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Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND: Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS: To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.

Child, Preschool↗
PubMed1996

Genetic diversity of human parvovirus B19: sequence analysis of the VP1/VP2 gene from multiple isolates.

To evaluate the genetic variability of human parvovirus B19, the complete coding region of the VP1/VP2 structural proteins of 29 B19 isolates obtained from 25 infected patients were sequenced and compared with each other and with two previously published B19 isolates. The VP1/VP2 gene was amplified by PCR using B19-specific oligonucleotide primers and the amplification products were sequenced directly. Overall, the average nucleotide and predicted amino acid identity among B19 isolates was high. Sequential virus isolates from the same cases and isolates obtained from two cases linked by transmission in the same household were essentially identical. Sequence variation was minimal among isolates obtained from a single community-wide B19 outbreak, ranging between 0 and 10 (0.4%) base substitutions, although there appeared to be more than one genetic lineage circulating in the outbreak. A comparison with 18 additional isolates from distinct epidemiological settings found greater variability. These isolates differed from each other by between 11 (0.5%) and 112 (4.8%) base substitutions. B19 isolates from Xi'an, China, were significantly different from other isolates at both the nucleotide and amino acid levels, and were more closely related to a single isolate from Japan, obtained 10 years earlier, than to isolates from other countries. Isolates examined in this study included distinct genotypes from patients with similar clinical presentations and similar genotypes from patients with diverse clinical presentations. These data suggest that geographically defined genetic lineages of B19 may exist and that no particular B19 genotype was associated with a particular clinical outcome.

Adolescent↗
PubMed1996

Strain-specific reverse transcriptase PCR assay: means to distinguish candidate vaccine from wild-type strains of respiratory syncytial virus.

Candidate live-virus vaccines for respiratory syncytial virus are being developed and are beginning to be evaluated in clinical trials. To distinguish candidate vaccine strains from wild-type strains isolated during these trials, we developed PCR assays specific to two sets of candidate vaccine strains. The two sets were a group A strain (3A), its three attenuated, temperature-sensitive variant strains, a group B strain (2B), and its four attenuated, temperature-sensitive variant strains. The PCR assays were evaluated by testing 18 group A wild-type strains, the 3A strains, 9 group B wild-type strains, and the 2B strains. PCR specific to group A wild-type strains amplified only group A wild-type strains, and 3A-specific PCR amplified only 3A strains. PCR specific to group B wild-type strains amplified all group A and group B strains but gave a 688-bp product for group B wild-type strains, a 279-bp product for 2B strains, a 547-bp product for all group A strains, and an additional 688-bp product for some group A strains, including 3A strains. These types of PCR assays can, in conjunction with other methods, be used to efficiently distinguish candidate vaccine strains from other respiratory syncytial virus strains.

Base Sequence↗
PubMed1996

Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern.

Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) caused excessive disease in infants upon subsequent natural infection with RSV. Recent studies with BALB/c mice have suggested that T cells are important contributors to lung immunopathology during RSV infection. In this study, we investigated vaccine-induced enhanced disease by immunizing BALB/c mice with live RSV intranasally or with FI-RSV intramuscularly. The mice were challenged with RSV 6 weeks later, and the pulmonary inflammatory response was studied by analyzing cells obtained by bronchoalveolar lavage 4 and 8 days after challenge. FI-RSV-immunized mice had an increased number of total cells, granulocytes, eosinophils, and CD4+ cells but a decreased number of CD8+ cells. The immunized mice also had a marked increase in the expression of mRNA for the Th2-type cytokines interleukin-5 (IL-5) and IL-13 as well as some increase in the expression of IL-10 (a Th2-type cytokine) mRNA and some decrease in the expression of IL-12 (a Th1-type cytokine) mRNA. The clear difference in the pulmonary inflammatory response to RSV between FI-RSV- and live-RSV-immunized mice suggests that this model can be used to evaluate the disease-enhancing potential of candidate RSV vaccines and better understand enhanced disease.

Animals↗
PubMed1995

Analyses of homologous rotavirus infection in the mouse model.

The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild-type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus-specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge.

Animals↗
PubMed1995

Protective and disease-enhancing immune responses to respiratory syncytial virus.

The National Institutes of Health, Centers for Disease Control and Prevention, and World Health Organization jointly sponsored a workshop on protective and disease-enhancing immune responses to respiratory syncytial virus (RSV). The primary purpose of the meeting was to discuss protective and disease-enhancing immune responses to RSV in the context of opportunities and barriers to the development of RSV vaccines. Although both live attenuated and subunit vaccines have been developed, it is not yet clear if any of these vaccines will be safe and effective. The fact that neither the disease-enhancing nor the protective immune response to RSV is well understood or well characterized is an important barrier to development of these vaccines. Studies in animal model systems and newly developed immunologic tools, however, provide hope that these barriers can be overcome and a safe and effective RSV vaccine can be developed.

Animals↗
PubMed1995

Parvovirus B19 infection in hospital workers: community or hospital acquisition?

A suspected nosocomial outbreak of parvovirus B19 infection in a maternity ward was investigated in February 1994. Questionnaires were administered and sera collected from maternity ward staff (n = 91), other ward staff in the same hospital (n = 101), and maternity ward staff at a nearby hospital (n = 81). Blood donors (n = 265) were used as community controls. Recent infection (parvovirus B19 IgM positivity) in susceptible persons (parvovirus B19 IgG-negative or IgM-positive) was common among all 4 groups (23%-30%). This high rate of recent infection occurred during a large community outbreak of fifth disease. Environmental samples collected from a room where a stillborn parvovirus B19-infected fetus was delivered were positive for parvovirus B19 DNA. Thus, this suspected nosocomial outbreak actually reflected transmission outside the hospital, but contaminated environmental surfaces were identified as one potential source for transmission of parvovirus B19.

Antibodies, Viral↗
PubMed1995

Serologic evidence of an association between enteroviruses and the onset of type 1 diabetes mellitus. Pittsburgh Diabetes Research Group.

Serum was collected from 128 patients < or = 18 years of age admitted to the Children's Hospital of Pittsburgh with new-onset insulin-dependent diabetes mellitus (IDDM) and from 120 control-patients who were frequency-matched to case-patients for age, sex, and date of bleed. Serum was tested for IgM against 14 enterovirus serotypes: coxsackieviruses B1-B6 and A9, echoviruses 4, 6, 9, 11, 30, and 34, and enterovirus 71. Case-children 13-18 years of age were more likely than control-patients to be IgM-positive for 9 of 14 serotypes (P < or = .05 for each). In contrast, case-children 10-12 years of age and 1-9 years of age were each more likely than age-matched control-children to be IgM positive for 1 serotype (P < or = .05 for each). In addition, the association between IgM positivity and IDDM occurred earlier in girls than in boys. These data support an association between IDDM and enterovirus IgM positivity in older children.

Adolescent↗
PubMed1994

Immunochemiluminescent Southern blot assay for polymerase chain reaction detection of human parvovirus B19 DNA.

Human parvovirus B19 is not only an acute self-limited infection causing erythema infectiosum, transient aplastic crisis, foetal hydrops and arthritis but can also be a chronic infection causing chronic anaemia and associated with chronic neuropathy and vasculitis. Serologic studies have proven to be the most sensitive way to detect acute infection in the immunologically normal patient while polymerase chain reaction (PCR) assays for B19 DNA are the most sensitive way to detect chronic infection. The ability to detect B19 in clinical specimens can be further increased with a second amplification step using nested primers. However, nested PCR is both time consuming and enhances the risk of false-positive results due to contaminating DNA. In this study, we developed a sensitive immunochemiluminescent Southern blot assay for detecting PCR amplified B19 DNA with a digoxigenin labelled primer. The sensitivity and specificity of this assay were comparable to nested PCR and at least 100-fold more sensitive than a single PCR amplification.

Blotting, Southern↗
PubMed1994

Chemiluminescent microwell hybridization assay for direct detection of human parvovirus B19 DNA.

A method for the direct detection of human parvovirus DNA in serum samples that uses a digoxigenin-labeled RNA probe to hybridize with target B19 DNA, followed by capture of the hybrid onto a microtiter plate wells previously coated with a second oligonucleotide probe was developed. The captured hybrid is then detected with anti-digoxigenin-alkaline phosphatase conjugate and chemiluminescent substrate and the reaction read on a scintillation counter. The relative sensitivities of the microwell and standard dot blot hybridization assays were compared. The chemiluminescent microwell hybridization assay was more sensitive than dot-blot hybridization and could be performed in a few hours. This format, therefore, permits rapid and sensitive detection of parvovirus DNA suitable for the clinical setting.

Base Sequence↗
PubMed1994

Genetic heterogeneity of the attachment glycoprotein G among group A respiratory syncytial viruses.

Fifteen independent group A respiratory syncytial virus (RSV) isolates were compared by sequencing a 300-nucleotide interval encoding a variable region of the attachment glycoprotein G. The viruses compared included the reference strains Long (USA 1956), A2 (Australia 1961), and 669 (Sweden 1959), along with 13 clinical isolates obtained at different times and locations throughout the United States. Representatives of all six antigenic subgroups, recognized by reactivity patterns with monoclonal antibodies, were compared. The maximum sequence heterogeneity within the G glycoprotein region compared was 15.7% of nucleotide sequences and 26% of amino acid sequences, more than twice the difference observed between Long and A2. Half of the nucleotide changes encoded amino acid substitutions, possibly indicating that the protein interval compared was subject to immune selection. Because the ratio of nucleotide to amino acid substitutions was nearly constant for all degrees of genetic divergence, the potential range of sequence divergence among group A RSV has probably not yet been attained. There was little correlation between the patterns of reactivity against a panel of monoclonal antibodies and sequence relationships among the 15 isolates. The sequence information showed multiple genotypes circulating simultaneously in the same community and very similar genotypes circulating in widely separated communities and during different years. Genetic analyses of RSV strains can provide important information about the relationships between RSV infections.

Amino Acid Sequence↗
PubMed1994

Enterovirus 71 infections and neurologic disease--United States, 1977-1991.

Since first described in 1974, enterovirus 71 infections have been associated with severe neurologic disease, and widespread infection was suspected in 1987. To investigate enterovirus 71 activity further, data were reviewed for isolations reported nationally during 1977-1991, virology laboratories were contacted regarding isolations during 1985-1989, and medical records were reviewed for respective patients, 1985-1989. From 1977 to 1991, 193 culture-confirmed enterovirus 71 infections were identified: > or = 1 isolate each year. In 1987, 45 persons in 17 states were infected compared with a maximum of 22 persons in 1-8 states in the other years. Of these 45, 27 (60%) had the following: paralysis (6), Guillain-Barré syndrome (1), meningitis (18), or encephalitis (2). Enterovirus 71 has been endemic in the United States since at least 1977, was identified more frequently in 1987 than in other years, and continues to be an occasional cause of severe neurologic disease.

Adolescent↗
PubMed1994

Echovirus 30 infection and aseptic meningitis in parents of children attending a child care center.

In July 1992, 13 parents with children attending a child care center (CCC) developed aseptic meningitis (AM) due to echovirus 30 (E30). To determine the extent of illness and risk factors for transmission, survey and blood specimens were collected from CCC families and teachers and from adult and pediatric controls. Infection was defined as the presence of anti-E30 IgM antibodies. CCC parents (60%, 67/111) and children (75%, 79/105) had significantly higher infection rates than did teachers (14%, 3/22), adult controls (24%, 10/41), and pediatric controls (24%, 17/70). Infected CCC parents had more severe illness (18% [12/65] had AM; 11% [7/65] were hospitalized) than did infected CCC children (3% [2/79] had AM and 1% [1/79] were hospitalized). More frequent handwashing among teachers compared with parents and among mothers of toddlers was associated with significantly lower rates of infection (P < or = .05). Education of parents about good handwashing practices may reduce transmission of E30 and other infectious agents from children to adults.

Adult↗
PubMed1994

Antigenic analysis of current wild type and vaccine strains of measles virus.

The antigenic properties of vaccine and wild type strains of measles virus were compared. Serum specimens from vaccinated persons, persons infected during the prevaccine era, or mice experimentally vaccinated with the hemagglutinin (H) protein from vaccine virus neutralized vaccine virus and a wild type measles virus from 1989 equally well. In contrast, serum specimens from patients with recent measles virus infection and mice experimentally vaccinated with the H protein from the wild type virus from 1989 neutralized wild type virus with titers 4-8 times higher than those to vaccine virus. Several H protein-specific monoclonal antibodies could differentially recognize vaccine or wild type virus. These data show that the H proteins of the recent wild type viruses contain both conserved and new or modified antigenic determinants and are consistent with previous studies that described genetic drift in the H proteins of recent wild type viruses.

Animals↗
PubMed1994

National surveillance for respiratory syncytial virus, United States, 1985-1990.

Respiratory syncytial virus (RSV) causes pneumonia and bronchiolitis in infants and young children and serious disease in the elderly and persons with compromised immune systems. To determine the temporal and geographic patterns of RSV outbreaks in the United States, monthly reports from 74 laboratories were analyzed for July 1985 through June 1990. RSV outbreaks were identified in 197 (93%) of the 211 laboratory years analyzed, with widespread activity beginning each fall, peaking in winter, and returning to baseline in April or May. Each year, the timing of outbreaks did not differ significantly between most regions; the few differences were small, and no region consistently had early or late outbreaks. These findings are consistent with RSV transmission within communities rather than between communities or regions. Health care personnel should consider the possibility of RSV infection in their treatment and prevention efforts from November through April each year in the United States.

Aged↗
PubMed1994

Cytokine response to respiratory syncytial virus stimulation of human peripheral blood mononuclear cells.

A key impediment to developing respiratory syncytial virus (RSV) vaccines is a lack of understanding of enhanced disease that occurred in children who received a formalin-inactivated RSV (FI-RSV) vaccine. Studies in mice have suggested that the FI-RSV vaccine induces a TH2 and live RSV induces a TH1 memory T cell response. In this study, the cytokine mRNA response of peripheral blood mononuclear cells (PBMC) from adults and children with and without previous RSV infection was characterized using a semiquantitative polymerase chain reaction (PCR). PBMC from 22 subjects previously infected with RSV usually had RSV-specific increases in TH1 cytokine-specific mRNA (interferon-gamma [IFN-gamma] mRNA, 20; interleukin [IL]-2 mRNA, 12; IL-5 mRNA, 6; and IL-4 mRNA, 0). PBMC from RSV antibody-negative children had no RSV-specific increases in IFN-gamma, IL-2, or IL-4 mRNA; 1 of 7 had an increase in IL-5 mRNA. These data indicate that naturally acquired RSV induces a TH1 memory T cell response.

Adolescent↗