1,674 research outputs found
Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation
Myelofibrosis is a myeloproliferative neoplasm that results in cytopenia, bone marrow fibrosis and extramedullary hematopoiesis. Allogeneic hematopoietic stem cell transplantation is the only curative treatment but is associated with a risk of delayed engraftment and graft failure. In this study, patients with myelofibrosis (n=31) and acute myeloid leukemia (n=31) were analyzed for time to engraftment, graft failure and engraftment-related factors. Early and late neutrophil engraftment and late thrombocyte engraftment were significantly delayed in patients with myelofibrosis as compared to acute myeloid leukemia, and graft failure only occurred in myelofibrosis (6%). Only spleen size had a significant influence on engraftment efficiency in myelofibrosis patients. To analyze the cause for the engraftment defect, clearance of hematopoietic stem cells from peripheral blood was measured and immunohistological staining of bone marrow sections was performed. Numbers of circulating CD34+ were significantly reduced at early time points in myelofibrosis patients, whereas CD34+CD38- and colony-forming cells showed no significant difference in clearance. Staining of bone marrow sections for homing proteins revealed a loss of VCAM-1 in myelofibrosis with a corresponding significant increase in the level of soluble VCAM-1 within the peripheral blood. In conclusion, our data suggest that reduced engraftment and graft failure in myelofibrosis patients is caused by an early pooling of CD34+ hematopoietic stem cells in the spleen and a bone marrow homing defect caused by the loss of VCAM-1. Improved engraftment in myelofibrosis might be achieved by approaches that reduce spleen size and cleavage of VCAM-1 in these patients prior to hematopoietic stem cell transplantation
Ab initio simulations of liquid NaSn alloys: Zintl anions and network formation
Using the Car-Parrinello technique, ab initio molecular dynamics simulations
are performed for liquid NaSn alloys in five different compositions (20, 40,
50, 57 and 80 % sodium). The obtained structure factors agree well with the
data from neutron scattering experiments. The measured prepeak in the structure
factor is reproduced qualitatively for most compositions. The calculated and
measured positions of all peaks show the same trend as function of the
composition.\\ The dynamic simulations also yield information about the
formation and stability of Sn clusters (Zintl anions) in the liquid. In our
simulations of compositions with 50 and 57 % sodium we observe the formation of
networks of tin atoms. Thus, isolated tin clusters are not stable in such
liquids. For the composition with 20 % tin only isolated atoms or dimers of tin
appear, ``octet compounds'' of one Sn atom surrounded by 4 Na atoms are not
observed.Comment: 12 pages, Latex, 3 Figures on reques
Automated 3D trabecular bone structure analysis of the proximal femur—prediction of biomechanical strength by CT and DXA
The standard diagnostic technique for assessing osteoporosis is dual X-ray absorptiometry (DXA) measuring bone mass parameters. In this study, a combination of DXA and trabecular structure parameters (acquired by computed tomography [CT]) most accurately predicted the biomechanical strength of the proximal femur and allowed for a better prediction than DXA alone.
An automated 3D segmentation algorithm was applied to determine specific structure parameters of the trabecular bone in CT images of the proximal femur. This was done to evaluate the ability of these parameters for predicting biomechanical femoral bone strength in comparison with bone mineral content (BMC) and bone mineral density (BMD) acquired by DXA as standard diagnostic technique.
One hundred eighty-seven proximal femur specimens were harvested from formalin-fixed human cadavers. BMC and BMD were determined by DXA. Structure parameters of the trabecular bone (i.e., morphometry, fuzzy logic, Minkowski functionals, and the scaling index method [SIM]) were computed from CT images. Absolute femoral bone strength was assessed with a biomechanical side-impact test measuring failure load (FL). Adjusted FL parameters for appraisal of relative bone strength were calculated by dividing FL by influencing variables such as body height, weight, or femoral head diameter.
The best single parameter predicting FL and adjusted FL parameters was apparent trabecular separation (morphometry) or DXA-derived BMC or BMD with correlations up to r = 0.802. In combination with DXA, structure parameters (most notably the SIM and morphometry) added in linear regression models significant information in predicting FL and all adjusted FL parameters (up to R
adj = 0.872) and allowed for a significant better prediction than DXA alone.
A combination of bone mass (DXA) and structure parameters of the trabecular bone (linear and nonlinear, global and local) most accurately predicted absolute and relative femoral bone strength
Vortex Dynamics in Dissipative Systems
We derive the exact equation of motion for a vortex in two- and three-
dimensional non-relativistic systems governed by the Ginzburg-Landau equation
with complex coefficients. The velocity is given in terms of local gradients of
the magnitude and phase of the complex field and is exact also for arbitrarily
small inter-vortex distances. The results for vortices in a superfluid or a
superconductor are recovered.Comment: revtex, 5 pages, 1 encapsulated postscript figure (included), uses
aps.sty, epsf.te
41Ca in tooth enamel. part I: A biological signature of neutron exposure in atomic bomb survivors
The detection of 41Ca atoms in tooth enamel using accelerator mass spectrometry is suggested as a method capable of reconstructing thermal neutron exposures from atomic bomb survivors in Hiroshima and Nagasaki. In general, 41Ca atoms are produced via thermal neutron capture by stable 40Ca. Thus any 41Ca atoms present in the tooth enamel of the survivors would be due to neutron exposure from both natural sources and radiation from the bomb. Tooth samples from five survivors in a control group with negligible neutron exposure were used to investigate the natural 41Ca content in tooth enamel, and 16 tooth samples from 13 survivors were used to estimate bomb-related neutron exposure. The results showed that the mean 41Ca/Ca isotope ratio was (0.17 ± 0.05) Ă— 10-14 in the control samples and increased to 2 Ă— 10-14 for survivors who were proximally exposed to the bomb. The 41Ca/Ca ratios showed an inverse correlation with distance from the hypocenter at the time of the bombing, similar to values that have been derived from theoretical free-in-air thermal-neutron transport calculations. Given that Îł-ray doses were determined earlier for the same tooth samples by means of electron spin resonance (ESR, or electron paramagnetic resonance, EPR), these results can serve to validate neutron exposures that were calculated individually for the survivors but that had to incorporate a number of assumptions (e.g. shielding conditions for the survivors).Fil: Wallner, A.. Ludwig Maximilians Universitat; Alemania. Universitat Technical Zu Munich; Alemania. Universidad de Viena; AustriaFil: Ruhm, W.. Helmholtz Center Munich German Research Center For Environmental Health; Alemania. Ludwig Maximilians Universitat; AlemaniaFil: Rugel, G.. Ludwig Maximilians Universitat; Alemania. Universitat Technical Zu Munich; AlemaniaFil: Nakamura, N.. Radiation Effects Research Foundation; JapĂłnFil: Arazi, Andres. Universitat Technical Zu Munich; Alemania. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Faestermann, T.. Universitat Technical Zu Munich; AlemaniaFil: Knie, K.. Universitat Technical Zu Munich; Alemania. Ludwig Maximilians Universitat; AlemaniaFil: Maier, H. J.. Ludwig Maximilians Universitat; AlemaniaFil: Korschinek, G.. Universitat Technical Zu Munich; Alemani
New Results for the Correlation Functions of the Ising Model and the Transverse Ising Chain
In this paper we show how an infinite system of coupled Toda-type nonlinear
differential equations derived by one of us can be used efficiently to
calculate the time-dependent pair-correlations in the Ising chain in a
transverse field. The results are seen to match extremely well long large-time
asymptotic expansions newly derived here. For our initial conditions we use new
long asymptotic expansions for the equal-time pair correlation functions of the
transverse Ising chain, extending an old result of T.T. Wu for the 2d Ising
model. Using this one can also study the equal-time wavevector-dependent
correlation function of the quantum chain, a.k.a. the q-dependent diagonal
susceptibility in the 2d Ising model, in great detail with very little
computational effort.Comment: LaTeX 2e, 31 pages, 8 figures (16 eps files). vs2: Two references
added and minor changes of style. vs3: Corrections made and reference adde
Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?
Background: Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR-and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow for the identification of patients who might benefit from TKI treatments targeting MET and to narrow in on the diagnostic assessment of MET. Methods: 222 tumor tissues of patients with NSCLC were analyzed concerning c-MET expression and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a microarray format employing immunohistochemistry (IHC). Furthermore, protein expression and MET activation was correlated with the amplification status by Fluorescence in Situ Hybridization (FISH). Results: Correlation was observed between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation coefficient r(s) = 0.41;p 0.05). c-MET gene amplification was detected in eight of 214 patients (3.7 %). No significant association was observed between c-MET amplification, c-MET protein expression and phosphorylation. Conclusion: Our data indicate, that neither expression of c-MET nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. We propose to take into account analyzing the phosphorylation status of MET by IHC to select patients for MET targeting therapies. Signaling of the receptor and the activation of downstream molecules might be more crucial for the benefit of therapeutics targeting MET receptor tyrosine kinases than expression levels alone
Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation
Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings.
We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups “ACR”, “infection”, “combined ACR and infection” and “no pathologic process”. No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation
- …