Alterations in EGFR, KRAS, and ALK are oncogenic drivers lung cancer, but how signaling influences immunity the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes because drugs that inhibit immune checkpoints like PD-1 PD-L1 have clinical benefit. Here, we show activation of AKT-mTOR pathway tightly regulates expression vitro vivo. Both IFNγ-mediated induction was dependent on mTOR. In human adenocarcinomas squamous cell carcinomas, membranous...

The Center for Biostabilization at UC Davis is attempting to stabilize mammalian cells in the dry state. We review here some of lessons from nature that we have been applying this enterprise, including use trehalose, a disaccharide found high concentrations many anhydrobiotic organisms, biological structures, both vitro and vivo. Trehalose has useful properties purpose least one case—human blood platelets—introducing sugar may be sufficient achieve stabilization. Nucleated cells, however,...

Abstract Objective —To test the hypotheses that preparation method, exposure to shear force, and collagen affect release of growth factors from equine platelet-rich plasma (PRP). Sample Population —PRP obtained 6 horses. Procedures was prepared via 2 methods (tube automated) subjected treatment conditions (resting, detergent, 21- 25-gauge needles, [10 20 μg/mL]). Concentrations platelet-derived factor, isoform BB (PDGF-BB); transforming factor β, 1 (TGFβ ); insulin-like (IGF-1) were...

Increasingly, evidence suggests a role for systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation airborne particulate matter. The authors evaluated blood cell parameters and markers platelet activation mice exposed concentrated ambient matter (CAPs) from San Joaquin Valley California, region with severe (PM) pollution episodes. an average 88.5 μg/m3 CAPs size range less than 2.5 μm 6 h/day 5 days per week 2 weeks. Platelets were analyzed by flow...

SEL1L is a well-known protein in the endoplasmic reticulum associated degradation (ERAD) pathway. While it known to be expressed platelets, has never been shown play an active role. Here we find evidence that regulates platelet function. We first identified through study of Atypical Equine Thrombasthenia (AET), autosomal recessive disorder found Thoroughbred horses. A missense variant (c.1810A>G p.Ile604Val) was AET-affected horses, which show with decreased expression. intracellular...

Background Cats with hypertrophic cardiomyopathy ( HCM ) are at risk for development of systemic thromboembolic disease. However, the relationship between platelet activation state and cardiovascular parameters associated is not well described. Objectives To characterize by flow cytometric evaluation P‐selectin semiquantitative Western blot analysis soluble platelet‐endothelial cell adhesion molecule‐1 sPECAM ‐1). Animals Eight normal healthy cats (controls) owned staff students School...

Background: There is currently no simple analytical tool for the evaluation of hypercoagulability in cats. The Platelet Function Analyzer‐100 ® (PFA‐100; Dade Behring Inc., Deerfield, IL, USA) a bench‐top machine that evaluates platelet function by measuring closure time (CT) citrated whole blood under high shear conditions. We hypothesized cats with hypertrophic cardiomyopathy (HCM) have up‐regulated function, which shortens their CT and increases risk thromboembolic events. Objectives:...

To assess platelet count, mean volume (MPV), metabolic characteristics, and function in a dimethyl sulfoxide (DMSO)-stabilized canine frozen concentrate (PC).11 units of commercial PC 6% DMSO fresh platelet-rich plasma from 6 healthy control dogs.PCs were thawed, the following data collected: thaw time, MPV, pH, PCO2, PO2 HCO3-, glucose, lactate content. Phosphatidylserine translocation was determined by use flow cytometry. Fresh dogs served as source platelets for cytometric analysis.At...

Abstract Objectives – To assess platelet function of a commercial dimethyl‐sulfoxide (DMSO)‐stabilized frozen concentrate (PC) using turbidimetric aggregometry. Design In vitro analysis. Setting Research laboratory in school veterinary medicine. Animals Five units PC 6% DMSO were studied. Fresh platelet‐rich plasma (PRP), with and without DMSO, from 6 healthy dogs used as controls. Interventions Turbidimetric aggregation was measured after initiation by addition adenosine diphosphate (ADP),...

Abstract Objective —To determine whether platelet growth factors are preserved in supernatants obtained from rehydrated trehalose-stabilized, freeze-dried (lyophilized) equine platelets and those stimulate fibroblast proliferation migration enhance fibroblast-associated contraction a collagen gel assay. Animals —6 clinically normal adult horses. Procedures —Blood samples were 6 horses, washed prepared via differential centrifugation. Washed physiologic buffer with mixture of trehalose...

Background:Bleeding in racing horses associated with exercise appears to be multifactorial, and clinical investigation into severe cases rarely occurs. Previously, we reported a bleeding diathesis Thoroughbred mare. Herein, describe the cellular physiology of this defect, provide diagnostic tool for identifying it, demonstrate that dysfunction is heritable. Hypothesis:The subject has heritable defect platelet secretion reduces thrombin generation absence additional plasma factors delays...

Increasing evidence suggests a role for systemic pro-coagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation airborne particulate matter (PM). We evaluated platelet activation, cytokines and pulmonary gene expression mice exposed concentrated ambient (CAPs) summer 2008 (S08) winter 2009 (W09) from San Joaquin Valley California, region with severe PM pollution episodes. Additionally, we characterized both exposures including organic compounds, metals, polycyclic...

Bleeding in racing horses associated with exercise appears to be multifactorial, and clinical investigation into severe cases rarely occurs. Previously, we reported a bleeding diathesis Thoroughbred mare. Herein, describe the cellular physiology of this defect, provide diagnostic tool for identifying it, demonstrate that dysfunction is heritable.The subject has heritable defect platelet secretion reduces thrombin generation absence additional plasma factors delays onset production even...

Platelet function defects are rare causes of bleeding diatheses; however, disease prevalence might be underestimated because diagnosis requires assessment specific parameters platelet activation.The goal this study was to characterize the clinical presentation canine Scott syndrome (CSS), an intrinsic defect first identified in a closed colony German Shepherds (GSD).Eleven (n = 6 female) client-owned GSD affected with CSS that sought veterinary care for one or more episodes abnormal...

Background Two congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function response to collagen thrombin stimulation. Hypothesis/Objectives Platelet dysfunction horses this second results from secretory defect. Animals affected 6 clinically normal horses. Methods Ex vivo study. Washed platelets were examined for (1) expression of the α II b‐β3 integrin; (2) fibrinogen binding...

Abstract Objective —To measure the frequency and magnitude of reduced fibrinogen binding in a population horses from Thoroughbred breeding farm. Animals —444 horses, 1 to 27 years old, including 316 females, 72 geldings, 56 sexually intact males. Procedures —Blood was collected into tubes containingacid citrate dextrose adenine, washed platelets were examined by use flow cytometry for their ability bind fibrinogen. Results —Data regarding activated normally distributed, with nearly identical...

Objectives Hypothermia is a common complication of anesthesia, particularly in cats. Some veterinarians insulate the extremities cats as preventive measure, and there evidence that heating dogs decreases rate heat loss from core. This study investigated whether active warming or passive insulation resulted slower decrease rectal temperature during anesthesia. Methods Female were assigned via block randomization to (cotton toddler socks), (heated socks) control group (uncovered extremities)....

This study aimed to investigate pharmacokinetics of fluoxetine in horses and validate a method for liquid chromatography mass spectrometry analysis serum levels. Fluoxetine were determined using 10 healthy, adult horses. following single oral dose (0.25 mg/kg) blood samples collected prior at several time points over 7 days administration. Serum concentrations its bioactive metabolite norfluoxetine measured coupled an accurate mass/high-resolution spectrometer. Pharmacokinetic parameters...

Abstract OBJECTIVE To determine pharmacokinetics and pharmacodynamics after oral administration of a single dose clopidogrel to horses. ANIMALS 6 healthy adult PROCEDURES Blood samples were collected before at various times up 24 hours (2 mg/kg). Reactivity platelets from each blood sample was determined by optical aggregometry phosphorylation vasodilator-stimulated phosphoprotein (VASP). Concentrations the active metabolite derivative (CAMD) measured in use liquid chromatography–tandem mass...

PICO Question In dogs with chronic pain, is acupuncture alone, compared to a placebo, more efficacious in alleviating pain and pain-related dysfunction? Clinical bottom line Category of research Treatment. Number type study designs reviewed Three controlled studies were critically appraised. Strength evidence Moderate. Outcomes reported Administration either fluoxetine or clomipramine adult reduces symptoms fear anxiety. Conclusion Both are effective reducing acral lick dermatitis tail...

Introduction: The authors previously investigated the use of epinephrine at 1:400,000 dilution to prevent scrotal hematoma but found no significant reduction in hematomas. We hypothesized that higher concentrations would reduce incidence Methods: Male cats trapped for Midwestern University College Veterinary Medicine’s Trap-Neuter-Return program were assigned one three treatment groups this randomized control trial: LRS (A), 1:40,000 (B), or 1:120,000 (C). Each patient received 0.2 mL as a...