An ATP-activated channel is involved in mitogenic stimulation of human T lymphocytes

We investigated the effect of pharmacologic modulation of the ATP receptor on intracellular ion changes and proliferative response of human peripheral blood lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP (ATPe) triggered in these cells an increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and plasma membrane depolarization. Whereas both Ca2+ release from intracellular stores and influx across the plasma membrane were detected in the whole PBL population, only Ca2+ influx was observed in T cells. In the presence of near physiologic extracellular Na+ concentrations (125 mmol/L), Ca2+ permeability through the ATPe-gated channel was very low, suggesting a higher selectivity for monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic ATP (BzATP) increased [Ca2+]i in the presence but not the absence of extracellular Ca2+ and also caused plasma membrane depolarization. The covalent blocker oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+ influx and plasma membrane depolarization, but had no effect on Ca2+ release from stores. Stimulation with ATPe alone had no significant effects on PBL 3H-thymidine incorporation. On the contrary, ATPe or BzATP had a synergistic effect on DNA synthesis stimulated by selective T-cell mitogens such as phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs (mixed lymphocyte cultures). Treatment with oATP inhibited mitogenic stimulation by these receptor-directed agents but not by the combined application of the Ca2+ ionophore ionomycin and phorbol myristate acetate. Interleukin-2 partially relieved inhibition by oATP. These results suggest that human T lymphocytes express a plasma membrane channel gated by ATPe that is involved in mitogenic stimulation.     

Radionuclide esophageal and intestinal transit scintigraphy in patients undergoing radiation therapy

Radiation esophagitis and enteritis are common and significant side effects of radiation therapy. Non-invasive assessment of functional and/or anatomic changes responsible for the symptoms produced by radiation esophagitis and enteritis has been unsatisfactory. This paper demonstrates the value of radionuclide esophageal and intestinal transit scintigraphy in patients undergoing mediastinal or abdominal radiation.     

Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients

Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Activates the NLRP3 Inflammasome in Human Macrophages,Leading to the Release of Proinflammatory Cytokines

The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive oxygen species (ROS) generation and Cdt-induced increases in extracellular ATP levels. Increases in extracellular ATP levels contribute to the activation of the P2X₇ purinergic receptor, leading to K⁺ efflux. The relationship between the abilities of the active toxin subunit CdtB to function as a lipid phosphatase, activate the NLRP3 inflammasome, and induce a proinflammatory cytokine response is discussed. These studies provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as Aggregatibacter actinomycetemcomitans.     

A Review of Autism Spectrum Disorders (ASD) from A Perspective of Classical Chinese Medicine (CCM)

Introduction Autism is a complex developmental disability that typically appears during the first two years of man's life and is the result of a neurological disorder that affects the functioning of the brain,and the     

Kinematic analysis of dynamic lumbar motion in patients with lumbar segmental instability using digital videofluoroscopy

The study design is a prospective, case–control. The aim of this study was to develop a reliable measurement technique for the assessment of lumbar spine kinematics using digital video fluoroscopy in a group of patients with low back pain (LBP) and a control group. Lumbar segmental instability (LSI) is one subgroup of nonspecific LBP the diagnosis of which has not been clarified. The diagnosis of LSI has traditionally relied on the use of lateral functional (flexion–extension) radiographs but use of this method has proven unsatisfactory. Fifteen patients with chronic low back pain suspected to have LSI and 15 matched healthy subjects were recruited. Pulsed digital videofluoroscopy was used to investigate kinematics of lumbar motion segments during flexion and extension movements in vivo. Intersegmental linear translation and angular displacement, and pathway of instantaneous center of rotation (PICR) were calculated for each lumbar motion segment. Movement pattern of lumbar spine between two groups and during the full sagittal plane range of motion were analyzed using ANOVA with repeated measures design. Intersegmental linear translation was significantly higher in patients during both flexion and extension movements at L5–S1 segment (p < 0.05). Arc length of PICR was significantly higher in patients for L1–L2 and L5–S1 motion segments during extension movement (p < 0.05). This study determined some kinematic differences between two groups during the full range of lumbar spine. Devices, such as digital videofluoroscopy can assist in identifying better criteria for diagnosis of LSI in otherwise nonspecific low back pain patients in hope of providing more specific treatment.