comment: 6 pages, 4 figures, by the STAR collaboratio
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