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101.
Tchieu JH Fana F Fink JL Harper J Nair TM Niedner RH Smith DW Steube K Tam TM Veretnik S Wang D Gribskov M 《Nucleic acids research》2003,31(1):342-344
102.
Ren J Hintz KK Roughead ZK Duan J Colligan PB Ren BH Lee KJ Zeng H 《American journal of physiology. Heart and circulatory physiology》2003,284(5):H1800-H1807
Women with functional ovaries have a lower cardiovascular risk than men and postmenopausal women. However, estrogen replacement therapy remains controversial. This study examined the effect of ovarian hormone deficiency and estrogen replacement on ventricular myocyte contractile function and PKB/Akt activation. Nulliparous female rats were subjected to bilateral ovariectomy (Ovx) or sham operation (sham). A subgroup of Ovx rats received estrogen (E(2)) replacement (40 microg. kg(-1). day(-1)) for 8 weeks. Mechanical and intracellular Ca(2+) properties were evaluated including peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dL/dt), fura 2 fluorescence intensity (FFI), and decay rate. Levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), phospholamban (PLB), and Akt were assessed by Western blot. Ovx promoted body weight gain associated with reduced serum E(2) and uterine weight, all of which were abolished by E(2). Ovx depressed PS and +/-dL/dt, prolonged TPS, TR(90), and decay rate, and enhanced resting FFI, all of which, with the exception of TPS, were restored by E(2). Ovx did not alter the levels of SERCA2a, PLB, and total Akt, but significantly reduced Akt activation [phosphorylated Akt (pAkt)], pAkt/Akt, and the SERCA2a-to-PLB ratio. These alterations in protein expression were restored by E(2). E(2) enhanced PS and +dL/dt in vitro, which was abolished by the E(2) receptor antagonist ICI-182780. Ovx reduced myocyte Ca(2+) responsiveness and lessened stimulating frequency-induced decline in PS, both ablated by E(2). These data suggest that mechanical and protein functions of ventricular myocytes are directly regulated by E(2). 相似文献
103.
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
104.
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
105.
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
106.
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
107.
Tehranchian S Akbarzadeh T Fazeli MR Jamalifar H Shafiee A 《Bioorganic & medicinal chemistry letters》2005,15(4):1023-1025
A series of 1-[1,2,4-triazol-3-yl] and 1-[1,3,4-thiadiazol-2-yl]-3-methylthio-6,7-dihydrobenzo[c]thiophen-4(5H)ones were synthesized and tested to demonstrate in vitro antimicrobial activity. Some of these compounds exhibited a good activity against Staphylococcus aureus, S. epidermidis and Bacillus subtilis. 相似文献
108.
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
109.
110.
Fariba Ahmadizar N. Charlotte Onland-Moret Anthonius de Boer Geoffrey Liu Anke H. Maitland-van der Zee 《PloS one》2015,10(9)