The Experts below are selected from a list of 4065 Experts worldwide ranked by ideXlab platform
Heba H. Mostafa - One of the best experts on this subject based on the ideXlab platform.
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attenuated herpes simplex virus 1 hsv 1 expressing a mutant form of icp6 stimulates a strong immune response that protects mice against hsv 1 induced corneal Disease
Journal of Virology, 2018Co-Authors: David J Davido, Eleain M Tu, Andreu Gazquez Casals, Jahnu P Reddy, Heba H. Mostafa, Maria Korom, Hong WangAbstract:We previously isolated a herpes simplex virus 1 (HSV-1) mutant, KOS-NA, that carries two nonsynonymous mutations in UL39, resulting in L393P and R950H amino acid substitutions in infected cell protein 6 (ICP6). Our published data studying KOS-NA pathogenesis strongly suggest that one of these ICP6 substitutions expressed from KOS-NA, R950H, severely impaired acute viral replication in the eyes and trigeminal ganglia of mice after inoculation onto the cornea and consequently impaired establishment and reactivation from latency. Because of its significant neuroattenuation, we tested KOS-NA as a potential prophylactic vaccine against HSV-1 in a mouse model of corneal infection. KOS-NA stimulated stronger antibody and T cell responses than a replication-competent ICP0-null mutant and a replication-incompetent ICP8-null mutant optimized for immunogenicity. Immunizations with the ICP0−, ICP8−, and KOS-NA viruses all reduced replication of wild-type HSV-1 challenge virus in the corneal epithelium to similar extents. Low immunizing doses of KOS-NA and the ICP8− virus, but not the ICP0− virus, protected mice against Eyelid Disease (blepharitis). Notably, only KOS-NA protected almost completely against corneal Disease (keratitis) and greatly reduced latent infection by challenge virus. Thus, vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated Disease of the eye, even at a very low immunizing dose. These results suggest that KOS-NA may be the foundation of an effective prophylactic vaccine to prevent or limit HSV-1 ocular Diseases. IMPORTANCE HSV-1 is a ubiquitous human pathogen that infects the majority of the world's population. Although most infections are asymptomatic, HSV-1 establishes lifelong latency in infected sensory neurons, from which it can reactivate to cause deadly encephalitis or potentially blinding eye Disease. No clinically effective vaccine is available. In this study, we tested the protective potential of a neuroattenuated HSV-1 mutant (KOS-NA) as a vaccine in mice. We compared the effects of immunization with KOS-NA to those of two other attenuated viruses, a replication-competent (ICP0−) virus and a replication-incompetent (ICP8−) virus. Our data show that KOS-NA proved superior to the ICP0- and ICP8-null mutants in protecting mice from corneal Disease and latent infection. With its significant neuroattenuation, severe impairment in establishing latency, and excellent protective effect, KOS-NA represents a significant discovery in the field of HSV-1 vaccine development.
Jonathan G Crowston - One of the best experts on this subject based on the ideXlab platform.
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prevalence of signs and symptoms of ocular surface Disease in individuals treated and not treated with glaucoma medication
Clinical and Experimental Ophthalmology, 2012Co-Authors: Sudipta Ghosh, Fleur Ohare, Ecosse L Lamoureux, Rasik B Vajpayee, Jonathan G CrowstonAbstract:Background: To determine the prevalence of signs and symptoms of ocular surface Disease in two hospital-based cohorts; glaucoma patients and non-glaucoma patients. Design: A cross-sectional, comparative case series. Participants: Glaucoma patients (n = 300) prescribed topical glaucoma medications for ≥6 months were compared with control patients (n = 100) who were not applying prescribed topical medications. Methods: A validated self-report questionnaire was used to elicit the extent of ocular symptoms. Signs of ocular surface and Eyelid Disease were assessed along with medication history. Main Outcome Measures: Signs and symptoms of ocular surface pathology were determined including the tear film break-up time, fluorescein staining of the cornea and conjunctiva, meibomian gland dysfunction and Schirmer's test. Results: A significant increase in the prevalence of ocular surface Disease signs was observed in the glaucoma population, 70.3%, compared with controls, 33% (P < 0.001). The overall prevalence of clinically significant ocular surface Disease symptoms was not significantly different between cohorts, 30.7% versus 24.0%, respectively (P = 0.252). Logistic regression analysis showed that the number of anti-glaucoma medications and duration of therapy were key predictors of significant ocular surface Disease signs in the glaucoma group. There was no significant correlation between signs and symptoms of ocular surface Disease in either group after adjusting for age and gender. Conclusions: Signs and symptoms of ocular surface Disease are relatively common in older patients, but signs of ocular surface Disease are significantly higher in individuals who instil topical glaucoma therapy.
Hong Wang - One of the best experts on this subject based on the ideXlab platform.
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attenuated herpes simplex virus 1 hsv 1 expressing a mutant form of icp6 stimulates a strong immune response that protects mice against hsv 1 induced corneal Disease
Journal of Virology, 2018Co-Authors: David J Davido, Eleain M Tu, Andreu Gazquez Casals, Jahnu P Reddy, Heba H. Mostafa, Maria Korom, Hong WangAbstract:We previously isolated a herpes simplex virus 1 (HSV-1) mutant, KOS-NA, that carries two nonsynonymous mutations in UL39, resulting in L393P and R950H amino acid substitutions in infected cell protein 6 (ICP6). Our published data studying KOS-NA pathogenesis strongly suggest that one of these ICP6 substitutions expressed from KOS-NA, R950H, severely impaired acute viral replication in the eyes and trigeminal ganglia of mice after inoculation onto the cornea and consequently impaired establishment and reactivation from latency. Because of its significant neuroattenuation, we tested KOS-NA as a potential prophylactic vaccine against HSV-1 in a mouse model of corneal infection. KOS-NA stimulated stronger antibody and T cell responses than a replication-competent ICP0-null mutant and a replication-incompetent ICP8-null mutant optimized for immunogenicity. Immunizations with the ICP0−, ICP8−, and KOS-NA viruses all reduced replication of wild-type HSV-1 challenge virus in the corneal epithelium to similar extents. Low immunizing doses of KOS-NA and the ICP8− virus, but not the ICP0− virus, protected mice against Eyelid Disease (blepharitis). Notably, only KOS-NA protected almost completely against corneal Disease (keratitis) and greatly reduced latent infection by challenge virus. Thus, vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated Disease of the eye, even at a very low immunizing dose. These results suggest that KOS-NA may be the foundation of an effective prophylactic vaccine to prevent or limit HSV-1 ocular Diseases. IMPORTANCE HSV-1 is a ubiquitous human pathogen that infects the majority of the world's population. Although most infections are asymptomatic, HSV-1 establishes lifelong latency in infected sensory neurons, from which it can reactivate to cause deadly encephalitis or potentially blinding eye Disease. No clinically effective vaccine is available. In this study, we tested the protective potential of a neuroattenuated HSV-1 mutant (KOS-NA) as a vaccine in mice. We compared the effects of immunization with KOS-NA to those of two other attenuated viruses, a replication-competent (ICP0−) virus and a replication-incompetent (ICP8−) virus. Our data show that KOS-NA proved superior to the ICP0- and ICP8-null mutants in protecting mice from corneal Disease and latent infection. With its significant neuroattenuation, severe impairment in establishing latency, and excellent protective effect, KOS-NA represents a significant discovery in the field of HSV-1 vaccine development.
Maria Korom - One of the best experts on this subject based on the ideXlab platform.
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attenuated herpes simplex virus 1 hsv 1 expressing a mutant form of icp6 stimulates a strong immune response that protects mice against hsv 1 induced corneal Disease
Journal of Virology, 2018Co-Authors: David J Davido, Eleain M Tu, Andreu Gazquez Casals, Jahnu P Reddy, Heba H. Mostafa, Maria Korom, Hong WangAbstract:We previously isolated a herpes simplex virus 1 (HSV-1) mutant, KOS-NA, that carries two nonsynonymous mutations in UL39, resulting in L393P and R950H amino acid substitutions in infected cell protein 6 (ICP6). Our published data studying KOS-NA pathogenesis strongly suggest that one of these ICP6 substitutions expressed from KOS-NA, R950H, severely impaired acute viral replication in the eyes and trigeminal ganglia of mice after inoculation onto the cornea and consequently impaired establishment and reactivation from latency. Because of its significant neuroattenuation, we tested KOS-NA as a potential prophylactic vaccine against HSV-1 in a mouse model of corneal infection. KOS-NA stimulated stronger antibody and T cell responses than a replication-competent ICP0-null mutant and a replication-incompetent ICP8-null mutant optimized for immunogenicity. Immunizations with the ICP0−, ICP8−, and KOS-NA viruses all reduced replication of wild-type HSV-1 challenge virus in the corneal epithelium to similar extents. Low immunizing doses of KOS-NA and the ICP8− virus, but not the ICP0− virus, protected mice against Eyelid Disease (blepharitis). Notably, only KOS-NA protected almost completely against corneal Disease (keratitis) and greatly reduced latent infection by challenge virus. Thus, vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated Disease of the eye, even at a very low immunizing dose. These results suggest that KOS-NA may be the foundation of an effective prophylactic vaccine to prevent or limit HSV-1 ocular Diseases. IMPORTANCE HSV-1 is a ubiquitous human pathogen that infects the majority of the world's population. Although most infections are asymptomatic, HSV-1 establishes lifelong latency in infected sensory neurons, from which it can reactivate to cause deadly encephalitis or potentially blinding eye Disease. No clinically effective vaccine is available. In this study, we tested the protective potential of a neuroattenuated HSV-1 mutant (KOS-NA) as a vaccine in mice. We compared the effects of immunization with KOS-NA to those of two other attenuated viruses, a replication-competent (ICP0−) virus and a replication-incompetent (ICP8−) virus. Our data show that KOS-NA proved superior to the ICP0- and ICP8-null mutants in protecting mice from corneal Disease and latent infection. With its significant neuroattenuation, severe impairment in establishing latency, and excellent protective effect, KOS-NA represents a significant discovery in the field of HSV-1 vaccine development.
Stephen C Pflugfelder - One of the best experts on this subject based on the ideXlab platform.
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correlation of the schirmer 1 and fluorescein clearance tests with the severity of corneal epithelial and Eyelid Disease
Archives of Ophthalmology, 2000Co-Authors: Angelo Macri, Stephen C PflugfelderAbstract:Objective To evaluate the correlations of the fluorescein clearance test (FCT) and the Schirmer 1 test with the severity of corneal epithelial and Eyelid Disease in normal patients and patients with tear film disorders due to meibomian gland Disease (MGD) and/or aqueous tear deficiency (ATD). Methods Nineteen normal control subjects, 16 patients with MGD associated with rosacea, 21 patients with noninflammatory atrophic MGD, and 43 patients with ATD were enrolled. There was a similar age and sex distribution in each group. Each patient completed a symptom severity questionnaire that consisted of 11 questions and then underwent a panel of diagnostic tests in the following order: assessment of corneal and conjunctiva sensation with the Cochet-Bonnet esthesiometer, FCT, assessment of corneal fluorescein staining, Schirmer 1 test (5 minutes without anesthesia), and biomicroscopic examination of the Eyelid margins and meibomian glands. The FCT was performed with a fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus. By studying the best area under the receiver operating characteristic curves, we developed a formula that combined the FCT and Schirmer test results, which we termed the FCT corrected by Schirmer test. Results The FCT showed stronger correlation with ocular irritation symptoms ( r = 0.35, P r = 0.54, P Conclusions Corneal epithelial Disease is correlated with decreased aqueous tear production and delayed tear clearance, whereas Eyelid and MGD are correlated with delayed tear clearance. The FCT corrected by Schirmer 1 test improves the correlations of the FCT with ocular irritation symptoms, corneal epithelial and Eyelid pathologic signs, and corneal and conjunctival sensitivity for patients with MGD and ATD.
