58 research outputs found
The Vehicle, Spring 1983
Vol. 24, No. 2
Table of Contents
A-B-C-D-E-F-G-H....Beth Kennypage 1
Contemporary IssuesBrook Wilsonpage 1
BlackJohn Stockmanpage 2
BeatGraham Lewispage 2
Catholic DazeSuzanne Hornpage 4
AfricaGraham Lewispage 5
The Friendly SkiesRajendra Sinhanpage 5
BreadKen Kempckepage 7
PhotographLinda Fraembspage 8
SnapshotMaggie Kennedypage 9
PoemAnne Smithpage 9
Activities on IceKerri Mahatpage 11
Beecham\u27s Orchard And VineyardBecky Lawsonpage 11
PoemKarri Mahatpage 12
Sneak PreviewsMaggie Kennedypage 12
ZooKen Kempckepage 12
PhotographNick Haskettpage 13
The Slave HouseCraig Barnespage 13
The Nomad Preacher\u27s SermonStacey Flanniganpage 16
Owl Creek RevisitedScott Graypage 16
Thought On CopperGraham Lewispage 20
OutfielderKen Kempckepage 20
HoneymoonJohn Stockmanpage 21
Candy Wrapper Dream GirlStacey Flanniganpage 21
PhotographLinda Fraembspage 22
October DreamMarlene Weekspage 23
IndistinctionStacey Flanniganpage 24
Taking InventorySara Farrispage 24
Flying In From K-Mart, NebraskaMichelle Mitchellpage 25
PhotographNick Haskettpage 26
Bone ChinaMichelle Mitchellpage 27
She Was A DollNick Haskettpage 30
The Seventh DayGeoffrey Andrespage 31
Blade Of Grass (On A Golf Course)Ken Kempckepage 31
PoemKen Kempckepage 32
Cigarette SmokeJean M. Davispage 33
Future LoveR. Lawsonpage 34
PhotographNick Haskettpage 35
Dancing In The StreetBetsy Acklinpage 35
PhotographLinda Fraembspage 38
CleoMarlene Weekspage 39
Teddy BearKen Kempckepage 39
PreludeBecky Lawsonpage 40https://thekeep.eiu.edu/vehicle/1043/thumbnail.jp
Soluble Rank Ligand Produced by Myeloma Cells Causes Generalised Bone Loss in Multiple Myeloma
Patients with multiple myeloma commonly develop focal osteolytic bone disease, as well as generalised osteoporosis. The mechanisms underlying the development of osteoporosis in patients with myeloma are poorly understood. Although disruption of the RANKL/OPG pathway has been shown to underlie formation of focal osteolytic lesions, its role in the development of osteoporosis in myeloma remains unclear. Increased soluble RANKL in serum from patients with myeloma raises the possibility that this molecule plays a key role. The aim of the present study was to establish whether sRANKL produced by myeloma cells contributes directly to osteoporosis. C57BL/KaLwRij mice were injected with either 5T2MM or 5T33MM murine myeloma cells. 5T2MM-bearing mice developed osteolytic bone lesions (p<0.05) with increased osteoclast surface (p<0.01) and reduced trabecular bone volume (p<0.05). Bone volume was also reduced at sites where 5T2MM cells were not present (p<0.05). In 5T2MM-bearing mice soluble mRANKL was increased (p<0.05), whereas OPG was not altered. In contrast, 5T33MM-bearing mice had no changes in osteoclast surface or trabecular bone volume and did not develop osteolytic lesions. Soluble mRANKL was undetectable in serum from 5T33MM-bearing mice. In separate experiments, RPMI-8226 human myeloma cells were transduced with an human RANKL/eGFP construct, or eGFP alone. RPMI-8226/hRANKL/eGFP cells, but not RPMI-8226/eGFP cells, stimulated osteoclastic bone resorption (p<0.05) in vitro. Sub-cutaneous injection of NOD/SCID mice with RPMI-8226/hRANKL/eGFP or RPMI-8226/eGFP cells resulted in tumour development in all mice. RPMI-8226/hRANKL/eGFP-bearing mice exhibited increased serum soluble hRANKL (p<0.05) and a three-fold increase in osteoclast number (p<0.05) compared to RPMI-8226/eGFP-bearing mice. This was associated with reduced trabecular bone volume (27%, p<0.05), decreased trabecular number (29%, p<0.05) and increased trabecular thickness (8%, p<0.05). Our findings demonstrate that soluble RANKL produced by myeloma cells causes generalised bone loss, suggesting that targeting RANKL may prevent osteoporosis in patients with myeloma
Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer
This study aimed to identify subpopulations of prostate cancer cells that are responsible for the initiation of bone metastases. Using rapidly dividing human prostate cancer cell lines, we identified mitotically quiescent subpopulations (<1%), which we compared with the rapidly dividing populations for patterns of gene expression and for their ability to migrate to the skeletons of athymic mice. The study used 2-photon microscopy to map the presence/distribution of fluorescently labeled, quiescent cells and luciferase expression to determine the presence of growing bone metastases. We showed that the mitotically quiescent cells were very significantly more tumorigenic in forming bone metastases than fast-growing cells (55 vs. 15%) and had a unique gene expression profile. The quiescent cells were not uniquely stem cell like, with no expression of CD133 but had the same level expression of other putative prostate stem cell markers (CD44 and integrins α2/β1), when compared to the rapidly proliferating population. In addition, mitotic quiescence was associated with very high levels of C-X-C chemokine receptor type 4 (CXCR4) production. Inhibition of CXCR4 activity altered the homing of quiescent tumor cells to bone. Our studies suggest that mitotic dormancy is a unique phenotype that facilitates tumor cell colonization of the skeleton in prostate cancer.—Wang, N., Docherty, F., Brown, H. K., Reeves, K., Fowles, A., Lawson, M., Ottewell, P. D., Holen, I., Croucher, P. I., Eaton, C. L. Mitotic quiescence, but not unique “stemness,” marks the phenotype of bone metastasis-initiating cells in prostate cancer
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial
Background:
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.
Methods:
The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).
Findings:
Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92).
Interpretation:
These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial
Background:
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.
Methods:
The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).
Findings:
Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92).
Interpretation:
These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
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The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study
Abstract: Purpose: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down’s syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. Methods: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. Results: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23–41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). Conclusions: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21
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