Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive patients with malignant ventricular arrhythmias and implantable cardioverterdefibrillators with a mean age of 62.7 +/- 12.2 years and a mean left ventricular ejection fraction of 0.37 +/- 11.0. Taq polymorphism of ET-1 was detected using our original polymerase chain reaction method. The polymerase chain reaction product with a length of 358 basepairs (bp) (primers 5'-CAA ACC GAT GTC CTC TGT A-3' and 5'-ACC AAA CAC ATT TCC CTA TT-3') in its non-mutated form contains a target sequence for TaqI restrictive enzyme, while a mutated product loses this cleavage site. Of 26 patients, nine (34%) had recurrent palpitations and eight (30.8%) had syncopes during their malignant arrhythmias. Nineteen patients were given amiodarone after implantable cardioverter-defibrillator insertion and seven were not treated with amiodarone. Fifteen patients had (++), 11 (+-) and 0 (- -) ET-1 genotype. The risk for syncopes was associated with the (++) genotype of the ET-1 gene (P = 0.01). Patients receiving amiodarone had significantly higher frequency of the (++) genotype (P = 0.011). All our results indicate that the presence of the ET-1 genotype (++) in patients with structural heart disease, severe left ventricular dysfunction and malignant ventricular arrhythmias increases the risk for these patients of hemodynamic collapse during these arrhythmias.
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PMID:Endothelin-1 gene polymorphism in patients with malignant arrhythmias. 1583 69

There are an increasing number of radiation therapy patients with hip prosthesis. The common method of minimizing treatment planning inaccuracies is to avoid radiation beams to transit through the prosthesis. However, the beams often exit through them, especially when the patient has a double-prosthesis. Modern treatment planning systems employ algorithms with improved dose calculation accuracies but even these algorithms may not predict the dose accurately at high atomic number interfaces. The current study evaluates the dose calculation accuracy of three common dose calculation algorithms employed in two commercial treatment planning systems. A hip prosthesis was molded inside a cylindrical phantom and the dose at several points within the phantom at the interface with prosthesis was measured using thermoluminescent dosimeters. The measured doses were then compared to the predicted ones by the planning systems. The results of the study indicate all three algorithms underestimate the dose at the prosthesis interface, albeit to varying degrees, and for both low- and high-energy x rays. The measured doses are higher than calculated ones by 5-22% for Pinnacle Collapsed Cone Convolution algorithm, 2-23% for Eclipse Acuros XB, and 6-25% for Eclipse Analytical Anisotropic Algorithm. There are generally better agreements for AXB algorithm and the worst results are for the AAA.
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PMID:Evaluation of dose calculation accuracy of treatment planning systems at hip prosthesis interfaces. 2831 12

Pathogens and allergens are deemed as two contrasting facets of host immune status, deficiency and exuberant. In silico domain analysis of a diverse panel of pathogen and allergen proteins has revealed the shortcoming of this notion. Both the pathogen and allergen proteins elicit immune activation, with the outcome of immune agitation depending on the pathogen strain, allergen exposure duration, and host factors. Pathogens can replicate within the host and constantly irritate the immune system, leading to blood coagulation, respiratory collapse and death. Allergens, being non-viable, can only provoke the immune system transiently; however, depending on the allergen dose and extent exposed to, inflammation and fatality can occur. In silico analysis of pathogen and allergen proteins showed the conserved domains to be AAA, WR1, VKc, Kelch, Hr1, HAMP, HELICc, Dak2, CHAD, CHASE2, Galanin, PKS_TE, Robl_LC7, Excalibur, DISIN, etc. This exciting discovery can have far-reaching effects in drug target identification approaches.
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PMID:Under the superficial dichotomy pathogen and allergen are two manifestations of same immune activation and pathogenesis mechanisms. 2841 Aug 73

Diverse neuronal populations with distinct cellular morphologies coordinate the complex function of the nervous system. Establishment of distinct neuronal morphologies critically depends on signaling pathways that control axonal and dendritic development. The Sema3A-Nrp1/PlxnA4 signaling pathway promotes cortical neuron basal dendrite arborization but also repels axons. However, the downstream signaling components underlying these disparate functions of Sema3A signaling are unclear. Using the novel PlxnA4KRK-AAA knock-in male and female mice, generated by CRISPR/cas9, we show here that the KRK motif in the PlxnA4 cytoplasmic domain is required for Sema3A-mediated cortical neuron dendritic elaboration but is dispensable for inhibitory axon guidance. The RhoGEF FARP2, which binds to the KRK motif, shows identical functional specificity as the KRK motif in the PlxnA4 receptor. We find that Sema3A activates the small GTPase Rac1, and that Rac1 activity is required for dendrite elaboration but not axon growth cone collapse. This work identifies a novel Sema3A-Nrp1/PlxnA4/FARP2/Rac1 signaling pathway that specifically controls dendritic morphogenesis but is dispensable for repulsive guidance events. Overall, our results demonstrate that the divergent signaling output from multifunctional receptor complexes critically depends on distinct signaling motifs, highlighting the modular nature of guidance cue receptors and its potential to regulate diverse cellular responses.SIGNIFICANCE STATEMENT The proper formation of axonal and dendritic morphologies is crucial for the precise wiring of the nervous system that ultimately leads to the generation of complex functions in an organism. The Semaphorin3A-Neuropilin1/Plexin-A4 signaling pathway has been shown to have multiple key roles in neurodevelopment, from axon repulsion to dendrite elaboration. This study demonstrates that three specific amino acids, the KRK motif within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream signaling molecules to promote Sema3A-mediated cortical neuron dendritic elaboration, but not inhibitory axon guidance. Our results unravel a novel Semaphorin3A-Plexin-A4 downstream signaling pathway and shed light on how the disparate functions of axon guidance and dendritic morphogenesis are accomplished by the same extracellular ligand in vivo.
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PMID:Modular and Distinct Plexin-A4/FARP2/Rac1 Signaling Controls Dendrite Morphogenesis. 3249 77