Cellular mechanisms

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Functional antagonism, reduction in the responsiveness to a given agonist by activation of cellular mechanisms that produce a counterstimulus to the cell. 

Anderson MS, Venanzi ES, Chen Z et al (2005) The cellular mechanism of AIRE control of T cell tolerance. Immunity 23 113... 

Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367 607-614... 

MDR-ABC Transporters. Figure 3 Detoxification cellular mechanisms. X, toxic compound X-OH, oxidized toxic compound GS-X, conjugated toxic compound OATP, organic anion transporting proteins CYPs, cytochromes GSH, glutathion UDPGIcUA, Uridine 5-diphosphoglucuronic acid PAPs, 3-phosphoadenylylsulfate. 

Protein trafficking is the transport of proteins to their correct subcellular compartments or to the extracellular space ( secretory pathway ). Endo- and exocytosis describe vesicle budding and fusion at the plasma membrane and are by most authors not included in the term protein trafficking. Protein quality control comprize all cellular mechanisms, monitoring protein folding and detecting aberrant forms. 

Westerblad, H., Lee, J.A., Lannergren, J., Allen, D.G. (1991). Cellular mechanisms of fatigue in skeletal muscle. Am. J. Physiol. 261, CI95-C209. 

Fornazzari L, Wilkinson DA, Kapur BM, et al Cerebellar, cortical and functional impairment in toluene abusers. Acta Neurol Scand 67 319—329, 1983 Franks NP, Lieb WR Molecular and cellular mechanisms of general anaesthesia. Nature 367 607-614, 1994... 

Covey LS, Classman AH A meta-analysis of double-blind placebo controlled trials of clonidine for smoking cessation. Br J Addict 86 991—998, 1991 Covey LS, Classman AH, Stetner F Naltrexone effects on short-term and long-term smoking cessation.] Addict Dis 18 31 0, 1999 Covey LS, Sullivan MA, Johnston A, et al Advances in non-nicotine pharmacotherapy for smoking cessation. Drugs 39 17-31, 2000 Dani JA, De Biasi M Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 70 439 46, 2001... 

Techniques for Tentatively Identifying Mechanisms of Action. Once the mechanism by which a toxin kills has been assessed, and toxin reasonably purified, it becomes relevant to try and ascertain as efficiently as possible the cellular mechanisms "tar-getted" by the toxin. This is a necessary step before final analysis of action using pure toxin and site-specific procedures such as the patch-clamp technique. 

While the ECG is an invaluable tool for the observation of heart rate and rhythm, as well as for the diagnosis of conduction abnormalities, ischaemia, and infarcts, its detailed interpretation is not without pitfalls. One reason for this is that different changes in cardiac cellular behaviour may give rise to very similar effects on the ECG. This makes it difficult to draw conclusions from a patient s ECG to the underlying (sub-)cellular mechanisms. This issue is usually referred to as the inverse problem. ... 

Greengard, P, Benfenati, F and Valtorta, F (1994) Synapsin I, an active-binding protein regulating synaptic vesicle traffic in the nerve terminal. In Molecular and Cellular Mechanisms of Neurotransmitter Release (Eds Starjne, L, Greengard, P, Grillner, S, Hokfelt, T and Ottoson, D), Raven Press, New York, pp. 31 5. 

The second major difficulty is that cells and tissues in the body are exposed to numerous metabolites displaying different structures compared to the parent molecules present in plant foods. For example, it has been suggested that the metabolites of lycopene may be responsible for reducing the risk of developing prostate cancer. These metabolites may interact with nuclear receptors such as PPARs, LXR, and others. " Future research is needed to produce metabolites (enzymatically or chemically) in order to elucidate their cellular mechanisms and thus clarify their effects on human health. 

Vorbrodt, A.W., Lossinsky, A.S., Dobrogowska, D.H. and Wisniewski, H.M. (1993). Cellular mechanisms of the blood-brain barrier (BBB) opening to albumin-gold complex. Histol. Histopathol. 8, 51-61. 

L. V. Kochian, Cellular mechanisms of aluminum toxicity and resistance in plants. Aiwu Rev. Plan Physiol. Plant Mol. Biol. 46 231 (1995). 

Owens, M. J. (1997). Molecular and cellular mechanisms of antidepressants drugs. Depress. Anxiety, 4, 153-9. 

D19. Dinarello, C. A., Okusawa, S., and Gelfland, J. A., Interleukin-1 induces a shock-like state in rabbits Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. In Molecular and Cellular Mechanisms of Septic Shock. Alan R. Liss, New York, 243-263... 

One note of caution with regard to these types of studies is that one must take into account any other cellular mechanisms for substrate and/or product depletion. For example, in studies of enzymes that act on protein substrates, one must ensure that the substrate and products are isolated from cells under conditions that do not promote their destruction. In the case of kinases, for example, one must ensure that cellular phosphatases are inhibited during cell lysis and sample preparation, to ensure that substrate buildup is not the result of phosphatase-catalyzed dephosphorylation of the kinase product. 

Biological Transport Phenomena in the Gastrointestinal Tract Cellular Mechanisms... 

Fox DA University of Houston, Houston, TX Cellular mechanisms of rod-mediated visual deficits resulting from developmental lead exposure (rat) National Institute of Environmental Health Sciences... 

Mardones, P and Rigotti, A, 2004. Cellular mechanisms of vitamin E uptake Relevance in alpha-tocopherol metabolism and potential implications for disease. J Nutr Biochem 15, 252-260. 

Magistretti, P. J. Pellerin, L. (1999). Cellular mechanisms of brain energy... 

McCormick, D. A. Williamson, A. (1991). Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine possible cellular mechanisms of histaminergic control of arousal. J. Neurosci 11, 3188-99. 

Bailey, C.R, Connor, M. Opioids cellular mechanisms of tolerance and physical dependence. Curr. Opin. Pharmacol. 5 60, 2005. 

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