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81.
OBJECTIVE: To determine whether the frequency of nuclear grooves in intermediate squamous cells in cervical smears is related to inflammatory or neoplastic events. STUDY DESIGN: Sixty benign and 40 neoplastic, nonatrophic cervical smears, collected by conventional methods and stained by Papanicolaou stain, were selected for this study. Twenty smears of the benign cohort showed evidence of inflammation. The neoplastic cohort comprised 20 smears representative of low grade and 20 of high grade squamous intraepithelial lesion (LSIL and HSIL, respectively), with 50% in each group showing evidence of inflammation. The patients, of mixed ethnic backgrounds, were between 18 and 45 years of age. The frequency of nuclear grooves in 100 morphologically benign intermediate squamous cells were determined in each case. The results were evaluated by statistical analysis. RESULTS: The study established that the presence of inflammation had no impact on the frequency of nuclear grooves in benign intermediate squamous cells in either benign or neoplastic smears. When compared with benign smears, there was no increase in the frequency of nuclear grooves in LSIL. Smears of HSIL showed the highest frequency of nuclear grooves. The difference between HSIL and other groups was statistically significant (P < .01). CONCLUSION: The frequency of nuclear grooves in either normal or neoplastic smears is unrelated to inflammation. In smears with neoplastic changes, an increase in grooved nuclei occurred in HSIL. The mechanism and significance of this observation are unknown and warrant further study. 相似文献
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Ubl JJ Grishina ZV Sukhomlin TK Welte T Sedehizade F Reiser G 《American journal of physiology. Lung cellular and molecular physiology》2002,282(6):L1339-L1348
Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin. 相似文献
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The surface topography and structural features of interleukin-2 (IL-2) in relation to its interaction with the α subunit of its receptor (IL-2Rα) have been probed by limited tryptic digestion followed by detailed structural analyses. Four sensitive cleavage sites in IL-2 (Lys8, Lys9, Lys35, and Arg38) were identified as surface amino acids, suggesting that they are potential binding sites for IL-2Rα. To examine the involvement of these residues in IL-2Rα binding, a truncated IL-2 molecule lacking the amino-terminal residues through Arg38 was generated and it was found to be incapable of binding IL-2Rα in a solid-phase receptor binding sequencing assay. These studies have led to the conclusion that the IL-2Rα contact region of IL-2 includes residues Lys35 and Arg38. This finding is supported by the refined three-dimensional structure of IL-2 in which these residues are located outside of the compact bundle of four helices and thus are readily available for interaction with IL-2Rα. 相似文献
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Noda K Kitami T Gai WP Chegini F Jensen PH Fujimura T Murayama K Tanaka K Mizuno Y Hattori N 《Biochemical and biophysical research communications》2005,331(1):309-317
Ubiquitin is one of the major components of Lewy bodies (LB), the pathological hallmark of Parkinson's disease (PD). Here, we identified that a phosphorylated form of IkappaBalpha (pIkappaBalpha), an inhibitor of NF-kappaB, and SCF(beta-TrCP), the ubiquitin ligase of pIkappaBalpha, are components of LB in brains of PD patients. In vitro studies identified those proteins in the ubiquitin- and alpha-synuclein (known as the major component of LB)-positive LB-like inclusions generated in dopaminergic SH-SY5Y cells treated with MG132, a proteasome inhibitor. Intriguingly, IkappaBalpha migration into such ubiquitinated inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide known to block phosphorylation of IkappaBalpha, although this peptide did not influence cell viability under proteasomal inhibition. Our results indicate that phosphorylation of IkappaBalpha plays a role in the formation of IkappaBalpha-containing inclusions caused by proteasomal dysfunction, and that the generation of such inclusion is independent of cell death caused by impairment of proteasome. 相似文献
85.
Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics 总被引:6,自引:0,他引:6
Kaiser BK Barahmand-Pour F Paulsene W Medley S Geraghty DE Strong RK 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(5):2878-2884
The NKG2x/CD94 family of C-type lectin-like immunoreceptors (x = A, B, C, E, and H) mediates surveillance of MHC class Ia cell surface expression, often dysregulated during infection or tumorigenesis, by recognizing the MHC class Ib protein HLA-E that specifically presents peptides derived from class Ia leader sequences. In this study, we determine the affinities and interaction thermodynamics between three NKG2x/CD94 receptors (NKG2A, NKG2C, and NKG2E) and complexes of HLA-E with four representative peptides. Inhibitory NKG2A/CD94 and activating NKG2E/CD94 receptors bind HLA-E with indistinguishable affinities, but with significantly higher affinities than the activating NKG2C/CD94 receptor. Despite minor sequence differences, the peptide presented by HLA-E significantly influenced the affinities; HLA-E allelic differences had no effect. These results reveal important constraints on the integration of opposing activating and inhibitory signals driving NK cell effector functions. 相似文献
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Fariba Ahmadizar N. Charlotte Onland-Moret Anthonius de Boer Geoffrey Liu Anke H. Maitland-van der Zee 《PloS one》2015,10(9)
Aim
To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.Methods & Design/ Results
PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84–0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94–0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33–1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60–12.94 vs. 2.64; 95% CI: 1.29–5.40).Conclusions
Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding, anemia and fatigue were improved by the addition of bevacizumab. 相似文献88.
Anna Sircova Fariba Karimi Evgeny N. Osin Sungmin Lee Petter Holme Daniel Str?mbom 《PloS one》2015,10(3)
In a situation with a limited common resource, cooperation between individuals sharing the resource is essential. However, people often act upon self-interest in irrational ways that threaten the long-term survival of the whole group. A lack of sustainable or environmentally responsible behavior is often observed. In this study, we examine how the maximization of benefits principle works in a wider social interactive context of personality preferences in order to gain a more realistic insight into the evolution of cooperation. We used time perspective (TP), a concept reflecting individual differences in orientation towards past, present, or future, and relevant for making sustainable choices. We developed a personality-driven agent-based model that explores the role of personality in the outcomes of social dilemmas and includes multiple facets of diversity: (1) The agents have different behavior strategies: individual differences derived by applying cluster analysis to survey data from 22 countries (N = 10,940) and resulting in 7 cross-cultural profiles of TP; (2) The non-uniform distribution of the types of agents across countries; (3) The diverse interactions between the agents; and (4) diverse responses to those interactions in a well-mixed population. As one of the results, we introduced an index of overall cooperation for each of the 22 countries, which was validated against cultural, economic, and sustainability indicators (HDI, dimensions of national culture, and Environment Performance Index). It was associated with higher human development, higher individualism, lower power distance, and better environmental performance. The findings illustrate how individual differences in TP can be simulated to predict the ways people in different countries solve the personal vs. common gain dilemma in the global limited-resource situation. This interdisciplinary approach to social simulation can be adopted to explain the possible causes of global environmental issues and to predict their possible outcomes. 相似文献
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