Transport of apolipoproteins A-I and A-II by human thoracic duct lymph

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in 2 subjects before and 3 subjects after renal transplantation. Lymph triglyceride transport was ~83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659±578 mg/d for apolipoprotein A-I and 109±59 mg/d for apolipoprotein A-II among the 5 subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81±8%) and apolipoprotein A-II (90±11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein3

Characterization of hepatic low density lipoprotein binding and cholesterol metabolism in normal and homozygous familial hypercholesterolemic subjects

Patients with familial hypercholesterolemia have elevated levels of plasma low density lipoproteins (LDL), increased hepatic synthesis of apolipoprotein B-containing lipoproteins, defective binding of low density lipoproteins to fibroblasts, and premature atherosclerosis. The role of a hepatic low density lipoprotein receptor in normal man and its importance in the pathogenesis of familial hypercholesterolemia have not been previously determined. In the present study, direct comparison was made of the binding of LDL to hepatic membranes from normal and receptor-negative homozygous familial hypercholesterolemic subjects. The effects of calcium, EDTA, and temperature on the binding of lipoproteins to the hepatic membranes were also evaluated. At 4°C, no significant difference in specific binding of LDL to hepatic membranes from normal and familial hypercholesterolemic subjects was observed. At 37°C, both total and specific binding of LDL were significantly reduced in patients with familial hypercholesterolemia. Hepatic membrane binding of LDL from the two patients homozygous for receptor-negative familial hypercholesterolemia was 53 and 59% of normal. The activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase was normal; however, the total hepatic cholesterol and cholesteryl ester content was significantly increased from 53 to 129%. These results indicate that patients with familial hypercholesterolemia have a defect in the interaction of hepatic membranes with low density lipoproteins. This defect may lead to accelerated atherosclerosis by decreasing the cellular catabolism of LDL and enhancing the production of LDL, which is characteristic of patients homozygous for familial hypercholesterolemia

Demographics of paediatric renal replacement therapy in Europe: 2007 annual report of the ESPN/ERA-EDTA registry

Item does not contain fulltext1 juli 201

Ice core measurements of 14CH4 show no evidence of methane release from methane hydrates or old permafrost carbon during a large warming event 11,600 years ago

Thawing permafrost and marine methane hydrate destabilization in the Arctic and elsewhere have been proposed as large sources of methane to the atmosphere in the future warming world. To evaluate this hypothesis it is useful to ask whether such methane releases happened during past warming events. The two major abrupt warming events of the last deglaciation, Oldest Dryas - Bølling (OD-B, ≈ 14,500 years ago) and Younger Dryas - Preboreal (YD-PB; ≈11,600 years ago), were associated with large (up to 50%) increases in atmospheric methane (CH4) concentrations. The sources of these large warming-driven CH4 increases remain incompletely understood, with possible contributions from tropical and boreal wetlands, thawing permafrost as well as marine CH4 hydrates. We present new measurements of 14C of paleoatmospheric CH4 over the YD-PB transition from ancient ice outcropping at Taylor Glacier, Antarctica. 14C can unambiguously identify CH4 emissions from "old carbon" sources, such as permafrost and CH4 hydrates. The only prior study of paleoatmospheric 14CH4 (from Greenland ice) suggested that wetlands were the main driver of the YD-PB CH4 increase, but the results were weakened by an unexpected and poorly understood 14CH4 component from in situ cosmogenic production directly in near-surface ice. In this new study, we have been able to accurately characterize and correct for the cosmogenic 14CH4 component. All samples from before, during and after the abrupt warming and associated CH4 increase yielded 14CH4 values that are consistent with 14C of atmospheric CO2 at that time, indicating a purely contemporaneous methane source. These new measurements rule out the possibility of large CH4 releases to the atmosphere from methane hydrates or old permafrost carbon in response to the large and rapid YD-PB warming. To the extent that the characteristics of the YD-PB warming are comparable to those of the current anthropogenic warming, our measurements suggest that large future atmospheric methane increases from old carbon sources in the Arctic are unlikely. Instead, our measurements indicate that global wetlands will likely respond to the warming with increased methane emissions. © European Geosciences UnionYellow Posters session, Y7

Detrusor response to outlet obstruction

Bladder responses to outlet obstruction are thought to involve muscular hyperplasia, increased pressure, and finally, decompensation. While these things probably do occur, the process of bladder response to obstruction also includes loss of reflex control and deposition of collagen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47058/1/345_2004_Article_BF00327002.pd

Sensitivity in Multiobjective Programming by Differential Equations Methods. The Case of Homogeneous Functions

Proceedings of the Second International Conference on Multi-Objective Programming and Goal Programming, Torremolinos, Spain, May 16-18, 1996.The purpose of this paper is to characterize for convex multiobjective programming, the situations in which the sensitivity with respect to the right side vector of the constraints can be obtained as a solution of a dual program.Publicad

The H-band Emitting Region of the Luminous Blue Variable P Cygni: Spectrophotometry and Interferometry of the Wind

This is the final version of the article. Available from American Astronomical Society / IOP Publishing via the DOI in this record.We present the first high angular resolution observations in the near-infrared H band (1.6 μm) of the luminous blue variable star P Cygni. We obtained six-telescope interferometric observations with the CHARA Array and the MIRC beam combiner. These show that the spatial flux distribution is larger than expected for the stellar photosphere. A two-component model for the star (uniform disk) plus a halo (two-dimensional Gaussian) yields an excellent fit of the observations, and we suggest that the halo corresponds to flux emitted from the base of the stellar wind. This wind component contributes about 45% of the H-band flux and has an angular FWHM = 0.96 mas, compared to the predicted stellar diameter of 0.41 mas. We show several images reconstructed from the interferometric visibilities and closure phases, and they indicate a generally spherical geometry for the wind. We also obtained near-infrared spectrophotometry of P Cygni from which we derive the flux excess compared to a purely photospheric spectral energy distribution. The H-band flux excess matches that from the wind flux fraction derived from the two-component fits to the interferometry. We find evidence of significant near-infrared flux variability over the period from 2006 to 2010 that appears similar to the variations in the Hα emission flux from the wind.We acknowledge with thanks the variable star observations from the AAVSO International Database contributed by observers worldwide and used in this research. Support for Ritter Astrophysical Research Center during the time of the observations was provided by the National Science Foundation Program for Research and Education with Small Telescopes (NSF-PREST) under grant AST-0440784 (N.D.M.). This work was also supported by the National Science Foundation under grants AST-0606861 and AST-1009080 (D.R.G.). N.D.R. gratefully acknowledges his current CRAQ postdoctoral fellowship. We are grateful for the insightful comments of A. F. J. Moffat that improved portions of the paper, discussions with Paco Najarro and Luc Dessart about spectroscopic modeling of P Cygni, and support of the MIRC 6 telescope beam combiner by Ettore Pedretti. Institutional support has been provided by the GSU College of Arts and Sciences and by the Research Program Enhancement fund of the Board of Regents of the University System of Georgia, administered through the GSU Office of the Vice President for Research. Operational funding for the CHARA Array is provided by the GSU College of Arts and Sciences, by the National Science Foundation through grants AST-0606958 and AST-0908253, by the W. M. Keck Foundation, and by the NASA Exoplanet Science Institute. We thank the Mount Wilson Institute for providing infrastructure support at Mount Wilson Observatory. The CHARA Array, operated by Georgia State University, was built with funding provided by the National Science Foundation, Georgia State University, the W. M. Keck Foundation, and the David and Lucile Packard Foundation. This research was conducted in part using the Mimir instrument, jointly developed at Boston University and Lowell Observatory and supported by NASA, NSF, and the W. M. Keck Foundation. J.D.M. acknowledges University of Michigan and NSF AST-0707927 for support of MIRC construction and observations. D.P.C. acknowledges support under NSF AST-0907790 to Boston University. We gratefully acknowledge all of this support. This research has made use of the SIMBAD database operated at CDS, Strasbourg, France

MicroRNA Controlled Adenovirus Mediates Anti-Cancer Efficacy without Affecting Endogenous MicroRNA Activity

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3′ un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3′ UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×1010 viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets