Estimation of deformation gradient and strain from cine-PC velocity data

Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial velocity field measurements. These data allow densely spaced material points to be tracked throughout the whole heart cycle using, for example, the Fourier tracking algorithm. To process the tracking results for myocardial deformation and strain quantification, we developed a method that is based on fitting the tracking results to an appropriate local deformation model. We further analyzed the accuracy and precision of the method and provided performance predictions for several local models. In order to validate the method and the theoretical performance analysis, we conducted controlled computer simulations and a phantom study. The results agreed well with expectations. Human heart data were also acquired and analyzed, and provided encouraging results. At the signal-to-noise ratio (SNR) level and spatial resolution expected in clinical settings, the study predicts strain quantification accuracy and precision that may allow the technique to become a practical and powerful noninvasive approach for the study of cardiac function, although clinically acceptable data acquisition strategies for three-dimensional (3-D) data are still a challenge.     

Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle

Attempts to immunise sheep against natural infestations by Lucilia cuprina larvae have not been effective. Yet it is known that the larvae excrete the immunosuppressant ammonium bicarbonate. The effect of larval ammonium and nonionic ammonia on immunopathobiology was evaluated in 12 infested sheep. The concentration of ammonium in veins draining infested sites was measured in another group of four sheep. Mean jugular unionized ammonia concentration increased 3.5 to 5.6 times above pre-infested control levels. Mean venous ammonium concentrations draining infested sites were 13 times higher than pre-infested jugular or carotid levels. Increases in jugular ammonia concentrations correlated with increased number of larvae, area of infestation, earlier death, neutropenia, eosinopenia, lymphocytopenia, large declines in serum globulins and zinc, and large rises in toxic neutrophils. The high concentrations of toxic unionized ammonia in blood directly permanently damaged neutrophils and lymphocytes and depressed serum globulin production. The results show that the ammonium from the excreta of larvae of L. cuprina may be highly immunosuppressive.     

Hand, space and attentional asymmetries in goal-directed manual aiming

Two experiments were conducted to explore the interaction of the two cerebral hemispheres in motor control, by examining hand, space and attentional asymmetries in goal-directed aiming. In Experiment 1, right-handed subjects moved to targets more quickly with their right hand than their left hand. In addition, each hand was faster when moving in its own hemispace. Although in a control condition, movements were initiated more quickly with the left hand, visual distractors disrupted left hand performance more than right hand performance. For contralateral aiming, ipsilateral distractors caused the greatest interference. In Experiment 2, when targets and distractors were all presented at the midline, a right hand advantage was found for movement time along with a left hand advantage for reaction time, independent of target and distractor location. Our findings are discussed in terms of a right hemisphere role in movement preparation and the allocation of attention in space, and greater left hemisphere involvement in movement execution.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.     

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

NMR spectroscopy of human post mortem cerebrospinal fluid: distinction of Alzheimer''s disease from control using pattern recognition and statistics

Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele-specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine-to-adenine transition in the first base of codon 13 of c-Ki-ras which replaced wild-type glycine with serine, indicating that a putative glycine-to-aspartic acid change is not necessarily the critical event for c-Ki-ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer.     

Platinum concentrations in urban road dust and soil, and in blood and urine in the United Kingdom

Increasing Pt concentrations from vehicle catalysts have been reported from a number of countries. Analysis of Pt and Pd in soils and road dusts taken from areas of high and low traffic flows in SE England show concentrations of Pt in the range < 0.30-40.1 ng g-1 and Pd in the range < 2.1-57.9 ng g-1. Higher concentrations of Pt are associated with high traffic densities. Samples taken from streets of lower traffic flows were found to contain the lower concentrations of the ranges. Pilot studies of Pt concentrations in blood and urine using ICP-MS have been carried out. Platinum concentrations in whole blood were: precious metal workers, 780-2170, mean 1263 pmol l-1 (0.152-0.423, mean 0.246 microgram l-1); motorway maintenance workers, 645-810, mean 744 pmol l-1 (0.126-0.158, mean 0.145 microgram l-1); Imperial College staff, 590-713, mean 660 pmol l-1 (0.115-0.139, mean 0.129 microgram l-1). Platinum concentrations in urine in pmol Pt per mmol creatinine were: precious metal workers, 122-682, mean 273 [0.21-1.18, mean 0.47 microgram Pt (g creatinine)-1]; motorway maintenance workers, 13-78, mean 33.7 [0.022-0.135, mean 0.058 microgram Pt (g creatinine)-1]; Imperial College staff, 28-130, mean 65.6 [0.048-0.224, mean 0.113 microgram Pt (g creatinine)-1]. Detection limits were 0.03 microgram l-1 for both blood and urine. The possible health effects of increasing Pt in the environment are discussed. Platinum provides an excellent example of the significance of speciation in metal toxicity. Platinum allergy is confined to a small group of charged compounds that contain reactive ligand systems, the most effective of which are chloride ligand systems. Metallic Pt is considered to be biologically inert and non allergenic and since the emitted Pt is probably in the metallic or oxide form, the sensitising potential is probably very low. Platinum from road dusts, however, can be solubilised, and enter waters, sediments, soils and the food chain. There is at present no evidence for any adverse health effects from Pt in the general environment, particularly allergic reactions.