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1.
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
2.
TERUAKI HONGO CHIEKO WATANABE SHUICHI OKADA NORIKO INOUE SHUHEI YAJIMA YUJI FUJII TAKEHIKO OHZEKI 《Pediatrics international》2003,45(1):60-64
BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer. 相似文献
3.
Beginning in the late 1980s, after a long period of declining interest in home care for the terminally ill, several projects and experiments were initiated in the Netherlands. This article describes this trend and provides background information on the Dutch health services, a definition of terminal home care, and statistical information about the different types of home care in the Netherlands. Findings from 3 recent studies of these projects and experiments are presented along with the guidelines for providing good terminal home care formulated by the Dutch Health Council in 1991. 相似文献
4.
Yasuhiko Tamada Hiromichi Takama Toshihiko Ikeya Takashi Yokochi Hijiri Mori Yoshinari Matsumoto 《The Journal of dermatology》1995,22(12):913-916
Lewis Y (Ley) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Ley. In the bulbar and suprabulbar portion of anagen hair follicles, Ley antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Ley antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Ley antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation. 相似文献
5.
结肠回肠反流与回肠黏膜结肠化相关性的实验研究 总被引:2,自引:0,他引:2
目的探讨结肠回肠反流后回肠末端黏膜结肠化的机制.方法取SD大鼠60只,均为雄性,体重25¨3∞g,随机分为实验组和对照组,分别进行末端回肠-盲肠侧侧吻合术或回肠末端手术缝线,2个月后处死动物并取组织进行观察.结果实验组术后一般状况良好.大体形态学观察:实验组回肠末端黏膜表现为绒毛萎缩、间距增宽、沟变浅、光滑性增强.病理组织学:实验组表现为黏膜绒毛萎缩、间距增宽、沟变浅、上皮细胞变短、杯状细胞增多.电镜观察:实验组可见绒毛变小、变短或脱落;微绒毛变短、分布不均匀;杯状细胞数目在非坏死区增多.结论结肠-回肠反流后可导致回肠末端黏膜结肠化的变化,它可能是慢性末端回肠炎的发病基础或前期表现. 相似文献
6.
目的:探讨原发性高血压(EH)患者血浆中肾上腺髓质素前体N端20肽(PAMP)与左室肥厚的相互关系。方法:观察62例EH患者血浆PAMP的变化以及与左室重量指数之间的关系。结果:经超声心动图检查显示,62例EH患者中伴左室肥厚者42例,无左室肥厚患者20例。EH伴左室肥厚患者血浆PAMP浓度较无左室肥厚患者明显增高(65·8±12·0)∶(60·8±9·0)ng/L,P<0·05。结论:EH患者血浆PAMP的升高可能为机体的代偿反应,有助于改善患者的预后。 相似文献
7.
8.
The response of periodontal nerves to experimentally induced occlusal trauma in rat molars was assessed by immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels, and by computerized image analysis. The occlusal surface on the left upper first molar of 8-wk-old male Wistar rats was raised approximately 1 min under ether anaesthesia. The rats were perfusion-fixed on d 1, 2, 3, 4, and 7 after bite-raising and then decalcified for 2–3 wk. Frozen sagittal cryostat sections were stained by the avidin-biotin complex method. By the second day after bite-raising many Ruffini endings were swollen and their outline unclear at the light microscopic level. Transmission electron microscopy disclosed PGP 9.5 reaction products within Ruffini endings that had unusually long cytoplasmic projections extending through enlarged slits of the Schwann sheaths and also diffuse extracellular PGP 9.5-immunoreactivity near the Ruffini endings. From d 2 to 4, thin nerve fibres on the pressure side of the periodontal ligament were orientated irregularly and had a prominent beaded appearance. An increase in beaded nerve terminals occurred at d 2–4 post elevation, and decreased later. These results suggest that occlusal trauma induces specific changes in the distribution and shape of nerve terminals in the periodontal ligament. 相似文献
9.
Corticospinal projections in adult rodents arise exlusively from layer V neurons in the sensorimotor cortex. These neurons are topographically organized in their connections to spinal cord targets. Previous studies in rodents have shown that the mature distribution pattern of corticospinal neurons develops during the first 2 weeks postnatal from an initial widespread pattern that includes the visual cortex to a distribution restricted to the sensorimotor cortex. To determine whether specificity in corticospinal connections also emerges from an intially diffuse set of projections, we have studied the outgrowth of corticospinal axons and the formation of terminal arbors in developing hamsters. The sensitive fluorescent tracer 1, 1′, dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorat (DiI) was used to label corticospinal axons from the visual cortex or from small regions of the forelimb or hindlimb sensorimotor cortex in living animals at 4–17 days postnatal. Initially axon outgrowth was imprecise. Some visual cortical axons extended transiently beyond their permanent targets in the pontine nuclei, by growing through the pyramidal decussation and in some cases extending as far caudally as the lumbar enlargement. Forelimb sensorimotor axons also extended past their targets in the cervical enlargement, in many cases growing in the corticospinal tract to lumbar levels of the cord. By about 17 days postnatal these misdirected axons or axon segments were withdrawn from the tract. Despite these errors in axon trajectories within the corticospinal tract, terminal arbors branching into targets in the spinal gray matter were topographically appropriate from the earliest stages of innervation. Thus visula cortical axons never formed connections in the spinal cord, forelimb sensorimotor axons arborized only in the cervical enlargement, and hindlimb cortical axons terminated only in the lumbar cord at all stages of development examined. Corticospinal arbors formed from collaterals that extended at right angles from the shafts of primary axons, most likely by the process of interstitial branching after the primary growth cone had extended past the target. Once collaterals extended into the spinal gray matter, highly branched terminal arbors formed within 2–4 days, beginning at about 4 and 8 days postnatal for the cervical and lumbar enlargements, respectively. These results show that specificity in connectivity is achieved by selectivty growth of axon collaterals in to appropriate spinal targets from the beginning and not by the later remodeling of intially diffuse connections. In contrast, errors occur in the initial outgrowth of axons in the corticospinal tract, which are subsequently corrected. Copyright © 1994 Wiley-Liss, Inc. 相似文献
10.
晚期肺癌的中医证候研究 总被引:18,自引:0,他引:18
目的 探讨晚期肺癌的主要中医证候。方法 采用回顾性与前瞻性相结合的方法进行临床观察。结果 经 χ2 检验 ,不同中医证候的晚期肺癌组之间有显著性差异 (P <0 0 1) ,而血瘀证、气虚证、痰证、阴虚证最为多见 ;晚期非小细胞肺癌与晚期小细胞肺癌的中医证型没有显著性差异。结论 晚期肺癌的中医证候以血瘀证、气虚证、痰证、阴虚证为主 ;晚期非小细胞肺癌与小细胞肺癌的中医证候无明显差异。 相似文献