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991.
Wynn L. Walker Elliot M. Landaw Richard E. Dickerson David S. Goodsell 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(11):5634-5639
Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences. 相似文献
992.
993.
This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect. 相似文献
994.
O. Boerman W. Oyen G. Storm M Corvo L. van Bloois J. W M van der Meer F. Corstens 《Annals of the rheumatic diseases》1997,56(6):369-373
OBJECTIVES—Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with 99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > 99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that 99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.
相似文献
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with 99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > 99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that 99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.
相似文献
995.
While the benefits of training manuals can hardly be questioned, they are exceedingly limited in reducing variability attributed to the "therapist factor." We propose that manuals provide a useful outline of the general principles of a therapeutic approach, but can only reduce therapist variability at the expense of other essential therapeutic phenomena. Manuals cannot adequately convey, for example, how the effective therapist functions as a model of adult living and as a person who provides guidance. We suggest that such an experience cannot readily be packaged in manualized form, though manuals may serve as a useful beginning. Recommendations for therapist manualized training include greater attention to the subtleties of human relationships and adequately conveying that any technique is effective only when catalysed by a living, relational process. 相似文献
996.
The experimental and clinical results of the self-expanding nitinol coil stent have been reviewed. Animal data have shown that the stent is safe and provokes a mild proliferative response, similar to previously studied balloon-expandable stents. Data from femoral and popliteal arteries are supportive of long-term patency in these arteries, which are typically associated with unfavorable results from other stents. Data from coronary implantations in patients show that the stent can be safely used to treat coronary lesions of both simple and complex natures. Long-term results of these patients compare favorably with existing data in similar lesions using other stents. A larger clinical trial using the new flat wire design stent is required to test whether further stent expansion may contribute to low restenosis rates. 相似文献
997.
Doing it right the first time: quality improvement and the contaminant blood culture. 总被引:5,自引:3,他引:2
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F I Weinbaum S Lavie M Danek D Sixsmith G F Heinrich S S Mills 《Journal of clinical microbiology》1997,35(3):563-565
The aim of the project was to determine whether the rate of contaminant blood cultures could be reduced by using a team of dedicated phlebotomists. Comparisons were made between adult patients requiring blood cultures for suspected bacteremia on medical and surgical units before and after the introduction and withdrawal of a dedicated blood culture team. The results showed that a significant reduction in the contaminant blood culture rate was achieved by the blood culture team (P < 0.001; chi(2) test). Therefore, in our experience, the rate of contaminant blood cultures can be reduced in a teaching hospital by using a team of dedicated phlebotomists. Calculations made with our data and those published by others suggest that cost savings from reducing false-positive blood cultures are greater than the cost of the blood culture team. 相似文献
998.
A new implantable bladder volume-monitoring device based on the impedance measurement of the detrusor muscle is described.
The system is completely autonomous and forms a mixed-signal (analogue/digital) feedback loop with a neuro-stimulator to rectify
bladder dysfunctions (incontinence and retention) through neuromuscular stimulation techniques. A programmable instrumentation
amplifier and a signal processing block, to eliminate the artefacts caused by the patient’s movements, have been designed
and tested. The layout for the signal processing block has been realised in 0.8 μm BiCMOS technology. 相似文献
999.
M. D. Mashkovskii V. A. Parshin R. B. Parimbetova 《Bulletin of experimental biology and medicine》1997,123(3):257-259
It is found that the cholinomimetic aceclidine stimulates learning and memory processes and exerts antiamnestic effect in
rats with conditioned avoidance reaction. The effect of aceclidine is not inferior to that of amiridin and surpasses that
of physostigmine.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 296–298, March, 1997 相似文献
1000.