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A Cationic Peptide, TAT-Cd 0 , Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Jose, Gilbert G. ; Larsen, Inna V. ; Gauger, Joshua ; [et al.]

Association for Research in Vision and Ophthalmology (ARVO) ; 2013

In: Investigative Opthalmology & Visual Science Vol. 54, No. 2 ( 2013-02-05), p. 1070-

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In: Investigative Opthalmology & Visual Science, Association for Research in Vision and Ophthalmology (ARVO), Vol. 54, No. 2 ( 2013-02-05), p. 1070-

Type of Medium: Online Resource

ISSN: 1552-5783

URL: Article

DOI: 10.1167/iovs.12-10250

Language: English

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Publication Date: 2013

detail.hit.zdb_id: 2009858-3

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Ocular Distribution, Spectrum of Activity, and In Vivo Viral Neutralization of a Fully Humanized Anti-Herpes Simplex Virus IgG Fab Fragment following Topical Application

Berdugo, Marianne ; Larsen, Inna V. ; Abadie, Claire ; [et al.]

American Society for Microbiology ; 2012

In: Antimicrobial Agents and Chemotherapy Vol. 56, No. 3 ( 2012-03), p. 1390-1402

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In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 56, No. 3 ( 2012-03), p. 1390-1402

Abstract: Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC 50 and MEC 90 , respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. The in vivo efficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, but not as much as with trifluridine (TFT). AC-8 treatment reduced viral titers but less than trifluridine. AC-8 did not display any toxicity to the cornea or other structures in the eye. In summary, topical instillation of an anti-HSV FAb can be used on both intact and ulcerated corneas. It is well tolerated and does not alter reepithelialization. Further studies to improve the antiviral effect are needed for AC-8 to be considered for therapeutic use.

Type of Medium: Online Resource

ISSN: 0066-4804 , 1098-6596

URL: Article

DOI: 10.1128/AAC.05145-11

RVK:

XA 24552

Language: English

Publisher: American Society for Microbiology

Publication Date: 2012

detail.hit.zdb_id: 1496156-8

SSG: 12

SSG: 15,3

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Insertion of the βGeo Promoter Trap into the Fem1c Gene of ROSA3 Mice

Schlamp, Cassandra L. ; Thliveris, Andrew T. ; Li, Yan ; [et al.]

Informa UK Limited ; 2004

In: Molecular and Cellular Biology Vol. 24, No. 9 ( 2004-05-01), p. 3794-3803

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In: Molecular and Cellular Biology, Informa UK Limited, Vol. 24, No. 9 ( 2004-05-01), p. 3794-3803

Type of Medium: Online Resource

ISSN: 1098-5549

URL: Article

DOI: 10.1128/MCB.24.9.3794-3803.2004

Language: English

Publisher: Informa UK Limited

Publication Date: 2004

detail.hit.zdb_id: 1474919-1

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Proteasome Inhibition Increases the Efficiency of Lentiviral Vector-Mediated Transduction of Trabecular Meshwork

Aktas, Zeynep ; Rao, Hongyu ; Slauson, Sarah R. ; [et al.]

Association for Research in Vision and Ophthalmology (ARVO) ; 2018

In: Investigative Opthalmology & Visual Science Vol. 59, No. 1 ( 2018-01-16), p. 298-

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In: Investigative Opthalmology & Visual Science, Association for Research in Vision and Ophthalmology (ARVO), Vol. 59, No. 1 ( 2018-01-16), p. 298-

Type of Medium: Online Resource

ISSN: 1552-5783

URL: Article

DOI: 10.1167/iovs.17-22074

Language: English

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Publication Date: 2018

detail.hit.zdb_id: 2009858-3

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Genomic, Phylogenetic, and Recombinational Characterization of Herpes Simplex Virus 2 Strains

Kolb, Aaron W. ; Larsen, Inna V. ; Cuellar, Jacqueline A. ; [et al.]

American Society for Microbiology ; 2015

In: Journal of Virology Vol. 89, No. 12 ( 2015-06-15), p. 6427-6434

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In: Journal of Virology, American Society for Microbiology, Vol. 89, No. 12 ( 2015-06-15), p. 6427-6434

Abstract: Herpes simplex virus 2 (HSV-2) is a major global pathogen, infecting 16% of people 15 to 49 years old worldwide and causing recurrent genital ulcers. Little is known about viral factors contributing to virulence, and there are currently only two genomic sequences available. In this study, we determined nearly complete genomic sequences of six additional HSV-2 isolates, using Illumina MiSeq. We report that HSV-2 has a genomic overall mean distance of 0.2355%, which is less than that of HSV-1. There were approximately 100 amino-acid-encoding and indels per genome. Microsatellite mapping found a bias toward intergenic regions in the nonconserved microsatellites and a genic bias in all detected tandem repeats. Extensive recombination between the HSV-2 strains was also strongly implied. This was the first study to analyze multiple HSV-2 sequences, and the data will be valuable in future evolutionary, virulence, and structure-function studies. IMPORTANCE HSV-2 is a significant worldwide pathogen, causing recurrent genital ulcers. Here we present six nearly complete HSV-2 genomic sequences, and, with the addition of two previously sequenced strains, for the first time genomic, phylogenetic, and recombination analysis was performed on multiple HSV-2 genomes. Our results show that microsatellite mapping found a bias toward intergenic regions in the nonconserved microsatellites and a genic bias in all detected tandem repeats and confirm that chimpanzee herpesvirus 1 (ChHV-1) is a separate species and that each of the HSV-2 strains is a genomic mosaic.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.00416-15

Language: English

Publisher: American Society for Microbiology

Publication Date: 2015

detail.hit.zdb_id: 1495529-5

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A Cationic TAT Peptide Inhibits Herpes Simplex Virus Type 1 Infection of Human Corneal Epithelial Cells

Larsen, Inna V. ; Brandt, Curtis R.

Mary Ann Liebert Inc ; 2010

In: Journal of Ocular Pharmacology and Therapeutics Vol. 26, No. 6 ( 2010-12), p. 541-547

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In: Journal of Ocular Pharmacology and Therapeutics, Mary Ann Liebert Inc, Vol. 26, No. 6 ( 2010-12), p. 541-547

Type of Medium: Online Resource

ISSN: 1080-7683 , 1557-7732

URL: Article

DOI: 10.1089/jop.2010.0076

Language: English

Publisher: Mary Ann Liebert Inc

Publication Date: 2010

detail.hit.zdb_id: 2049089-6

SSG: 15,3

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Disease parameters following ocular herpes simplex virus type 1 infection are similar in male and female BALB/C mice

Kolb, Aaron W. ; Ferguson, Sarah A. ; Larsen, Inna V. ; [et al.]

Public Library of Science (PLoS) ; 2023

In: PLOS ONE Vol. 18, No. 6 ( 2023-6-15), p. e0287194-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2023-6-15), p. e0287194-

Abstract: Sex related differences in the incidence or severity of infection have been described for multiple viruses. With herpes simplex viruses, the best example is HSV-2 genital infection where women have a higher incidence of infection and can have more severe infections than men. HSV-1 causes several types of infections including skin and mucosal ulcers, keratitis, and encephalitis in humans that do not appear to have a strong biological sex component. Given that mouse strains differ in their MHC loci it is important to determine if sex differences occur in multiple strains of mice. Our goal was to answer two questions: Are virus related sex differences present in BALB/C mice and does virulence of the viral strain have an effect? We generated a panel of recombinant HSV-1 viruses with differing virulence phenotypes and characterized multiple clinical correlates of ocular infection in BALB/c mice. We found no sex-specific differences in blepharitis, corneal clouding, neurovirulence, and viral titers in eye washes. Sex differences in neovascularization, weight loss and eyewash titers were observed for some recombinants, but these were not consistent across the phenotypes tested for any recombinant virus. Considering these findings, we conclude that there are no significant sex specific ocular pathologies in the parameters measured, regardless of the virulence phenotype following ocular infection in BALB/c mice, suggesting that the use of both sexes is not necessary for the bulk of ocular infection studies.

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0287194

DOI: 10.1371/journal.pone.0287194.g001

DOI: 10.1371/journal.pone.0287194.g002

DOI: 10.1371/journal.pone.0287194.g003

DOI: 10.1371/journal.pone.0287194.g004

DOI: 10.1371/journal.pone.0287194.g005

DOI: 10.1371/journal.pone.0287194.g006

DOI: 10.1371/journal.pone.0287194.g007

DOI: 10.1371/journal.pone.0287194.t001

DOI: 10.1371/journal.pone.0287194.s001

DOI: 10.1371/journal.pone.0287194.s002

DOI: 10.1371/journal.pone.0287194.s003

DOI: 10.1371/journal.pone.0287194.r001

DOI: 10.1371/journal.pone.0287194.r002

DOI: 10.1371/journal.pone.0287194.r003

DOI: 10.1371/journal.pone.0287194.r004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2023

detail.hit.zdb_id: 2267670-3

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Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Ray, Kausik K ; Colhoun, Helen M ; Szarek, Michael ; [et al.]

Elsevier BV ; 2019

In: The Lancet Diabetes & Endocrinology Vol. 7, No. 8 ( 2019-08), p. 618-628

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In: The Lancet Diabetes & Endocrinology, Elsevier BV, Vol. 7, No. 8 ( 2019-08), p. 618-628

Type of Medium: Online Resource

ISSN: 2213-8587

URL: Article

DOI: 10.1016/S2213-8587(19)30158-5

Language: English

Publisher: Elsevier BV

Publication Date: 2019

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Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

Schwartz, Gregory G. ; Szarek, Michael ; Bittner, Vera A. ; [et al.]

American Diabetes Association ; 2021

In: Diabetes Care Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227

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In: Diabetes Care, American Diabetes Association, Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227

Abstract: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P & lt; 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

Type of Medium: Online Resource

ISSN: 0149-5992 , 1935-5548

URL: Article

DOI: 10.2337/dc20-2842

Language: English

Publisher: American Diabetes Association

Publication Date: 2021

detail.hit.zdb_id: 1490520-6

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Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Schwartz, Gregory G. ; Szarek, Michael ; Bittner, Vera A. ; [et al.]

Elsevier BV ; 2021

In: Journal of the American College of Cardiology Vol. 78, No. 5 ( 2021-08), p. 421-433

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In: Journal of the American College of Cardiology, Elsevier BV, Vol. 78, No. 5 ( 2021-08), p. 421-433

Type of Medium: Online Resource

ISSN: 0735-1097

URL: Article

DOI: 10.1016/j.jacc.2021.04.102

RVK:

XA 17760

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 1468327-1

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