Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Viral immunopathology). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Laurentian University

1. Michael, Paul. Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways .

Degree: 2016, Laurentian University

Sepsis and septic shock are the leading causes of death in intensive care units in North America. Approximately 800,000 cases of sepsis are reported every year in the USA and 215,000 will succumb to the disease despite aggressive antibiotic and supportive care [1-7]. The incidence of sepsis is increasing at a rate of 9% per year even with advances in the understanding of the pathophysiology of the disease [1]. Sepsis is commonly induced by bacterial and viral infections. Influenza A is the virus that causes the flu. The most recent pandemic caused by Influenza A (H1N1) demonstrated the potential of this virus to cause severe complications (viral induced sepsis characterized by pneumonia, acute respiratory distress and acute lung injury). This study investigated the inflammatory mediators of sepsis in H1N1 infected adults and from adults with bacterial induced sepsis. For H1N1 infections lung tissue and sera samples were characterized. Lung tissue showed hemorrhage, and interstitial congestion. Cytokine staining of these tissues revealed the presence of TNF-α, IFN-γ and IL-1β primarily from the recruited leukocytes. In addition TUNEL assay revealed apoptosis occurring in these same cell populations. ELISA quantification of sera from H1N1 infected adults also demonstrated high levels of TNF-α, IFN-γ and IL-1β at 113 pg/mL, 49 pg/mL and 26 pg/mL respectively. The sera also were able to induce apoptosis in cultured fibroblasts that was mediated through STAT1 signalling. The sera from bacterial induced sepsis were characterized for the presence of other cytokines and chemokines. TNF-α was consistently detected in all septic samples. Chemokine expression was more variable across the septic samples. The identification of different mediators of inflammation during sepsis will not only increase the basic knowledge about the progression of sepsis but would allow for the development of biomarkers that could better predict the progression of sepsis to more severe or fatal forms and allow for earlier intervention and treatment of these cases.

Subjects/Keywords: sepsis; inflammatory cytokines; H1N1 influenza A; viral pneumonia; apoptosis,; immunopathology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Michael, P. (2016). Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways . (Thesis). Laurentian University. Retrieved from https://zone.biblio.laurentian.ca/handle/10219/2766

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Michael, Paul. “Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways .” 2016. Thesis, Laurentian University. Accessed January 23, 2019. https://zone.biblio.laurentian.ca/handle/10219/2766.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Michael, Paul. “Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways .” 2016. Web. 23 Jan 2019.

Vancouver:

Michael P. Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways . [Internet] [Thesis]. Laurentian University; 2016. [cited 2019 Jan 23]. Available from: https://zone.biblio.laurentian.ca/handle/10219/2766.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Michael P. Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways . [Thesis]. Laurentian University; 2016. Available from: https://zone.biblio.laurentian.ca/handle/10219/2766

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Soumana, Djade I. Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation.

Degree: Biochemistry and Molecular Pharmacology, Biochemistry and Molecular Pharmacology, 2015, U of Massachusetts : Med

The Hepatitis C Virus (HCV) is a global health problem as it afflicts an estimated 170 million people worldwide and is the major cause of viral hepatitis, cirrhosis and liver cancer. HCV is a rapidly evolving virus, with 6 major genotypes and multiple subtypes. Over the past 20 years, HCV therapeutic efforts have focused on identifying the best-in-class direct acting antiviral (DAA) targeting crucial components of the viral lifecycle, The NS3/4A protease is responsible for processing the viral polyprotein, a crucial step in viral maturation, and for cleaving host factors involved in activating immunity. Thus targeting the NS3/4A constitutes a dual strategy of restoring the immune response and halting viral maturation. This high priority target has 4 FDA approved inhibitors as well as several others in clinical development. Unfortunately, the heterogeneity of the virus causes seriously therapeutic challenges, particularly the NS3/4A protease inhibitors (PIs), which suffer from both the rapid emergence of drug resistant mutants as well as a lack of pan-genotypic activity. My thesis research focused on filling two critical gaps in our structural understanding of inhibitor binding modes. The first gap in knowledge is the molecular basis by which macrocyclization of PIs improves antiviral activity. Macrocycles are hydrophobic chains used to link neighboring chemical moieties within an inhibitor and create a structurally pre-organized ligand. In HCV PIs, macrocycle come in two forms: a P1 - P3 and P2 - P4 strategy. I investigated the structural and thermodynamic basis of the role of macrocyclization in reducing resistance susceptibility. For a rigorous comparison, we designed and synthesized both a P1 - P3 and a linear analog of grazoprevir, a P2 - P4 inhibitor. I found that, while the P2 - P4 strategy is more favorable for achieving potency, it does not allow the inhibitor sufficient flexibility to accommodate resistance mutations. On the other hand, the P1 - P3 strategy strikes a better balance between potency and resistance barrier. The second gap my thesis addresses is elucidating the structural basis by which highly potent protease inhibitors function in genotype 1 but not in genotype 3, despite having an 87% sequence similarity. After mapping the amino acids responsible for this differential efficacy in genotypes 1 and 3, I engineered a 1a3a chimeric protease for crystallographic studies. My structural characterization of three PIs in complex with both the 1a3a and genotype 1 protease revealed that the loss of inhibitor efficacy in the 1a3a and GT-3 proteases is a consequence of disrupted electrostatic interactions between amino acids 168 and 155, which is critical for potent binding of quinoline and isoindoline based PIs. Here, I have revealed details of molecular and structural basis for the lack of PI efficacy against GT-3, which are needed for design of pan-genotypic inhibitors. Advisors/Committee Members: Celia A. Schiffer, Ph.D..

Subjects/Keywords: Hepacivirus; Viral Nonstructural Proteins; Protease Inhibitors; Hepatitis C; Drug Resistance; Biochemistry; Immunopathology; Immunoprophylaxis and Therapy; Molecular Biology; Structural Biology; Virology; Virus Diseases

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Soumana, D. I. (2015). Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/803

Chicago Manual of Style (16th Edition):

Soumana, Djade I. “Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation.” 2015. Doctoral Dissertation, U of Massachusetts : Med. Accessed January 23, 2019. http://escholarship.umassmed.edu/gsbs_diss/803.

MLA Handbook (7th Edition):

Soumana, Djade I. “Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation.” 2015. Web. 23 Jan 2019.

Vancouver:

Soumana DI. Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2015. [cited 2019 Jan 23]. Available from: http://escholarship.umassmed.edu/gsbs_diss/803.

Council of Science Editors:

Soumana DI. Hepatitis C Virus: Structural Insights into Protease Inhibitor Efficacy and Drug Resistance: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2015. Available from: http://escholarship.umassmed.edu/gsbs_diss/803

3. Bhela, Siddheshvar. Role of microRNA-155 in Herpes Simplex Virus Pathogenesis.

Degree: 2015, University of Tennessee – Knoxville

Ocular infection with herpes simplex virus 1 (HSV-1) can result in a chronic immunoinflammatory stromal keratitis (SK) lesion that is a significant cause of human blindness. These lesions are mainly orchestrated by IFN-gamma producing CD4+ T cells (Th1) and neutrophils. HSV being neurotropic in nature can also disseminate into the brain and lead to herpes simplex encephalitis (HSE). In this study we investigated the role of miR-155 in the pathogenesis of HSK and HSE. The first part of the dissertation (I) reviews literature regarding the contribution of miRNAs in innate and adaptive immune responses. It also focuses on their involvement in neuroinflammation during inflammatory and viral diseases. In the second part (II) we investigated the role of miR-155 in HSV-1 latency and HSE. We observed that miR-155-/- (microRNA-155 knockout) mice are highly susceptible to HSE and zosteriform lesions. These miR-155-/- animals also show increased viral reactivation from latency when compared to the control WT (wild type) animals. One explanation for these observations was diminished CD8 T cell effector responses in miR-155-/- animals. In the third part (III) we evaluate the role of miR-155 in the pathogenesis of SK. Our results showed that miR-155 expression is increased in corneas after HSV-1 infection and suppression of miR-155 production resulted in milder lesions that was associated with diminished Th1 and Th17 responses as well as reduced inflammatory cytokine production. Collectively, these studies identified a novel role for miR-155 in regulating HSE and promoting inflammation during HSK.

Subjects/Keywords: miRNA; CD4 T cells; CD8 T cells; Viral immunopathology; Inflammation; Immune System Diseases; Virus Diseases

…16 Host miRNAs regulating viral and cellular genes… …16 Viral miRNAs regulating host and viral genes… …infection and have elevated viral titers in the brain but no difference in the cornea… …60 Figure 2.3 Viral replication in the brain is the cause of encephalitis in the miR… …and miR-155KO mice show impaired viral clearance from both brain and skin......... 69… 

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bhela, S. (2015). Role of microRNA-155 in Herpes Simplex Virus Pathogenesis. (Doctoral Dissertation). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_graddiss/3322

Chicago Manual of Style (16th Edition):

Bhela, Siddheshvar. “Role of microRNA-155 in Herpes Simplex Virus Pathogenesis.” 2015. Doctoral Dissertation, University of Tennessee – Knoxville. Accessed January 23, 2019. https://trace.tennessee.edu/utk_graddiss/3322.

MLA Handbook (7th Edition):

Bhela, Siddheshvar. “Role of microRNA-155 in Herpes Simplex Virus Pathogenesis.” 2015. Web. 23 Jan 2019.

Vancouver:

Bhela S. Role of microRNA-155 in Herpes Simplex Virus Pathogenesis. [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2015. [cited 2019 Jan 23]. Available from: https://trace.tennessee.edu/utk_graddiss/3322.

Council of Science Editors:

Bhela S. Role of microRNA-155 in Herpes Simplex Virus Pathogenesis. [Doctoral Dissertation]. University of Tennessee – Knoxville; 2015. Available from: https://trace.tennessee.edu/utk_graddiss/3322

.