Stronger inflammatory/cytotoxic T cell response in women identified by microarray analysis

Women develop chronic inflammatory autoimmune diseases like lupus more often than men. The mechanisms causing the increased susceptibility are incompletely understood, although estrogen is believed to contribute. Chronic immune stimulation characterizes many autoimmune disorders. We hypothesized that repeated stimulation may cause a different T cell immune response in women than men. Microarray approaches were used to compare gene expression in T cells from healthy men and women with and without repeated stimulation. Four days following a single stimulation only 25% of the differentially expressed, gender-biased genes were expressed at higher levels in the women. In contrast, following restimulation 72% were more highly expressed in women. Immune response genes were significantly over-represented among the genes upregulated in women, and among the immune response genes, the inflammatory/cytotoxic effector genes interferon gamma (IFNG), lymphotoxin beta (LTB), granzyme A (GZMA), interleukin-12 receptor beta2 (IL12RB2), and granulysin (GNLY) were among those overexpressed to the greatest degree. In contrast, IL17A was the only effector gene more highly expressed in men. Estrogen response elements were identified in the promoters of half of the overexpressed immune genes in women, and in <10% of the male biased genes. The differential expression of inflammatory/cytotoxic effector molecules in restimulated female T cells may contribute to the differences in autoimmune diseases between women and men

Acoustic measurement of lubricant-film thickness distribution in ball bearings

An oil-film thickness monitoring system capable of providing an early warning of lubrication failure in rolling element bearings has been developed. The system is used to measure the lubricant-film thickness in a conventional deep groove ball bearing (shaft diameter 80 mm, ball diameter 12.7 mm). The measurement system comprises a 50 MHz broadband ultrasonic focused transducer mounted on the static outer raceway of the bearing. Typically the lubricant-films in rolling element bearings are between 0.1-1.0 μm in thickness and so are significantly smaller than the ultrasonic wavelength. A quasistatic spring model is used to calculate oil-film thickness from the measured reflection coefficient data. An accurate triggering system has been developed to enable multiple reflection coefficient measurements to be made as the contact ellipse sweeps over the measurement location. Experiments are described in which the loading conditions and rotational speed are varied. Lubricant-film thickness distributions measured ultrasonically are described and are shown to agree well with the predictions from classical elastohydrodynamic (EHD) lubrication theory, particularly at high radial loads and low rotary speeds. A range of parameters affecting the performance of the measurement are discussed and the limits of operation of the measurement technique defined. © 2006 Acoustical Society of America

Cost of inpatient rehabilitation care in the Department of Veterans Affairs

Abstract—We investigated the determinants of inpatient rehabilitation costs in the Department of Veterans Affairs (VA) and examined the relationship between length of stay (LOS) and discharge costs using data from VA and community rehabilitation hospitals. We estimated regression models to identify patient characteristics associated with specialized inpatient rehabilitation costs. VA data included 3,535 patients discharged from 63 facilities in fiscal year 2001. We compared VA costs to community rehabilitation hospitals using a sample from the Uniform Data System for Medical Rehabilitation of 190,112 patients discharged in 1999 from 697 facilities. LOS was a strong predictor of cost for VA and non-VA hospitals. Functional status, measured by Functional Independence Measure (FIM) scores at admission, was statistically significant but added little explanatory value after controlling for LOS. Although FIM scores were associated with LOS, FIM scores accounted for little variance in cost after controlling for LOS. These results are most applicable to researchers conducting cost-effectiveness analyses.average costs, billing, charges, cost, health economics, micro-cost methods, reimbursement, rehabilitation, VA, veterans

Oxidative Stress, T Cell DNA Methylation, and Lupus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107387/1/art38427.pd

Preliminary Evidence That High-Dose Vitamin C has a Vascular Disrupting Action in Mice

High intravenous doses of vitamin C (ascorbic acid) have been reported to benefit cancer patients but the data are controversial and there is incomplete knowledge of what physiological mechanisms might be involved in any response. Vitamin C is taken up efficiently by cells expressing SVCT2 transporters and since vascular endothelial cells express SVCT2, we explored the hypothesis that administration of high dose vitamin C (up to 5 g/kg) to mice might affect vascular endothelial function. A single administration of vitamin C to mice induced time- and dose-dependent increases in plasma concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), a marker for vascular disrupting effects. Responses were comparable to those for the tumor vascular disrupting agents vadimezan and fosbretabulin. High-dose vitamin C administration decreased tumor serotonin concentrations, consistent with the release of serotonin from platelets and its metabolism to 5-HIAA. High-dose vitamin C also significantly increased the degree of hemorrhagic necrosis in tumors removed after 24 hours, and significantly decreased tumor volume after 2 days. However, the effect on tumor growth was temporary. The results support the concept that vitamin C at high dose increases endothelial permeability, allowing platelets to escape and release serotonin. Plasma 5-HIAA concentrations could provide a pharmacodynamic biomarker for vitamin C effects in clinical studies

Compositional Impact of Io Volcanic Emissions on Jupiter's Magnetosphere and the Icy Galilean Moons

The magnetospheric ion population of Jupiter is dominated by the 1000 kg/s of iogenic material constantly ejected by IO volcanism as neutral gas (approx. 1 kg/s goes out as high speed dust grains), subsequent atmospheric losses to the IO torus, and radial transport of torus ions throughout the magnetosphere. As that magnetosphere is greatly distended in radial size by the iogenic plasma loading, so are surfaces of the other Galilean moons also significantly, and perhaps even dominantly, affected by iogenic plasma bombardment, e.g. at the level up to 0.2 kg/s heavy ions (mostly O and S) onto Europa as per local plasma ion measurements. In comparison, cometary impacts onto IO deliver about 0.02 kg/s of impact ejecta to Europa via ballistic transfer through the Jupiter system. The magnetosphere of this system operates as a powerful engine to produce and transport ions from the IO source to the surfaces of these other moons, and any future orbiter missions to these moons must account for surface distributions of the iogenic material and its chemical effects before real assessments can be made of sensible chemical materials otherwise arising from primordial formation and subsequent evolution of these moons. This is a fundamental problem of space weathering that must be addressed for all planetary bodies with thin atmospheres and direct surface exposure to their space plasma environments. Long-standing debates from Galileo Orbiter measurements about the origins of hydrate sulfates at Europa present examples of this problem, as to whether the sulfates arise from oceanic minerals or from iogenic sulfur chemistry. Any orbiter or landed mission to Europa for astrobiological investigations would further need to separate the potential chemical biosignatures of life or its precursors from the highly abundant background of iogenic material. Although no single ion carries a tag identifying it as of iogenic or other origin, the elemental abundance distributions of ions to be measured throughout the jovian magnetosphere and in the local moon environments can act as tracers if we know from direct measurements and models the distributions at the mostly likely sources, i.e. at IO. However, our knowledge of these abundances are very limited from earlier in-situ and remote measurements, mainly confined to major (S, O) and some minor (Na, K, Cl) species with abundances at or above a few percent relative to O. Future in-situ plasma measurements by the planned Jupiter Europa Orbiter and Jupiter Ganymede Orbiter missions should extend the abundance coverage to minor and even trace elemental species. For Europa astrobiological investigations it is also important to specify iogenic inputs and surface processing of isotopic species. We discuss the range of abundance distributions arising from models for IO hot volcanic emissions, and from the subsequent dynamics of ion injection, magnetospheric transport, and icy moon surface bombardment

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO2-induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke

Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment.

Lysophosphatidic acid (LPA) is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation. LPA receptors were expressed at significantly higher levels on Common Myeloid Progenitors (CMP) than either multipotent Hematopoietic Stem/Progenitor Cells (HSPC) or Common Lymphoid Progenitors (CLP) suggesting that LPA acts on committed myeloid progenitors. Functional studies demonstrated that LPA enhanced migration, induced cell proliferation and reduced apoptosis of isolated CMP, but had no effect on either HSPC or CLP. Analysis of adult and fetal human bone marrow sections showed that PPAP2A, (the enzyme which degrades LPA) was highly expressed in the osteoblastic niche but not in the perivascular regions, whereas Autotaxin (the enzyme that synthesizes LPA) was expressed in perivascular regions of the marrow. We propose that a gradient of LPA with the highest levels in peri-sinusoidal regions and lowest near the endosteal zone, regulates the localization, proliferation and differentiation of myeloid progenitors within the bone marrow marrow

Leeches (Annelida: Hirudinida) of Northern Arkansas

Twenty-one lotic and lentic environments throughout central and northern Arkansas were surveyed for the presence of leeches during June 2004 and April, July - October 2005. Fourteen species of leeches {Helobdella elongata, Helobdella papillata, Helobdella stagnalis, Placobdella cryptobranchii, Placobdella multilineata, Placobdella ornata, Placobdella papillifera, Placobdella parasitica, Placobdella phaler a, Placobdella picta, Haemopis marmorata, Erpobdella fervida, Erpobdella microstoma, and Erpobdella punctata) representing 3 families were collected. Five species (H. elongata, P. cryptobranchii, P. multilineata, H. marmorata, and E. fervida) are reported from Arkansas for the first time. The natural history of the 22 species of leeches now known from Arkansas is reviewed