Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions

Gene therapy may be an important adjuvant for treating cancer in the pleural space. The initial results of retroviral gene transfer to cancer cells in malignant pleural effusions revealed that transduction was markedly inhibited, and studies to characterize the inhibitory factor(s) were performed. The inhibition was contained within the soluble, rather than cellular, components of the effusions and was demonstrated with amphotropic, gibbon ape leukemia virus, and vesicular stomatitis virus-glycoprotein pseudotyped retroviral vectors. After excluding complement proteins, a series of studies identified chondroitin sulfates (CSs) as the inhibitory substances. First, treatment of the effusions with mammalian hyaluronidase or chondroitinases, but not Streptomyces hyaluronidase, abolished the inhibitory activity. Second, addition of exogenous CS glycosaminoglycans mimicked the inhibition observed with pleural effusions. Third, immunoassays and biochemical analyses of malignant pleural effusion specimens revealed CS in relevant concentrations within pleural fluid. Fourth, proteoglycans/glycosaminoglycans isolated from the effusions inhibited retroviral gene transfer. Analyses of the mechanism of inhibition indicate that the chondroitin sulfates interact with vector in solution rather than at the target cell surface. These results suggest that drainage of the malignant pleural effusion, and perhaps enzymatic pretreatment of the pleural cavity, will be necessary for efficient retroviral vector mediated gene delivery to pleural metastases.     

Video-assisted thoracoscopic surgery (VATS). Endoscopic thoracoplasty technique

STUDY DESIGN: The study of two patients whose rib deformity was treated using a new endoscopic thoracoplasty technique is reported. OBJECTIVES: To report a new endoscopic thoracoplasty technique for the treatment of rib deformities associated with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Thoracoplasty has traditionally been performed as an open procedure, often necessitating additional incisions and/or tissue dissection. METHODS: Two children with significant rib humps associated with idiopathic scoliosis were treated with a new endoscopic thoracoplasty technique. RESULTS: Both children showed dramatic cosmetic improvement of their rib deformity. CONCLUSIONS: The indications for the use of video-assisted thoracoscopic surgery in the treatment of pediatric spinal deformity are expanding. We have extended our video-assisted thoracoscopic surgery repertoire to include endoscopic thoracoplasty for treatment of rib deformities associated with idiopathic scoliosis. The technique for endoscopic thoracoplasty is discussed, and illustrative cases are presented.     

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The possible contamination of groundwater by the insecticide carbofuran was assessed with the behavior assessment model (BAM) and groundwater pollution-potential model (GWP). Dissipation coefficients of this insecticide in two subtropical soils at different moisture contents and soil temperatures were studied by determining the degradation and adsorption of the herbicide in soils. Movement of carbofuran was studied by leaching the insecticide in a soil column in the laboratory. Under 40% field capacity and at 25 degrees C, more than 80% of carbofuran residue was found in both Luchu clay and Yuanlin silty clay loam after incubation for 63 days. The results indicate that the higher the moisture content in the soil, the less the carbofuran residue under the soil moisture below the field capacity. Carbofuran tends to dissipate more easily in Yuanlin soil than in Luchu soil. The distribution coefficient (Kd) with r2 of 0.69 and 0.92 for Luchu and Yuanlin soils, respectively, was found using the first-order kinetics law. In leaching experiment, carbofuran exhibited easier movement in Luchu than in Yuanlin soil.     

Behavioral sensitization is induced by intravenous self-administration of cocaine by rats

Salicylate-kodein is a widely used analgesic agent, particularly in outpatient practice. Salicylates have been incriminated in hepatic injury while kodein may induce biliary spasm. We report here a case of granulomatous hepatitis attributed to prolonged intake of this combination, which has never been reported previously to our knowledge.     

RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes

The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.     

Noise Equivalent Power of Background Limited Thermal Detectors at Submillimeter Wavelengths

With the advent of large submillimeter telescopes at high, dry sites, the atmospheric background noise in a moderate bandwidth can be low enough to challenge the ability of instrument designers to produce sufficiently low noise bolometers to be background limited. We compare the predictions for the noise power of a bolometer observing through an emissive atmosphere, considering the effect of atmospheric absorption, telescope optical efficiency, and detector optical efficiency, with measurements through the atmosphere over Mauna Kea.     

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.