The αβ T Cell Receptor Clustering Upon Superantigen/MHC Recognition

Antigen recognition by T cells is the key event for the antigen specific immune responses to be triggered. This recognition is initiated by the binding of the T cell receptor (TCR) to antigen peptide/major histocompatibility complex (MHC) on the surface of the antigen presenting cells. TCR on most of the T cells is a heterodimer composed of α and β chains which are associated with CD3 γδε as well as ζ chains, the signal transmission molecules. The dynamics of this TCR complex upon antigen/MHC recognition, however, has not been well understood. In this paper the authors analyse the configuration of TCR complex on T cells from a TCR β chain gene transgenic mouse (TGM) strain. Unlike many other TGM strains reported, a considerable proportion of T cells from this TGM expresses both transgene-encoded (Vβ3) and endogenous TCR β chains on their surface. By immunoprecipitation and immunoblotting analysis of T cells stimulated with a superantigen, staphylococcal enterotoxin B (SEB), the authors found that Vβ3 was coprecipitated with Vβ8, demonstrating the clustering of TCR αβ upon superantigen/MHC recognition.     

Do vascular surgery patients need a cardiology work-up? A review of pre-operative cardiac clearance guidelines in vascular surgery.

OBJECTIVES: to outline the appropriate pre-operative cardiac work-up for patients who are scheduled for major peripheral vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a review of the literature focusing on studies that have correlated the pre-operative cardiac work-up patients receive to the cardiac morbidity and mortality following vascular surgery. Only studies with level A evidence were included. RESULTS: peri-operative beta blockade has been shown to decrease cardiac complications after vascular surgery in all risk groups. Non-invasive cardiac testing is only necessary for patients in the intermediate/high risk group. Coronary revascularization should only be considered after a positive non-invasive cardiac test. CONCLUSIONS: patients must be risk stratified pre-operatively based on history and physical examination. Low risk patients should receive peri-operative beta blockade only with no further non-invasive testing. On the other hand, intermediate and high risk patients should undergo non-invasive cardiac testing before going to the operating room.     

Motor cortex injury has different behavioral and anatomical effects in early and late adolescence

Although there are many studies investigating the effects of early cortical injury on brain and behavioral development in laboratory animals, there are virtually no studies examining the effects of cortical injury in adolescence. The purpose of present study was to investigate the effects of unilateral motor cortex lesion received in early and late adolescence periods (Postnatal days 35 and 55 [P35, P55]) on spontaneous neural reorganization and behavioral recovery in adulthood. Rats were given unilateral motor cortex lesions at P35 or P55 and their motor behaviors were compared to sham controls in adulthood. The results of behavioral tests (skilled reaching, postural asymmetry, sunflower seed manipulation, forepaw inhibition in swimming) revealed that rats with P35 lesions had significant functional deficits whereas the rats with P55 lesions showed nearly complete recovery. Golgi-Cox analysis of pyramidal neurons showed bilateral hypertrophy of dendritic fields in the remaining sensorimotor cortex in P55 but not P35 rat brains. Thus, there appears to be an age-related pattern of morphological and behavioral changes in response to cortical injury in the early and late adolescent periods leading to better functional recovery from later injuries, much as is seen in human children.     

Cross-validated models of the relationships between neck muscle electromyography and three-dimensional head kinematics during gaze behavior

The object of this study was to model the relationship between neck electromyography (EMG) and three-dimensional (3-D) head kinematics during gaze behavior. In two monkeys, we recorded 3-D gaze, head orientation, and bilateral EMG activity in the sternocleidomastoid, splenius capitis, complexus, biventer cervicis, rectus capitis posterior major, and occipital capitis inferior muscles. Head-unrestrained animals fixated and made gaze saccades between targets within a 60° × 60° grid. We performed a stepwise regression in which polynomial model terms were retained/rejected based on their tendency to increase/decrease a cross-validation-based measure of model generalizability. This revealed several results that could not have been predicted from knowledge of musculoskeletal anatomy. During head holding, EMG activity in most muscles was related to horizontal head orientation, whereas fewer muscles correlated to vertical head orientation and none to small random variations in head torsion. A fourth-order polynomial model, with horizontal head orientation as the only independent variable, generalized nearly as well as higher order models. For head movements, we added time-varying linear and nonlinear perturbations in velocity and acceleration to the previously derived static (head holding) models. The static models still explained most of the EMG variance, but the additional motion terms, which included horizontal, vertical, and torsional contributions, significantly improved the results. Several coordinate systems were used for both static and dynamic analyses, with Fick coordinates showing a marginal (nonsignificant) advantage. Thus, during gaze fixations, recruitment within the neck muscles from which we recorded contributed primarily to position-dependent horizontal orientation terms in our data set, with more complex multidimensional contributions emerging during the head movements that accompany gaze shifts. These are crucial components of the late neuromuscular transformations in a complete model of 3-D head-neck system and should help constrain the study of premotor signals for head control during gaze behaviors.     

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so‐called “metformin‐associated lactic acidosis” (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin‐treated patients. Metformin therapy does not necessarily induce metformin accumulation, just as metformin accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia does not necessarily induce lactic acidosis. In contrast to the conventional view, MALA probably accounts for a smaller proportion of cases than either metformin‐unrelated lactic acidosis or metformin‐induced lactic acidosis. Lastly, this review highlights the need for substantial improvements in the reporting of cases of lactic acidosis in metformin‐treated patients. Accordingly, we propose a check‐list as a guide to clinical practice.     

Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.     

Characteristics and outcomes of recurrent atrial fibrillation after prior failed pulmonary vein isolation

Journal of Interventional Cardiac Electrophysiology - The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized...