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Biomedical subjects

A Ma

Publications and source records attributed to A Ma.

At least 19 recordsLinked to original sources

A high-resolution anthropomorphic voxel-based tomographic phantom for proton therapy of the eye.

Proton therapy is increasingly used in medical treatments for cancer patients due to the sharp dose conformity offered by the characteristic Bragg peak. Proton beam interactions with the eye will be simulated using the MCNPX Monte Carlo code and available nuclear cross-section data to calculate the dose distribution in the eye gel and surrounding organs. A high-resolution eye model will be employed using a 3D geometrical voxel-based anthropomorphic head phantom obtained from the Visible Human Project (female data). Manual segmentation of the eye, carried out by the Medical Physics group at the University of Surrey resulted in 15 identified structures. This work emphasizes the use of a realistic phantom for accurately predicting dose deposition by protons.

Anthropometry↗

Quantum Monte Carlo study of the Ne atom and the Ne+ ion.

We report all-electron and pseudopotential calculations of the ground-state energies of the neutral Ne atom and the Ne(+) ion using the variational and diffusion quantum Monte Carlo (DMC) methods. We investigate different levels of Slater-Jastrow trial wave function: (i) using Hartree-Fock orbitals, (ii) using orbitals optimized within a Monte Carlo procedure in the presence of a Jastrow factor, and (iii) including backflow correlations in the wave function. Small reductions in the total energy are obtained by optimizing the orbitals, while more significant reductions are obtained by incorporating backflow correlations. We study the finite-time-step and fixed-node biases in the DMC energy and show that there is a strong tendency for these errors to cancel when the first ionization potential (IP) is calculated. DMC gives highly accurate values for the IP of Ne at all the levels of trial wave function that we have considered.

Journal Article↗

VEGF-A regulates the expression of VEGF-C in human retinal pigment epithelial cells.

AIM: To determine the expression and regulation of vascular endothelial growth factor C (VEGF-C), and its receptor VEGFR-3, in human retinal pigment epithelial (RPE) cells and to consider their angiogenic role in choroidal neovascularisation (CNV). METHOD: The expression of VEGF-C and VEGFR-3 in cultured human RPE was confirmed by immunostaining, PCR, western blotting, and ELISA. Cultured RPE cells were exposed to VEGF-A and glucose and VEGF-C and VEGFR-3 changes in gene expression determined by RT-PCR. Secreted VEGF-C protein in conditioned media from RPE was examined by western blotting and ELISA analysis. The ability of VEGF-C to elicit tube formation in choroidal endothelial cells was assayed by an in vitro Matrigel model. RESULT: VEGF-A and glucose upregulated VEGF-C mRNA expression and increased the secretion of VEGF-C protein into the culture medium. VEGF-A, but not glucose alone, stimulated VEGFR-3 mRNA expression. VEGF-C acted synergistically with VEGF-A to promote in vitro tube formation by choroidal endothelial cells. CONCLUSION: VEGF-A has a critical role in the orchestration of VEGF-C expression in RPE cells and the synergistic action of VEGF-C with VEGF-A may play an important part in the aetiology of CNV.

Cells, Cultured↗

A pilot study of ranolazine in patients with intermittent claudication.

AIM: This pilot study provides preliminary information regarding safety and changes in exercise performance during treatment with ranolazine extended-release in patients with reproducible claudication during exercise treadmill testing (ETT). METHODS: We enrolled 45 patients with documented peripheral arterial disease, reproducible claudication on ETT, and ankle-brachial indices <0.85 at rest that decreased by at least 0.15% or 20% immediately postexercise. Randomized patients received double-blind treatment with either ranolazine 1 000 mg b.i.d. (n=22) or placebo (n=23) for 4 weeks. RESULTS: Compared with baseline, peak walking time (PWT) increased (mean+/-SEM) by 53+/-34 s with ranolazine (P=0.13) and by 41+/-33 s with placebo (P=0.22). Pain-free walking time during ETT increased by 62+/-18 s with ranolazine (P=0.002) and 36+/-18 s with placebo (P=0.045). Supplemental analyses, excluding patients with baseline exercise duration (16 min and (12 min, showed additional improvement with ranolazine on PWT. CONCLUSIONS: Ranolazine was well tolerated and these data provide a rationale for proceeding with a definitive trial.

Acetanilides↗

All-electron quantum Monte Carlo calculations for the noble gas atoms He to Xe.

We report all-electron variational and diffusion quantum Monte Carlo (VMC and DMC) calculations for the noble gas atoms He, Ne, Ar, Kr, and Xe. The calculations were performed using Slater-Jastrow wave functions with Hartree-Fock single-particle orbitals. The quality of both the optimized Jastrow factors and the nodal surfaces of the wave functions declines with increasing atomic number Z, but the DMC calculations are tractable and well behaved in all cases. We discuss the scaling of the computational cost of DMC calculations with Z.

Journal Article↗

Scheme for adding electron-nucleus cusps to Gaussian orbitals.

A simple scheme is described for introducing the correct cusps at nuclei into orbitals obtained from Gaussian basis set electronic structure calculations. The scheme is tested with all-electron variational quantum Monte Carlo (VMC) and diffusion quantum Monte Carlo (DMC) methods for the Ne atom, the H2 molecule, and 55 molecules from a standard benchmark set. It greatly reduces the variance of the local energy in all cases and slightly improves the variational energy. This scheme yields a general improvement in the efficiency of all-electron VMC and DMC calculations using Gaussian basis sets.

Journal Article↗

Cardioprotective effects of peroxisome proliferator activated receptor gamma activators on acute myocarditis: anti-inflammatory actions associated with nuclear factor kappaB blockade.

OBJECTIVE: To test the hypothesis that activation of peroxisome proliferator activated receptor gamma (PPAR-gamma) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor kappaB (IkappaB) alpha induction, blockade of nuclear factor kappaB (NF-kappaB), and inhibition of inflammatory cytokine expression. METHODS: EAM was induced in Lewis rats by immunisation with porcine cardiac myosin. PPAR-gamma activators 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) and pioglitazone (PIO) were administered to rats with EAM. RESULTS: Enhanced PPAR-gamma expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of 15d-PGJ2 and PIO greatly reduced the severity of myocarditis and suppressed myocardial mRNA and protein expression of inflammatory cytokines in rats with EAM. In addition, treatment with PPAR-gamma activators enhanced IkappaB concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-kappaB was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ2 treated and PIO treated groups. CONCLUSIONS: PPAR-gamma may have a role in the pathophysiology of EAM. Because an increase in IkappaB expression and inhibition of translocation of the NF-kappaB subunit p65 to the nucleus in inflammatory cells correlated with the protective effects of PPAR-gamma activators, these results suggest that PPAR-gamma activators act sequentially through PPAR-gamma activation, IkappaB induction, blockade of NF-kappaB activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-gamma activators such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.

Acute Disease↗

Neutron-fluence-to-dose conversion coefficients in an anthropomorphic phantom.

A set of fluence-to-effective-dose conversion coefficients has been calculated for neutrons with energies <20 MeV using a high-resolution anthropomorphic phantom (Zubal model) and the MCNPX code. The calculation used 13 monodirectional monoenergetic neutron beams in the energy range 10(-9) to 20 MeV, under three different source irradiation configurations: anterior-posterior, posterior-anterior and left lateral. Dose calculations were performed for 18 selected organs of the body, for which the International Commission on Radiological Protection and the International Commission on Radiological Units and Measurements have set tissue weighting factors for the determination of the effective dose. Another set of neutron-fluence-to-effective-dose conversion coefficients was also calculated with the proposed modification wR from ICRP Publication 92. From comparison between the dose results calculated and the data reported for the MIRD and VIPMAN models, it can be concluded that, although some discrepancies exist between the Zubal model and the two other models, there is good agreement in the left lateral irradiation geometry.

Anthropometry↗

T cell-independent interleukin 15Ralpha signals are required for bystander proliferation.

Cytokine driven or "bystander" proliferation of T cells occurs in vivo independently of major histocompatibility complex-T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8(+) T cells. Surprisingly, IL-15Ralpha(-/-) CD8(+) T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8(+) T cells fail to proliferate in IL-15Ralpha(-/-) mice. Normal mice reconstituted with IL-15Ralpha(-/-) bone marrow cells also fail to exhibit bystander responses. Thus, CD8(+) T cell independent IL-15Ralpha signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8(+) T cells proliferate in IL-15Ralpha(-/-) mice after treatment with IL-15. Therefore, IL-15Ralpha signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Ralpha supports memory phenotype CD8(+) T cell proliferation, and suggest novel mechanisms by which memory CD8(+) T cells are maintained in vivo.

Adoptive Transfer↗

Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.

BACKGROUND & AIMS: Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression. METHODS: Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively. RESULTS: Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed increased resistance to monochloramine. In vivo, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression. CONCLUSIONS: SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.

3T3 Cells↗

Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130(Cas).

Focal adhesion kinase (FAK) is an important regulator of integrin signaling in adherent cells and accordingly its activity is significantly modulated during mitosis when cells detach from the extracellular matrix. During mitosis, FAK becomes heavily phosphorylated on serine residues concomitant with its inactivation and dephosphorylation on tyrosine. Little is known about the regulation of FAK activity by serine phosphorylation. In this report, we characterize two novel sites of serine phosphorylation within the C-terminal domain of FAK. Phosphorylation-specific antibodies directed to these sites and against two previously characterized sites of serine phosphorylation were used to study the regulated phosphorylation of FAK in unsynchronized and mitotic cells. Among the four major phosphorylation sites, designated pS1-pS4, phosphorylation of pS1 (Ser722) is unchanged in unsynchronized and mitotic cells. In contrast, pS3 and pS4 (Ser843 and Ser910) exhibit increased phosphorylation during mitosis. In vitro peptide binding experiments provide evidence that phosphorylation of pS1 (Ser722) may play a role in modulating FAK binding to the SH3 domain of the adapter protein p130(Cas).

Animals↗

Integration and the performance of healthcare networks: do integration strategies enhance efficiency, profitability, and image?

PURPOSE: This study examines the integration effects on efficiency and financial viability of the top 100 integrated healthcare networks (IHNs) in the United States. THEORY: A contingency-strategic theory is used to identify the relationship of IHNs' performance to their structural and operational characteristics and integration strategies. METHODS: The lists of the top 100 IHNs ranked in two years, 1998 and 1999, by the SMG Marketing Group were merged to create a database for the study. Multiple indicators were used to examine the relationship between IHNs' characteristics and their performance in efficiency and financial viability. A path analytical model was developed and validated by the Mplus statistical program. Factors influencing the top 100 IHNs' images, represented by attaining ranking among the top 100 in two consecutive years, were analysed. RESULTS AND CONCLUSION: No positive associations were found between integration and network performance in efficiency or profits. Longitudinal data are needed to investigate the effect of integration on healthcare networks' financial performance.

Journal Article↗

[Poison effect of plant granules on Oncomelania hupensis].

Plant granules (phi 2-3 mm) made of starch, gelatin and medicine plant powder were used to kill Oncomelania hupensis. The results showed that after eating the plant granules, the mortality of the snail was 92.5%-100% within 24 hrs. The poison effect of the plant granules was much better than that of others, e.g., they could kill snails 12-24 h earlier than Niclosamidum (1 x 10(-3) g.L-1). In a field experiment, the snail mortality was up to 61.5% by using plant granules.

Animals↗

[Effect of folic acid and supplemented with vitamin A and vitamin E on depressing teratogenesis induced by cyclophosphamide].

The effect of folic acid and the combined effect of folic acid(FA) + vitamin A + vitamin E on the prevention of teratogenesis induced by cyclophosphamide during pregnancy were observed. The results showed that cyclophosphamide resulted a decreased weight and length of the fetuses, an increased rate of neural tube defects and a retardation of ossification centers. The neural tube defects rates in the groups with no any supplementation, supplemented with folic acid alone and supplemented with FA + vitamin A + vitamin E were 87.27%, 42.93% and 30.08% respectively(P < 0.01). The supplementation of FA or the combined supplementation resulted also in greater fetal weight and length, increased ossification of supraoccipital bone (P < 0.01). The study suggested that the combined effect of FA, vitamin A and vitamin E was superior to FA alone.

Animals↗

Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF-kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappaB responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo.

Animals↗

Fifth-order raman spectrum of an atomic liquid: simulation and instantaneous-normal-mode calculation

Experimental artifacts and technical difficulties in carrying out theoretical calculations have consistently frustrated attempts to obtain the two-dimensional (5th-order) Raman spectrum of a liquid. We report here a new theoretical development: the first microscopic numerical simulation of the 5th-order Raman signal in a liquid. Comparison with an instantaneous-normal-mode treatment, a fully microscopic model which interprets liquid dynamics as arising from coherent harmonic modes, shows that the 5th-order spectrum reveals profound effects stemming from dynamical anharmonicity.

Journal Article↗

The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues.

Proapoptotic Bcl-2 family members have been proposed to play a central role in regulating apoptosis. However, mice lacking bax display limited phenotypic abnormalities. As presented here, bak(-/-) mice were found to be developmentally normal and reproductively fit and failed to develop any age-related disorders. However, when Bak-deficient mice were mated to Bax-deficient mice to create mice lacking both genes, the majority of bax(-/-)bak(-/-) animals died perinatally with fewer than 10% surviving into adulthood. bax(-/-)bak(-/-) mice displayed multiple developmental defects, including persistence of interdigital webs, an imperforate vaginal canal, and accumulation of excess cells within both the central nervous and hematopoietic systems. Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis.

Abnormalities, Multiple↗