The Vehicle, Fall 1990

Table of Contents Poetry Loss of the SpokenMatt Mansfieldpage 6-7 A Wyeth ReproductionLynn A. Rafoolpage 8 CornerSuzanna Portpage 9 FatherSuzanna Portpage 10 Past two,Victoria Bennettpage 11 VertigoVictoria Bennettpage 12 HeatVictoria Bennettpage 13 Pre-HistoryLuiz da Silveirapage 14 BloomsLuiz da Silveirapage 15 Hashimoto\u27s Thyrotoxicosis at Key WestAnthony Smithpage 16 Davy by the Pawn ShopAnthony Smithpage 17 Art UntitledMark Randallpage 19 UntitledMark Randallpage 20 UntitledSteve Reyespage 21 UntitledSteve Reyespage 22 Photographs UntitledSteve Beamerpage 24-25 UntitledSteve Beamerpage 26 UntitledSteve Beamerpage 27 Prose YikesMichael Brownpage 29 Thirty Minutes or LessSteve Fitzgeraldpage 30-35 Telling StoriesMatt Mansfieldpage 36-40 Interview Poet Donald HallMatt Mansfieldpage 42-44 Authors Biographiespage 46-47https://thekeep.eiu.edu/vehicle/1054/thumbnail.jp

The Vehicle, Spring 1999

Vol. 40, No. 2 Table of Contents Poetry Eve\u27s DaughterSylvia Whippopage 1 When We Wore Canoes On Our ShouldersMandy Watsonpage 2 This Is Not A Poem About GrandpaJake Tolbertpage 3 Old relationshipsBrandi Kinneypage 5 UntitledErin Winnerpage 6 BraverySylvia Whippopage 6 deep dark closetNicole Smithpage 7 Belly EarthTara Coburnpage 9 The River and FireJake Tolbertpage 10 UntitledAutumn Williamspage 12 Action PotentialKim Evanspage 13 Chimerical (a song for children)D.M. Attrapepage 14 UntitledAutumn Williamspage 16 UntitledMatthew Armstrongpage 18 Building YouSylvia Whippopage 19 RunningKim Evanspage 20 Walking Jenn to WorkJake Tolbertpage 22 Looking InKim Hunterpage 23 Void Between Me and WisconsinMandy Watsonpage 24 Artwork UntitledWendy Finchpage 4 MeditationJennifer Lundpage 8 UntitledSteve Drakepage 15 MemoriesJennifer Lundpage 21 UntitledKathryn Kolasinskipage 25 Prose FoundKim Hunterpage 26 A Day in the Life of William Baxter, DriverDaniel Fitzgeraldpage 32https://thekeep.eiu.edu/vehicle/1072/thumbnail.jp

The Vehicle, Spring 1999

Vol. 40, No. 2 Table of Contents Poetry Eve\u27s DaughterSylvia Whippopage 1 When We Wore Canoes On Our ShouldersMandy Watsonpage 2 This Is Not A Poem About GrandpaJake Tolbertpage 3 Old relationshipsBrandi Kinneypage 5 UntitledErin Winnerpage 6 BraverySylvia Whippopage 6 deep dark closetNicole Smithpage 7 Belly EarthTara Coburnpage 9 The River and FireJake Tolbertpage 10 UntitledAutumn Williamspage 12 Action PotentialKim Evanspage 13 Chimerical (a song for children)D.M. Attrapepage 14 UntitledAutumn Williamspage 16 UntitledMatthew Armstrongpage 18 Building YouSylvia Whippopage 19 RunningKim Evanspage 20 Walking Jenn to WorkJake Tolbertpage 22 Looking InKim Hunterpage 23 Void Between Me and WisconsinMandy Watsonpage 24 Artwork UntitledWendy Finchpage 4 MeditationJennifer Lundpage 8 UntitledSteve Drakepage 15 MemoriesJennifer Lundpage 21 UntitledKathryn Kolasinskipage 25 Prose FoundKim Hunterpage 26 A Day in the Life of William Baxter, DriverDaniel Fitzgeraldpage 32https://thekeep.eiu.edu/vehicle/1072/thumbnail.jp

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris

Objective: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. Methods: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). Results: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. Conclusions: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA

Minimal regulation of platelet activity by PECAM-1

PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, αIIbβ3, even though both receptors signal through Src-kinase regulation of PLCγ2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCγ2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation

Chemical Genetics Reveals an RGS/G-Protein Role in the Action of a Compound

We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-αq (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-αq signaling complex, and define new mutations in both RGS and G-αq, including a unique hypo-adapation allele of G-αq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation

A 19-SNP coronary heart disease gene score profile in subjects with type 2 diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study baseline characteristics

Background The coronary risk in diabetes (CoRDia) trial (n = 211) compares the effectiveness of usual diabetes care with a self-management intervention (SMI), with and without personalised risk information (including genetics), on clinical and behavioural outcomes. Here we present an assessment of randomisation, the cardiac risk genotyping assay, and the genetic characteristics of the recruits. Methods Ten-year coronary heart disease (CHD) risk was calculated using the UKPDS score. Genetic CHD risk was determined by genotyping 19 single nucleotide polymorphisms (SNPs) using Randox’s Cardiac Risk Prediction Array and calculating a gene score (GS). Accuracy of the array was assessed by genotyping a subset of pre-genotyped samples (n = 185). Results Overall, 10-year CHD risk ranged from 2–72 % but did not differ between the randomisation groups (p = 0.13). The array results were 99.8 % concordant with the pre-determined genotypes. The GS did not differ between the Caucasian participants in the CoRDia SMI plus risk group (n = 66) (p = 0.80) and a sample of UK healthy men (n = 1360). The GS was also associated with LDL-cholesterol (p = 0.05) and family history (p = 0.03) in a sample of UK healthy men (n = 1360). Conclusions CHD risk is high in this group of T2D subjects. The risk array is an accurate genotyping assay, and is suitable for estimating an individual’s genetic CHD risk. Trial registration This study has been registered at ClinicalTrials.gov; registration identifier NCT0189178

Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>A critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model.</p> <p>Methods</p> <p>Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (<it>E. coli </it>strain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d. <it>vs </it>q.w. <it>vs </it>q.w. × 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis.</p> <p>Results</p> <p>Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.</p> <p>Conclusion</p> <p>These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.</p

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff

Co-designing Urban Living Solutions to Improve Older People’s Mobility and Well-Being

Mobility is a key aspect of active ageing enabling participation and autonomy into later life. Remaining active brings multiple physical but also social benefits leading to higher levels of well-being. With globally increasing levels of urbanisation alongside demographic shifts meaning in many parts of the world this urban population will be older people, the challenge is how cities should evolve to enable so-called active ageing. This paper reports on a co-design study with 117 participants investigating the interaction of existing urban spaces and infrastructure on mobility and well-being for older residents (aged 55 + years) in three cities. A mixed method approach was trialled to identify locations beneficial to subjective well-being and participant-led solutions to urban mobility challenges. Spatial analysis was used to identify key underlying factors in locations and infrastructure that promoted or compromised mobility and well-being for participants. Co-designed solutions were assessed for acceptability or co-benefits amongst a wider cross-section of urban residents (n = 233) using online and face-to-face surveys in each conurbation. Our analysis identified three critical intersecting and interacting thematic problems for urban mobility amongst older people: The quality of physical infrastructure; issues around the delivery, governance and quality of urban systems and services; and the attitudes and behaviors of individuals that older people encounter. This identified complexity reinforces the need for policy responses that may not necessarily involve design or retrofit measures, but instead might challenge perceptions and behaviors of use and access to urban space. Our co-design results further highlight that solutions need to move beyond the generic and placeless, instead embedding specific locally relevant solutions in inherently geographical spaces, populations and processes to ensure they relate to the intricacies of place