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Biomedical subjects

R C Welliver

Publications and source records attributed to R C Welliver.

At least 55 records · Page 3Linked to original sources
PubMed1989

Respiratory syncytial virus-specific antibody responses in immunoglobulin A and E isotypes to the F and G proteins and to intact virus after natural infection.

We studied the antibody response to the fusion (F) and attachment (G) proteins of respiratory syncytial virus and to purified intact virus in the respiratory secretions of 29 infants and children. The goal of the study was to determine whether the immune response to either of the glycoproteins occurred predominantly in the immunoglobulin A (IgA) as opposed to the IgE isotype, which would indicate that one protein subunit would be a better candidate as a potential vaccine. Antibody responses were determined by using an enzyme-linked immunosorbent assay with purified F and G proteins and sucrose gradient-purified intact virus as targets. Infants and children were capable of developing an antibody response in both the IgA and IgE isotypes to each target antigen. The magnitude of the antibody response to the F protein was essentially similar to that to the intact virus, while responses to the G protein were diminished in infants. A slightly more favorable ratio of IgA to IgE responses was observed against the F protein in comparison to the G protein. While neither protein subunit had the ideal characteristics of inducing an IgA response in the absence of an IgE response, the F protein seems to be a better candidate for use as a vaccine, on the basis of better IgA/IgE ratios.

Antibodies, Viral↗
PubMed1988

Detection, pathogenesis, and therapy of respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood. The unique pathogenesis of lower respiratory illness due to RSV offers some intriguing clues to the role of the human immune system in both protection against and development of respiratory illness. More than any other virus, rapid diagnostic techniques have been especially successful in identifying RSV infection. Many of these techniques could be easily adaptable to diagnosis of influenza virus infection and other agents. Finally, ribavirin therapy of RSV infection represents one of the few instances in which antiviral therapy has been shown to be effective for respiratory illnesses. Fundamental observations in these areas in the case of RSV infection open up new and exciting pathways for investigation of respiratory infection due to other viral, chlamydial, and mycoplasmal agents.

Child, Preschool↗
PubMed1988

Immunology of respiratory viral infections.

Viral infections of the respiratory tract represent a major cause of morbidity and inconvenience in all age groups. In addition, several thousand deaths can be attributed annually to these infections, especially those occurring at the extremes of age. Knowledge of the nature of the immune response in the respiratory tract is essential to vaccine development and to understanding disease pathogenesis. This chapter describes advances in our understanding of how the immune system contributes to eradication of infection, prevention of subsequent infection, and pathogenesis of disease itself.

Antibody Formation↗
PubMed1988

The release of leukotrienes in the respiratory tract during infection with respiratory syncytial virus: role in obstructive airway disease.

Samples of nasopharyngeal secretions from a group of 73 infants with bronchiolitis or upper respiratory illness alone during infection with respiratory syncytial virus were analyzed for leukotriene C4 (LTC4) content using a reverse-phase high-pressure liquid chromatography assay with confirmation by radioimmunoassay. Titers of respiratory syncytial virus (RSV)-specific IgE in nasopharyngeal secretion (NPS) specimens were determined using an enzyme-linked immunosorbent assay. The highest concentrations of LTC4 were found in the first 3 to 8 days after the onset of illness, and LTC4 was detectable in progressively lower concentrations in samples obtained up to 28 days after the onset of illness. LTC4 was detected in samples of NPS obtained in the acute phase of illness from 67% of infants with bronchiolitis due to RSV and in 33% of samples of NPS obtained during the same interval from infants with upper respiratory illness alone (p less than 0.025). Concentrations of LTC4 in children with bronchiolitis were 5-fold higher (1271 pg/ml) than the mean concentration of LTC4 in children with upper respiratory illness (224 pg/ml, p less than 0.02). LTC4 was detected in 83% of the children developing an RSV-IgE response and in 24% of subjects not developing an RSV-IgE response (p less than 0.001). Quantities of LTC4 measured in NPS were directly correlated with the magnitude of the RSV-IgE response in secretions (r = 0.33, p less than 0.02). These studies lend support to previous investigations suggesting that severe bronchiolitis due to RSV results from IgE-mediated hypersensitivity reactions to viral antigens, with release of chemical mediators of airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Parainfluenza virus bronchiolitis. Epidemiology and pathogenesis.

An investigation of the epidemiology and pathogenesis of bronchiolitis due to parainfluenza virus (PV) was carried out. Bronchiolitis due to PV occurred most commonly in non-Caucasian males. Breast-fed infants exhibited a reduced risk of developing bronchiolitis. Once an episode of PV bronchiolitis occurred, both exposure to cigarette smoke and bottle feeding were associated with an increased frequency of recurrent wheezing, and subsequent infection with respiratory virus almost uniformly resulted in wheezing. Cell-mediated immune responses to PV antigen and titers of PV-specific IgE were greater among patients with bronchiolitis than among patients with upper respiratory tract infection. The epidemiology and pathogenesis of bronchiolitis due to PV is similar to that of respiratory syncytial virus. Lower respiratory tract infection may predispose to episodes of bronchoconstriction on subsequent exposure to cigarette smoke or other viral infections.

Antigens, Viral↗
PubMed1986

Predictive value of respiratory syncytial virus-specific IgE responses for recurrent wheezing following bronchiolitis.

To determine whether the magnitude of the respiratory syncytial virus (RSV)-specific IgE response at the time of an episode of RSV bronchiolitis in infancy accurately predicts the development of subsequent wheezing episodes, we observed 38 infants prospectively from the time of an episode of infantile bronchiolitis through 48 months of age. Peak RSV-IgE titers were measured at the time of the bronchiolitis episode using an ELISA procedure. Notation was made of both the number of subsequent wheezing episodes reported by parents and the number documented by a physician. Subsequent wheezing was documented by a physician in 20% of infants who did not develop an RSV-IgE response at the time of the bronchiolitis episode and in 70% of those with the highest responses (P less than 0.025). These results suggest that the magnitude of the RSV-IgE response at the time of RSV bronchiolitis is a useful prognostic indicator for recurrent wheezing.

Antibody Specificity↗
PubMed1985

Respiratory syncytial virus-specific IgE responses following infection: evidence for a predominantly mucosal response.

In order to determine whether IgE production occurs predominantly at mucosal or systemic sites, we studied the production of respiratory syncytial virus (RSV)-specific antibody in serum and nasopharyngeal secretions (NPS) from 41 patients with RSV infection using an enzyme-linked immunosorbent assay. RSV-IgE was found in higher titer in samples of NPS than in simultaneously obtained serum specimens at all phases of illness. Despite the excess dilution incurred in the collection process, RSV-IgE was frequently detected in NPS specimens while it was undetectable in serum. In 20 selected subjects, ratios of RSV antibody in NPS:serum were 2.00 for RSV-IgE, 2.42 for RSV-IgA, and 0.01 for RSV-IgG. Also the geometric mean value of ratios of RSV-IgE:RSV-IgG was 1.74 in NPS and 0.05 in serum, while the geometric mean value of ratios of RSV-IgA:RSV-IgG were 1.85 in NPS and 0.09 in serum. These data suggest that IgE production occurs predominantly at mucosal surfaces.

Antibodies, Viral↗
PubMed1985

Defective regulation of immune responses in croup due to parainfluenza virus.

In order to determine if defects in regulation of immune responses play a role in the pathogenesis of croup, we studied 37 infants and children with either croup or upper respiratory illness alone due to parainfluenza virus (PV). PV-specific IgE responses were determined by an enzyme-linked immunosorbent assay, cell-mediated immune responses to PV antigen were studied by in vitro lymphocyte transformation assays, and suppressor cell function was determined by addition of histamine to lymphocyte transformation assays. In comparison to patients with upper respiratory illness alone, patients with croup had increased production of PV-specific IgE antibody, increased lymphoproliferative responses to PV antigen, and diminished histamine-induced suppression of lymphocyte transformation responses to PV. These results suggest that a defect in suppressor function exists among croup patients. Similar defects have been demonstrated in bronchiolitis and atopic diseases, providing an immunologic link between the three illnesses.

Antibody Formation↗
PubMed1984

Unique epidemiology of nosocomial infection in a children's hospital.

A prospective study of the epidemiology of nosocomial infections was undertaken in a large pediatric hospital. Infections were identified during a 12-month period with the use of medical record audits, indices identifying high-risk patients, and analysis of positive cultures and rapid diagnostic tests for viruses, fungi, and bacteria. The attack rate of the entire hospital population surveyed was 4.1 nosocomial infections per 100 patients discharged. In contrast with studies of patients in general hospitals that included comparatively few children, the most common sites of nosocomial infections were the respiratory and gastrointestinal tracts. Staphylococcus aureus was the most commonly isolated pathogen. However, rotavirus was identified more frequently than Escherichia coli, and documented viral infections were more common than infections caused by gram-negative bacilli.

Child↗
PubMed1984

Defective regulation of immune responses in respiratory syncytial virus infection.

The relationship of suppressor cell numbers and function to virus-specific IgE response was determined in 72 infants with respiratory syncytial virus (RSV) infection. Monoclonal antibodies to membrane antigens were used to enumerate OKT4 and OKT8 antigen-positive cells, and suppressor cell function as quantitated by the degree of suppression of lymphocyte mitogenesis induced by incubation of lymphocyte cultures with histamine. Patients with bronchiolitis had fewer OKT8-positive cells during convalescence than patients with other forms of illness due to RSV (p less than 0.05). An inverse correlation of OKT8-positive cell numbers and peak IgE titers was observed (p less than 0.01). Histamine-induced suppression was also reduced in patients with bronchiolitis (p less than 0.05). In patients with repeated infection, improved histamine-induced suppression was associated with reduced virus-specific IgE titers and the absence of wheezing. Defects in immunoregulation may underlie previously recognized immunologic and pharmacologic abnormalities in patients with bronchiolitis.

Acute Disease↗