120 research outputs found
The efficacy of recombinant thrombopoietin in murine and nonhuman primate models for radiation-induced myelosuppression and stem cell transplantation
Radiation-induced pancytopenia proved to be a suitable model system in
mice and rhesus monkeys for studying thrombopoietin (TPO) target cell
range and efficacy. TPO was highly effective in rhesus monkeys exposed to
the mid-lethal dose of 5 Gy (300 kV x-rays) TBI, a model in which it
alleviated thrombocytopenia, promoted red cell reconstitution, accelerated
reconstitution of immature CD34+ bone marrow cells, and potentiated the
response to growth factors such as GM-CSF and G-CSF. In contrast to the
results in the 5 Gy TBI model, TPO was ineffective following
transplantation of limited numbers of autologous bone marrow or highly
purified stem cells in monkeys conditioned with 8 Gy TBI. In the 5 Gy
model, a single dose of TPO augmented by GM-CSF 24 h after TBI was
effective in preventing thrombocytopenia. The strong erythropoietic
stimulation may result in iron depletion, and TPO treatment should be
accompanied by monitoring of iron status. This preclinical evaluation thus
identified TPO as a potential major therapeutic agent for counteracting
radiation-induced pancytopenia and demonstrated pronounced stimulatory
effects on the reconstitution of immature CD34+ hemopoietic cells with
multilineage potential. The latter observation explains the potentiation
of the hematopoietic responses to G-CSF and GM-CSF when administered
concomitantly. It also predicts the effective use of TPO to accelerate
reconstitution of immature hematopoietic cells as well as possible
synergistic effects in vivo with various other growth factors acting on
immature stem cells and their direct lineage-committed progeny. The
finding that a single dose of TPO might be sufficient for a clinically
significant response emphasizes its potency and is of practical relevance.
The heterogeneity of the TPO response encountered in the various models
used for evaluation points to multiple mechanisms operating on the TPO
response and heterogeneity of its target cells. Mechanistic mouse studies
made apparent that the response of multilineage cells shortly after TBI to
a single administration of TPO is quantitatively more important for
optimal efficacy than the lineage-restricted response obtained at later
intervals after TBI and emphasized the importance of a relatively high
dose of TPO to overcome initial c-mpl-mediated clearance. Further
elucidation of mechanisms determining efficacy might very well result in a
further improvement, e.g., following transplantation of limited numbers of
stem cells. Adverse effects of TPO administration to myelosuppressed or
stem cell transplanted experimental animals were not observed
Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar
The branching ratios and Angular distributions for J/psi decays to Lambda
Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure
Rho GTPase function in flies: insights from a developmental and organismal perspective.
Morphogenesis is a key event in the development of a multicellular organism and is reliant on coordinated transcriptional and signal transduction events. To establish the segmented body plan that underlies much of metazoan development, individual cells and groups of cells must respond to exogenous signals with complex movements and shape changes. One class of proteins that plays a pivotal role in the interpretation of extracellular cues into cellular behavior is the Rho family of small GTPases. These molecular switches are essential components of a growing number of signaling pathways, many of which regulate actin cytoskeletal remodeling. Much of our understanding of Rho biology has come from work done in cell culture. More recently, the fruit fly Drosophila melanogaster has emerged as an excellent genetic system for the study of these proteins in a developmental and organismal context. Studies in flies have greatly enhanced our understanding of pathways involving Rho GTPases and their roles in development
Mineral nutrition of vegetable crops: XXV - Mineral nutrition of new zealand spinach plant (Tetragonia expansa Murr.)
The present work was carried out in order to study: a - the effect of omission and presence of the macronutrients and boron on the growth of the plants; b - deficiency symptoms of macronutrients, as well of boron; c - the effect of the deficiency of each nutrient on the chemical composition of the plants. Young spinach plants were grown in pots containing pure quartz sand. Several times a day the plants were irrigated by percolation with nutrient solutions. The treatments were: complete solution and deficient solution, in which each one of the macronutrients was omitted as well boron. Soon as the malnutrition symptoms appered, the plants were harvested and analysed chemically. - symptoms of malnutrition are easily observed for N, K, Ca and B. - symptoms of malnutrition for P, S and Mg are not easily identified. - the nutrient content, in dry matter, in deficient leaves and healthy leaves is:O trabalho teve como objetivo estudar alguns aspectos da nutrição mineral do espinafre (Tetragonia expansa Murr.) no que concerne: 1 - Efeitos da omissão dos macronutrientes e do boro, na obtenção de um quadro sintomatológico; 2 - Efeitos das carências na produção de matéria seca e composição química da planta. Mudas com trinta dias de idade foram transplantadas para soluções nutritivas carentes nos macronutrientes e/ou em boro. A coleta das plantas foi realizada quando os sintomas de deficiência se tornaram evidentes. No material seco procedeu-se a análise química. Os dados mostram que: 1 - os sintomas visuais de deficiência de N, K, Ca e B apresentam-se bem definidos; sendo que os de P, Mg e S são de difícil caracterização ; 2 - os teores dos nutrientes em plantas sadias e deficientes são
Measurements of J/psi --> p \bar{p}
The process J/\psi --> p \bar{p} is studied using 57.7 X 10^6 J/\psi events
collected with the BESII detector at the Beijing Electron Positron Collider.
The branching ratio is determined to be Br(J/\psi --> p \bar{p})=(2.26 +- 0.01
+- 0.14) X 10^{-3}, and the angular distribution is well described by
\frac{dN}{d cos\theta_p}=1+\alpha\cos^2\theta_p with \alpha = 0.676 +- 0.036 +-
0.042, where \theta_p is the angle between the proton and beam directions. The
value of \alpha obtained is in good agreement with the predictions of
first-order QCD.Comment: 6 pages, 2 figures, RevTex4, Submitted to Phys.Lett.
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Electron Paramagnetic Resonance of Lanthanides
Many applications of lanthanides exploit their electron spin relaxation properties. Double electron electron measurements of distances are possible because of the relatively long relaxation times of Gd3 . Relaxation enhancement measurements of distance are possible because of the much shorter relaxation times of other lanthanides. Magnetic resonance imaging contrast agents use the long relaxation time of the S state Gd3 ion, and NMR shift reagents use the fast relaxation of selected other lanthanides. Other than Gd3 and the isoelectronic Eu2 ion, spin relaxation of the lanthanides is so fast that their EPR spectra can be observed only in the liquid helium temperature range. In this chapter the EPR properties of each of the lanthanides is briefly summarized, with an emphasis on electron spin relaxatio
Effect of the synergistic anion on electron paramagnetic resonance spectra of iron-transferrin anion complexes is consistent with bidentate binding of the anion
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