High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.     

人端粒酶逆转录酶启动子介导的靶向性肿瘤基因治疗的研究进展

端粒酶与肿瘤发生发展的关系是近年来肿瘤研究领域的热点之一．端粒的磨耗限制大多数体细胞的复制,肿瘤细胞主要通过转录上调端粒酶限制成分催化亚基端粒酶逆转录酶（hTERT）维持端粒长度．由于hTERT启动子区域已被克隆,其特点也已被鉴定,hTERT启动子介导的靶向性肿瘤基因治疗成为研究的热点．我们综述了hTERT启动子介导的靶向性肿瘤基因治疗最新研究进展．     

Central nervous system high-resolution magnetic resonance imaging: effect of increasing spatial resolution on resolving power

Resolving power is a useful measure of the magnetic resonance (MR) imager-determined ability to discriminate subtle disease. Optimizing the resolving power produces the best MR images. The resolving power improves with higher spatial resolution, signal-to-noise ratio, and object contrast. Resolving power degrades with increased patient motion, which can be associated with prolonged imaging times. High and low object contrast 0.35-T MR images of the central nervous system are compared at different levels of spatial resolution and signal-to-noise ratios. In systems that have a marginal signal-to-noise ratio, the resolving power can actually decrease when higher spatial resolution is used due to further lowering of signal-to-noise ratio and to increased motion resulting from longer imaging times. This decreases the conspicuity of small, low contrast lesions.     

MRI-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis low back pain—case series of an innovative new technique

European Radiology - To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis pain. Patients with a positive response to...     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

MASSIVE LOWER GASTROINTESTINAL HAEMORRHAGE SECONDARY TO METASTATIC SQUAMOUS CELL CARCINOMA OF THE LUNG

SUMMARY Clinically significant symptoms due to gastrointestinal metastases from primary lung cancers is rare. A case of life-threatening lower gastrointestinal haemorrhage secondary to metastatic squamous cell carcinoma of the lung is reported. Previous reports of such metastases are reviewed, with reference to management and prognosis. After resection of colonic metastases from squamous cell lung cancer, survival is similar to that for primary disease. It is suggested that patients with known or suspected squamous cell lung cancer presenting with lower gastrointestinal symptoms be managed as aggressively as those with no previous history of disease.