Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotropin releasing hormone (TRH) stimulates an increase in plasma cortisol in horses with pars intermedia dysfunction (PPID, Cushing's disease). A similar phenomenon is observed in humans with Cushing's disease or Nelson's syndrome. The mechanism of the response in humans is not known, but an alteration in receptor expression, selectivity or responsiveness in abnormal corticotropes has been proposed. Horses with PPID, unlike humans, almost exclusively have adenomas of pars intermedia (PI) rather than pars distalis (PD) origin. Therefore, the mechanism responsible for the TRH response observed in horses likely differs. We proposed that TRH directly stimulates the PI in normal and PPID-affected horses to release proopiomelanocortin (POMC) derived peptides. Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses. The ability of TRH to directly stimulate release of POMC peptides was confirmed using PI and PD tissue explants. The presence of TRH receptor mRNA in PI tissue from both normal and PPID horses was confirmed using reverse transcriptase polymerase chain reaction. We conclude that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors normally expressed on melanotropes. The increase in plasma cortisol following TRH in horses with PPID is likely attributable to the release of ACTH from the hyperplastic PI.
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PMID:Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants. 1611 43

Global stability is analyzed for a general mathematical model of HIV-1 pathogenesis proposed by Nelson and Perelson [11]. The general model include two distributed intracellular delays and a combination therapy with a reverse transcriptase inhibitor and a protease inhibitor. It is shown that the model exhibits a threshold dynamics: if the basic reproduction number is less than or equal to one, then the HIV-1 infection is cleared from the T-cell population; whereas if the basic reproduction number is larger than one, then the HIV-1 infection persists and the viral concentration maintains at a constant level.
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PMID:Global stability of an HIV-1 model with distributed intracellular delays and a combination therapy. 2057 92

Mathematical models have shed light on the dynamics of HIV- 1 infection in vivo. In this paper, we generalize continuous mathematical models of drug therapy for HIV-1 by Perelson et al. (Science 271:1582-1586, 1996) and Perelson and Nelson (SIAM Rev 41:3-44, 1999) on time scales, i.e., a nonempty closed subset of real numbers in order to derive new discrete models that predict the total concentration of plasma virus as a function of time. One of our main goals is to compare discrete mathematical models with the continuous model in Perelson et al. (1996) where HIV infected patients were given protease inhibitors and sampled frequently thereafter. For the comparison, we use experimental data collected in Perelson et al. (1996) and estimate the parameters such as the virion clearance rate and the rate of loss of infected cells by fitting the total concentration of plasma virus to this data set. Our results show that discrete systems describe the best fit. In the previous models of this study, the efficacy of protease inhibitor is assumed to be perfect. Motivated by Perelson and Nelson (1999), we end the paper with a mathematical model of imperfect protease inhibitor and reverse transcriptase (RT) inhibitor combination therapy of HIV-1 infection on time scales with its stability analysis.
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PMID:Continuous and discrete modeling of HIV-1 decline on therapy. 3248 70