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81.
T Goldman AL Hallin CM Hoffman LE Piilonen D Preston RD Bolton MD Cooper JS Frank PA Heusi GE Hogan FG Mariam HS Matis RE Mischke VD Sandberg GH Sanders U Sennhauser R Werbeck RA Williams D Grosnick SC Wright SL Wilson R Hofstadter EB Hughes MW Ritter VL Highland J McDonough 《Canadian Metallurgical Quarterly》1987,36(5):1543-1546
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UA Temann B Prasad MW Gallup C Basbaum SB Ho RA Flavell JA Rankin 《Canadian Metallurgical Quarterly》1997,16(4):471-478
Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung. 相似文献
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A model of recognition is described based on cell properties in the ventral cortical stream of visual processing in the primate brain. At a critical intermediate stage in this system, 'Elaborate' feature sensitive cells respond selectively to visual features in a way that depends on size (+/- 1 octave), orientation (+/- 45 degrees) but does not depend on position within central vision (+/- 5 degrees). These features are simple conjunctions of 2-D elements (e.g. a horizontal dark area above a dark smoothly convex area). They can arise either as elements of an object's surface pattern or as a 3-D component bounded by an object's external contour. By requiring a combination of several such features without regard to their position within the central region of the visual image, 'Pattern' sensitive cells at higher levels can exhibit selectivity for complex configurations that typify objects seen under particular viewing conditions. Given that input features to such Pattern sensitive cells are specified in approximate size and orientation, initial cellular 'representations' of the visual appearance of object type (or object example) are also selective for orientation and size. At this level, sensitivity to object view (+/- 60 degrees) arises because visual features disappear as objects are rotated in perspective. Processing is thus viewer-centred and the neurones only respond to objects seen from particular viewing conditions or 'object instances'. Combined sensitivity to multiple features (conjunctions of elements) independent of their position, establishes selectivity for the configurations of object parts (from one view) because rearranged configurations of the same parts yield images lacking some of the 2-D visual features present in the normal configuration. Different neural populations appear to be selectively tuned to particular components of the same biological object (e.g. face, eyes, hands, legs), perhaps because the independent articulation of these components gives rise to correlated activity in different sets of input visual features. Generalisation over viewing conditions for a given object can be established by hierarchically pooling outputs of view-condition specific cells with pooling operations dependent on the continuity in experience across viewing conditions. Different object parts are seen together and different views are seen in succession when the observer walks around the object. The view specific coding that characterises the selectivity of cells in the temporal lobe can be seen as a natural consequence of selective experience of objects from particular vantage points. View specific coding for the face and body also has great utility in understanding complex social signals, a property that may not be feasible with object-centred processing. 相似文献
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PURPOSE: There is speculation that the CO2 in carbogen (95% O2, 5% CO2) can block the vasoconstrictive effects of oxygen. However, it has recently been shown that blood flow in human tumors is variable while patients breathe carbogen. Furthermore, we have shown a consistent decrease in tumor blood flow (TBF) with carbogen breathing in the rat window chamber model. Also, we have previously shown that there is no significant difference in tumor growth time after radiation with air vs. carbogen breathing. This study was designed to investigate the effects of carbogen breathing on blood flow and oxygen levels in a solid tumor. METHODS: Measurements were made in Fischer-344 rats with 8-10 mm diameter R3230Ac tumors transplanted either within the quadriceps muscle (n = 16) or subcutis (n = 14). Nontumor-bearing quadriceps muscle was studied in six other rats. After a 20-minute air-breathing baseline, rats breathed carbogen for an additional 40 minutes. Partial pressure of oxygen (pO2) was continuously monitored at one position for 60 minutes using 9-12 microm diameter oxygen microelectrodes. Blood flow was simultaneously monitored in all animals using laser Doppler flowmetry (1-2 probes/tumor). RESULTS: Blood flow changes during carbogen breathing were variable in all tissues and intratumoral heterogeneity was observed. Despite variability in blood flow, pO2 consistently increased in normal muscle but varied in both tumor sites. During carbogen breathing, the percent pO2 measurements greater than the baseline average were 99.5% +/- 0.4% (mean +/- SEM), 42.7% +/- 13.8%, and 79.8% +/- 11.0% in normal muscle, subcutaneous tumor, and muscle tumor, respectively. To show the magnitude of change, average pO2 values during air and carbogen breathing were calculated for each site. Normal muscle increased from 14.9 +/- 2.3 to 39.0 +/- 6.4 mm Hg (paired t-test; p = 0.009). Muscle tumors showed a rise from 14.6 +/- 3.2 to 34.5 +/- 8.2 mm Hg (p = 0.019). However, pO2 in subcutaneous tumors remained unchanged, with a pO2 of 7.3 +/- 2.0 mm Hg on air and 7.3 +/- 4.1 mm Hg (p = 0.995) during carbogen breathing. CONCLUSIONS: Carbogen had no consistent effect on blood flow and was ineffective at increasing tumor pO2. These results may partially explain why carbogen breathing failed to improve the efficacy of radiation in this tumor model when transplanted subcutaneously. 相似文献
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The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of the anaphase-promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from mitosis, and APC has been implicated as a target for the checkpoint intervention. We show that the human checkpoint protein hMAD2 prevents activation of APC by forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2 arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein exists in two-folded states: a tetramer and a monomer. Both the tetramer and the monomer bind to CDC20, but only the tetramer inhibits activation of APC and blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for inhibition, and a change in hMAD2 structure may play a role in transducing the checkpoint signal. There are at least three different forms of mitotic APC that can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at metaphase, a CDC20-APC binary complex active in degrading specific substrates at anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an upstream signal to inhibit activation of APC. 相似文献
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Endoluminal revascularizaion of left main coronary artery vessels is considered to be relatively contraindicated because of a high procedural mortality and restenosis rate. This report describes the first successful case of endovascular stenting in an unprotected left main coronary artery stenosis in a heart transplant patient. 相似文献