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81.
Chamakou AC Dede E Moutafi A Thanopoulos V Chryssanthopoulos S Loukopoulou S Pitsavos C Stefanadis C Davos CH 《Cytokine》2012,57(1):130-135
Introduction
Inflammation and neurohormonal activation are considered to be involved in the development of earlier and/or later complications in congenital heart disease patients, even after a successful repair of the lesion. It is not yet clarified what is the role of the therapeutic interventions in the occurrence of such a response and how it could be associated with possible postoperative complications.Aim
We sought to assess the inflammatory and neurohormonal response to transcatheter closure of secundum type atrial septal defects (ASD) over a six-month follow-up period. We also evaluated the association between the respective markers and catheterization data as well as echocardiographic measurements.Methods
Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), N-terminal-proatrial natriuretic peptide (NT-proANP) and N-terminal-probrain natriuretic peptide (NT-proBNP) were assessed and echocardiographic measurements were performed in twenty-eight patients with atrial septal defect prior to, and at the first, second and sixth months post transcatheter closure. Thirty-three age-matched healthy volunteers were also enrolled.Results
IL-6 plasma levels, although higher preoperatively, [physical logarithm (ln) IL-6: 3.37 ± 0.66 vs 2.92 ± 0.44 pg/ml, p = 0.015], reached control levels postoperatively, at the end of the third month, whereas TNF-α and IL-10 were not influenced by the procedure. NT-proANP levels were elevated preoperatively compared to the control group (ln NT-proANP 3.78 ± 0.572 vs 3.48 ± 0.30, p = 0.031), with a further significant increase during the 1st month (ln NT-proANP 3.78 ± 0.572 vs 4.2 ± 0.42, p = 0.006), following the pattern of the left atrial volume enlargement, and remained high even 6 months after the procedure .On the other hand, the initially normal concentrations of NT-proBNP, after a transient significant increase during the first month postoperatively (ln NT-proBNP 3.56 ± 0.94 vs 4.58 ± 0.91, p < 0.0001) returned to the controls’ levels at the end of the third month. Preoperative concentrations of NT-proANP positively correlated with NT-proBNP concentrations and pulmonary to systemic flow ratio (Qp/Qs).Conclusions
Transcatheter closure could improve, on a mid- term basis, the inflammatory process but natriuretic peptides’ secretion continues in parallel with left atrial volume increase. Further follow up is required to determine the long-term progress of the inflammatory and neurohormonal response to the procedure. 相似文献82.
Kentsis A Reed C Rice KL Sanda T Rodig SJ Tholouli E Christie A Valk PJ Delwel R Ngo V Kutok JL Dahlberg SE Moreau LA Byers RJ Christensen JG Woude GV Licht JD Kung AL Staudt LM Look AT 《Nature medicine》2012,18(7):1118-1122
Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and survival of cancer cells. Thus, using a loss-of-function RNA interference genomic screen, we identified the aberrant expression of hepatocyte growth factor (HGF) as a crucial element in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples we studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1), concomitant inhibition of FGFR1 and MET blocked this compensatory HGF upregulation, resulting in sustained logarithmic cell killing both in vitro and in xenograft models in vivo. Our results show a widespread dependence of AML cells on autocrine activation of MET, as well as the key role of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers. 相似文献
83.
E Tsompanidou EL Denham MJ Sibbald XM Yang J Seinen AW Friedrich G Buist JM van Dijl 《PloS one》2012,7(9):e44646
Staphylococcus aureus is an important human pathogen that is renowned both for its rapid transmission within hospitals and the community, and for the formation of antibiotic resistant biofilms on medical implants. Recently, it was shown that S. aureus is able to spread over wet surfaces. This motility phenomenon is promoted by the surfactant properties of secreted phenol-soluble modulins (PSMs), which are also known to inhibit biofilm formation. The aim of the present studies was to determine whether any cell surface-associated S. aureus proteins have an impact on colony spreading. To this end, we analyzed the spreading capabilities of strains lacking non-essential components of the protein export and sorting machinery. Interestingly, our analyses reveal that the absence of sortase A (SrtA) causes a hyper-spreading phenotype. SrtA is responsible for covalent anchoring of various proteins to the staphylococcal cell wall. Accordingly, we show that the hyper-spreading phenotype of srtA mutant cells is an indirect effect that relates to the sortase substrates FnbpA, FnbpB, ClfA and ClfB. These surface-exposed staphylococcal proteins are known to promote biofilm formation, and cell-cell interactions. The hyper-spreading phenotype of srtA mutant staphylococcal cells was subsequently validated in Staphylococcus epidermidis. We conclude that cell wall-associated factors that promote a sessile lifestyle of S. aureus and S. epidermidis antagonize the colony spreading motility of these bacteria. 相似文献
84.
D Coggon G Ntani KT Palmer VE Felli R Harari LH Barrero SA Felknor D Gimeno A Cattrell C Serra M Bonzini E Solidaki E Merisalu RR Habib F Sadeghian M Kadir SS Warnakulasuriya K Matsudaira B Nyantumbu MR Sim H Harcombe K Cox MH Marziale LM Sarquis F Harari R Freire N Harari MV Monroy LA Quintana M Rojas EJ Salazar Vega EC Harris S Vargas-Prada JM Martinez G Delclos FG Benavides M Carugno MM Ferrario AC Pesatori L Chatzi P Bitsios M Kogevinas K Oha T Sirk A Sadeghian RJ Peiris-John N Sathiakumar 《PloS one》2012,7(7):e39820
Background
The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample.Methods/Principal Findings
A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI).Conclusions/Significance
The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively. 相似文献85.
Yimer G Aderaye G Amogne W Makonnen E Aklillu E Lindquist L Yamuah L Feleke B Aseffa A 《PloS one》2008,3(3):e1809
Background
To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia.Methodology/Principal Findings
In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg.Conclusions/Significance
Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk. 相似文献86.
Sakkas GK Karatzaferi C Zintzaras E Giannaki CD Liakopoulos V Lavdas E Damani E Liakos N Fezoulidis I Koutedakis Y Stefanidis I 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(6):R1721-R1729
Hemodialysis patients exhibit insulin resistance (IR) in target organs such as liver, muscles, and adipose tissue. The aim of this study was to identify contributors to IR and to develop a model for predicting glucose intolerance in nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived from OGTT data. Measurements included liver and muscle fat infiltration and central adiposity by computed tomography scans, body composition by dual energy X-ray absorptiometer, sleep quality by full polysomnography, and functional capacity and quality of life (QoL) by a battery of exercise tests and questionnaires. Cut-off points, as well as sensitivity and specificity calculations were based on IR (insulin sensitivity index by Matsuda) using a receiver operator characteristics (ROC) curve analysis. Fifteen patients were assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content and visceral adiposity were significantly higher in the IGT group. IR indices strongly correlated with sleep disturbances, visceral adiposity, functional capacity, and QoL. Visceral adiposity, O2 desaturation during sleep, intrahepatic fat content, and QoL score fitted into the model for predicting glucose intolerance. A ROC curve analysis identified an intrahepatic fat content of > 3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep seemed to be involved at some point in the development of glucose intolerance in hemodialysis patients. Means of reducing fat depots in the liver and splachnic area might prove promising in combating IR and cardiovascular risk in hemodialysis patients. 相似文献
87.
The effect of sodium chloride on the gelatinization and rheological properties of wheat and potato starches has been studied using differential scanning calorimetry, dynamic mechanical thermal analysis, and electron spin resonance techniques. All samples contained 60% water (w/w wet starch basis) and the salt content ranged from 0 to 16% (g/100 g starch-water). The presence of salt affected the onset (T(o)), peak (T(p)), and end (T(e)) temperatures of gelatinization, gelatinization enthalpy (DeltaH), storage modulus (G'), and rotational mobility coefficient (D(rot)), and the effect differed by salt concentration. 1H-NMR was used in parallel in order to elucidate how salts affect the properties of water in starch suspensions and in aqueous salt solutions according to their position on the Hofmeister series classification. The obtained results suggest that the mechanism of starch gelatinization in salt solutions can be attributed to the effect of solute on water properties and direct polymer-solute interactions. These two effects conflict with one another and result in complex effect patterns depending on the concentration of the salts. 相似文献
88.
Andrew Fairbairn Eleni Asouti Julie Near Danièle Martinoli 《Vegetation History and Archaeobotany》2002,11(1-2):41-54
Analysis of charred plant macro-remains, including wood charcoals, cereals, seeds, tubers and fruits from the Neolithic site
of ?atalh?yük has indicated complex patterns of plant resource use and exploitation in the Konya plain during the early Holocene.
Evidence presented in this paper shows that settlement location was not dictated by proximity to high quality arable land
and direct access to arboreal resources (firewood, timber, fruit producing species). A summary of the patterns observed in
sample composition and species representation is outlined here together with preliminary interpretations of these results
within their broader regional context.
Received September 4, 2001 / Accepted April 9, 2002 相似文献
89.
Kim E. Haworth Ira Islam Matthew Breen Wendy Putt Eleni Makrinou Matthew Binns David Hopkinson Yvonne Edwards 《Mammalian genome》2001,12(8):622-629
We describe the construction of a dog embryonic head/neck cDNA library and the isolation of the dog homolog of the Treacher
Collins Syndrome gene, TCOF1. The protein shows a similar three-domain structure to that described for human TCOF1, but the dog gene lacks exon 10 and
contains two exons not present in the human sequence. In addition, exon 19 is differentially spliced in the dog. How these
structural differences relate to TCOF1 phosphorylation is discussed. Isolation of a genomic clone allowed the exon/intron
boundaries to be characterized and the dog TCOF1 gene to be mapped to CF Chr 4q31, a region syntenic to human Chr 5. Genetic analysis of DNA of dogs from 13 different breeds
identified nine DNA sequence variants, three of which gave rise to amino acid substitutions. Grouping dogs according to head
type showed that a C396T variant, leading to a Pro117Ser substitution, is associated with skull/face shape in our dog panel.
The numbers are small, but the association between the T allele and brachycephaly, broad skull/short face, was highly significant
(p= 0.000024). The short period of time during which the domestic dog breeds have been established suggests that this mutation
has arisen only once in the history of dog domestication.
Received: 12 January 2001 / Accepted: 1 April 2001 相似文献
90.
Cognitive functions are stored in the connectome, the wiring diagram of the brain, which exhibits non-random features, so-called motifs. In this work, we focus on bidirectional, symmetric motifs, i.e. two neurons that project to each other via connections of equal strength, and unidirectional, non-symmetric motifs, i.e. within a pair of neurons only one neuron projects to the other. We hypothesise that such motifs have been shaped via activity dependent synaptic plasticity processes. As a consequence, learning moves the distribution of the synaptic connections away from randomness. Our aim is to provide a global, macroscopic, single parameter characterisation of the statistical occurrence of bidirectional and unidirectional motifs. To this end we define a symmetry measure that does not require any a priori thresholding of the weights or knowledge of their maximal value. We calculate its mean and variance for random uniform or Gaussian distributions, which allows us to introduce a confidence measure of how significantly symmetric or asymmetric a specific configuration is, i.e. how likely it is that the configuration is the result of chance. We demonstrate the discriminatory power of our symmetry measure by inspecting the eigenvalues of different types of connectivity matrices. We show that a Gaussian weight distribution biases the connectivity motifs to more symmetric configurations than a uniform distribution and that introducing a random synaptic pruning, mimicking developmental regulation in synaptogenesis, biases the connectivity motifs to more asymmetric configurations, regardless of the distribution. We expect that our work will benefit the computational modelling community, by providing a systematic way to characterise symmetry and asymmetry in network structures. Further, our symmetry measure will be of use to electrophysiologists that investigate symmetry of network connectivity. 相似文献