42 research outputs found
Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection
<p>Abstract</p> <p>Background</p> <p>Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.</p> <p>Methods</p> <p>Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.</p> <p>Results</p> <p>Seven individual protein spots were identified as either significantly increased (α<sub>2</sub>-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α<sub>2</sub>-macroglobulin, are included in existing non-invasive serum marker panels.</p> <p>Conclusion</p> <p>Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.</p
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The Broad-Spectrum Antiviral Compound ST-669 Restricts Chlamydial Inclusion Development and Bacterial Growth and Localizes to Host Cell Lipid Droplets within Treated Cells
Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this
study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria
and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species
of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial
and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common
mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that
eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae
grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization.
Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized
to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular
growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a
lipid droplet-dependent process
Dose-Volume Effect of Bladder and Rectal Filling during Intracavitary High-Dose-Rate Brachytherapy
S1956 The Frequency of Endoscopic Diagnosis Other Than Esophageal Varices in Patients with Portal Hypertension and Esophageal Varices
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Fuel Flexibility in Gasification
In order to increase efficiencies of carbonizers, operation at high pressures is needed. In addition, waste biomass fuels of opportunity can be used to offset fossil fuel use. The National Energy Technology Laboratory (NETL) Fluidized Bed Gasifier/Combustor (FBG/C) was used to gasify coal and mixtures of coal and biomass (sawdust) at 425 psig. The purpose of the testing program was to generate steady state operating data for modeling efforts of carbonizers. A test program was completed with a matrix of parameters varied one at a time in order to avoid second order interactions. Variables were: coal feed rate, pressure, and varying mixtures of sawdust and coal types. Coal types were Montana Rosebud subbituminous and Pittsburgh No. 8 bituminous. The sawdust was sanding waste from a furniture manufacturer in upstate New York. Coal was sieved from -14 to +60 mesh and sawdust was sieved to -14 mesh. The FBG/C operates at a nominal 425 psig, but pressures can be lowered. For the tests reported it was operated as a jetting, fluidized bed, ash-agglomerating gasifier. Preheated air and steam are injected into the center of the bottom along with the solid feed that is conveyed with cool air. Fairly stable reactor internal flow patterns develop and temperatures stabilize (with some fluctuations) when steady state is reached. At nominal conditions the solids residence time in the reactor is on the order of 1.5 to 2 hours, so changes in feed types can require on the order of hours to equilibrate. Changes in operating conditions (e.g. feed rate) usually require much less time. The operating periods of interest for these tests were only the steady state periods, so transient conditions were not monitored as closely. The test matrix first established a base case of operations to which single parameter changes in conditions could be compared. The base case used Montana Rosebud at a coal feed rate of 70 lbm/hr at 425 psig. The coal sawdust mixtures are reported as percent by weight coal to percent by weight sawdust. The mixtures of interest were: 65/35 subbituminous, 75/25 subbituminous, 85/15 subbituminous, and 75/25 bituminous. Steady state was achieved quickly when going from one subbituminous mixture to another, but longer when going from subbituminous to bituminous coal. The most apparent observation when comparing the base case to subbituminous coal/sawdust mixtures is that operating conditions are nearly the same. Product gas does not change much in composition and temperatures remain nearly the same. Comparisons of identical weight ratios of sawdust and subbituminous and bituminous mixtures show considerable changes in operating conditions and gas composition. The highly caking bituminous coal used in this test swelled up and became about half as dense as the comparable subbituminous coal char. Some adjustments were required in accommodating changes in solids removal during the test. Nearly all the solids in the bituminous coal sawdust were conveyed into the upper freeboard section and removed at the mid-level of the reactor. This is in marked contrast to the ash-agglomerating condition where most solids are removed at the very bottom of the gasifier. Temperatures in the bottom of the reactor during the bituminous test were very high and difficult to control. The most significant discovery of the tests was that the addition of sawdust allowed gasification of a coal type that had previously resulted in nearly instant clinkering of the gasifier. Several previous attempts at using Pittsburgh No. 8 were done only at the end of the tests when shutdown was imminent anyway. It is speculated that the fine wood dust somehow coats the pyrolyzed sticky bituminous coal particles and prevents them from agglomerating quickly. As the bituminous coal char particles swell, they are carried to the cooler upper regions of the reactor where they re-solidify. Other interesting phenomena were revealed regarding the transport (rheological) properties of the coal sawdust mixtures. The coal sawdust mixtures segregate quickly when transported. This is visibly apparent. To prevent bridges and ratholes from developing in the lowest coal feed hopper, it is normally fluidized. When feeding the coal sawdust mixtures the fluidizing gas was turned off to prevent segregation. The feed system worked as well with no fluidizing gas when using the mixtures as it did with fluidizing gas and only coal. In addition, it was inadvertently discovered that greatly increased pressure above the feeder resulted in greatly increased flow with the mixtures. Increased pressure above the feeder with coal only results in quickly plugging the feed system. Also, it was learned that addition of sawdust reduces the system loss during conveying compared to coal only. This is in spite of overall smaller particle sizes with the coal sawdust mixtures