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.     

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     

Cortical control of neurally-mediated arrhythmogenic properties of desacetyl lamatoside C: The role of the posterior hypothalamus

Functional ablation of the cerebral cortex by cortical spreading depression (CSD) significantly increased the dose of desacetyl lanatoslde C required to induce A-V block and ventricular fibrillation. To examine the role of the posterior hypothalamus in the increased resistance of decorticated rats to arrhythmia induced by toxic doses of desacetyl lanatoside C, four groups of animals were injected with this drug: group 1 rats had a craniotomy; group 2 rats had a craniotomy and functional decortication; group 3 rats had a craniotomy and a hypothalamic lesion; and group 4 rats had a craniotomy, hypothalamic lesion and functional decortification. The dose of drug required to induce A-V block and ventricular fibrillation was significantly less in group 1, than in groups 2,3 and 4, and there was no statistically significant difference between these last three groups. These results are consistent with the hypothesis that the increased resistance to arrhythmia induced by desacetyl lanatoside C in decorticated rats is mediated by the posterior hypothalamus.     

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.     

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.     

Nitric oxide reduces hypophagia induced by threonine free diet in the rat

Food intake and concentrations of glutamic (GLU) and aspartic (ASP) acids in the nucleus accumbens were monitored in male Sprague–Dawley rats fed a threonine free diet. These variables were measured before and after an intracerebroventricular injection of 20 nmole nitroprusside (NP), a non-enzymatic nitric oxide donor. The same variables were also monitored in: (a) rats fed a threonine free diet and injected with saline; (b) animals fed a standard diet and injected with nitroprusside; (c) rats fed a standard diet and injected with saline. The results showed that the threonine-free diet reduced food intake and GLU and ASP concentrations in the accumbens. NP reduced the hypophagia, but it did not change GLU and ASP levels in rats fed the threonine-free diet. In animals fed the standard diet, NP increased GLU and ASP concentration, and food intake. No change was found in the animals with saline injection. These findings suggest that nitric oxide reduces the hypophagia in the rats fed a threonine-free diet. The lack of increase in GLU and ASP concentration in the nucleus accumbens of the hypophagic rats indicates that NP acts on hypophagia independently by GLU and ASP.