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101.
We established an in vitro model of the phagocytosis of Mycobacterium tuberculosis by human peripheral blood monocytes to evaluate the subsequent inhibition of intracellular replication of the organism. Highly purified T cells (94% CD3(+)/CD16(-)) or natural killer (NK) cells (96% CD16(+)/CD3(-)) isolated by Percoll discontinuous density gradient of peripheral blood mononuclear cells were incubated with M. tuberculosis-infected monocyte monolayers. Monocytes were lysed immediately and at 4, 7, and 10 d after infection for quantification of intracellular replication, which was assessed by quantitative plating techniques as colony-forming units (CFU). Whereas control monocytes permitted intracellular replication, T cells activated monocytes to kill 77% (p < 0.01) of intracellular M. tuberculosis compared with control monocytes by 10 d after infection. NK cells activated monocytes to kill 84% (p < 0.01) of M. tuberculosis in comparison with control monocytes. Lymphokine (IL-2)-activated-killer (LAK) cells were capable of activating monocytes to kill 97% (p < 0.01) of the intracellular organisms compared with control monocytes. In purified protein derivative (PPD)-positive donors, PPD-specific-CD4(+) lymphocytes stimulated monocytes to kill intracellular M. tuberculosis in a Class II major histocompatibility complex-restricted manner. In contrast, in PPD-negative donors, CD4(-) lymphocytes activated monocytes in a genetically unrestricted manner. Both T cell supernatant and NK cell supernatant generated from cocultivation with M. tuberculosis-infected monocytes also activated monocytes to augment mycobactericidal function. In conclusion, T cells, NK cells, LAK cells, and their supernatants activated mycobactericidal function of monocytes, although these pathways of activation differed in terms of antigenic specificity and genetic restriction. 相似文献
102.
Phthalimidomethyl derivatives 1, encompassing a wide range of leaving group abilities, are rapidly hydrolysed to the corresponding phthalamic acid via rate-determining attack at the phthalimide carbonyl group. 相似文献
103.
Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer. 相似文献
104.
The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication
EM Kosnoski RL Yolton K Citek CE Hayes RB Evans 《Canadian Metallurgical Quarterly》1998,69(4):211-227
BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use. 相似文献
105.
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108.
This work presents a nonlinear adaptive dynamic surface air speed and a flight path angle control design procedure for the longitudinal dynamics of a generic hypersonic flight vehicle. The proposed design scheme takes into account the magnitude, rate, and bandwidth constraints on the actuator signals. A new approach is used to enhance tracking performance and avoid a large initial control signal. The uncertain nonlinear functions in the flight vehicle model are approximated by using radial basis function neural networks. A detailed stability analysis of the designed controllers shows that all the signals of the closed‐loop system are uniformly ultimately bounded. The robust performance of the design scheme is verified through numerical simulations of the flight vehicle model for various parameter variation test cases. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society 相似文献
109.
Hans M. Amman Author Vitae David A. Kendrick Author Vitae Author Vitae 《Automatica》2008,44(6):1504-1510
Currently, there is a renewed interest in the use of optimal experimentation (adaptive control) in economics. Example are found in
[Amman and Kendrick, 1999],
[Amman and Kendrick, 2003],
[Cosimano, in?press],
[Cosimano and Gapen, 2005b],
[Cosimano and Gapen, 2005a],
[Cosimano and Gapen, 2006],
[Tesfaselassie et?al., 2007],
[Tucci, 1997],
[Wieland, 2000a] and [Wieland, 2000b]. In this paper we present the Beck & Wieland model [Beck, G., & Wieland, V. (2002). Learning and control in a changing economic environment. Journal of Economic Dynamics and Control, 26, 1359-1378] and the methodology to solve this model with time-varying parameters using the various control methods described in
[Kendrick, 1981] and [Kendrick, 2002]. Furthermore, we also provide numerical results using the DualPC software [Amman, H. M., & Kendrick, D. A. (1999). The DualI/DualPC software for optimal control models: User’s guide. Working paper, Austin, TX 78712, USA: Center for Applied Research in Economics, University of Texas] and show first evidence that optimal experimentation or Dual Control may produce better results than Expected Optimal Feedback. 相似文献
110.
AA Rodriquez JC Agre RL Harmon TM Franke ER Swiggum JT Curt 《Canadian Metallurgical Quarterly》1995,76(11):989-993
OBJECTIVE: Post-polio subjects experience functional deterioration many years after developing acute poliomyelitis and have been shown previously to have a deficit in strength recovery after isometric activity. This study characterized the size and stability of the motor units in a group of post-polio subjects with macro and single fiber electromyography (EMG) and correlated these variables with isometric strength, endurance, "work capacity," and strength recovery after fatiguing isometric exercise. DESIGN: A cohort of 12 post-polio subjects was tested for neuromuscular function. Electromyographic variables were determined on a separate day. SETTING: Volunteers were recruited from the community and tested in our neuromuscular research laboratory. SUBJECTS: A volunteer sample was obtained from advertisements. All subjects acknowledged post-polio syndrome symptoms. MAIN OUTCOME MEASURES: Neuromuscular variables were isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, tension time index, and recovery of torque at 10 minutes. Electromyographic variables were macro EMG and single fiber EMG (percent blocking and jitter). RESULTS: Macro EMG amplitude was ninefold the control value, and both jitter and blocking were greatly increased in comparison to control values. Isometric strength significantly (p < .05) correlated negatively with macro EMG amplitude. CONCLUSIONS: The weakest subjects had the greatest number of muscle fibers within the motor unit (as measured by macro EMG amplitude). Jitter and blocking did not correlate with neuromuscular function. 相似文献