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91.
Temporally and spatially resolved mapping of protein abundance patterns within the mammalian brain is of significant interest for understanding brain function and molecular etiologies of neurodegenerative diseases; however, such imaging efforts have been greatly challenged by complexity of the proteome, throughput and sensitivity of applied analytical methodologies, and accurate quantitation of protein abundances across the brain. Here, we describe a methodology for comprehensive spatial proteome mapping that addresses these challenges by employing voxelation integrated with automated microscale sample processing, high-throughput liquid chromatography (LC) system coupled with high-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, and a "universal" stable isotope labeled reference sample approach for robust quantitation. We applied this methodology as a proof-of-concept trial for the analysis of protein distribution within a single coronal slice of a C57BL/6J mouse brain. For relative quantitation of the protein abundances across the slice, an 18O-isotopically labeled reference sample, derived from a whole control coronal slice from another mouse, was spiked into each voxel sample, and stable isotopic intensity ratios were used to obtain measures of relative protein abundances. In total, we generated maps of protein abundance patterns for 1028 proteins. The significant agreement of the protein distributions with previously reported data supports the validity of this methodology, which opens new opportunities for studying the spatial brain proteome and its dynamics during the course of disease progression and other important biological and associated health aspects in a discovery-driven fashion.  相似文献   
92.
Implementing DNA diagnostics in clinical practice for extremely heterogeneous diseases such as hearing loss is challenging, especially when attempting to reach high sensitivity and specificity in a cost‐effective fashion. Next generation sequencing has enabled the development of such a test, but the most commonly used genomic target enrichment methods such as hybridization‐based capture suffer from restrictions. In this study, we have adopted a new flexible approach using microdroplet PCR‐based technology for target enrichment, in combination with massive parallel sequencing to develop a DNA diagnostic test for autosomal recessive hereditary hearing loss. This approach enabled us to identify the genetic basis of hearing loss in 9 of 24 patients, a success rate of 37.5%. Our method also proved to have high sensitivity and specificity. Currently, routine molecular genetic diagnostic testing for deafness is in most cases only performed for the GJB2 gene and a positive result is typically only obtained in 10–20% of deaf children. Individuals with mutations in GJB2 had already been excluded in our selected set of 24 patients. Therefore, we anticipate that our deafness test may lead to a genetic diagnosis in roughly 50% of unscreened autosomal recessive deafness cases. We propose that this diagnostic testing approach represents a significant improvement in clinical practice as a standard diagnostic tool for children with hearing loss. © 2012 Wiley Periodicals, Inc.  相似文献   
93.
Sclerosing cholangitis: CT findings   总被引:5,自引:0,他引:5  
The value of computed tomography (CT) in the detection of primary sclerosing cholangitis (PSC) in the intrahepatic and extrahepatic biliary systems was assessed by comparing CT scans of 20 cases of PSC with cholangiographic findings. In 16 of 19 cases of extrahepatic duct disease demonstrated with cholangiography, CT demonstrated abnormalities of the common hepatic duct, or bile duct, including duct stenosis, mural nodularity, duct dilatation, wall thickening, and mural enhancement. CT demonstrated intrahepatic disease in all 20 cases, including duct dilatation, duct stenosis, pruning, and beading. CT was superior to cholangiography in characterization of the status of the intrahepatic duct system in 11 of 20 cases. In addition, CT demonstrated extrabiliary complications of PSC in 12 cases and superimposed cholangiocarcinoma in three cases. While cholangiography remains the standard for diagnosis and follow-up of PSC, CT can provide valuable information about the extent and complications of the disease.  相似文献   
94.
PURPOSE: To implement and optimize cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) in the rat cerebral and cerebellar cortex during electrical paw stimulation. MATERIALS AND METHODS: fMRI of the cerebral and cerebellar cortex was performed during electrical paw stimulation on a 7-T MRI system (MRRS, Guilford, UK) comparing the blood oxygenation level-dependent (BOLD) and CBV-weighted contrast with different ultrasmall particles of iron oxide (USPIO) contrast doses (NC100150, 30 mg Fe/mL; Amersham Health, Oslo, Norway) and different TE. RESULTS: Doses of 15 and 20 mg/kg USPIO at TE = T*2 or TE = 14 msec almost doubled the contrast-to-noise ratio (CNR) of the activated areas in the cerebral cortex without affecting the overall signal-to-noise ratio (SNR) or the incidence of activation (100%). In the cerebellum the SNR decreased significantly with an increasing contrast dose. At a dose of 15 mg/kg, the CNR was slightly smaller than the CNR measured in the BOLD images, but the activation incidence seemed to be doubled. At 20 mg/kg, the CNR was slightly increased, but the activation incidence was lower. At both contrast doses the venous artifacts disappeared. CONCLUSION: A USPIO contrast dose of 20 mg/kg proved to be beneficial for fMRI in the rat, even though it affected the CNR and SNR in the cerebral and the cerebellar cortex differentially.  相似文献   
95.
96.
Tyramine induces coma in phenelzine-treated dogs with liver disease. The objective of the present investigation was to examine the influence of tyramine in these monoamine oxidase-inhibited dogs on the kinetics of Tc-99m-diethylenetriamine penta-acetic acid (Tc-99m-DTPA) during its first passage through the brain by nuclear imaging techniques. The study began with anesthetized mongrel dogs (n = 10) in a supine position over the camera detector. Data acquisition was started simultaneously after the rapid intracarotid injection of Tc-99m-DTPA (5 mCi) and 60 0.5-sec images of the brain were taken. Tyramine induced increased uptake with a concomitant impairment in the elimination of Tc-99m-DTPA from the brain of these phenelzine-treated animals with hepatic injury (n = 5) as compared to pretreated animals serving as a control group or phenelzine-treated animals without liver disease. This was accompanied by an appreciable reduction in hemispheric cerebral blood flow (50.5 +/- 19.3 vs. 110 +/- 16 ml/100 g/min), respectively. Increased cerebrovascular permeability of Tc-99m-DTPA and decreased cerebral blood flow occurred concomitantly with increased cerebrospinal fluid pressure and elevation in cerebrospinal fluid catecholamines of monoamine oxidase-inhibited animals with hepatic injury.  相似文献   
97.
Ulnar nerve(UN) injuries are a common complaint amongst overhead athletes. The UN is strained during periods of extreme valgus stress at the elbow, especially in the late-cocking and early acceleration phases of throwing. Although early ulnar collateral ligament(UCL) reconstruction techniques frequently included routine submuscular UN transposition, this is becoming less common with more modern techniques. We review the recent literature on the sites of UN compression, techniques to evaluate the UN nerve, and treatment of UN pathology in the overhead athlete. We also discuss our preferred techniques for selective decompression and anterior transposition of the UN when indicated. More recent studies support the use of UN transpositions only when there are specific preoperative symptoms. Athletes with isolated ulnar neuropathy are increasingly being treated with subcutaneous anterior transposition of the nerve rather than submuscular transposition. When ulnar neuropathy occurs with UCL insufficiency, adoption of the muscle-splitting approach for UCL reconstructions, as well as using a subcutaneous UN transposition have led to fewer postoperative complications and improved outcomes. Prudent handling of the UN in addition to appropriate surgical technique can lead to a high percentage of athletes who return to competitive sports following surgery for ulnar neuropathy.  相似文献   
98.
99.
Surface shield: device to reduce personnel radiation exposure   总被引:2,自引:0,他引:2  
A simple device is described that can reduce personnel exposure from scatter radiation by up to 75%. The device consists of an oblong piece of shielding (0.75-mm lead equivalent) that is taped to the side of the patient during percutaneous renal stone removal and other interventional procedures. Contrary to other shields and barriers, this does not interfere with access to the patient. Scatter exposure data from phantom studies are presented and the rationale for surface shielding discussed.  相似文献   
100.
Ingraham  LM; Boxer  LA; Haak  RA; Baehner  RL 《Blood》1981,58(4):830-835
We have studied membrane fluidity changes in polymorphonuclear leukocytes (PMN) during phagocytosis. Membrane fluidity was assessed by electron spin resonance (ESR) using a nitroxide-substituted stearic acid analog (5DS) as a spin probe. PMN from normal subjects and from 3 CGD patients (2 males, 1 female) were incubated in Kreb's Ringers phosphate with or without opsonized zymosan. ESR spectra were obtained and the order parameter (S), which is inversely related to membrane fluidity, was calculated. Without zymosan addition, S for normal (0.638) and for CGD (0.635) were not significantly different (p less than 0.35). The S values indicate that under resting conditions the molecular environment of the CGD membrane is similar to that of normal PMN membranes. However, with addition of opsonized zymosan, the normal, but not the CGD, PMN showed a significant increase (CGD, S = 0.638; normal, S = 0.647; p less than 0.001). This change in S for the normals is consistent with a more restricted movement of 5DS. Treatment of normal PMN with a mixture of scavengers specific for H2O2 (catalase, 1600 U/ml), O2-.(superoxide dismutase, 100 micrograms/ml), and for HO., (sodium benzoate, 1mM) during zymosan stimulation gave S values similar to those of resting cells. Catalase alone also lowered S value, suggesting that H2O2 was instrumental in causing the initial S value increase. This idea was supported by studies in which CGD cells were incubated with zymosan in the presence of glucose oxidase, an enzyme that catalyzes glucose oxidation resulting in the direct reduction of molecular oxygen to H2O2. Our results indicate that reduced O2 by- products, particularly H2O2, can cause altered biophysical properties of PMN membrane during phagocytosis.  相似文献   
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