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991.
BD Lowes W Minobe WT Abraham MN Rizeq TJ Bohlmeyer RA Quaife RL Roden DL Dutcher AD Robertson NF Voelkel DB Badesch BM Groves EM Gilbert MR Bristow 《Canadian Metallurgical Quarterly》1997,100(9):2315-2324
Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction. 相似文献
992.
JB Crawley L Rawlinson FV Lali TH Page J Saklatvala BM Foxwell 《Canadian Metallurgical Quarterly》1997,272(23):15023-15027
Interleukin-2 (IL-2) is a potent T cell mitogen. However, the signaling pathways by which IL-2 mediates its mitogenic effect are not fully understood. One of the members of the mitogen-activated protein kinase (MAPK) family, p42/44MAPK (ERK2/1), is known to be activated by IL-2. We have now investigated the response to IL-2 of two other members of the MAP kinase family, p54MAP kinase (stress-activated protein kinase (SAPK)/Jun-N-terminal kinase (JNK)) and p38MAP kinase (p38/Mpk2/CSBP/RK), which respond primarily to stressful and inflammatory stimuli (e.g. tumor necrosis factor-alpha, IL-1, and lipopolysaccharide). Here we show that IL-2, and another T cell growth factor, IL-7, activate both SAPK/JNK and p38MAP kinase. Furthermore, inhibition of p38MAP kinase activity with a specific pyrinidyl imidazole inhibitor SB203580 that prevents activation of its downstream effector, MAPK-activating protein kinase-2, correlated with suppression of IL-2- and IL-7-driven T cell proliferation. These data indicate that in T cells p38MAP kinase has a role in transducing the mitogenic signal. 相似文献
993.
The NMR structure of the 98 residue beta-elicitin, cryptogein, which induces a defence response in tobacco, was determined using 15N and 13C/15N labelled protein samples. In aqueous solution conditions in the millimolar range, the protein forms a discrete homodimer where the N-terminal helices of each monomer form an interface. The structure was calculated with 1047 intrasubunit and 40 intersubunit NOE derived distance constraints and 236 dihedral angle constraints for each subunit using the molecular dynamics program DYANA. The twenty best conformers were energy-minimized in OPAL to give a root-mean-square deviation to the mean structure of 0.82 A for the backbone atoms and 1.03 A for all heavy atoms. The monomeric structure is nearly identical to the recently derived X-ray crystal structure (backbone rmsd 0.86 A for residues 2 to 97) and shows five helices, a two stranded antiparallel beta-sheet and an omega-loop. Using 1H,15N HSQC spectroscopy the pKa of the N- and C-termini, Tyr12, Asp21, Asp30, Asp72, and Tyr85 were determined and support the proposal of several stabilizing ionic interactions including a salt bridge between Asp21 and Lys62. The hydroxyl hydrogens of Tyr33 and Ser78 are clearly observed indicating that these residues are buried and hydrogen bonded. Two other tyrosines, Tyr47 and Tyr87, show pKa's > 12, however, there is no indication that their hydroxyls are hydrogen bonded. Calculations of theoretical pKa's show general agreement with the experimentally determined values and are similar for both the crystal and solution structures. 相似文献
994.
OS Lawal TA Afolabi KO Adebowale BM Ogunsanwo SA Bankole 《Journal of the science of food and agriculture》2005,85(15):2655-2659
Effects of selected Hofmeister anions, namely Na2SO4, NaCl, NaBr, NaI, NaClO4 and NaSCN, on the functional properties of a protein isolate prepared from lablab seeds (Lablab purpureus) were investigated. The results of water absorption capacity indicated that highest water absorption was recorded in solutions of Na2SO4, and the lowest in NaSCN solutions. Reduction in water absorption capacity followed the Hofmeister series in the order Na2SO4 > NaCl > NaBr, NaI > NaClO4 > NaSCN. Protein solutions prepared in chaotropic (NaI, NaClO4, NaSCN) salts had better foam capacity, foam stability, emulsifying activity and emulsion stability than solutions prepared with kosmotropic salts (Na2SO4, NaCl, NaBr). The results also indicate that increase in foam capacity and stability followed the Hofmeister series in the order Na2SO4 < NaCl < NaBr, NaI < NaClO4 < NaSCN. When least gelation concentration (LGC) was used as the index of gelation capacity, at various salts concentrations, the lowest LGC were observed in NaSCN and the highest LGC in protein solutions prepared with Na2SO4. Copyright © 2005 Society of Chemical Industry 相似文献
995.
WM Coleman BM Lawrence SH Craven 《Journal of the science of food and agriculture》2004,84(10):1223-1228
The undesirable top notes or off‐notes found in mint, clary sage, and cedarwood oils could be quantitatively determined using a non‐equilibrated solid phase microextraction/gas chromatography/selected ion monitoring/mass spectrometry (SPME/GC/SIM‐MS) technique. Using the low threshold components, dimethyl sulfide, 2‐methylpropanal, 2‐methylbutanal, and 3‐methylbutanal, which are associated with the off‐notes of these oils, their levels could be reproducibly quantitatively determined. The highest level of off‐notes was found in a sample of Scotch spearmint oil where the levels of the four constituents were, dimethyl sulfide (238 µg g?1), 2‐methylpropanal (286 µg g?1), 2‐methylbutanal (1048 µg g?1) and 3‐methylbutanal (1489 µg g?1). These quantitative results in combination with sensory evaluations could provide for a powerful overall assessment of essential oil quality. Copyright © 2004 Society of Chemical Industry 相似文献
996.
997.
OBJECTIVES: To study the benefits of a clinical pharmacokinetic service in optimising phenytoin use in the Western Cape. DESIGN: Assessment of the response to treatment was based on the number of seizures during the 3 months before entering the study (first baseline period), 3 months after entering the study (second baseline period) and 3 months before the termination of the study (test period). Patients kept a seizure diary throughout the study. The Michaelis-Menten model was used to calculate doses and predict steady-state serum concentrations. SETTING: Nine epilepsy clinics. SUBJECTS: One hundred and ninety-five (113 black and 82 coloured) compliant people with epilepsy receiving generic phenytoin monotherapy. OUTCOME MEASURES: Reduction in seizure frequency and adverse effects. RESULTS: A reduction in seizure frequency (64.8% compared with pre-optimisation) was experienced by 64.9% of patients. Mean seizure frequency was reduced from 3.39 to 1.18 per month. Reductions in seizure frequency of 100% and more than 50% were reported by 39.2% and 58.7% of patients, respectively. Adverse effects of phenytoin were reduced from 20.5% at the first visit to 3.2% at the last visit. CONCLUSION: The clinical pharmacokinetic dosing service for phenytoin applied in this study contributed significantly to the success of epilepsy management. 相似文献
998.
999.
P Franchetti L Cappellacci GA Sheikha HN Jayaram VV Gurudutt T Sint BP Schneider WD Jones BM Goldstein G Perra A De Montis AG Loi P La Colla M Grifantini 《Canadian Metallurgical Quarterly》1997,40(11):1731-1737
The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides. 相似文献
1000.
One hundred and twenty-nine Charnley acetabular components were acquired at the time of revision surgery and a tribological investigation undertaken. The relative occurrence of pitting in the unworn and worn regions of the sockets suggest that most of the cement ingress occurs during the early part of the service life. The penetration depth of the explanted sockets was determined using the shadowgraph technique. Observation of the profiles in the wear planes suggest that, in general, the creep component was not a significant proportion of the overall change in the inner bore of the socket. Using weighted ordinary least squares regression, in which the intercept was not assumed to be zero, mean penetration and wear volume rates of 0.02 (SE = 0.02) mm/year and 55 (SE = 5) mm3/year, respectively, were recorded and are in agreement with other retrieval studies. In neither case was the intercept found to be significantly different from zero. A mean clinical wear factor, Kclinical, equal to 2.1 (SE = 0.2) x 10(-6) mm3/N m was calculated which is considerably larger than that found in laboratory experiments which purport to reflect in vivo conditions. In this analysis, a significant positive intercept was observed [96 (SE = 36) mm3] and may be evidence of the small initial penetration due to creep reported in simulator experiments. A strong positive association between kclinical and the arithmetical mean roughness, Ra, of the femoral head was also demonstrated although the rate of change was not as great as that cited for laboratory experiments. 相似文献