A novel gamma radiation-inactivated sabin-based polio vaccine.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts.

Development of a Rhinovirus Inoculum Using a Reverse Genetics Approach.

Background: Experimental inoculation is an important tool for common cold and asthma research. Producing rhinovirus (RV) inocula from nasal secretions has required prolonged observation of the virus donor to exclude extraneous pathogens. We produced a RV-A16 inoculum using reverse genetics and determined the dose necessary to cause moderate colds in seronegative volunteers.

Self-administered acupressure for treating adult psychiatric patients with constipation: a randomized controlled trial.

Background: Constipation has a high prevalence rate (>30 %) in psychiatric patients with psychotropic drugs. Common pharmacological and non-pharmacological interventions for constipation might have longer-term negative and adverse effects that would outweigh their short-term efficacy in symptom reduction. This randomized controlled trial aims to investigate the effect of self-administered acupressure for the management of constipation, in hospitalized psychiatric patients.

Reverse genetics system for studying human rhinovirus infections.

Human rhinovirus (HRV) contains a 7.2 kb messenger-sense RNA genome which is the template for reproducing progeny viruses after it enters the cytoplasm of a host cell. Reverse genetics refers to the regeneration of progeny viruses from an artificial cDNA copy of the RNA genome of an RNA virus.

Infectivity assays of human rhinovirus-A and -B serotypes.

Infectivity is a fundamental property of viral pathogens such as human rhinoviruses (HRVs). This chapter describes two methods for measuring the infectivity of HRV-A and -B serotypes: end point dilution (TCID50) assay and plaque assay. End point dilution assay is a quantal, not quantitative, assay that determines the dilution of the sample at which 50 % of the aliquots have infectious virus.

Growth of human rhinovirus in H1-HeLa cell suspension culture and purification of virions.

HeLa cell culture is the most widely used system for in vitro studies of the basic biology of human rhinovirus (HRV). It is also useful for making sufficient quantities of virus for experiments that require highly concentrated and purified virus. This chapter describes the protocols for producing a large amount of HeLa cells in suspension culture, using these cells to grow a large quantity of virus of HeLa-adapted HRV-A and -B serotypes, and making highly concentrated virus stock and highly purified virions.

Molecular identification and quantification of human rhinoviruses in respiratory samples.

PCR-based molecular assays have become standard diagnostic procedures for the identification and quantification of human rhinoviruses (HRVs) and other respiratory pathogens in most, if not all, clinical microbiology laboratories. Molecular assays are significantly more sensitive than traditional culture-based and serological methods. This advantage has led to the recognition that HRV infections are common causes for not only upper airway symptoms but also more severe lower respiratory illnesses.

Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations.

Background: Detection of either viral or bacterial pathogens is associated with wheezing in children; however, the influence of both bacteria and viruses on illness symptoms has not been described.

Objective: We evaluated bacterial detection during the peak rhinovirus season in children with and without asthma to determine whether an association exists between bacterial infection and the severity of rhinovirus-induced illnesses.

Methods: Three hundred eight children (166 with asthma and 142 without asthma) aged 4 to 12 years provided 5 consecutive weekly nasal samples during September and scored cold and asthma symptoms daily.

Comparison of viral load in individuals with and without asthma during infections with rhinovirus.

Rationale: Most virus-induced attacks of asthma are caused by rhinoviruses (RVs).

Objectives: To determine whether people with asthma are susceptible to an increased viral load during RV infection.

Methods: Seventy-four children (4-18 yr old) were enrolled; 28 with wheezing, 32 with acute rhinitis, and 14 without respiratory tract symptoms.

Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions.

Rationale: Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined.

Objectives: To determine whether acute wheezing exacerbations due to HRV-C are associated with increased hospital attendances due to acute respiratory illnesses (ARIs).

Methods: Clinical information and nasal samples were collected prospectively from 197 children less than 5 years of age, presenting to hospital with an acute wheezing episode.

Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression.

Background: Eosinophils in asthmatic airways are associated with risk of exacerbations. The most common cause of asthma exacerbations is viral respiratory infections, particularly human rhinovirus (HRV).

Objective: To determine the mechanism by which eosinophils may influence virus-induced responses.

Detection of viruses in young children with fever without an apparent source.

Objective: Fever without an apparent source is common in young children. Currently in the United States, serious bacterial infection is unusual. Our objective was to determine specific viruses that might be responsible.

Comparison of the etiology of viral respiratory illnesses in inner-city and suburban infants.

Background: The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct.

Methods: We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin.

Human rhinovirus species and season of infection determine illness severity.

Rationale: Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses.

Objectives: To identify factors that influence the severity of HRV illnesses.

Methods: HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection.

Prevalence of and risk factors for human rhinovirus infection in healthy aboriginal and non-aboriginal Western Australian children.

Background: Human rhinovirus (HRV) species C (HRV-C) have been associated with frequent and severe acute lower respiratory infections and asthma in hospitalized children. The prevalence of HRV-C among healthy children and whether this varies with ethnicity is unknown.

Objective: To describe the prevalence of HRV species and their associations with demographic, environmental and socioeconomic factors in healthy Aboriginal and non-Aboriginal children.

Increased H1N1 infection rate in children with asthma.

Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009-2010 flu season.

Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma.

Methods: One hundred and eighty children, 4-12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily.

Negative control of TLR3 signaling by TICAM1 down-regulation.

Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 (TICAM1, also called TRIF) is an important adaptor protein in TLR3 and TLR4 signaling pathways that mediate proinflammatory cytokine and IFN responses. Negative regulation of TICAM1 by exogenous viral protease or by endogenous caspase and proteasome have been reported to shut down TICAM1-mediated signaling. In this study, we discovered that down-regulation of TICAM1, but not other components in this signaling pathway, occurred in a natural process of TLR3 activation induced by double-stranded RNA or human rhinovirus (RV) infection in airway epithelial cells and various other cell types.

Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.

Rationale: Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood.

Objective: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing.

Methods: A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth.

Pseudomonas aeruginosa suppresses interferon response to rhinovirus infection in cystic fibrosis but not in normal bronchial epithelial cells.

Despite increased morbidity associated with secondary respiratory viral infections in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, the underlying mechanisms are not well understood. Here, we investigated the effect of P. aeruginosa infection on the innate immune responses of bronchial epithelial cells to rhinovirus (RV) infection.

Lower airway rhinovirus burden and the seasonal risk of asthma exacerbation.

Rationale: Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds.

Objectives: To evaluate viral strain and load in a prospective asthma cohort during a natural cold.

Real-world comparison of two molecular methods for detection of respiratory viruses.

Background: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories.

Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C.

A recently recognized human rhinovirus species C (HRV-C) is associated with up to half of HRV infections in young children. Here we propagated two HRV-C isolates ex vivo in organ culture of nasal epithelial cells, sequenced a new C15 isolate and developed the first, to our knowledge, reverse genetics system for HRV-C. Using contact points for the known HRV receptors, intercellular adhesion molecule-1 (ICAM-1) and low-density lipoprotein receptor (LDLR), inter- and intraspecies footprint analyses predicted a unique cell attachment site for HRV-Cs.

An RNA replication-center assay for high content image-based quantifications of human rhinovirus and coxsackievirus infections.

Background: Picornaviruses are common human and animal pathogens, including polio and rhinoviruses of the enterovirus family, and hepatitis A or food-and-mouth disease viruses. There are no effective countermeasures against the vast majority of picornaviruses, with the exception of polio and hepatitis A vaccines. Human rhinoviruses (HRV) are the most prevalent picornaviruses comprising more than one hundred serotypes.