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排序方式: 共有692条查询结果,搜索用时 9 毫秒
151.
VK Reddy A Valasinas A Sarkar HS Basu LJ Marton B Frydman 《Canadian Metallurgical Quarterly》1998,41(24):4723-4732
Eight analogues of 1N,12N-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1, 2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained (three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). 1N,12N-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the 4N, 9N-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1, 2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action. 相似文献
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153.
Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover in an autocrine/paracrine manner. In this study, we tested the hypothesis that these wound-healing fibroblast-like cells and locally generated Ang II are involved in other repairing tissue. To test this hypothesis, we used a granuloma pouch model, where a subcutaneous air sac is created followed by injection of croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of myoFb was determined by immunohistochemical alpha-smooth muscle actin (alpha-SMA) labeling and collagen accumulation by picrosirius red staining. Angiotensin converting enzyme (ACE) and Ang II receptor binding were detected by in vitro quantitative autoradiography using 125I-351A and 125I[Sar1, Ile8]Ang II, respectively, while Ang II receptor subtype was defined by displacement studies using either an AT1 (losartan) or AT2 (PD123177) receptor antagonist. Cells expressing ACE were determined by immunohistochemistry. Ang II content in pouch tissue was measured by radioimmunoassay following HPLC separation while its capacity to generate Ang II was assessed in tissue bath, with and without exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch tissue was examined by determining hydroxyproline content in response to lisinopril, AT1 or AT2 receptor antagonists (losartan or PD123177). In pouch tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14 and 21; (2) morphologic evidence of collagen deposition evident at day 4, which gradually became more extensive thereafter; (3) ACE and Ang II receptor binding was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and AT1 receptors; (6) picogram quantities of Ang II (per g tissue) was evident on days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril and losartan, but not PD123177, significantly attenuated pouch weight and accumulation of collagen. Thus, in this model of cutaneous repair, the appearance of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1 receptor binding. Signals involved in the appearance of myoFb remain uncertain. Further studies are required to address the regulation of Ang II generation in pouch tissue of the rat. 相似文献
154.
VK Singh K Bajpai S Biswas W Haq MY Khan KB Mathur 《Canadian Metallurgical Quarterly》1997,4(5-6):285-297
Endogenous opioid peptides and opiates like morphine produce their pharmacological effects through the membrane bound opioid receptors. These receptors belong to a superfamily of G-protein-coupled receptors, all of which possess seven membrane-spanning regions. Structure-activity relationship studies of opioids opened up new avenues for the pharmacological characterization of the opioid receptors. As a further advancement in this direction, molecular cloning has led to the identification of three different types of opioid receptors -- OP1 (delta), OP2 (kappa) and OP3 (mu) -- thereby supporting the results of earlier pharmacological studies which postulated their existence. The three opioid receptors are highly homologous. Consequent to the development of highly specific and selective agonists and antagonists, it was proposed that the three types of opioid receptors could be further categorized into different subtypes. However, the molecular biology data generated so far do not support the presence of the various subtypes of the three well-characterized opioid receptors. Recent strides towards the advancement of our knowledge relating to the molecular biology of these receptors have been reviewed in this article. 相似文献
155.
AV Tokar' VN Zhebel' VK Serkova AIa Litoshenko EV Temnaia 《Canadian Metallurgical Quarterly》1994,(7-8):36-40
A study was made as well as a comparison of values of the cholesterol (Chs) lipid fractions concentrations, and of those of the lipid peroxidation processes activity (LPP) and the gluthathione antioxidant system (AOS) status in male subjects aged from 45 to 59 years, healthy individuals and patients with stable angina pectoris and myocardial infarction (micro- and macrofocal) during cicatrizing stage (health resort rehabilitation stage). In patients with various forms of IHD total cholesterol is raised as are atherogenic lipoproteins, and atherogenicity index, intensification being noted of LPO along with a considerable decrease in functional potencies of AOS. Similar pattern of changes of LPO and AOS in patients with stable angina pectoris and myocardial infarction (MI) during cicatrization stage certainly warrants correction of these systems not only in acute phase of MI but at the stage of rehabilitation as well. 相似文献
156.
Radionuclide scintigraphy with osteotropic radiopharmaceuticals labelled 99Tc proved highly sensitive in assessment of local inflammation. Osteoscintigraphy allows detection of preclinical and pre-x-ray lesions in the joints in RA and assessment of the treatment efficacy. Characteristic signs of the radionuclide distribution and accumulation can serve as a prompt in differential diagnosis of RA, DOA, reactive and gouty arthritis. 相似文献
157.
158.
159.
Algorithms for the generation of intricate shapes resulting from the iteration of algebraic transformations are presented. A special convergence test makes possible the production of a visually striking class of displayable objects. Several illustrations are chosen as examples of the diversity of forms which result from this technique. 相似文献
160.