Constitutive expression of the Wilms'' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program

OBJECTIVE: To characterize relationships among blood pressure, pulse rate, vitamin C status and other protective and risk factors for older British people, from a national survey. DESIGN: A cross-sectional analysis of survey data. SETTING: A population study, representative of mainland Britain. SUBJECTS: Among 914 people of both sexes living in the community, 373 were taking blood-pressure-lowering drugs and were therefore excluded from the analyses. INTERVENTIONS: Completion of an interview on health, lifestyle and dietary habits, recording of a 4-day dietary record, anthropometry and taking of a blood sample to determine haematological and biochemical status. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures, pulse rate, indices of micronutrient status including plasma ascorbate concentration, nutrient intake and haematology. RESULTS: Plasma ascorbate concentration was inversely correlated to systolic and diastolic blood pressures and pulse rate. Other covariates of blood pressure included age, sex, domicile, plasma retinol, fibrinogen and gamma-tocopherol concentrations, erythrocyte count, prothrombin time and urine sodium: creatinine ratio. Covariates of pulse rate included sex, domicile, plasma fibrinogen and platelet count. Blood pressure was also correlated to intake of vitamin C. CONCLUSIONS: Plasma ascorbate concentration and intake of vitamin C are covariates of blood pressure in older people living in Britain. New intervention studies are now needed, to test for possible causalities.     

Normal and pathological NCAT image and phantom data based on physiologically realistic left ventricle finite-element models

The four-dimensional (4-D) NURBS-based cardiac-torso (NCAT) phantom, which provides a realistic model of the normal human anatomy and cardiac and respiratory motions, is used in medical imaging research to evaluate and improve imaging devices and techniques, especially dynamic cardiac applications. One limitation of the phantom is that it lacks the ability to accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). The goal of this work was to enhance the 4-D NCAT phantom by incorporating a physiologically based, finite-element (FE) mechanical model of the left ventricle (LV) to simulate both normal and abnormal cardiac motions. The geometry of the FE mechanical model was based on gated high-resolution X-ray multislice computed tomography (MSCT) data of a healthy male subject. The myocardial wall was represented as a transversely isotropic hyperelastic material, with the fiber angle varying from -90 degrees at the epicardial surface, through 0 degrees at the midwall, to 90 degrees at the endocardial surface. A time-varying elastance model was used to simulate fiber contraction, and physiological intraventricular systolic pressure-time curves were applied to simulate the cardiac motion over the entire cardiac cycle. To demonstrate the ability of the FE mechanical model to accurately simulate the normal cardiac motion as well as the abnormal motions indicative of CAD, a normal case and two pathologic cases were simulated and analyzed. In the first pathologic model, a subendocardial anterior ischemic region was defined. A second model was created with a transmural ischemic region defined in the same location. The FE-based deformations were incorporated into the 4-D NCAT cardiac model through the control points that define the cardiac structures in the phantom which were set to move according to the predictions of the mechanical model. A simulation study was performed using the FE-NCAT combination to investigate how the differences in contractile function between the subendocardial and transmural infarcts manifest themselves in myocardial Single photon emission computed tomography (SPECT) images. The normal FE model produced strain distributions that were consistent with those reported in the literature and a motion consistent with that defined in the normal 4-D NCAT beating heart model based on tagged magnetic resonance imaging (MRI) data. The addition of a subendocardial ischemic region changed the average transmural circumferential strain from a contractile value of -0.09 to a tensile value of 0.02. The addition of a transmural ischemic region changed average circumferential strain to a value of 0.13, which is consistent with data reported in the literature. Model results demonstrated differences in contractile function between subendocardial and transmural infarcts and how these differences in function are documented in simulated myocardial SPECT images produced using the 4-D NCAT phantom. Compared with the original NCAT beating heart model, the FE mechanical model produced a more accurate simulation for the cardiac motion abnormalities. Such a model, when incorporated into the 4-D NCAT phantom, has great potential for use in cardiac imaging research. With its enhanced physiologically based cardiac model, the 4-D NCAT phantom can be used to simulate realistic, predictive imaging data of a patient population with varying whole-body anatomy and with varying healthy and diseased states of the heart that will provide a known truth from which to evaluate and improve existing and emerging 4-D imaging techniques used in the diagnosis of cardiac disease.     

Tomographic reconstruction using an adaptive tetrahedral mesh defined by a point cloud

Medical images in nuclear medicine are commonly represented in three dimensions as a stack of two-dimensional images that are reconstructed from tomographic projections. Although natural and straightforward, this may not be an optimal visual representation for performing various diagnostic tasks. A method for three-dimensional (3-D) tomographic reconstruction is developed using a point cloud image representation. A point cloud is a set of points (nodes) in space, where each node of the point cloud is characterized by its position and intensity. The density of the nodes determines the local resolution allowing for the modeling of different parts of the image with different resolution. The reconstructed volume, which in general could be of any resolution, size, shape, and topology, is represented by a set of nonoverlapping tetrahedra defined by the nodes. The intensity at any point within the volume is defined by linearly interpolating inside a tetrahedron from the values at the four nodes that define the tetrahedron. This approach creates a continuous piecewise linear intensity over the reconstruction domain. The reconstruction provides a distinct multiresolution representation, which is designed to accurately and efficiently represent the 3-D image. The method is applicable to the acquisition of any tomographic geometry, such as parallel-, fan-, and cone-beam; and the reconstruction procedure can also model the physics of the image detection process. An efficient method for evaluating the system projection matrix is presented. The system matrix is used in an iterative algorithm to reconstruct both the intensity and location of the distribution of points in the point cloud. Examples of the reconstruction of projection data generated by computer simulations and projection data experimentally acquired using a Jaszczak cardiac torso phantom are presented. This work creates a framework for voxel-less multiresolution representation of images in nuclear medicine.     

Helical SPECT using axially truncated data

In this study, use of a helical orbit in performing a long object SPECT scan with parallel, cone, fan, rotated fan, varying focal-length cone, divergent, and astigmatic collimators is proposed. Sufficient-data scanning helical orbits for these collimation geometries are developed. Both a single-detector system and a multi-detector system are considered. In order to verify the authors' orbit design requirement, the iterative ML-EM algorithm is used to reconstruct images of a long Defrise phantom. The phantom height is five times the height of the detectors. Computer simulations are performed and exact reconstructions are obtained. The proposed sufficient helical orbit pitch will facilitate performing whole body SPECT and PET scans that demand an exact reconstruction     

Conserved neuron promoting activity in Drosophila and vertebrate laminin alpha1

Drosophila S2 cells were transfected with constructs that code for two portions of the Drosophila laminin alpha chain. Construct recalphaL coded for domains III, I/II, and G of laminin alpha. Construct recalphaS coded for only the COOH-most 12% of the I/II domain and the G domain. The corresponding polypeptides were isolated and characterized from the culture media. The recalphaL chain partly formed disulfide-linked heterotrimers with the endogenously produced beta and gamma laminin chains. Like normal Drosophila laminin, a substrate coating of either recalphaL or recalphaS supported neuron differentiation and neurite extension of primary Drosophila embryo cell cultures. However, at the same low concentrations, only Drosophila laminin-1, but neither recalphaL nor recalphaS supported myogenesis in these cultures. Previously, an overlapping set of dodecapeptides that covered a region of the murine laminin alpha1 chain similar to recalphaS had been synthesized and tested for cell culture support properties (Nomizu, M., Kim, W. H., Yamamura, K., Utani, A., Otaka, A., Roller, P. P., Kleinman, H. K., and Yamada, Y. (1995) J. Biol. Chem. 270, 20583-20590). The Drosophila laminin alpha homologues of the six most active vertebrate dodecapeptides were now synthesized and tested as substrates for differentiation of primary Drosophila embryo cells. Peptides that contained either the Drosophila sequence SIKVGV or the murine homologue, SIKVAV, provided support for neurite extension.     

Iterative reconstruction with attenuation compensation fromcone-beam projections acquired via nonplanar orbits

Single photon emission computed tomography (SPECT) imaging with cone-beam collimators provides improved sensitivity and spatial resolution for imaging small objects with large field-of-view detectors. It is known that Tuy's cone-beam data sufficiency condition must be met to obtain artifact-free reconstructions. Even though Tuy's condition was derived for an attenuation-free situation, the authors hypothesize that an artifact-free reconstruction can be obtained even if the cone-beam data are attenuated, provided the imaging orbit satisfies Tuy's condition and the exact attenuation map is known. In the authors' studies, emission data are acquired using nonplanar circle-and-line orbits to acquire cone-beam data for tomographic reconstructions. An extended iterative ML-EM (maximum likelihood-expectation maximization) reconstruction algorithm is derived and used to reconstruct projection data with either a pre-acquired or assumed attenuation map. Quantitative accuracy of the attenuation corrected emission reconstruction is significantly improved     

A secreted proform of neutrophil proteinase 3 regulates the proliferation of granulopoietic progenitor cells

Myeloid leukemia cells, the human promyelocytic cell line HL-60, and a subpopulation of normal marrow cells produce a leukemia-associated inhibitor (LAI) that reversibly downmodulates DNA synthesis of normal granulopoietic progenitor cells colony-forming unit granulocyte-macrophage (CFU-GM). We isolated an active 125-kD component of LAI from HL-60 conditioned medium (CM), subjected it to cyanogen bromide cleavage and show by amino acid sequencing of the resulting peptides that it consists of a complex of the serine proteinase inhibitor alpha1-antitrypsin and a 31-kD fragment that retained the S-phase inhibitory activity, but resisted sequencing. This finding suggested that the 31-kD fragment originated from one of the neutrophil serine proteases (ie, elastase, proteinase 3, or cathepsin G) produced by normal promyelocytes, as well as HL-60 cells, for storage in primary granules and partly secreted during synthesis as enzymatically inactive proforms. Immunoblot analysis showed that the 125-kD complex contained proteinase 3 (PR3), and immunoprecipitation of PR3 from HL-60 CM abrogated the S-phase inhibitory activity, whereas immunoprecipitation of cathepsin G or elastase did not. Immunoprecipitation of PR3 from CM of a subpopulation of normal marrow cells also abrogated the S-phase inhibitory effect. Furthermore, CM from rat RBL and murine 32D cell lines transfected with human PR3 both reduced the fraction of CFU-GM in S-phase with 30% to 80% at 1 to 35 ng/mL PR3, whereas CM of the same cells transfected with cathepsin G or elastase did not. Also, an enzymatically silent mutant of PR3 exerted full activity, showing that the S-phase modulatory effect is not dependent on proteolytic activity. Amino acid sequencing of biosynthetically radiolabeled PR3 showed that PR3 from transfected cells is secreted after synthesis as proforms retaining amino terminal propeptides. In contrast, mature PR3 extracted from mature neutrophils has only minor activity. The inhibitory effect of secreted PR3 is reversible and abrogated by granulocyte (G)- or granulocyte-macrophage colony-stimulating factor (GM-CSF). Experiments with highly purified CD34(+) bone marrow cells suggested that PR3 acts directly on the granulopoietic progenitor cells. These observations suggest a role for PR3 in regulation of granulopoiesis, and possibly in suppression of normal granulopoiesis in leukemia.     

Changing Frames of Mobility through Radical Policy Interventions? The Stockholm Congestion Tax

The introduction of a congestion tax was a significant moment in the management of mobility in Stockholm. This paper critically examines this apparent consensus on confronting car based mobility, by analysing how mobility was framed at key stages in policy making, from the 1970s through to the trial in 2006 and subsequent implementation. Changing transport objectives are compared, and winners and losers are traced in relation to motility and environmental quality. The paper argues that a car-based automobility frame survives, even in the implementation of a radical policy of congestion taxation.     

Zygosity and intrauterine growth of twins

Six hundred seventy-eight sonar measurements of the fetal biparietal diameter (BPD) were used to assess the intrauterine growth of 182 twins between 18 and 40 weeks' gestation. These values, as well as the weight and body length at birth, were related to the zygosity, which was determined by sex of the infants, histologic examination of placenta, or blood grouping. The mean BPD of twin 1 was larger than that of twin 2 in both monozygotic and dizygotic pairs throughout the study period (P less than .001). The size of BPD of the dizygotic infants exceeded that of the monozygotic among both twin 1 (P less than .001) and twin 2 (P less than .001). The absolute intrapair differences of birth length and weight were larger among dizygotic than among monozygotic twins. These findings suggest that in late pregnancy a substantial one-way intertwin transfusion among monochorial twins does not occur frequently enough to mask the inherent genetically determined similarity between the twins. The appearance already in the second trimester of the difference in the longitudinally monitored BPD between monozygotic and dizygotic twins suggests that the discrepancy is determined early in gestation.