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MBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET
Dekker B Keen H Lyons S Disley L Hastings D Reader A Ottewell P Watson A Zweit J 《Nuclear medicine and biology》2005,32(3):241-252
A noninvasive method of measuring programmed cell death in the tumors of cancer patients using positron-emission tomography (PET) would provide valuable information regarding their response to therapeutic intervention. Our strategy is to radiolabel annexin V, a protein that binds to phosphatidylserine moieties that are translocated to the external leaflet of plasma membranes during apoptosis. We developed a phosphatidylserine-ELISA capable of distinguishing wild type from point mutant annexin V that is known to have a lower phosphatidylserine binding affinity. A maltose-binding protein/annexin V chimera was synthesized and purified with high yield using amylose resin. We showed that it bound to phosphatidylserine in the ELISA as well as to that exposed on apoptotic Jurkat cells; therefore, it was used in the development of a method for radiolabeling annexin V using iodine radionuclides. MBP-annexin V retained its phosphatidylserine binding properties on direct iodination, but at high levels of oxidizing agents (iodogen and chloramine T), its specificity for phosphatidylserine was compromised. (124)I-MBP-annexin V was successfully used to image Fas-mediated hepatic cell death in BDF-1 mice using PET. In conclusion, we have shown that MBP-annexin V and the phosphatidylserine ELISA are useful tools for the development of methods for radiolabeling annexin V for PET imaging. 相似文献
84.
Williams HA Robinson S Julyan P Zweit J Hastings D 《European journal of nuclear medicine and molecular imaging》2005,32(12):1473-1480
Purpose PET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, 60Cu, 61Cu, 62Cu and 64Cu, to assess their merits for different PET imaging applications. Methods Spatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for 60Cu, 61Cu, 62Cu and 64Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for 60Cu, 61Cu and 64Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N4-methyl)thiosemicarbazone (Cu-PTSM). Results 60Cu and 62Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM. 61Cu and 64Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast. 61Cu-PTSM and 64Cu-PTSM are associated with radiation doses similar to [18F]-fluorodeoxyglucose, whilst the doses for 60Cu-PTSM and 62Cu-PTSM are lower and more comparable with H215O. Conclusion The physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers. 相似文献
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Low-income families face an enormous burden to achieve economic security since the deterioration of a guaranteed safety net. Health insurance coverage is uneven, affordable childcare falls short of demand, and wage earnings insufficiently support family needs. This analysis focuses on recent trends in family formation, the impact of policy changes on families of color and of immigrant status, and explores the daily challenges and coping strategies low-income families use to survive despite insufficient resources. Four key findings emerge from this body of knowledge: (1) Low-income families experience severe hardships when relying on cash assistance, work, or a combination of both; (2) Low-income families are resilient and resourceful; (3) Low-income families face significant barriers to using public and private services along with increasing earnings from work; and (4) The quality of life for families of color and immigrant families is directly affected by employment and service sector practices. Future research needs to focus on identifying the critical unmet needs of low-income families. 相似文献
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BACKGROUND AND PURPOSE: Diabetes mellitus (DM)-related neuropathic arthropathy of the foot is a destructive bone and joint process. The effect of cast immobilization and non-weight bearing on bone loss has not been well studied. The purpose of this case report is to describe the changes in bone mineral density (BMD) of the calcaneus in the feet of a patient with acute neuropathic arthropathy during total contact cast immobilization. CASE DESCRIPTION: The patient was a 34-year-old woman with type 1 DM, renal failure requiring dialysis, and a 7-week duration of neuropathic arthropathy of the midfoot. Intervention included total contact casting and minimal to no weight bearing for 10 weeks, with transition to therapeutic footwear. Ultrasound-derived estimates of BMD were taken of both involved and uninvolved calcanei. OUTCOME: Bone mineral density decreased for the involved foot (from 0.25 g/cm(2) to 0.20 g/cm(2)) and increased for the uninvolved foot (from 0.27 g/cm(2) to 0.31 g/cm(2)) during casting. DISCUSSION: The low initial BMD and further loss during casting suggest the need for transitional bracing and a well-monitored return to full activity to minimize the risk of recurrence and progression of foot deformity. 相似文献
87.
Russell A. Barkley James E. Hastings Robert E. Tousel Susan E. Tousel 《Journal of behavior therapy and experimental psychiatry》1976,7(3):227-230
The influence of a token economy in a residential treatment facility for delinquents was evaluated in three areas of behavior: (a) in-house chore performance, (b) littering in the facility, and (c) school performance as reflected in daily evaluations by teachers. Chore performance and littering were influenced favorably by the token system. School performance, however, appeared to be unaffected by the reversal of the token program. Reasons for this finding are discussed and the need underscored that existing token systems evaluate the effectiveness of their program contingencies on a regular basis. 相似文献
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Cetra D. Hastings Inger Brekke A. Attramadal Vidar Hansson 《International journal of andrology》1980,3(1-6):72-81
The present paper describes some physicochemical properties of the soluble 3α-oxidoreductases in the rat testis and prostate, and comparison with rat epididymal 3α-oxidoreductase, published previously (Hastings & Hansson 1979). The testicular enzyme shows properties very similar to that in the epididymis (size, stability, pH optium) except for minor differences in charge (iso-electric point). The prostatic enzyme revealed a slightly higher molecular weight, and was more sensitive to heating than those in the testis and epididymis, whereas the iso-electric point was the same as that in the testis (pI-5.25). The enzymes in all tissues exhibit very similar shapes (f/fo 1.14-1.17).
The similar properties of the testicular and prostate 3α-oxidoreductases to those previously reported for that in the epididymis may indicate that these enzymes represent identical peptide chains. The small differences observed in size, temperature stability and change may be due to their presence in different environments. 相似文献
The similar properties of the testicular and prostate 3α-oxidoreductases to those previously reported for that in the epididymis may indicate that these enzymes represent identical peptide chains. The small differences observed in size, temperature stability and change may be due to their presence in different environments. 相似文献
90.