CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition <it>in vivo </it>via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.</p> <p>Methods</p> <p>Normal and malignant lymphocytes were isolated from whole blood from patients with CLL and healthy volunteers. Enzyme activity was measured via radio-TLC assay and expression via FACS. Semi-quantititative RT-PCR for CD39 splice variants and platelet function tests were performed on several samples.</p> <p>Results</p> <p>Functional assays demonstrated that ADPase and ATPase activities were much higher in CLL cells than in total lymphocytes from the normal population on a per cell basis (p-value < 0.00001). CD39 activity was elevated in stage 0–2 CLL compared to stage 3–4 (p < 0.01). FACS of lymphocytes demonstrated CD39 expression on > 90% of normal and malignant B-lymphocytes and ~8% of normal T-lymphocytes. RT-PCR showed increased full length CD39 and splice variant 1.5, but decreased variant 1.3 in CLL cells. Platelet function tests showed inhibition of platelet activation and recruitment to ADP by CLL cells.</p> <p>Conclusion</p> <p>CD39 is expressed and active on CLL cells. Enzyme activity is higher in earlier stages of CLL and decreased enzyme activity may be associated with worsening disease. These results suggest that CD39 may play a role in the pathogenesis of malignancy and protect CLL patients from thrombotic events.</p

G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila.

We combined Gal4-UAS and the FLP recombinase-FRT and fluorescent reporters to generate cell clones that provide spatial, temporal and genetic information about the origins of individual cells in Drosophila melanogaster. We named this combination the Gal4 technique for real-time and clonal expression (G-TRACE). The approach should allow for screening and the identification of real-time and lineage-traced expression patterns on a genomic scale

Self-organization of vortices in type-II superconductors during magnetic relaxation

We revise the applicability of the theory of self-organized criticality (SOC) to the process of magnetic relaxation in type-II superconductors. The driving parameter of self-organization of vortices is the energy barrier for flux creep and not the current density. The power spectrum of the magnetic noise due to vortex avalanches is calculated and is predicted to vary with time during relaxation.Comment: RevTex, 5 pages, 2 PS figures. Accepted in Phys. Rev.

Numerical studies of the 2 and 3D gauge glass at low temperature

We report results from Monte Carlo simulations of the two- and three-dimensional gauge glass at low temperature using parallel tempering Monte Carlo. In two dimensions, we find strong evidence for a zero-temperature transition. By means of finite-size scaling, we determine the stiffness exponent theta = -0.39 +/- 0.03. In three dimensions, where a finite-temperature transition is well established, we find theta = 0.27 +/- 0.01, compatible with recent results from domain-wall renormalization group studies.Comment: 3 pages, 3 figures. Proceedings of "2002 MMM Conference", Tampa, F

A Physical Model to Estimate Snowfall over Land using AMSU-B Observations

In this study, we present an improved physical model to retrieve snowfall rate over land using brightness temperature observations from the National Oceanic and Atmospheric Administration's (NOAA) Advanced Microwave Sounder Unit-B (AMSU-B) at 89 GHz, 150 GHz, 183.3 +/- 1 GHz, 183.3 +/- 3 GHz, and 183.3 +/- 7 GHz. The retrieval model is applied to the New England blizzard of March 5, 2001 which deposited about 75 cm of snow over much of Vermont, New Hampshire, and northern New York. In this improved physical model, prior retrieval assumptions about snowflake shape, particle size distributions, environmental conditions, and optimization methodology have been updated. Here, single scattering parameters for snow particles are calculated with the Discrete-Dipole Approximation (DDA) method instead of assuming spherical shapes. Five different snow particle models (hexagonal columns, hexagonal plates, and three different kinds of aggregates) are considered. Snow particle size distributions are assumed to vary with air temperature and to follow aircraft measurements described by previous studies. Brightness temperatures at AMSU-B frequencies for the New England blizzard are calculated using these DDA calculated single scattering parameters and particle size distributions. The vertical profiles of pressure, temperature, relative humidity and hydrometeors are provided by MM5 model simulations. These profiles are treated as the a priori data base in the Bayesian retrieval algorithm. In algorithm applications to the blizzard data, calculated brightness temperatures associated with selected database profiles agree with AMSU-B observations to within about +/- 5 K at all five frequencies. Retrieved snowfall rates compare favorably with the near-concurrent National Weather Service (NWS) radar reflectivity measurements. The relationships between the NWS radar measured reflectivities Z(sub e) and retrieved snowfall rate R for a given snow particle model are derived by a histogram matching technique. All of these Z(sub e)-R relationships fall in the range of previously established Z(sub e)-R relationships for snowfall. This suggests that the current physical model developed in this study can reliably estimate the snowfall rate over land using the AMSU-B measured brightness temperatures

The topology of connections between rat prefrontal, motor and sensory cortices

The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001)

Flux front penetration in disordered superconductors

We investigate flux front penetration in a disordered type II superconductor by molecular dynamics (MD) simulations of interacting vortices and find scaling laws for the front position and the density profile. The scaling can be understood performing a coarse graining of the system and writing a disordered non-linear diffusion equation. Integrating numerically the equation, we observe a crossover from flat to fractal front penetration as the system parameters are varied. The value of the fractal dimension indicates that the invasion process is described by gradient percolation.Comment: 5 pages, 4 figures, to appear in Phys. Rev. Let

A Search for Pulsating, Mass-Accreting Components in Algol-Type Eclipsing Binaries

We present a status report on the search for pulsations in primary componants of Algols systems (oEA stars). Analysis of 21 systems with A0-F2 spectral type primaries revealed pulsations in two systems suggesting that of the order of ten persent of Algols primaries in this range are actually pulsators

Numerical studies of the two- and three-dimensional gauge glass at low temperature

We present results from Monte Carlo simulations of the two- and three-dimensional gauge glass at low temperature using the parallel tempering Monte Carlo method. Our results in two dimensions strongly support the transition being at T_c=0. A finite-size scaling analysis, which works well only for the larger sizes and lower temperatures, gives the stiffness exponent theta = -0.39 +/- 0.03. In three dimensions we find theta = 0.27 +/- 0.01, compatible with recent results from domain wall renormalization group studies.Comment: 7 pages, 10 figures, submitted to PR

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels

The cloning of the cDNA for the α1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these α1 subunits and the skeletal muscle α2/δ, β and γ subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the α1-, β- and γ-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The α1, β and γ mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle α2/δ subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the α1, β and γ subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner