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Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice.

BALB/c mice sensitized to vaccinia virus expressed G protein of respiratory syncytial virus (RSV) develop a Th2-type cytokine response and pulmonary eosinophilia when challenged with live RSV. In this study, BALB/c mice were immunized or challenged with an RSV mutant lacking the G and SH proteins or with DNA vaccines coding for RSV G or F protein. F or G protein DNA vaccines were capable of sensitizing for pulmonary eosinophilia. The absence of the G and/or SH protein in the infecting virus resulted in a consistent increase both in pulmonary natural killer cells and in gamma interferon and tumor necrosis factor expression, as well as, with primary infection, a variable increase in neutrophils and CD11b(+) cells. The development of pulmonary eosinophilia in formalin-inactivated RSV-vaccinated mice required the presence of the G and/or SH protein in the challenge virus. These data show that G and/or SH protein has a marked impact on the inflammatory and innate immune response to RSV infection.

Animals↗
PubMed1998

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Adolescent↗
PubMed1998

Antigenic and genetic diversity among the attachment proteins of group A respiratory syncytial viruses that have caused repeat infections in children.

Antigenic differences between the two major groups of respiratory syncytial (RS) virus may contribute to reinfections with these viruses. Additional variability occurs within the two major groups; the importance of intra-group variability in reinfections with RS virus has not been defined. Two pairs of group A viruses that had caused sequential infections in children showed G protein amino acid differences of up to 15%. Vaccinia viruses were constructed that expressed the G proteins from 2 of the paired group A isolates. Immunization of cotton rats with the recombinant vaccinia viruses provided equal protection against intranasal challenge by either of the RS viruses. Despite the amino acid differences between the two group A RS virus G proteins, these animal studies did not reveal differences in protection after immunization with the two G proteins. Precise definition of the role of RS virus antigenic variability in the establishment of reinfections in humans will require further investigations in humans.

Amino Acid Sequence↗
PubMed1998

Circulation patterns of genetically distinct group A and B strains of human respiratory syncytial virus in a community.

Human respiratory syncytial virus (HRSV) is classified into two major groups, A and B, each of which contains multiple variants. To characterize the molecular epidemiology of HRSV strains over time, sequencing studies of a variable region of the attachment protein gene from a single community in the United States during 5 successive years were performed. Phylogenetic analysis revealed distinct clades (genotypes) that were further classified in subtypes based on > or = 96% nucleotide similarity. Five genotypes and 22 subtypes among 123 group A HRSV isolates, and four distinct genotypes and six subtypes among 81 group B HRSV isolates were identified. One to two genotypes or subtypes accounted for > or = 50% of isolates from a given year. A shift in the predominant genotype or subtype occurred each year such that no genotype or subtype predominated for more than 1 of the 5 study years. The consistency in the displacement of the predominant strain suggests that a shift, even within the same group, is advantageous to the virus. It was hypothesized that the 'novel' strain is better able to evade previously induced immunity in the population and consequently either circulates more efficiently or is more pathogenic. The yearly shift in HRSV strains may contribute to the ability of HRSV to consistently cause yearly outbreaks of HRSV disease. These results also suggest that isolates may need to be characterized as to both group and genotype to fully understand protective immunity after natural infection and efficacy studies of candidate vaccines.

Amino Acid Sequence↗
PubMed1998

Outbreak of pneumonia in a long-term care facility: antecedent human parainfluenza virus 1 infection may predispose to bacterial pneumonia.

OBJECTIVES: To determine the causes of an outbreak of lobar pneumonia. DESIGN: Matched (1:2) case-control study. SETTING: A 70-bed chronic care facility for older people. PARTICIPANTS: Residents of the facility. RESULTS: Ten residents developed pneumonia over a 10-day period. Two residents died. One case-patient had Streptococcus pneumoniae bacteremia; another had polymerase chain reaction evidence of S. pneumoniae infection. No other etiologic agent was identified. Only four of 10 case-patients had received routine diagnostic cultures of blood or sputum before the administration of antibiotics. Symptoms of upper respiratory illness (URI) among residents before the pneumonia outbreak corresponded with elevation of antibodies to human parainfluenza virus 1 (HPIV1). In a matched case-control study, six of 10 case-patients, compared with five of 20 controls, had symptoms of URI during the preceding month (matched odds ratio (MOR) = 4.5, 95% CI = 0.8-33). Nine case-patients had serum available, and five of these had both serologic evidence of recent HPIV1 infection and recent URI, compared with two of 18 controls (MOR = 9.0, 95% CI = 1.2-208). Only three residents had documentation of pneumococcal vaccination. CONCLUSIONS: Noninfluenza viral infections may play a role in the pathogenesis of some bacterial pneumonias. S. pneumoniae was the cause of at least two pneumonias; lack of preantibiotic cultures may have interfered with isolation of S. pneumoniae in others. Recent HPIV1 infection was epidemiologically linked to subsequently developing pneumonia. Spread of HPIV1 in the facility may have contributed to increased susceptibility to S. pneumoniae and, potentially, to other bacterial pathogens.

Aged↗
PubMed1998

Simultaneous detection and identification of human parainfluenza viruses 1, 2, and 3 from clinical samples by multiplex PCR.

Reverse transcription (RT)-PCR assays have been widely described for use in the diagnosis of human parainfluenza viruses (HPIVs) and other respiratory virus pathogens. However, these assays are mostly monospecific, requiring separate amplifications for each HPIV type. In the present work, we describe multiplex RT-PCR assays that detect and differentiate HPIV serotypes 1, 2, and 3 in a combined reaction. Specifically, a mixture of three pairs of primers to conserved regions of the hemagglutinin-neuraminidase gene of each HPIV serotype was used for primary amplification, yielding amplicons with similar sizes. For typing, a second amplification was performed with a mixture of nested primers, yielding amplicons with sizes easily differentiated by agarose gel electrophoresis. A modified single-amplification RT-PCR assay with fluorescence-labeled nested primers, followed by analysis of the labeled products on an automated sequencing gel, was also evaluated. Fifteen temporally and geographically diverse HPIV isolates from the Centers for Disease Control and Prevention archives and 26 of 30 (87%) previously positive nasopharyngeal specimens (8 of 10 positive for HPIV serotype 1 [HPIV1], 9 of 10 positive for HPIV2, and 9 of 10 positive for HPIV3) were positive and were correctly typed by both assays. Negative results were obtained with naso- or oropharyngeal specimens and/or culture isolates of 33 unrelated respiratory tract pathogens, including HPIV4, enterovirus, rhinovirus, respiratory syncytial virus, adenovirus, influenza virus, and Streptococcus pneumoniae. Our multiplex RT-PCR assays provide sensitive, specific, and simplified tools for the rapid diagnosis of HPIV infections.

DNA Primers↗
PubMed1998

Cytotoxic T-lymphocyte precursor frequencies in BALB/c mice after acute respiratory syncytial virus (RSV) infection or immunization with a formalin-inactivated RSV vaccine.

A better understanding of the immune response to live and formalin-inactivated respiratory syncytial virus (RSV) is important for developing nonlive vaccines. In this study, major histocompatibility complex (MHC) class I- and II-restricted, RSV-specific cytotoxic T-lymphocyte precursor (CTLp) frequencies were determined in bronchoalveolar lavage (BAL) samples and spleen lymphocytes of BALB/c mice intranasally infected with live RSV or intramuscularly inoculated with formalin-inactivated RSV (FI-RSV). After RSV infection, both class I- and class II-restricted CTLps were detected by day 4 or 5 postinfection (p.i.). Peak CTLp frequencies were detected by day 7 p.i. The class II-restricted CTLp frequencies in the BAL following RSV infection were less than class I-restricted CTLp frequencies through day 14 p.i., during which class I-restricted CTLp frequencies remained elevated, but then declined by 48 days p.i. The frequencies of class II-restricted CTLps in the BAL were 2- to 10-fold less than those of class I-restricted CTLps. For spleen cells, frequencies of both MHC class I- and II-restricted CTLps to live RSV were similar. In contrast, class II-restricted CTLps predominated in FI-RSV-vaccinated mice. RSV challenge of vaccinated mice resulted in an increase in the frequency of class I-restricted CTLps at day 3 p.i. but did not enhance class II-restricted CTLp frequencies. These studies demonstrate differences in the CTLp response to live RSV infection compared with FI-RSV immunization and help define possible mechanisms of enhanced disease after FI-RSV immunization. In addition, these studies provide a quantitative means to address potential vaccine candidates by examining both MHC class I- and II-restricted CTLp frequencies.

Animals↗
PubMed1997

Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1beta.

Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1alpha and IL-1beta, and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R). The binding of IL-1alpha or IL-1beta to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs. Here we report the three-dimensional structure of IL-1beta bound to the extracellular domain of IL1R (s-IL1R) at 2.5 A resolution. IL-1beta binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1beta in a manner distinct from the structures of previously described cytokine-receptor complexes. The two receptor-binding regions on IL-1beta identified by site-directed mutagenesis both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.

Cloning, Molecular↗
PubMed1997

Parvovirus B19 quiescence during the course of human immunodeficiency virus infection in persons with hemophilia.

To detect and characterize parvovirus B19 infection during the course of progressive immune deficiency from human immunodeficiency virus (HIV), ten subjects enrolled in the Multicenter Hemophilia Cohort Study were followed for 6.4 to 15 years from HIV seroconversion through extreme immune deficiency. Four to five sera or plasma samples from each subject, collected at predetermined CD4+ lymphocyte levels, were tested for immunoglobulin G (IgG) and M (IgM) B19 antibodies and DNA. All 42 samples were positive for B19 IgG antibodies, and three were weakly positive for IgM antibodies. Only one sample, collected coincident with HIV seroconversion, was unequivocally positive for B19 DNA. No persistent hematologic adverse effects of B19 infection were observed. Thus, although B19 IgG antibodies are highly prevalent among HIV-infected persons with hemophilia or related disorders, B19 viremia and its hematologic consequences were not detected, even with severe depletion of CD4+ lymphocytes. If primary B19 infection occurs after immune deficiency, however, the consequences may be more adverse.

Adolescent↗
PubMed1997

Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics.

Croup is a common manifestation of respiratory tract infection in children, and human parainfluenza virus 1 (HPIV-1) is the agent most commonly associated with croup. In the United States, HPIV-1 produces a distinctive pattern of biennial epidemics of respiratory illness during the autumn months of odd-numbered years. National Hospital Discharge Survey data for croup hospitalizations among patients <15 years old between 1979 and 1993 were examined along with laboratory-based surveillance data on HPIV-1 activity in the United States. The mean annual number of croup hospitalizations was 41,000 (range, 27,000-62,000/year). Ninety-one percent of hospitalizations occurred among children <5 years of age. Minor peaks in croup hospitalizations occurred each year in February, and major peaks occurred in October of odd-numbered years, coincident with peak HPIV-1 activity. Each biennial epidemic of HPIV-1 was associated with 18,000 excess croup hospitalizations nationwide.

Adenovirus Infections, Human↗
PubMed1997

Diagnosis of measles with an IgM capture EIA: the optimal timing of specimen collection after rash onset.

The optimal timing for collection of a single serum specimen to diagnose measles by using a monoclonal antibody-capture EIA was evaluated. Results of testing paired serum samples from 166 measles cases with at least 1 IgM-positive specimen were analyzed. Among persons whose second samples were IgM-positive, the seropositivity rate for first samples was 77% when collected within 72 h and 100% when collected 4-11 days after rash onset. Among unvaccinated persons whose first samples were IgM-positive, the rate for IgM positivity of second specimens declined from 100% at 4 days to 94% at 4 weeks after rash onset, then declined further to 63% at 5 weeks. Some previously vaccinated persons became IgM-negative during the third week after rash onset. In general, a single serum specimen collected between 72 h and 4 weeks after rash onset can be used to diagnose most cases of measles with an IgM capture EIA.

Adolescent↗
PubMed1997

Priming with live respiratory syncytial virus (RSV) prevents the enhanced pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized with formalin-inactivated RSV.

To investigate enhanced disease associated with a formalin-inactivated (FI) respiratory syncytial virus (RSV) vaccine, we studied the pulmonary inflammatory response to RSV in BALB/c mice immunized with live RSV, FI-RSV, or combinations of the two. After RSV challenge, the number of granular cells, the ratio of CD4+/CD8+ lymphocytes, and the level of Th2-like cytokine mRNAs in the bronchoalveolar lavage specimens in mice immunized first with live RSV and then with FI-RSV were lower than that in FI-RSV-immunized mice and close to that in live RSV-immunized mice. These data suggest that prior live RSV infection prevents most of the enhanced inflammatory response seen in FI-RSV-immunized mice and might explain lack of enhanced disease in older FI-RSV-immunized children. A live RSV vaccine might similarly decrease the risk of enhanced disease with non-live RSV vaccines.

Animals↗
PubMed1997

Possible transmission of parvovirus B19 from intravenous immune globulin.

To look for genetic changes in human parvovirus B19 that might be associated with chronic infection, we sequenced B19 DNA obtained from serum specimens collected over an approximately 1-year period from a patient with systemic vasculitis. A comparison of the nucleotide sequences of the VP1/VP2 gene from four specimens revealed an abrupt change in the B19 genotype that coincided with initiation of intravenous immune globulin (IVIG) therapy. We suspect that one or more of the lots of IVIG administered to the patient were contaminated with B19. If true, this finding suggests that investigators must be careful in linking B19 infection to disease based on detection of B19 DNA in persons who have received multiple unit blood products.

Antibodies, Viral↗
PubMed1996

Comparative detection of measles-specific IgM in oral fluid and serum from children by an antibody-capture IgM EIA.

In vaccinated populations, the diagnosis of measles often requires laboratory confirmation. Serum tested by EIAs has proven sensitive and specific for diagnosing measles. For comparison of detection of measles-specific IgM in oral fluid and serum samples by an antibody-capture EIA, 163 Ethiopian infants who presented for routine measles vaccination were studied. Paired serum and oral fluid samples were collected before and 2 weeks after vaccination; 269 paired samples were adequate for analyses. Of the 104 serum samples that were IgM-positive, 95 (91%) of the paired oral fluid samples were IgM-positive. Of the 165 serum samples that were IgM-negative, 156 (95%) of the paired oral fluid samples were IgM-negative. The Pearson partial correlation coefficient for optical density readings from postvaccination oral fluid compared with serum was 0.81. Oral fluid appears to be an acceptable alternative to serum for measuring measles-specific IgM antibodies by an antibody-capture EIA.

Antibodies, Viral↗
PubMed1996

Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults.

Respiratory syncytial virus (RSV), the most important cause of lower respiratory disease in infants and young children, is rarely considered among the causes for community-acquired lower respiratory infection in adults. All noninstitutionalized adults hospitalized with community-acquired pneumonia in two Ohio counties were evaluated between December 1990 and May 1992. Fifty-three (4.4%) of 1195 adults admitted during the RSV seasons and 4 (1.0%) of 390 in the off-season had serologic evidence of RSV infection, making RSV one of the four most common pathogens identified. RSV-infected patients had clinical features (e.g., wheezing and rhonchi) that distinguished them from all non-RSV-infected patients and other features (e.g., nonelevated white blood cell counts) that distinguished them from those infected with bacterial or atypical agents. However, RSV infection was not diagnosed during hospitalization for any of the 57 RSV-infected patients. RSV should be considered in the differential diagnosis for adults hospitalized between November and April with community-acquired lower respiratory infection.

Adolescent↗
PubMed1996

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Child↗