Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues

To increase transgenic production of granulocyte-macrophage colony- stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA) were transfected into cells in culture or animals using particle-mediated gene-transfer technology. Normal peripheral blood mononuclear cells accumulated 20- fold greater levels of GM-CSF mRNA and secreted comparably greater amounts of cytokine after transfection with hGM-AUGUA expression vectors versus hGM-AUUUA. hGM-AUGUA mRNA was fivefold more stable (t 1/2 = 95 minutes) than hGM-AUUUA mRNA (t 1/2 = 20 minutes), accounting for elevated steady-state levels. Transfection site extracts and serum samples obtained 24 hours after gene transfer of hGM-AUGUA cDNA into mouse skin contained greater than 32 ng/mL and 650 pg/mL of GM-CSF protein, respectively, compared with 0.33 ng/mL and less than 8 pg/mL for hGM-AUUUA cDNA. GM-CSF produced from mGM-AUGUA cDNA transfected into rat abdominal epidermis induced a profound neutrophil infiltrate. These data suggest a novel strategy for enhanced production of biologically active cytokines by normal cells after in vivo gene transfer.     

Far-field potentials

Far-field potentials are produced by neural generators located at a distance from the recording electrodes. These potentials were initially characterized incorrectly as being of positive polarity, widespread distribution, and constant latency; however, recent advances have clearly demonstrated that far-field potentials may be either positive or negative depending upon the location of the electrodes with respect to the orientation of the dipole generator. Additionally, peak latencies in the far-field can vary with alterations in body position and the spatial distribution of far-field potentials, while widespread, is not uniform. Recent studies of far-field potentials suggest how such waveforms are produced when the symmetry of an action potential, as recorded by distant electrodes, is broken by such factors as differing conductivities of volume conductor compartments, direction of action potential propagation, size differentials in adjoining body segments, or the termination of action potential propagation in excitable tissue. Human, animal, and computer experiments support the preceding generalizations. These new explanations are directly applicable to such far-field potentials as the short latency somatosensory-evoked potential. Furthermore, since far-field potentials can also occur in muscle tissue, one should expect that these generalizations will hold with respect to electromyographic potentials. © 1993 John Wiley & Sons, Inc.     

ATM, an unexpected new target in metabolic syndrome

ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
Schneider et al. (2006)
Cell Metabolism: 4 (5): 377–389     

Work in progress: the application of temporal filtering techniques to hybrid subtraction in digital subtraction angiography

Temporal filtering methods were applied to iodine signal-to-noise ratio (SNR) restoration in intravenous hybrid subtraction digital subtraction angiography (DSA). For equal detected exposure rates hybrid subtraction had approximately 35% of the SNR of temporal subtraction. When matched filtering was applied to a DSA run, the filtered result had approximately two times higher SNR than the peak contrast image in the run. Thus, when matched filtering techniques were applied to the hybrid image sequence, the resultant SNR increased to about 70% of that of temporal subtraction. With an additional factor-of-two increase in exposure rate for the hybrid run, SNR parity with temporal subtraction could be achieved. This compared with a factor-of-nine increase in exposure that would be required if no filtering were performed. Experimental hybrid matched filter results, generated with intravenous canine DSA studies, supported the predictions in SNR performance.     

Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 α, 25-(OH)2D3

The hormone 1 α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)₂D₃ on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)₂D₃ at 5 μg/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)₂D₃ at 2 μg/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)₂D₃ at 2 μg/kg, each given on alternate days from day −3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)₂D₃ might be a potential dose-reducing agent for CsA in immunosuppressive therapy.     

Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: Report on 24 months of surveillance

Objective : To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization.
Methodology : Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described.
Results : Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days. Infection rates were significantly higher in lower birthweight groups. Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group. Antibiotic exposure averaged 12% of total admission days, less than previously published data.
Conclusions : The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.     

消旋棉酚拆分的研究——Ⅳ.苏(-)或(+)-1-(对硝基苯基)-1,3-二羟基丙胺-2为拆分剂

本文介绍以光学活性苏-1-(对硝基苯基)-1,3-二羟基丙胺-2为拆分剂,与消旋棉酚缩合,用常压柱色谱或溶剂结晶法分离得到两个光学纯的非对映体,然后分别水解得(+)和(-)-棉酚。     

Proton spectroscopic imaging (Dixon method) of the liver: clinical utility

The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases.