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1.
Lever M George PM Atkinson W Elmslie JL Slow S Molyneux SL Troughton RW Richards AM Frampton CM Chambers ST 《PloS one》2012,7(3):e32460
Background
Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease.Methods
The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic.Principal findings
In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion.Conclusions
Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. 相似文献2.
3.
Roberto?H?Higa Roberto?C?Togawa Arnaldo?J?Montagner Juliana?CF?Palandrani Igor?KS?Okimoto Paula?R?Kuser Michel?EB?Yamagishi Adauto?L?Mancini Goran?NeshichEmail author 《BMC bioinformatics》2004,5(1):107
Background
The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. 相似文献4.
The delivery of Ca2+ into cells by CaV channels provides the trigger for many cellular actions, such as cardiac muscle contraction and neurotransmitter release. Thus, a full understanding of Ca2+ permeation through these channels is critical. Using whole-cell voltage-clamp recordings, we recently demonstrated that voltage modulates the apparent affinity of N-type (CaV2.2) channels for permeating Ca2+ and Ba2+ ions. While we took many steps to ensure the high fidelity of our recordings, problems can occur when CaV currents become large and fast, or when currents run down. Thus, we use here single channel recordings to further test the hypothesis that permeating ions interact with N-type channels in a voltage-dependent manner. We also examined L-type (CaV1.2) channels to determine if these channels also exhibit voltage-dependent permeation. Like our whole-cell data, we find that voltage modulates N-channel affinity for Ba2+ at voltages > 0 mV, but has little or no effect at voltages < 0 mV. Furthermore, we demonstrate that permeation through L-channel is also modulated by voltage. Thus, voltage-dependence may be a common feature of divalent cation permeation through CaV1 and CaV2 channels (i.e. high-voltage activated CaV channels). The voltage dependence of CaV1 channel permeation is likely a mechanism mediating sustained Ca2+ influx during the plateau phase of the cardiac action potential. 相似文献
5.
Bevan KS Chung Suresh Selvarasu Andrea Camattari Jimyoung Ryu Hyeokweon Lee Jungoh Ahn Hongweon Lee Dong-Yup Lee 《Microbial cell factories》2010,9(1):50
Background
Pichia pastoris has been recognized as an effective host for recombinant protein production. A number of studies have been reported for improving this expression system. However, its physiology and cellular metabolism still remained largely uncharacterized. Thus, it is highly desirable to establish a systems biotechnological framework, in which a comprehensive in silico model of P. pastoris can be employed together with high throughput experimental data analysis, for better understanding of the methylotrophic yeast's metabolism. 相似文献6.
Michael Lever Peter M. George Sandy Slow David Bellamy Joanna M. Young Markus Ho Christopher J. McEntyre Jane L. Elmslie Wendy Atkinson Sarah L. Molyneux Richard W. Troughton Christopher M. Frampton A. Mark Richards Stephen T. Chambers 《PloS one》2014,9(12)
Background
Betaine is a major osmolyte, also important in methyl group metabolism. Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers. Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk?Methods
Plasma samples were collected from 475 subjects four months after discharge following an acute coronary admission. Death (n = 81), secondary acute MI (n = 87), admission for heart failure (n = 85), unstable angina (n = 72) and all cardiovascular events (n = 283) were recorded (median follow-up: 1804 days).Results
High and low metabolite concentrations were defined as top or bottom quintile of the total cohort. In subjects with diabetes (n = 79), high plasma betaine was associated with increased frequencies of events; significantly for heart failure, hazard ratio 3.1 (1.2–8.2) and all cardiovascular events, HR 2.8 (1.4–5.5). In subjects without diabetes (n = 396), low plasma betaine was associated with events; significantly for secondary myocardial infarction, HR 2.1 (1.2–3.6), unstable angina, HR 2.3 (1.3–4.0), and all cardiovascular events, HR 1.4 (1.0–1.9). In diabetes, high TMAO was a marker of all outcomes, HR 2.7 (1.1–7.1) for death, 4.0 (1.6–9.8) for myocardial infarction, 4.6 (2.0–10.7) for heart failure, 9.1 (2.8–29.7) for unstable angina and 2.0 (1.1–3.6) for all cardiovascular events. In subjects without diabetes TMAO was only significant for death, HR 2.7 (1.6–4.8) and heart failure, HR 1.9 (1.1–3.4). Adding the estimated glomerular filtration rate to Cox regression models tended to increase the apparent risks associated with low betaine.Conclusions
Elevated plasma betaine concentration is a marker of cardiovascular risk in diabetes; conversely low plasma betaine concentrations indicate increased risk in the absence of diabetes. We speculate that the difference reflects control of osmolyte retention in tissues. Elevated plasma TMAO is a strong risk marker in diabetes. 相似文献7.
Background
Influenza pandemic remains a serious threat to human health. Viruses of avian origin, H5N1, H7N7 and H9N2, have repeatedly crossed the species barrier to infect humans. Recently, a novel strain originated from swine has evolved to a pandemic. This study aims at improving our understanding on the pathogenic mechanism of influenza viruses, in particular the role of non-structural (NS1) protein in inducing pro-inflammatory and apoptotic responses.Methods
Human lung epithelial cells (NCI-H292) was used as an in-vitro model to study cytokine/chemokine production and apoptosis induced by transfection of NS1 mRNA encoded by seven infleunza subtypes (seasonal and pandemic H1, H2, H3, H5, H7, and H9), respectively.Results
The results showed that CXCL-10/IP10 was most prominently induced (> 1000 folds) and IL-6 was slightly induced (< 10 folds) by all subtypes. A subtype-dependent pattern was observed for CCL-2/MCP-1, CCL3/MIP-1α, CCL-5/RANTES and CXCL-9/MIG; where induction by H5N1 was much higher than all other subtypes examined. All subtypes induced a similar temporal profile of apoptosis following transfection. The level of apoptosis induced by H5N1 was remarkably higher than all others. The cytokine/chemokine and apoptosis inducing ability of the 2009 pandemic H1N1 was similar to previous seasonal strains.Conclusions
In conclusion, the NS1 protein encoded by H5N1 carries a remarkably different property as compared to other avian and human subtypes, and is one of the keys to its high pathogenicity. NCI-H292 cells system proves to be a good in-vitro model to delineate the property of NS1 proteins.8.
R. C. Elmslie 《BMJ (Clinical research ed.)》1938,1(4026):527-529
9.
10.
Scott Hafeman Cheryl London Robyn Elmslie Steven Dow 《Cancer immunology, immunotherapy : CII》2010,59(3):441-452
Malignant histiocytosis (MH) is an aggressive cancer derived from myeloid lineage cells in both dogs and humans. In dogs,
the tumor is characterized by the rapid development of metastatic tumors in multiple sites, including especially the lungs
and lymph nodes. Humans develop an analogous disease known as Langerhans cell histiocytosis, which primarily affects children
and young adults. Because these tumors are often resistant to conventional chemotherapy, there is a need for newer therapeutic
approaches. Systemic administration of liposomal clodronate (LC) has been shown to effectively deplete phagocytic cells (e.g.,
macrophages and dendritic cells) in mice. We investigated therefore whether LC could also be used to treat naturally occurring
MH in dogs. First, the susceptibility of canine MH cells to LC-mediated killing was assessed in vitro. Then the clinical safety
and effectiveness of LC as a treatment for MH was assessed in a pilot study in five pet dogs with spontaneous MH. We found
that canine MH cells were very susceptible to LC-induced apoptotic cell death, whereas other tumor cell lines were resistant
to killing by LC. Studies using labeled liposomes demonstrated that susceptibility to LC killing was directly related to the
efficiency of liposome uptake. In pet dogs with spontaneous MH, we found that a short course of LC treatment elicited significant
tumor regression in two of five treated animals. These findings suggest that liposomal delivery of clodronate and possibly
other bisphosphonates may offer an effective new approach to treatment of histiocytic neoplasms in dogs and humans. 相似文献