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41.
Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use Nα‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of Nα‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification. 相似文献
42.
目的 研究肿瘤相关抗原CA19-9在胃癌组织中的表达情况。方法 采用免疫组织化学方法对30例胃癌、癌旁组织、正常胃粘膜和30例胃溃疡组织中的CA19-9的表达情况进行了检测。结果 30例胃癌CA19-9阳性表达23例(76.7%,23/30)。其中胞浆和胞膜均阳性的16例(69.6%,16/23),而仅胞膜阳性5例(21.7%,5/23)。30例癌旁组织CA19-9阳性表达1例(3.3%,1/30)且为胞膜阳性。正常胃粘膜和胃溃疡组织中CA19-9表达均为阴性。在10例高分化腺癌组织中阳性4例,17例低分化腺癌组织中阳性16例,3例粘液癌全为阳性。结论 胃组织中CA19-9的表达可能成为胃癌的肿瘤标志之一,尤其适用于低分化腺癌和粘液癌,而对高分化腺癌不适合。 相似文献
43.
44.
强直性脊柱炎(ankylosing spondylitis,AS)是以中轴关节慢性炎症为主的原因不明的全身性免疫性疾病。其特点为几乎全部累及骶髂关节,常发生椎间盘纤维环及其附近韧带钙化和骨性强直,也可累及外周关节并造成关节软骨及骨的破坏,晚期可发生脊柱及外周关节强直、畸形以致严重功能受损[1]。所以我们必须强调重视AS骨质破坏发生机制的研究,有利于寻找有效药物,减少致残。1骶髂关节炎组织学研究较系统的骶髂关节炎组织学研究表明,AS的5个阶段不同程度存在滑膜炎、骨髓黏液样变、浅表软骨破坏、肌腱端炎、关节内纤维赘、新骨形成和骨性强直等众多病理表现;其中滑膜炎和软骨下骨髓黏液样变较肌腱端炎更能合理解 相似文献
45.
Christian J. Sauder Cheryl X. Zhang Malen A. Link W. Paul Duprex Kathryn M. Carbone Steven A. Rubin 《Vaccine》2009
The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence. 相似文献
46.
Jutta Liebau Stephanie Heidrich Alfred Berger Mayer Tenenhaus Hans-Oliver Rennekampff 《European journal of plastic surgery》2007,29(5):235-242
Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound
edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules
(laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness
grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing
keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to
54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to
0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong
laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin
1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both
transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on
the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression
of associated integrins are not impaired in chronic wounds.
Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002. 相似文献
47.
目的本文检测血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP-9)在大肠癌患者血清中的水平,探讨其与大肠癌恶性程度、浸润、转移的关系。方法用ELISA法对48例大肠癌患者及40例正常对照者血清VEGF和MMP-9进行检测。结果大肠癌患者血清VEGF、MMP-9的水平分别为(665.8±232.8)ng/L;(532.7±208.9)ug/L。显著高于对照组(391.6±135.2)ng/L;(317.8±132.2)ug/L(P<0.01)。并与组织分化程度、Duke’s分期有关。低分化者及C、D期患者较中、高度分化及A、B期高(P<0.01)。结论大肠癌患者血清VEGF和MMP-9水平增高,与肿瘤的组织分化程度、转移、分期有关,提示VEGF、MMP-9对大肠癌恶性程度的判断有一定的价值。 相似文献
48.
Cylindrical matrices were prepared by compression either of polyvinyl alcohol 100000 or mixtures of the excipient and a drug (sodium salicylate or theophylline). To modify the cylindrical shape, a hole was bored in the centre of the flat surface through both sides of the matrices. Different swellable systems were obtained applying an impermeable coating to one, two or three surfaces of the perforated matrices. The swelling of the perforated matrices was modified according to the number and the position of the coated surfaces (selective coating) and the loaded drug. Pseudo-zero order kinetics were obtained when the interior hole was the only uncoated surface. 相似文献
49.
50.
Automatic analysis of electromyography (EMG) signals, first operated in 1950 with analogic machines, steeply expanded from 1980 when fast computers and worthwhile programs became available. On-line measurement of response area and latency, averaging of low amplitude waves, fast sorting of motor unit potential shape parameters, computation of the “jitter” between two muscle fibers, turns/amplitude and spectral analysis of interferential pattern records, are some examples of programs currently offered in modern EMG machines. Other techniques are still reserved for research purposes: scanning EMG, decomposition of nerve and muscle compound potentials, measurement of the threshold and firing rate of motor units, trace analysis using tracking models. Finally, the credit for artificial intelligence systems (knowledge based systems, fuzzy logic, neuronal networks) is still not clearly stated. 相似文献