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21.
Jason A Roberts Michael S Roberts Andrew Semark Andrew A Udy Carl MJ Kirkpatrick David L Paterson Matthew J Roberts Peter Kruger Jeffrey Lipman 《BMC anesthesiology》2011,11(1):1-7
Background
Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam.Methods/Design
This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics.Discussion
The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues. 相似文献22.
Background
Protein complexes are important for understanding principles of cellular organization and functions. With the availability of large amounts of high-throughput protein-protein interactions (PPI), many algorithms have been proposed to discover protein complexes from PPI networks. However, existing algorithms generally do not take into consideration the fact that not all the interactions in a PPI network take place at the same time. As a result, predicted complexes often contain many spuriously included proteins, precluding them from matching true complexes.Results
We propose two methods to tackle this problem: (1) The localization GO term decomposition method: We utilize cellular component Gene Ontology (GO) terms to decompose PPI networks into several smaller networks such that the proteins in each decomposed network are annotated with the same cellular component GO term. (2) The hub removal method: This method is based on the observation that hub proteins are more likely to fuse clusters that correspond to different complexes. To avoid this, we remove hub proteins from PPI networks, and then apply a complex discovery algorithm on the remaining PPI network. The removed hub proteins are added back to the generated clusters afterwards. We tested the two methods on the yeast PPI network downloaded from BioGRID. Our results show that these methods can improve the performance of several complex discovery algorithms significantly. Further improvement in performance is achieved when we apply them in tandem.Conclusions
The performance of complex discovery algorithms is hindered by the fact that not all the interactions in a PPI network take place at the same time. We tackle this problem by using localization GO terms or hubs to decompose a PPI network before complex discovery, which achieves considerable improvement.23.
Bakker MF Verstappen SM Welsing PM Jacobs JW Jahangier ZN van der Veen MJ Bijlsma JW Lafeber FP;Utrecht Arthritis Cohort study group 《Arthritis research & therapy》2011,13(3):R70
Introduction
The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA). 相似文献24.
25.
Chen CP Chern SR Lin CJ Lee CC Wang W Tzen CY 《Genetic counseling (Geneva, Switzerland)》2005,16(1):49-57
During the period January 1987-July 2003, 59 cases of perinatally detected holoprosencephaly (HPE) with cytogenetic results were identified among 97,306 deliveries at Mackay Memorial Hospital. Among these 59 cases with HPE, 25 had euploidy, 27 had numerical aneuploidy, and 7 had structural aneuploidy. In the euploid cases, the male:female sex ratio was 0.39:1, whereas in the aneuploid cases, the ratio was 1:1. The mean (+/-SD) maternal ages for numerical aneuploidy, structural aneuploidy, and euploidy were 33.0 +/- 5.1 years, 27.9 +/- 2.1 years, and 27.8 +/- 5.0 years, respectively. The frequencies of associated major structural anomalies other than craniofacial defects in the cases with numerical aneuploidy, structural aneuploidy, and euploidy were 85.7%, 0%, and 16%, respectively. The present study of HPE suggests that a female excess appears only in the euploid cases, and advanced maternal age and structural anomalies are more commonly associated with the numerically aneuploid cases than the structurally aneuploid and euploid cases. 相似文献
26.
27.
Chern JH Chang CS Tai CL Lee YC Lee CC Kang IJ Lee CY Shih SR 《Bioorganic & medicinal chemistry letters》2005,15(19):4206-4211
The new pyridyl imidazolidinone derivative, 1-[5-(4'-chlorobiphenyl-4-yloxy)-3-methylpentyl]-3-pyridin-4-yl-imidazolidin-2-one (+/-)-1a, was synthesized and found to have an excellent antiviral activity against EV71 (IC50 = 0.009 microM). Therefore, both the enantiomers, (S)-(+)-1a and (R)-(-)-1a, have been prepared starting from readily available monomethyl (R)-3-methylglutarate (7) as a useful chiral building block and their antiviral activity was evaluated in a plaque reduction assay. Interestingly, we observed that the enantiomer (S)-(+)-1a was 10-fold more active against enterovirus71 (EV71) (IC50 = 0.003 microM) than the corresponding enantiomer (R)-(-)-1a (IC50 = 0.033 microM). Similar results were found against all five strains (1743, 2086, 2231, 4643, and BrCr) of EV71 tested. This demonstrated that the absolute configuration of the chiral carbon atom at the 3-position of the alkyl linker considerably influenced the anti-EV71 activity of these pyridyl imidazolidinones. 相似文献
28.
Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. Exon skipping is the most commonly known alternative splicing mechanism. A comprehensive database of alternative splicing by exon skipping is made available for the human genome data. 1,229 human genes are identified to exhibit alternative splicing by exon skipping. Availability: http://sege.ntu.edu.sg/wester/ashes/. 相似文献
29.
Chou JL Huang CL Lai HL Hung AC Chien CL Kao YY Chern Y 《The Journal of biological chemistry》2004,279(44):46271-46279
In the present study, we used the N terminus (amino acids 1 approximately 160) of type VI adenylyl cyclase (ACVI) as bait to screen a mouse brain cDNA library and identified Snapin as a novel ACVI-interacting molecule. Snapin is a binding protein of SNAP25, a component of the SNARE complex. Co-immunoprecipitation analyses confirmed the interaction between Snapin and full-length ACVI. Mutational analysis revealed that the interaction domains of ACVI and Snapin were located within amino acids 1 approximately 86 of ACVI and 33-51 of Snapin, respectively. Co-localization of ACVI and Snapin was observed in primary hippocampal neurons. Moreover, expression of Snapin specifically eliminated protein kinase C (PKC)-mediated suppression of ACVI, but not that of cAMP-dependent protein kinase (PKA) or calcium. Mutation of the potential PKC and PKA phosphorylation sites of Snapin did not affect the ability of Snapin to reverse the PKC inhibitory effect on ACVI. Phosphorylation of Snapin by PKC or PKA therefore might not be crucial for Snapin action on ACVI. In contrast, Snapin(Delta33-51), which harbors an internal deletion of amino acids 33-51 did not affect PKC-mediated inhibition of ACVI, supporting that amino acids 33-51 of Snapin comprises the ACVI-interacting region. Consistently, Snapin exerted no effect on PKC-mediated inhibition of an ACVI mutant (ACVI-DeltaA87), which lacked the Snapin-interacting region (amino acids 1-86). Snapin thus reverses its action via direct interaction with the N terminus of ACVI. Collectively, we demonstrate herein that in addition to its association with the SNARE complex, Snapin also functions as a regulator of an important cAMP synthesis enzyme in the brain. 相似文献
30.
Chen CP Lin SP Chern SR Lee CC Huang JK Wang W 《Genetic counseling (Geneva, Switzerland)》2006,17(2):185-189
A 34-year-old mother presented moderate mental retardation, short stature, microcephaly, and characteristic facial dysmorphism. Her 12-year-old daughter manifested moderate mental retardation, short stature, microcephaly, dysplastic external ear canals, hearing impairment, and characteristic facial dysmorphism. Cytogenetic analysis of the family revealed a normal karyotype, 46,XY, in the father, and a 46,XX,del(18)(q22.2) karyotype in both mother and daughter. Molecular marker analysis determined direct transmission of the distal 18q deletion from mother to daughter. The present case provides evidence of fertility of the affected females and a mother-to-daughter direct transmission in the familial 18q- syndrome. Identification of affected females with the 18q- syndrome should include genetic counseling of possible direct transmission and consideration of birth control or prenatal genetic testing at reproductive age. 相似文献