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Full-Text Articles in Medicine and Health Sciences
Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder
Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder
Department of Microbiology and Immunology Faculty Papers
Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …
We Can Do It Together: Par1/Par2 Heterodimer Signaling In Vsmcs., Rafal Pawlinski, Michael Holinstat
We Can Do It Together: Par1/Par2 Heterodimer Signaling In Vsmcs., Rafal Pawlinski, Michael Holinstat
Department of Medicine Faculty Papers
In this issue, Sevigny and colleagues demonstrate that a protease-activated receptor 1 (PAR1)-PAR2 heterodimer regulates vascular smooth muscle cell (VSMC) hyperplasia following vascular injury 1. PARs belong to a family of G-protein coupled receptors that are proteolytically activated by a variety of proteases 2, 3. Cleavage of PARs results in intracellular signaling mediated by activation of various G proteins including G12/13, Gq, and Gi 2, 4-6. The PAR family consists of 4 members, PAR1-PAR4, with PARs 1, 3, and 4 being primarily activated by thrombin, while PAR2 is activated by trypsin and …
Clinical Pharmacology As A Foundation For Translational Science., Scott A. Waldman, R J. Hohl, G L. Kearns, S J. Swan, A Terzic
Clinical Pharmacology As A Foundation For Translational Science., Scott A. Waldman, R J. Hohl, G L. Kearns, S J. Swan, A Terzic
Department of Pharmacology and Experimental Therapeutics Faculty Papers
The evolution of enabling technologies and their associated perspectives into molecular mechanisms underlying disease has extended beyond the abilities of scientific and clinical structures to advance their translation into new algorithms that improve the health of patients and populations.1 Research programs have yielded a vast array of novel molecules related to pathophysiological mechanisms that represent diagnostic and therapeutic targets which have the potential for personalized healthcare management. Yet, despite extraordinary scientific advances, routine successful translation of discovery into new therapeutic tools remains a distant vision. Beyond constraints in bridging discovery science with clinical translation due to obstacles in facilities, …
Chronic Diseases: The Emerging Pandemic., Andre Terzic, Scott A. Waldman
Chronic Diseases: The Emerging Pandemic., Andre Terzic, Scott A. Waldman
Department of Pharmacology and Experimental Therapeutics Faculty Papers
According to the 2011 World Health Organization Global Status Report, of the 57 million annual global deaths – a staggering 36 million or over 63% are due to chronic diseases.1 Four noncommunicable diseases - namely cardiovascular, cancer, diabetes, and chronic respiratory diseases - emerge as the leading cause of mortality in the world, accounting respectively for 17, 7.6, 4.2, and 1.3 million deaths based on the latest available global epidemiology data. By 2020, global deaths due to chronic diseases are projected to worsen by at least 15 to 20%. It is estimated that the four major noncommunicable diseases will …
Hydrophobicity As A Driver Of Mhc Class I Antigen Processing., Lan Huang, Matthew C Kuhls, Laurence C. Eisenlohr
Hydrophobicity As A Driver Of Mhc Class I Antigen Processing., Lan Huang, Matthew C Kuhls, Laurence C. Eisenlohr
Department of Microbiology and Immunology Faculty Papers
The forces that drive conversion of nascent protein to major histocompatibility complex (MHC) class I-restricted peptides remain unknown. We explored the fundamental property of overt hydrophobicity as such a driver. Relocation of a membrane glycoprotein to the cytosol via signal sequence ablation resulted in rapid processing of nascent protein not because of the misfolded luminal domain but because of the unembedded transmembrane (TM) domain, which serves as a dose-dependent degradation motif. Dislocation of the TM domain during the natural process of endoplasmic reticulum-associated degradation (ERAD) similarly accelerated peptide production, but in the context of markedly prolonged processing that included nonnascent …
The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai
The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). Aspirin and clopidogrel are two frequently used anti-clotting agents with different mechanisms of action. Since LRPT may potentially be co-administered with either one of these agents, these studies were conducted to assess the effects of steady-state LRPT on the antiplatelet activity of steady-state clopidogrel or aspirin. Bleeding time …