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.     

Prospective randomized evaluation of emergency extracorporeal shock wave lithotripsy (ESWL) on the short-time outcome of symptomatic ureteral stones

OBJECTIVE: Here, we report the results of a randomized controlled trial (RCT) assessing the efficacy of emergency ESWL (eESWL) on the short-term outcome of symptomatic ureteral stones. MATERIAL: The trial enrolled 100 patients admitted in emergency room for renal colic caused by a ureteral radioopaque [corrected] stone. Patients were randomized to medical therapy alone or combined with eESWL. eESWL was performed within 6 hours of the onset of renal colic without specific analgesia on a Lithostar lithotripter (Siemens Medical, Munich, Germany). The primary endpoints were the proportion of patients stone free rate after 48 hours (SF-48) and the cumulative proportion of patients discharged from the hospital after 48 and 72 hours. RESULTS: Ureteral stone's location was proximal and distal in respectively 46% and 54% of the patients; stone's mean size was 5.5 mm (range 2-10 mm). Median hospital stay was 3 days, ranging from 1 to 14 days. SF-48 in the control group varied from 76% for distal stones <5 mm to 28.6% for proximal stones >5 mm, averaging at 61%. On average, eESWL increased SF-48 by 13% (p: 0.126), the gain strictly depending on stone size and location. SF-48 increase ranged from 40% for proximal stones >5 mm to 1.8% for distal stone <5 mm. On average, eESWL increased the median duration of hospital stay by one day. This mean negative impact results from ESWL increasing significantly the duration of hospital stay in case of distal stone, while slightly shortened it for stones located proximally. CONCLUSION: This study demonstrated for the first time that rapidly performed ESWL is a valuable therapeutic option to improve elimination of ureteral stones and shorten duration of hospital stay, proven that the stone is located proximally to the iliac vessels.     

PET/CT imaging artifacts

The purpose of this paper is to introduce the principles of PET/CT imaging and describe the artifacts associated with it. PET/CT is a new imaging modality that integrates functional (PET) and structural (CT) information into a single scanning session, allowing excellent fusion of the PET and CT images and thus improving lesion localization and interpretation accuracy. Moreover, the CT data can also be used for attenuation correction, ultimately leading to high patient throughput. These combined advantages have rendered PET/CT a preferred imaging modality over dedicated PET. Although PET/CT imaging offers many advantages, this dual-modality imaging also poses some challenges. CT-based attenuation correction can induce artifacts and quantitative errors that can affect the PET emission images. For instance, the use of contrast medium and the presence of metallic implants can be associated with focal radiotracer uptake. Furthermore, the patient's breathing can introduce mismatches between the CT attenuation map and the PET emission data, and the discrepancy between the CT and PET fields of view can lead to truncation artifacts. After reading this article, the technologist should be able to describe the principles of PET/CT imaging, identify at least 3 types of image artifacts, and describe the differences between PET/CT artifacts of different causes: metallic implants, respiratory motion, contrast medium, and truncation.     

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)     

Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.

PURPOSE: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma. EXPERIMENTAL DESIGN: The in vitro and ex vivo tumor uptake of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments. RESULTS: In vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [(18)F]FLT and [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies. CONCLUSIONS: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.