Proteins clinical applications

P2. Pandian, M. R., Morgan, C. H., Carlton, E., and Serge, G. V., Modified immunoradiometric assay of parathyroid hormone-related protein Clinical application in the differential diagnosis of hypercalcemia. Clin. Chem. 38, 282-288 (1992). 

In contrast to other analytical methods, ion-selective electrodes respond to an ion activity, not concentration, which makes them especially attractive for clinical applications as health disorders are usually correlated to ion activity. While most ISEs are used in vitro, the possibility to perform measurements in vivo and continuously with implanted sensors could arm a physician with a valuable diagnostic tool. In-vivo detection is still a challenge, as sensors must meet two strict requirements first, minimally perturb the in-vivo environment, which could be problematic due to injuries and inflammation often created by an implanted sensor and also due to leaching of sensing materials second, the sensor must not be susceptible to this environment, and effects of protein adsorption, cell adhesion, and extraction of lipophilic species on a sensor response must be diminished [13], Nevertheless, direct electrolyte measurements in situ in rabbit muscles and in a porcine beating heart were successfully performed with microfabricated sensor arrays [18],... 

The use of triphenylethylene SERMs as Pgp inhibitors for clinical application has been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration, which is likely due to the involvement of proteins with the ability to bind these compounds. For instance, toremifene is able to reverse MDR and to sensitize human renal cancer cells to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in particular a 1-acid glycoprotein (AAG), which may limit its tissue availability (Braybrooke et al. 2000). In agreement with this, Chatterjee and Harris (1990) have shown that tamoxifen and 4-OH-tamoxifen were similarly potent in reversing MDR in Chinese hamster ovary (CHO) cells with acquired resistance to adriamycin. However, the addition of AAG (0.5 to 2 mg/ml, the range found in vivo) to cell cultures decreased the effect of tamoxifen on reversing MDR, and at the highest AAG concentration there was a complete reversal of the effects of... 

X 96) proteins simultaneously for automatic analysis (Houthaeve etal., 1997 Jensen etal., 1997). In clinical applications this method could be used to screen complete 2D gels and annotate them automatically with the protein identity (Hoogland et al., 1998). 

Chabot J-G, Dumont Y, St- Pierre JA, Tong Y, Dore S, et al. 1999. Anatomical approaches to study G-protein coupled peptide receptors. Peptidergic G-protein-coupled receptors from basic research to clinical application. Geppetti P, Muller-Esterl W, Regoli D, editors. Amsterdam lOS Press pp. 11-28. 

Pierobon, M. Reverse phase protein microarrays for clinical applications... 

Pierobon M, Belluco C, Liotta LA et al (2011) Reverse phase protein microarrays for clinical applications. Methods Mol Biol 785 3-12... 

There are obvious problems associated with the clinical application of proteomics that must be answered. First, proteins must be identified and described with respect to function and physiologic impact. Second, consensus is necessary regarding the testing and reporting of the proteins. Third, the implementation of the technology would require wide-spread access with an economically feasible method of delivery. Last, the methods would need to be reproducible and valid. The potential for the use of such technology is very likely in the next few decades and will have significant impact on the lives of heart failure patients. 

Parveen S, Sahoo SK. Nanomedicine clinical applications of polyethylene glycol conjugated proteins and drugs. Clin Pharmacokinet 2006 45 966-88. 

The potential utility of peptides as therapeutics with clinical applications is limited by its metabolic instability or poor transmembrane mobility. Consequently, the preparation of metabolically stable peptide analogs that can either mimic or block the function of natural peptides or enzymes is an important area of medicinal chemistry research. Synthesis of fluoroolefin amide isosteres, its incorporation in peptidomimetics, and the influence of that isosteric substitution on the inhibition of several enzymes such as peptidyl prolyl isomerases, dipeptidyl peptidase IV, and thermolysin is described. Moreover, protein folding and activity... 

This section will describe the features and clinical applications for each gene delivery system. The description will start with a common feature of both viral and nonviral gene delivery systems, the expression cassette for the therapeutic protein. 

Clinical Applications of Adeno-Associated Virus. There have been many preclinical demonstrations of successful production of therapeutic proteins by engineered AAV [37-39]. The major clini-... 

For readers familiar with biotechnology, biopharmaceutics, and the drug development process, and for those that focus on the application of biopharmaceuticals. Part II provides a brief overview of each class of macromolecule with respect to physiological role and clinical application. Additional detail for each FDA approved, recombinantly derived biopharmaceutical, and several other interesting therapeutic proteins, for each category of macromolecule... 

This chapter is divided into three sections. The first section covers renal tubule transport mechanisms. The nephron is divided structurally and functionally into several segments (Figure 15-1, Table 15-1). Many diuretics exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (aldosterone receptor blockers). The physiology of each segment is closely linked to the basic pharmacology of the drugs acting there, which is discussed in the second section. Finally, the clinical applications of diuretics are discussed in the third section. 

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