99 research outputs found
Gastrointestinal stromal tumour and hypoglycemia in a Fjord pony: Case report
<p>Abstract</p> <p>Background</p> <p>Neoplasia may cause hypoglycemia in different species including the horse, but hypoglycemia has not previously been reported in the horse associated with gastrointestinal stromal tumours.</p> <p>Case presentation</p> <p>A case of a gastrointestinal stromal tumour in a Fjord pony with severe recurrent hypoglycemia is presented. The mechanism causing the hypoglycemia was not established.</p> <p>Conclusion</p> <p>This case indicates that a gastrointestinal stromal tumour may cause hypoglycemia also in the horse.</p
Identification of DNA-Damage DNA-Binding Protein 1 as a Conditional Essential Factor for Cytomegalovirus Replication in Interferon-γ-Stimulated Cells
The mouse cytomegaloviral (MCMV) protein pM27 represents an indispensable factor for viral fitness in vivo selectively, antagonizing signal transducer and activator of transcription 2 (STAT2)-mediated interferon signal transduction. We wished to explore by which molecular mechanism pM27 accomplishes this effect. We demonstrate that pM27 is essential and sufficient to curtail the protein half-life of STAT2 molecules. Pharmacologic inhibition of the proteasome restored STAT2 amounts, leading to poly-ubiquitin-conjugated STAT2 forms. PM27 was found in complexes with an essential host ubiquitin ligase complex adaptor protein, DNA-damage DNA-binding protein (DDB) 1. Truncation mutants of pM27 showed a strict correlation between DDB1 interaction and their ability to degrade STAT2. SiRNA-mediated knock-down of DDB1 restored STAT2 in the presence of pM27 and strongly impaired viral replication in interferon conditioned cells, thus phenocopying the growth attenuation of M27-deficient virus. In a constructive process, pM27 recruits DDB1 to exploit ubiquitin ligase complexes catalyzing the obstruction of the STAT2-dependent antiviral state of cells to permit viral replication
Physician Experiences and Understanding of Genomic Sequencing in Oncology
The amount of information produced by genomic sequencing is vast, technically complicated, and can be difficult to interpret. Appropriately tailoring genomic information for nonâ geneticists is an essential next step in the clinical use of genomic sequencing. To initiate development of a framework for genomic results communication, we conducted eighteen qualitative interviews with oncologists who had referred adult cancer patients to a matched tumorâ normal tissue genomic sequencing study. In our qualitative analysis, we found varied levels of clinician knowledge relating to sequencing technology, the scope of the tumor genomic sequencing study, and incidental germline findings. Clinicians expressed a perceived need for more genetics education. Additionally, they had a variety of suggestions for improving results reports and possible resources to aid in results interpretation. Most clinicians felt genetic counselors were needed when incidental germline findings were identified. Our research suggests that more consistent genetics education is imperative in ensuring the proper utilization of genomic sequencing in cancer care. Clinician suggestions for results interpretation resources and results report modifications could be used to improve communication. Cliniciansâ perceived need to involve genetic counselors when incidental germline findings were found suggests genetic specialists could play a critical role in ensuring patients receive appropriate followâ up.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147187/1/jgc40187.pd
Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis
Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA
A systematic evaluation of the effect of thumb opponens splints on hand function in children with unilateral spastic cerebral palsy
Objective: To examine the effects of a neoprene thumb opponens splint on hand function during a self-selected activities of daily living task in children with unilateral spastic cerebral palsy with thumb-in-palm position of the affected hand. Design: Systematic evaluation of seven cases using a multiple baseline design across individuals. Setting: Outpatient clinic. Subjects: Seven children with unilateral cerebral palsy (2-7 years old), Manual Ability Classification System level 2-3 participated in the study. Interventions: Neoprene thumb opponens splints (McKie splint) were used. Children were followed for about four months. Baseline period ranged from 4 to 9 weeks, intervention period was two months and duration of follow-up one month. Main measures: Hand function was assessed using goal attainment scaling and visual analogue scales. Data was assessed visually. Results: In four children goal attainment scaling and/or visual analogue scale scores increased after introducing the splint. These effects remained when splints were not worn. Two children only benefited from the splint when it was worn. Thumb opponens splints were tolerated well by all children who participated in this study. Conclusions: Thumb opponens splints may have a positive effect on hand function in children with unilateral spastic cerebral palsy
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