A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin-alpha/beta and TNF-alpha in cultured endothelial cells.

BackgroundThe recruitment of lymphocytes to secondary lymphoid organs relies on interactions of circulating cells with high endothelial venules (HEV). HEV are exclusive to these organs under physiological conditions, but they can develop in chronically-inflamed tissues. The interaction of L-selectin on lymphocytes with sulfated glycoprotein ligands on HEV results in lymphocyte rolling, which represents the initial step in lymphocyte homing. HEV expression of GlcNAc6ST-2 (also known as HEC-GlcNAc6ST, GST-3, LSST or CHST4), an HEV-restricted sulfotransferase, is essential for the elaboration of L-selectin functional ligands as well as a critical epitope recognized by MECA-79 mAb.ResultsWe examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA) synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-alpha and lymphotoxin-alphabeta induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells.ConclusionThese observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

Health impact assessment of industrial development projects: a spatio-temporal visualization

Development and implementation of large-scale industrial projects in complex eco-epidemiological settings typically require combined environmental, social and health impact assessments. We present a generic, spatio-temporal health impact assessment (HIA) visualization, which can be readily adapted to specific projects and key stakeholders, including poorly literate communities that might be affected by consequences of a project. We illustrate how the occurrence of a variety of complex events can be utilized for stakeholder communication, awareness creation, interactive learning as well as formulating HIA research and implementation questions. Methodological features are highlighted in the context of an iron ore development in a rural part of Afric

A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin-α/β and TNF-α in cultured endothelial cells

BACKGROUND: The recruitment of lymphocytes to secondary lymphoid organs relies on interactions of circulating cells with high endothelial venules (HEV). HEV are exclusive to these organs under physiological conditions, but they can develop in chronically-inflamed tissues. The interaction of L-selectin on lymphocytes with sulfated glycoprotein ligands on HEV results in lymphocyte rolling, which represents the initial step in lymphocyte homing. HEV expression of GlcNAc6ST-2 (also known as HEC-GlcNAc6ST, GST-3, LSST or CHST4), an HEV-restricted sulfotransferase, is essential for the elaboration of L-selectin functional ligands as well as a critical epitope recognized by MECA-79 mAb. RESULTS: We examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA) synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-α and lymphotoxin-αβ induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells. CONCLUSION: These observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA

Exploring Radioisotopic Geochronology and Astrochronology

Numerical dating of the geologic record provides an essential framework for interpreting the rich history of our planet. Common applications include the determination of dates for extinction events and climate reorganizations, the assessment of rates of paleoenvironmental and paleobiologic change, and the correlation of rocks across vast expanses. Such investigations have yielded crucial insight into the mechanisms that shape Earth\u27s surface environments over geologic time. But as geologists increasingly pursue high (spatial) resolution stratigraphic analyses in deep time, the short temporal scales (\u3c100,000 years) of the processes investigated push the limits of high-­precision geochronology

Astronomical and Tectonic Influences on Climate and Deposition Revealed Through Radioisotopic Geochronology and Bayesian Age-Depth Modeling of the Early Eocene Green River Formation, Wyoming, USA

The Wilkins Peak Member (WPM) of the Green River Formation in Wyoming, USA, comprises alternating lacustrine and alluvial strata that preserve a record of terrestrial climate during the early Eocene climatic optimum. We use a Bayesian framework to develop age-depth models for three sites, based on new 40Ar/39Ar sanidine and 206Pb/238U zircon ages from seven tuffs. The new models provide two- to ten-fold increases in temporal resolution compared to previous radioisotopic age models, confirming eccentricity-scale pacing of WPM facies, and permitting their direct comparison to astronomical solutions. Starting at ca. 51 Ma, the median ages for basin-wide flooding surfaces atop six successive alluvial marker beds coincide with short eccentricity maxima in the astronomical solutions. These eccentricity maxima have been associated with hyperthermal events recorded in marine strata during the early Eocene. WPM strata older than ca. 51 Ma do not exhibit a clear relationship to the eccentricity solutions, but accumulated 31%–35% more rapidly, suggesting that the influence of astronomical forcing on sedimentation was modulated by basin tectonics. Additional high-precision radioisotopic ages are needed to reduce the uncertainty of the Bayesian model, but this approach shows promise for unambiguous evaluation of the phase relationship between alluvial marker beds and theoretical eccentricity solutions

Robot rights? Towards a social-relational justification of moral consideration \ud

Should we grant rights to artificially intelligent robots? Most current and near-future robots do not meet the hard criteria set by deontological and utilitarian theory. Virtue ethics can avoid this problem with its indirect approach. However, both direct and indirect arguments for moral consideration rest on ontological features of entities, an approach which incurs several problems. In response to these difficulties, this paper taps into a different conceptual resource in order to be able to grant some degree of moral consideration to some intelligent social robots: it sketches a novel argument for moral consideration based on social relations. It is shown that to further develop this argument we need to revise our existing ontological and social-political frameworks. It is suggested that we need a social ecology, which may be developed by engaging with Western ecology and Eastern worldviews. Although this relational turn raises many difficult issues and requires more work, this paper provides a rough outline of an alternative approach to moral consideration that can assist us in shaping our relations to intelligent robots and, by extension, to all artificial and biological entities that appear to us as more than instruments for our human purpose