Biochemical Underpinnings of Immune Cell Metabolic Phenotypes

The metabolism of immune cells affects their function and influences host immunity. This review explores how immune cell metabolic phenotypes reflect biochemical dependencies and highlights evidence that both the metabolic state of immune cells and nutrient availability can alter immune responses. The central importance of oxygen, energetics, and redox homeostasis in immune cell metabolism, and how these factors are reflected in different metabolic phenotypes, is also discussed. Linking immune cell metabolic phenotype to effector functions is important to understand how altering metabolism can impact the way in which immune cells meet their metabolic demands and affect the immune response in various disease contexts.National Institutes of Health (U.S.) (Grant R01CA168653)National Institutes of Health (U.S.) (Grant R01CA201276

Carbohydrate and protein contents of grain dusts in relation to dust morphology.

Grain dusts contain a variety of materials which are potentially hazardous to the health of workers in the grain industry. Because the characterization of grain dusts is incomplete, we are defining the botanical, chemical, and microbial contents of several grain dusts collected from grain elevators in the Duluth-Superior regions of the U.S. Here, we report certain of the carbohydrate and protein contents of dusts in relation to dust morphology. Examination of the gross morphologies of the dusts revealed that, except for corn, each dust contained either husk or pericarp (seed coat in the case of flax) fragments in addition to respirable particles. When viewed with the light microscope, the fragments appeared as elongated, pointed structures. The possibility that certain of the fragments within corn, settled, and spring wheat were derived from cell walls was suggested by the detection of pentoses following colorimetric assay of neutralized 2 N trifluoroacetic acid hydrolyzates of these dusts. The presence of pentoses together with the occurrence of proteins within water washings of grain dusts suggests that glycoproteins may be present within the dusts. With scanning electron microscopy, each dust was found to consist of a distinct assortment of particles in addition to respirable particles. Small husk fragments and "trichome-like" objects were common to all but corn dust

Transesophageal echocardiography (TEE)-induced Mallory-Weiss laceration in a patient who underwent aortic and mitral valve replacement -A case report-

Transesophageal echocardiography (TEE) is a relatively noninvasive and highly valuable diagnostic modality to monitor cardiac surgery. TEE is utilized to estimate the results of the surgical correction or the cardiac function on a real time basis. Accordingly, the frequency of TEE usage is increasing. Previous studies have shown low risk of TEE-associated complications; nonetheless, major gastrointestinal trauma can occur on a rare occasion. We herein present a case of Mallory-Weiss laceration after an intraoperative TEE examination

Impaired degranulation but enhanced cytokine production after FcɛRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound FcɛRI. Diacylglycerol kinase (DGK)ζ is a negative regulator of diacylglycerol-dependent signaling that acts by converting diacylglycerol to phosphatidic acid. We reported previously that DGKζ−/− mice have enhanced in vivo T cell function. Here, we demonstrate that these mice have diminished in vivo mast cell function, as revealed by impaired local anaphylactic responses. Concordantly, DGKζ−/− bone marrow–derived mast cells (BMMCs) demonstrate impaired degranulation after FcɛRI cross-linking, associated with diminished phospholipase Cγ activity, calcium flux, and protein kinase C–βII membrane recruitment. In contrast, Ras-Erk signals and interleukin-6 production are enhanced, both during IgE sensitization and after antigen cross-linking of FcɛRI. Our data demonstrate dissociation between cytokine production and degranulation in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenuation of FcɛRI signals

Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells

Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio. Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship F32 CA132358)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Damon Runyon Cancer Research FoundationBurroughs Wellcome FundSmith Family FoundationNational Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest

Objectives. During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA. Design. Twenty-two pigs were randomized into the RIPC group (n=11) and the control group (n=11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60min DHCA at 18 degrees C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses. Results. Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4hours of the arrest, (pPeer reviewe

Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin

BackgroundLong-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear.ObjectiveIn the current study, we examined temporal aspects of the exposure-response relationship between airborne endotoxin exposure, longitudinal change in FEV1, and respiratory symptoms in a cohort of Chinese cotton textile workers.MethodsThis prospective cohort study followed 447 cotton textile workers from 1981 to 2006. at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV1 level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and > or = 5 years).Results and conclusionsPast exposure to endotoxin was associated with reduced FEV1 level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV1 for those hired < 5 years before baseline than for those who were hired > or = 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough