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Gerald L DeNardo Arutselvan Natarajan Saphon Hok Julie Perkins Monique Cosman Sally J DeNardo Felice C Lightstone Gary R Mirick Laird A Miers Rodney L Balhorn 《Journal of nuclear medicine》2007,48(8):1338-1347
Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting. 相似文献
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Sally J Wellard RN BA Renal Cert MN Colleen Rolls RN RM Child Hlth Cert BAppSc Grad Dip Child Development MEdSt de Sales Ferguson RN BA BEd MN 《Journal of advanced nursing》1995,21(4):737-742
An Australian school of nursing's attempt to introduce an evaluation process required by management for clinical educators involved in undergraduate preregistration education is discussed Reliance on student feedback and clinical agencies' perceptions of the quality of teaching were seen as inadequate mechanisms for evaluation The evaluation process adopted incorporated observation of the educators together with self-reflection on their performance We conclude that post-briefings were poorly used and generally not reflective Educators relied heavily on their clinical skills and used a limited range of teaching strategies Whilst evaluation of clinical educators was time consuming and therefore costly, it is argued that it is essential to the integrity of the course The evaluation process has provided direction for support and development of clinical educators within the context of the curriculum 相似文献
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Sally M Davis 《Journal of advanced nursing》1995,21(5):951-959
This qualitative study was undertaken at two neuro-rehabihtation centres in England, with the aim of exploring the nurses' understanding of health education and health promotion and their role within it, and their perception of illness and wellness related to disability The principle of methodical triangulation was employed using questionnaires, group interviews and content analysis of client care plans Although the nurses had difficulty distinguishing between health promotion and health education, differences did emerge which were supported by the literature The nurses generally identified their role as being one of health promotion However, they tended to equate wellness with physical independence As a result of the study a health promotion model based on the principles of self-empowerment is suggested, which could be used as a framework for rehabilitation nurses and other professionals to enable them to focus on health and wellness rather than illness and disability 相似文献
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Graeme Penington Sally Warmington Susan Hull Nicholas Freijah 《ANZ journal of surgery》1992,62(10):774-779
Aspects of peri-operative management, amputation level and rehabilitation of the lower limb amputee are reported in the context of a review of a rehabilitation service for amputees which includes an integrated prosthetic service. Two hundred admissions were reviewed and some complex cases described. It is concluded that: a very close liaison between the surgeon and the rehabilitation team (ideally with pre-operative consultation) is in the patient's best interests; any person previously walking (or a potential walker) should be considered for a trial of prosthetic walking; an integrated prosthetic service enhances the efficiency of the rehabilitation service; and that modification of the current Artificial Limb Scheme to allow manufacture of first definitive limbs in prosthetic rehabilitation units would further enhance service to patients. 相似文献
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