Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Hofstetter J [original query] |
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Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival
De La Cruz JA , Ganesh T , Diebold BA , Cao W , Hofstetter A , Singh N , Kumar A , McCoy J , Ranjan P , Smith SME , Sambhara S , Lambeth JD , Gangappa S . PLoS One 2021 16 (7) e0254632 Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44. |
Oxidative stress pathway gene transcription after bovine respiratory syncytial virus infection in vitro and ex vivo.
Hofstetter AR , Sacco RE . Vet Immunol Immunopathol 2019 219 109956 Studies in mouse and lamb models indicate important roles of reactive oxygen species (ROS) in the pathology and immune response to respiratory syncytial virus (RSV). The role of ROS in bovine RSV (BRSV) infection of calves remains unclear. BRSV naturally infects calves, leading to similar disease course, micro- and macro-lesions, and symptomology as is observed in RSV infection of human neonates. Furthermore, humans, lambs, and calves, but not mice, have an active lung oxidative system involving lactoperoxidase (LPO) and the dual oxidases (DUOX) 1 and 2. To gain insight into the role of ROS in the BRSV-infected lung, we examined gene expression in infected bovine cells using qPCR. A panel of 19 primers was used to assay ex vivo and in vitro BRSV-infected cells. The panel targeted genes involved in both production and regulation of ROS. BRSV infection significantly increased transcription of five genes in bovine respiratory tract cells in vitro and ex vivo. PTGS2 expression more than doubled in both sample types. Four transcripts varied significantly in lung lesions, but not non-lesion samples, compared with uninfected lung. This is the first report of the transcriptional profile of ROS-related genes in the airway after BRSV infection in the natural host. |
Mitochondrial Junction Region as Genotyping Marker for Cyclospora cayetanensis.
Nascimento FS , Barta JR , Whale J , Hofstetter JN , Casillas S , Barratt J , Talundzic E , Arrowood MJ , Qvarnstrom Y . Emerg Infect Dis 2019 25 (7) 1314-1319 Cyclosporiasis is an infection caused by Cyclospora cayetanensis, which is acquired by consumption of contaminated fresh food or water. In the United States, cases of cyclosporiasis are often associated with foodborne outbreaks linked to imported fresh produce or travel to disease-endemic countries. Epidemiologic investigation has been the primary method for linking outbreak cases. A molecular typing marker that can identify genetically related samples would be helpful in tracking outbreaks. We evaluated the mitochondrial junction region as a potential genotyping marker. We tested stool samples from 134 laboratory-confirmed cases in the United States by using PCR and Sanger sequencing. All but 2 samples were successfully typed and divided into 14 sequence types. Typing results were identical among samples within each epidemiologically defined case cluster for 7 of 10 clusters. These findings suggest that this marker can distinguish between distinct case clusters and might be helpful during cyclosporiasis outbreak investigations. |
Genotyping Genetically Heterogeneous Cyclospora cayetanensis Infections to Complement Epidemiological Case Linkage.
Barratt JLN , Park S , Nascimento FS , Hofstetter J , Plucinski M , Casillas S , Bradbury RS , Arrowood MJ , Qvarnstrom Y , Talundzic E . Parasitology 2019 146 (10) 1-33 Sexually reproducing pathogens such as Cyclospora cayetanensis often produce genetically heterogeneous infections where the number of unique sequence types detected at any given locus varies depending on which locus is sequenced. The genotypes assigned to these infections quickly become complex when additional loci are analysed. This genetic heterogeneity confounds the utility of traditional sequence-typing and phylogenetic approaches for aiding epidemiological trace-back, and requires new methods to address this complexity. Here, we describe an ensemble of two similarity-based classification algorithms, including a Bayesian and heuristic component that infer the relatedness of C. cayetanensis infections. The ensemble requires a set of haplotypes as input and assigns arbitrary distances to specimen pairs reflecting their most likely relationships. The approach was applied to data generated from a test cohort of 88 human fecal specimens containing C. cayetanensis, including 30 from patients whose infections were associated with epidemiologically defined outbreak clusters of cyclosporiasis. The ensemble assigned specimens to plausible clusters of genetically related infections despite their complex haplotype composition. These relationships were corroborated by a significant number of epidemiological linkages (P < 0.0001) suggesting the ensemble's utility for aiding epidemiological trace-back investigations of cyclosporiasis. |
Evaluation of Multilocus Sequence Typing of Cyclospora cayetanensis based on microsatellite markers.
Hofstetter JN , Nascimento FS , Park S , Casillas S , Herwaldt BL , Arrowood MJ , Qvarnstrom Y . Parasite 2019 26 3 Cyclospora cayetanensis is a human parasite transmitted via ingestion of contaminated food or water. Cases of C. cayetanensis infection acquired in the United States often go unexplained, partly because of the difficulties associated with epidemiologic investigations of such cases and the lack of genotyping methods. A Multilocus Sequence Typing (MLST) method for C. cayetanensis based on five microsatellite loci amplified by nested PCR was described in 2016. The MLST loci had high variability, but many specimens could not be assigned a type because of poor DNA sequencing quality at one or more loci. We analyzed Cyclospora-positive stool specimens collected during 1997-2016 from 54 patients, including 51 from the United States. We noted limited inter-specimen variability for one locus (CYC15) and the frequent occurrence of unreadable DNA sequences for two loci (CYC3 and CYC13). Overall, using the remaining two loci (CYC21 and CYC22), we detected 17 different concatenated sequence types. For four of five clusters of epidemiologically linked cases for which we had specimens from >1 case-patient, the specimens associated with the same cluster had the same type. However, we also noted the same type for specimens that were geographically and temporally unrelated, indicating poor discriminatory power. Furthermore, many specimens had what appeared to be a mixture of sequence types at locus CYC22. We conclude that it may be difficult to substantially improve the performance of the MLST method because of the nucleotide repeat features of the markers, along with the frequent occurrence of mixed genotypes in Cyclospora infections. |
Risk of rotavirus nosocomial spread after inpatient pentavalent rotavirus vaccination
Hofstetter AM , Lacombe K , Klein EJ , Jones C , Strelitz B , Jacobson E , Ranade D , Ward ML , Mijatovic-Rustempasic S , Evans D , Wikswo M , Bowen MD , Parashar UD , Payne DC , Englund JA . Pediatrics 2017 141 (1) BACKGROUND: Infants born prematurely or with underlying conditions are at increased risk of severe rotavirus disease and associated complications. Given the theoretical risk of nosocomial transmission of vaccine-type rotavirus, rotavirus vaccination is recommended for infants at or after discharge from neonatal care settings. Because the first dose should be administered by 104 days of age, some infants may be age-ineligible for vaccination if delayed until discharge. METHODS: This prospective cohort included infants admitted to an urban academic medical center between birth and 104 days who received care in intensive care settings. Pentavalent human-bovine reassortant rotavirus vaccine (RV5) was used, per routine clinical care. Stool specimens were collected weekly (February 2013-April 2014) and analyzed for rotavirus strains using real-time reverse transcription-polymerase chain reaction. Demographic and vaccine data were collected. RV5 safety was not assessed. RESULTS: Of 385 study infants, 127 were age-eligible for routine vaccinations during hospitalization. At discharge, 32.7% were up-to-date for rotavirus vaccination, compared with 82.7% for other vaccinations. Of rotavirus-unvaccinated infants, 42.6% were discharged at age >104 days and thus vaccination-ineligible. Of 1192 stool specimens collected, rotavirus was detected in 13 (1.1%): 1 wild-type strain from an unvaccinated infant; 12 vaccine-type strains from 9 RV5-vaccinated infants. No vaccine-type rotavirus cases were observed among unvaccinated infants (incidence rate: 0.0 [95% confidence interval: 0.0-1.5] cases per 1000 patient days at risk). CONCLUSIONS: These data suggest that delaying rotavirus vaccination until discharge from the hospital could lead to missed vaccination opportunities and may be unnecessary in institutions using RV5 with comparable infection control standards. |
Rapamycin does not impede survival or induction of antibody responses to primary and heterosubtypic influenza infections in mice
Liepkalns JS , Pandey A , Hofstetter AR , Kumar A , Jones EN , Cao W , Liu F , Levine MZ , Sambhara S , Gangappa S . Viral Immunol 2016 29 (8) 487-493 Impairment of immune defenses can contribute to severe influenza infections. Rapamycin is an immunosuppressive drug often used to prevent transplant rejection and is currently undergoing clinical trials for treating cancers and autoimmune diseases. We investigated whether rapamycin has deleterious effects during lethal influenza viral infections. We treated mice with two concentrations of rapamycin and infected them with A/Puerto Rico/8/1934 (A/PR8), followed by a heterosubtypic A/Hong Kong/1/68 (A/HK68) challenge. Our data show similar morbidity, mortality, and lung viral titer with both rapamycin treatment doses compared to untreated controls, with a delay in morbidity onset in rapamycin high dose recipients during primary infection. Rapamycin treatment at high dose also led to increase in percent cytokine producing T cells in the spleen. However, all infected animals had similar serum antibody responses against A/PR8. Post-A/HK68 challenge, rapamycin had no impeding effect on morbidity or mortality and had similar serum antibody levels against A/PR8 and A/HK68. We conclude that rapamycin treatment does not adversely affect morbidity, mortality, or antibody production during lethal influenza infections. |
RIG-I ligand enhances the immunogenicity of recombinant H7HA protein
Cao W , Liepkalns JS , Kamal RP , Reber AJ , Kim JH , Hofstetter AR , Amoah S , Stevens J , Ranjan P , Gangappa S , York IA , Sambhara S . Cell Immunol 2016 304-305 55-8 Avian H7N9 influenza virus infection with fatal outcomes continues to pose a pandemic threat and highly immunogenic vaccines are urgently needed. In this report we show that baculovirus-derived recombinant H7 hemagglutinin protein, when delivered with RIG-I ligand, induced enhanced antibody and T cell responses and conferred protection against lethal challenge with a homologous H7N9 virus. These findings indicate the potential utility of RIG-I ligands as vaccine adjuvants to increase the immunogenicity of recombinant H7 hemagglutinin. |
NADPH oxidase 1 is associated with altered host survival and t cell phenotypes after influenza A virus infection in mice
Hofstetter AR , De La Cruz JA , Cao W , Patel J , Belser JA , McCoy J , Liepkalns JS , Amoah S , Cheng G , Ranjan P , Diebold BA , Shieh WJ , Zaki S , Katz JM , Sambhara S , Lambeth JD , Gangappa S . PLoS One 2016 11 (2) e0149864 The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. |
A highly immunogenic vaccine against A(H7N9) influenza virus
Cao W , Liepkalns J , Hassan AO , Kamal R , Hofstetter AR , Amoah S , Kim JH , Reber A , Stevens J , Katz JM , Gangappa S , York I , Mittal SK , Sambhara S . Vaccine 2016 34 (6) 744-9 Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/(H7N9) viral challenge suggesting its potential utility as a pandemic vaccine. |
Text message reminders for timely routine MMR vaccination: a randomized controlled trial
Hofstetter AM , DuRivage N , Vargas CY , Camargo S , Vawdrey DK , Fisher A , Stockwell MS . Vaccine 2015 33 (43) 5741-5746 OBJECTIVE: Measles-mumps-rubella (MMR) vaccination is important for preventing disease outbreaks, yet pockets of under-vaccination persist. Text message reminders have been employed successfully for other pediatric vaccines, but studies examining their use for MMR vaccination are limited. This study assessed the impact of text message reminders on timely MMR vaccination. STUDY DESIGN: Parents (n=2054) of 9.5-10.5-month-old children from four urban academically-affiliated pediatric clinics were randomized to scheduling plus appointment text message reminders, appointment text message reminder-only, or usual care. The former included up to three text reminders to schedule the one-year preventive care visit. Both text messaging arms included a text reminder sent 2 days before that visit. Outcomes included appointment scheduling, appointment attendance, and MMR vaccination by age 13 months, the standard of care at study sites. RESULTS: Children of parents in the scheduling plus appointment text message reminders arm were more likely to have a scheduled one-year visit than those in the other arms (71.9% vs. 67.4%, relative risk ratio (RRR) 1.07 [95% CI 1.005-1.13]), particularly if no appointment was scheduled before randomization (i.e., no baseline appointment) (62.1% vs. 54.7%, RRR 1.14 [95% CI 1.04-1.24]). One-year visit attendance and timely MMR vaccination were similar between arms. However, among children without a baseline appointment, those with parents in the scheduling plus appointment text message reminders arm were more likely to undergo timely MMR vaccination (61.1% vs. 55.1%, RRR 1.11 [95% CI 1.01-1.21]). CONCLUSION: Text message reminders improved timely MMR vaccination of high-risk children without a baseline one-year visit. |
Parental and provider preferences and concerns regarding text message reminder/recall for early childhood vaccinations
Hofstetter AM , Vargas CY , Kennedy A , Kitayama K , Stockwell MS . Prev Med 2013 57 (2) 75-80 OBJECTIVE: To assess parental, provider, and medical staff opinions about text message reminder/recall for early childhood vaccination. METHODS: A cross-sectional survey was conducted between January and March 2011 among 200 parents of 6-59month-old children, 26 providers, and 20 medical staff at four academically-affiliated pediatric practices in New York City with text messaging experience. Survey questions addressed interest in, preferences for, and concerns/barriers related to vaccine-related text message reminder/recall. RESULTS: Parents were primarily Latino, Spanish-speaking, and had a high school education or less. Most parents owned a text message-enabled cell phone (89%) and used text messaging services (97%). While 84% had never received health-related text messages, 88% were comfortable receiving them. Nearly all parents reported interest in receiving reminder/recall text messages, many endorsing them over phone calls and/or letters. Preferences included personalization, interactivity, and multiple messages. While 25% of parents had no concerns, 38% were concerned about incorrect numbers; only 6% worried about cost. Providers and staff were also supportive of vaccine-related text messages. Their biggest concerns were correct cell phone numbers, appointment availability, and increased call volume. CONCLUSION: Text message reminder/recall for early childhood vaccination was widely supported. Important barriers were identified that should be addressed to maximize their effectiveness. |
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