772 research outputs found

    PHYSICAL PERFORMANCE AND BODY COMPOSITION IN MAINTENANCE HEMODIALYSIS (MHD) PATIENTS

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    BackgroundMHD patients (pts) often display protein-energy wasting, sarcopenia & diminished physical performance. This study was undertaken to assess the relationship between body composition & physical performance in MHD pts.MethodsBody composition, assessed by dual energy x-ray absorptiometry and body mass index (BMI), were compared to 3 measures of physical performance: 6-minute walking distance (6-MW), sit-to-stand testing and stair climb. 52 clinically stable MHD pts (≥6 mo) and 21 matched normal controls were examined in this ongoing study.ResultsPts were 53±13SD yrs, 33% female; 38% diabetic; dialysis vintage was 62±52 months. Normals were 52 years and 43% female. MHD pts had higher % body fat than Normals. 6-MW and sit to stand cycles were much lower in MHD men and women than in Normal men and women. 6MW in MHD and Normals were 445 vs 630 meters, respectively (p<.001). In men but not women, time to climb 22 stairs was greater in MHD pts then in Normals (p=.03). Unadjusted analyses in MHD indicated that 6-MW distance correlated negatively with lean body mass index (LBMI, kg of LBM/m2; r=-0.37; p<0.01) and % body fat (r=-0.33; p= 0.02); stair climb time correlated negatively with lean leg mass (r=-0.32, p=0.03) and total leg mass (r=-0.29, p=0.045).). Sit-to-stand did not correlate with any body composition measure. 6-MW adjusted for age and gender correlated negatively with LBMI (r=-0.29; p=0.04).There were no associations between BMI (range, 19.8-44.2 kg/m2) and physical performance.ConclusionsThese findings indicate that adult MHD pts had a higher % body fat. Measures of physical performance were markedly reduced in MHD pts as compared to Normals. Physical performance in MHD, measured especially by 6-MW, correlated negatively with some measures of body composition, particularly with LBMI

    A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

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    During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

    Recursive construction of perfect DNA molecules from imperfect oligonucleotides

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    Making faultless complex objects from potentially faulty building blocks is a fundamental challenge in computer engineering, nanotechnology and synthetic biology. Here, we show for the first time how recursion can be used to address this challenge and demonstrate a recursive procedure that constructs error-free DNA molecules and their libraries from error-prone oligonucleotides. Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed. Our recursive construction procedure surpasses existing methods for de novo DNA synthesis in speed, precision, amenability to automation, ease of combining synthetic and natural DNA fragments, and ability to construct designer DNA libraries. It thus provides a novel and robust foundation for the design and construction of synthetic biological molecules and organisms

    Size of third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage

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    In patients with acute hydrocephalus after aneurysmal subarachnoid haemorrhage (SAH), lumbar drainage is possible if the obstruction is in the subarachnoid space (communicating hydrocephalus). In case of intraventricular obstruction (obstructive hydrocephalus), ventricular drainage is the only option. A small fourth ventricle is often considered a sign of obstructive hydrocephalus. We investigated whether the absolute or relative size of the fourth ventricle can indeed distinguish between these two types of hydrocephalus. On CT-scans of 76 consecutive patients with acute headache but normal CT and CSF, we measured the cross-sectional surface of the third and fourth ventricle to obtain normal planimetric values. Subsequently we performed the same measurements on 117 consecutive SAH patients with acute hydrocephalus. These patients were divided according to the distribution of blood on CT-scan into three groups: mainly intraventricular blood (n = 15), mainly subarachnoid blood (n = 54) and both intraventricular and subarachnoid blood (n = 48). The size of the fourth ventricle exceeded the upper limit of normal in 2 of the 6 (33%) patients with intraventricular blood but without haematocephalus, and in 15 of the 54 (28%) patients with mainly subarachnoid blood. The mean ratio between the third and fourth ventricle was 1.45 (SD 0.66) in patients with intraventricular blood and 1.42 (SD 0.91) in those with mainly subarachnoid blood. Neither fourth ventricular size nor the ratio between the third and fourth ventricles discriminates between the two groups. A small fourth ventricle does not necessarily accompany obstructive hydrocephalus and is therefore not a contraindication for lumbar drainage

    Psoriasis and Hypertension Severity: Results from a Case-Control Study

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    BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients

    Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

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    The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

    Characterization of ERK Docking Domain Inhibitors that Induce Apoptosis by Targeting Rsk-1 and Caspase-9

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    <p>Abstract</p> <p>Background</p> <p>The extracellular signal-regulated kinase-1 and 2 (ERK1/2) proteins play an important role in cancer cell proliferation and survival. ERK1/2 proteins also are important for normal cell functions. Thus, anti-cancer therapies that block all ERK1/2 signaling may result in undesirable toxicity to normal cells. As an alternative, we have used computational and biological approaches to identify low-molecular weight compounds that have the potential to interact with unique ERK1/2 docking sites and selectively inhibit interactions with substrates involved in promoting cell proliferation.</p> <p>Methods</p> <p>Colony formation and water soluble tetrazolium salt (WST) assays were used to determine the effects of test compounds on cell proliferation. Changes in phosphorylation and protein expression in response to test compound treatment were examined by immunoblotting and <it>in vitro </it>kinase assays. Apoptosis was determined with immunoblotting and caspase activity assays.</p> <p>Results</p> <p><it>In silico </it>modeling was used to identify compounds that were structurally similar to a previously identified parent compound, called <b>76</b>. From this screen, several compounds, termed <b>76.2</b>, <b>76.3</b>, and <b>76.4 </b>sharing a common thiazolidinedione core with an aminoethyl side group, inhibited proliferation and induced apoptosis of HeLa cells. However, the active compounds were less effective in inhibiting proliferation or inducing apoptosis in non-transformed epithelial cells. Induction of HeLa cell apoptosis appeared to be through intrinsic mechanisms involving caspase-9 activation and decreased phosphorylation of the pro-apoptotic Bad protein. Cell-based and <it>in vitro </it>kinase assays indicated that compounds <b>76.3 </b>and <b>76.4 </b>directly inhibited ERK-mediated phosphorylation of caspase-9 and the p90Rsk-1 kinase, which phosphorylates and inhibits Bad, more effectively than the parent compound <b>76</b>. Further examination of the test compound's mechanism of action showed little effects on related MAP kinases or other cell survival proteins.</p> <p>Conclusion</p> <p>These findings support the identification of a class of ERK-targeted molecules that can induce apoptosis in transformed cells by inhibiting ERK-mediated phosphorylation and inactivation of pro-apoptotic proteins.</p
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