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排序方式: 共有2420条查询结果,搜索用时 15 毫秒
31.
AP Krapcho E Menta A Oliva R Di Domenico L Fiocchi ME Maresch CE Gallagher MP Hacker G Beggiolin FC Giuliani G Pezzoni S Spinelli 《Canadian Metallurgical Quarterly》1998,41(27):5429-5444
The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates. 相似文献
32.
In the present work we investigated the mechanisms controlling the release of acetylcholine (ACh) and of gamma-aminobutyric acid (GABA) from cultures of amacrine-like neurons, containing a subpopulation of cells which are simultaneously GABAergic and cholinergic. We found that 81.2 +/- 2.8% of the cells present in the culture were stained immunocytochemically with an antibody against choline acetyltransferase, and 38.5 +/- 4.8% of the cells were stained with an antibody against GABA. Most of the cells containing GABA (87.0 +/- 2.9%) were cholinergic. The release of acetylcholine and GABA was mostly Ca2+-dependent, although a significant release of [3H]GABA occurred by reversal of its transporter. Potassium evoked the Ca2+-dependent release of [3H]GABA and [3H]acetylcholine, with EC50 of 31.0 +/- 1.0 mm and 21.6 +/- 1.1 mm, respectively. The Ca2+-dependent release of [3H]acetylcholine was significantly inhibited by 1 micrometer tetrodotoxin and by low (30 nm) omega-conotoxin GVIA (omega-CgTx GVIA) concentrations, or by high (300 nm) nitrendipine (Nit) concentrations. On the contrary, the release of [14C]GABA was reduced by 30 nm nitrendipine, or by 500 nm omega-CgTx GVIA, but not by this toxin at 30 nm. The release of either transmitters was unaffected by 200 nm omega-Agatoxin IVA (omega-Aga IVA), a toxin that blocks P/Q-type voltage-sensitive Ca2+ channels (VSCC). The results show that Ca2+-influx through omega-CgTx GVIA-sensitive N-type VSCC and through Nit-sensitive L-type VSCC induce the release of ACh and GABA. However, the significant differences observed regarding the Ca2+ channels involved in the release of each neurotransmitter suggest that in amacrine-like neurons containing simultaneously GABA and acetylcholine the two neurotransmitters may be released in distinct regions of the cells, endowed with different populations of VSCC. 相似文献
33.
AP Colombo C Eftimiadi AD Haffajee MA Cugini SS Socransky 《Canadian Metallurgical Quarterly》1998,25(6):465-474
The purpose of this investigation was to compare the levels of serum IgG2, the frequency of detection of Gm(23)-negative allotype and frequency of detection of FcgammaRIIa and FcgammaRIIIb receptor haplotypes in 32 refractory, 54 successfully treated and 27 periodontally healthy individuals. Refractory subjects showed mean full mouth attachment loss and/or >3 sites with attachment loss >2.5 mm within 1 year after both scaling and root planing, and surgery plus systemically administered tetracycline. Successfully treated subjects showed mean attachment level gain and no sites with attachment loss >2.5 mm 1 year post-therapy. Periodontally healthy subjects exhibited no pocket depth or attachment level >3 mm, and no evidence of progressing disease during 1 year of monitoring. Blood was obtained from each subject at baseline. Serum IgG2 and Gm(23) allotype were determined using radial immunodiffusion. DNA was extracted from whole blood and the FcgammaR genotypes determined using PCR and allele specific oligonucleotide probes. Significance of differences among clinical groups were sought using the Kruskal-Wallis or chi-square tests. Associations between 2 or more variables were tested using regression analysis. Refractory subjects exhibited higher mean attachment loss and pocket depth than successfully treated or periodontally healthy subjects. Smoking status did not differ significantly among groups. No significant differences in serum IgG2 levels and frequency of detection of Gm(23)-negative allotype were observed among the clinical groups. Serum IgG2 level was positively associated with the number of serum antibody responses to subgingival species (r=0.51, p<0.001). Subjects with the Gm(23)-negative allotype exhibited lower mean levels of serum IgG2 (3.06+/-0.3 versus 3.9+/-0.2, p<0.01) and mean number of serum antibodies to subgingival species (17.7+/-1.7 versus 23.3+/-1.4, p<0.05) than allotype positive individuals. No significant differences in FcgammaR haplotype distribution were observed among the 3 clinical groups. Associations of serum IgG2 level, Gm(23) allotype, FcgammaRIIa and FcgammaRIIIb receptor haplotypes and smoking status were weakly related or not related to clinical status. This lack of relationship may have been due to a reality of no relationship, or the inadvertent pooling of subjects where these factors were of primary importance with subjects in whom these factors played a less important role. 相似文献
34.
Z Zhu J Yao T Johns K Fu I De Bie C Macmillan AP Cuthbert RF Newbold J Wang M Chevrette GK Brown RM Brown EA Shoubridge 《Canadian Metallurgical Quarterly》1998,20(4):337-343
A drug with cationic characteristics such as procaine can be conveyed in a Carbomer hydrogel in two different ways: (i) in the form of salt in solution in the aqueous phase, and (ii) in the base form salified with the same polymer. Introduction of the drug into the hydrogel with different concentrations of polymer produced, in both cases, a reduction in viscosity in relation to drug concentration. The gels with procaine salified with the polymer showed greater viscosity. The drug release rate, in general, diminished with the increase in polymer concentration. Nevertheless, when this concentration was maintained, there was no variation in release rate when the viscosity produced as a consequence of drug concentration was changed. Gels with procaine salified with the carboxyvinylic polymer had a faster release rate than those with procaine in the hydrochloride form dissolved in the aqueous phase. These results have also been confirmed by a simulated absorption test. 相似文献
35.
36.
Since pneumotachograph masks are commonly used in studies of speech breathing, the purpose of this study was to measure the differences in respiratory volumetric and frequency measures during speech under two conditions: with and without a circumferentially vented pneumotachograph mask coupled to the face. Thus we sought to identify whether changes in breathing patterns occur with the use of a specific face mask, because these patterns are accepted as representative of normal speech breathing. Subjects were 10 normal-speaking women, each of whom produced a syllable train and a connected speech task, both at comfortable intensity levels. Respiratory measures were made using linearized magnetometers during speech production. The measurements included lung volume, rib cage volume, and abdominal volume at utterance initiation and termination, volume excursions during the utterance, and the number of breath groups during the speech task. There were no significant differences between the mask-on and mask-off conditions in volumetric and frequency measures. A significant task difference for abdominal initiation was found. It was concluded that the use of a circumferentially vented pneumotachograph mask does not alter the reliability of respiratory volume and frequency measures for studies of voice. 相似文献
37.
The study's objective was to examine whether there is evidence that colonoscopic polypectomy reduces the incidence of colorectal cancer. The records of all patients who underwent colonoscopic polypectomy by a single surgeon between 1974 and 1991 were reviewed. Patients with colorectal cancer diagnosed at the initial colonoscopy, with a history of colorectal cancer, inflammatory bowel disease or familial adenomatous polyposis or with only hyperplastic polyps were excluded. There were 1008 remaining patients, of whom 645 have attended at least one follow-up colonoscopic examination, and these 645 patients from the basis of the study, because the incidence of cancer is known exactly in this group. The mean period of follow up was 4.4 years and the mean number of follow-up colonoscopic examinations was 2.2. There was a total of 2847 person-years of colonoscopic follow up. The expected incidence of cancer, age and sex adjusted, is calculated using Australian epidemiological figures. The observed incidence of cancer was 3 cases (all asymptomatic) per 2847 person-years, which is indistinguishable from the general population's risk of 3.75 cases per 2847 person-years. Analysis of previous publications suggests that patients with adenomas are at an increased risk of developing colorectal cancer of about 2.5 times the general population's risk. If correct, then the observed incidence of 3 cases per 2847 person-years is less than the expected incidence of 9.4 cases per 2847 person-years. This analysis suggests colonoscopic polypectomy does reduce the incidence of colorectal cancer. 相似文献
38.
39.
An investigation into vehicle rollover prevention by coordinated control of active anti-roll bar and electronic stability program 总被引:1,自引:0,他引:1
Seongjin Yim Kwangki Jeon Kyongsu Yi 《International Journal of Control, Automation and Systems》2012,10(2):275-287
This paper presents a method for designing a controller that uses an active anti-roll bar (AARB) and an electronic stability program (ESP) for rollover prevention. ESP with longitudinal speed control (LSC) can carry out active braking to reduce vehicle speed and lateral acceleration to prevent a rollover. To enhance the rollover prevention capability of the ESP, an AARB is adopted. The controller for the AARB was designed based on linear quadratic (LQ) static output feedback (SOF) control methodology, which attenuates the effect of lateral acceleration on the roll angle and roll rate by control of the suspension stroke and the tire deflection of the vehicle. Although this AARB significantly increases ride comfort and rollover prevention, it has a drawback — the vehicle loses its maneuverability. Therefore, the ESP with LSC is used to overcome this drawback. Simulations showed that the proposed method was effective in preventing a rollover. 相似文献
40.
Based upon a new conception that the solid compressive pressure on a cake surface is not null, almost of all solid-liquid
separation operations have been re-examined. For cake filtration, the phenomenon caused by the solid compressive pressure
on a cake surface is discussed for thin cake. New expression and hindered sed-imentation theories are developed by above new
conception using Darcy’s equation. Application of the new conception to centrifugal filtration and tangential filtration is
also discussed. Above results lead to the conclusion that cake filtration, expression, hindered sedimentation, centrifugal
filtration and tangential filtration can be described with a unified theory, and the main difference between the operations
is only the boundary condition of cake. 相似文献