Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 37 records · Page 2Linked to original sources

PubMed2000

CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory syncytial virus in the BALB/c mouse.

CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells. CD40L is critically important for T-B cell and T cell-dendritic cell interactions. CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells. Respiratory syncytial virus (RSV) is an important pathogen of young children and the elderly, which causes bronchiolitis and pneumonia. Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsible for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empty control adenovirus vector or one expressing CD40L or were coimmunized with plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subsequently challenged with RSV. The kinetics of the intracellular and secreted cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO levels in lung lavage, rates of virus clearance, and anti-RSV Ab titers were determined. These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-gamma) cytokine responses, increases the expression of TNF-alpha and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses. These data suggest that CD40L may have the adjuvant properties needed to optimize the safety and efficacy of RSV vaccines.

Adenoviridae↗

PubMed2000

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Animals↗

PubMed2000

Circulation patterns of group A and B human respiratory syncytial virus genotypes in 5 communities in North America.

Human respiratory syncytial virus (HRSV) is a major cause of serious lower respiratory tract illness in infants, young children, and the elderly. To characterize the circulation patterns of HRSV strains, nucleotide sequencing of the C-terminal region of the G protein gene was performed on 34-53 isolates obtained from 5 communities during 1 epidemic year, representing distinct geographical locations in North America. Phylogenetic analysis revealed that 5-7 HRSV genotypes, including 1 or 2 predominant strains, circulated in each community. The patterns of genotypes were distinct between communities, and less diversity was seen between strains of the same genotype within than between communities. These findings are consistent with HRSV outbreaks' being community based in nature, although transmission of viruses between communities may occur. Several strains are probably introduced or circulate endemically in communities each year, and local factors-possibly immunity induced by previous years' strains-determine which strains predominate during an HRSV season.

Child↗

PubMed2000

Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia.

An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.

Agricultural Workers' Diseases↗

PubMed2000

Risk factors for Nipah virus infection among abattoir workers in Singapore.

During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.

Abattoirs↗

PubMed2000

TH(1)- and TH(2)-TYPE cytokine expression by activated t lymphocytes from the lung and spleen during the inflammatory response to respiratory syncytial virus.

RSV is an important cause of lower respiratory tract illness in infants and the elderly worldwide. The components involved in immunity and those that contribute to inflammation of RSV-induced disease are not clearly understood. To address the relationship between activation antigen and cytokine expression, intracellular levels of IL-2, IL-4, IL-5 and IFN-gamma were determined for CD3, CD44, CD49d, CD54, CD62L and CD102 lymphocytes from the bronchoalveolar lavage and spleen. To examine activation at the DNA level, lymphocytes expressing IL-2, IL-4, IL-5 or IFN-gamma were analysed for G2+M DNA content or phosphatidylserine expression (apoptosis). Trafficking of lymphocytes to the BAL was detected at day 5 p.i., peaked day 7 p.i., and predominately involved CD54(+)and CD102(+)lymphocytes expressing high levels of IL-2, IL-4, IL-5 and IFN-gamma. Lymphocytes expressing CD44(+), CD49d(+)and CD62L(lo)were also observed, however they expressed these cytokines to a lesser extent. DNA analysis of lymphocytes expressing IL-2 or IFN-gamma revealed higher G2'M levels compared to lymphocytes expressing IL-4 or IL-5, suggesting greater activation of Th(1)-type lymphocytes in the lung. These data demonstrate that RSV-induced pulmonary inflammation involves extensive cellular activation and cytokine expression, particularly by CD54(+)and CD102(+)lymphocytes in the lung.

Animals↗

PubMed2000

Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus.

The innate immune system contributes to the earliest phase of the host defense against foreign organisms and has both soluble and cellular pattern recognition receptors for microbial products. Two important members of this receptor group, CD14 and the Toll-like receptor (TLR) pattern recognition receptors, are essential for the innate immune response to components of Gram-negative and Gram-positive bacteria, mycobacteria, spirochetes and yeast. We now find that these receptors function in an antiviral response as well. The innate immune response to the fusion protein of an important respiratory pathogen of humans, respiratory syncytial virus (RSV), was mediated by TLR4 and CD14. RSV persisted longer in the lungs of infected TLR4-deficient mice compared to normal mice. Thus, a common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens.

Animals↗

PubMed2000

Using direct electrochemistry to probe rate limiting events during nitrate reductase turnover.

Protein film voltammetry of NarGH catalysing nitrate reduction under steady state conditions provides information on events occurring within the enzyme during the catalytic cycle. In this discussion we have focused on exploring the ability of two simple catalytic schemes to reproduce the voltammetric response of NarGH; electron transfer to the enzyme's active site being described either by interfacial electron exchange (Scheme 1) or intramolecular electron delivery via the operation of an electron relay centre (Scheme 2). When the two electron reduced, catalytically competent active site of the enzyme is generated from the oxidised form in 'rapid', non-rate limiting steps of the catalytic cycle, the voltammetric behaviour of NarGH cannot be reproduced. Rather under all the conditions investigated, one electron reduction of the active site from a semi-reduced to a fully-reduced state is found to be crucial to progression through the enzyme's catalytic cycle. The catalytically relevant semi- and fully-reduced oxidation states of the NarGH active site are most likely to correspond to the Mo(V) and Mo(IV) states of the Mo(MGD)2 centre, respectively, although it is not possible to rule out the possibility that they correspond to molybdopterin based oxidation states as observed in other enzymes. We suggest that the rate of either conformational rearrangement within the semi-reduced active site or intramolecular electron delivery to the active site constitutes a defining feature in the catalytic cycle of NarGH and results in the napp approximately 1 appearance of the catalytic waveform.

Electrochemistry↗

PubMed2000

Investigation of porcine parvovirus among persons with hemophilia receiving Hyate:C porcine factor VIII concentrate.

BACKGROUND: Porcine clotting factor has been used for more than 15 years to treat severe bleeding episodes in persons with hemophilia who have antibodies to human clotting factor. In 1996, QC procedures revealed for the first time the presence of porcine parvovirus (PPV) in the product. This report describes an investigation to determine the extent of product contamination and to evaluate past recipients of porcine clotting factor (Hyate:C, Speywood Biopharm) for evidence of PPV infection. STUDY DESIGN AND METHODS: Stored specimens from 22 lots of previously released Hyate:C were tested for the presence of PPV DNA by PCR and nested PCR assays. Serum specimens from 98 recipients of Hyate:C and 24 controls who did not receive Hyate:C were tested for PPV antibodies by an immunofluorescence assay. RESULTS: PPV DNA was detected in product from 21 of the 22 lots of Hyate:C, primarily by nested PCR testing. In contrast, none of the serum specimens from the 98 Hyate:C recipients tested positive for PPV IgG antibodies. CONCLUSION: The risk of human disease from percutaneous exposure to low levels of PPV seems to be low. Nevertheless, the theoretical risk of human infection with PPV has led to manufacturing changes, including PCR screening of all porcine plasma, which are designed to eliminate this risk.

Adult↗

PubMed2000

Bronchiolitis-associated hospitalizations among American Indian and Alaska Native children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness among infants and young children. Respiratory system diseases account for a large proportion of hospitalizations in American Indian and Alaska Native (AI/AN) children; however, aggregate estimates of RSV-associated hospitalizations among AI/AN children have not been made. METHODS: We used Indian Health Service hospitalization data from 1990 through 1995 to describe hospitalizations associated with bronchiolitis, the most characteristic clinical manifestation of RSV infection, among AI/AN children <5 years old. RESULTS: The overall bronchiolitis-associated hospitalization rate among AI/AN infants < 1 year old was considerably higher (61.8 per 1,000) than the 1995 estimated bronchiolitis hospitalization rate among all US infants (34.2 per 1,000). Hospitalization rates were higher among male infants (72.2 per 1,000) than among females infants (51.1 per 1,000). The highest infant hospitalization rate was noted in the Navajo Area (96.3 per 1,000). Hospitalizations peaked annually in January or February, consistent with national peaks for RSV detection. Bronchiolitis hospitalizations accounted for an increasing proportion of hospitalizations for lower respiratory tract illnesses. CONCLUSIONS: Bronchiolitis-associated hospitalization rates are substantially greater for AI/AN infants than those for all US infants. This difference may reflect an increased likelihood of severe RSV-associated disease or a decreased threshold for hospitalization among AI/AN infants with bronchiolitis compared with all US infants. AI/AN children would receive considerable benefit from lower respiratory tract illness prevention programs, including an RSV vaccine, if and when one becomes available.

Age Distribution↗

PubMed2000

Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse.

Chemokine mRNA expression by pulmonary leukocytes following infection of BALB/c mice with two strains of respiratory syncytial virus (RSV) and one strain of parainfluenza virus type 3 (PIV-3) was determined. The results suggest that RSV G and/or SH proteins inhibit early MIP-1alpha, MIP-1beta, MIP-2, MCP-1, and IP-10 mRNA expression. TCA-3 mRNA expression was found to be increased during PIV-3 infection.

Animals↗

PubMed2000

Respiratory syncytial virus infection and G and/or SH protein expression contribute to substance P, which mediates inflammation and enhanced pulmonary disease in BALB/c mice.

A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice and the effect of anti-SP F(ab)(2) antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment of RSV-infected mice with anti-SP F(ab)(2) antibodies suggested that SP may alter the natural killer cell response to primary and secondary infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest that SP may be an important contributor to the inflammatory response to RSV infection and that anti-SP F(ab)(2) antibodies might be used to ameliorate RSV-associated disease.

Animals↗

PubMed1999

Bronchiolitis-associated hospitalizations among US children, 1980-1996.

CONTEXT: Respiratory syncytial virus (RSV) causes more lower respiratory tract infections, often manifested as bronchiolitis, among young children than any other pathogen. Few national estimates exist of the hospitalizations attributable to RSV, and recent advances in prophylaxis warrant an update of these estimates. OBJECTIVES: To describe rates of bronchiolitis-associated hospitalizations and to estimate current hospitalizations associated with RSV infection. DESIGN AND SETTING: Descriptive analysis of US National Hospital Discharge Survey data from 1980 through 1996. PARTICIPANTS: Children younger than 5 years who were hospitalized in short-stay, non-federal hospitals for bronchiolitis. MAIN OUTCOME MEASURE: Bronchiolitis-associated hospitalization rates by age and year. RESULTS: During the 17-year study period, an estimated 1.65 million hospitalizations for bronchiolitis occurred among children younger than 5 years, accounting for 7.0 million inpatient days. Fifty-seven percent of these hospitalizations occurred among children younger than 6 months and 81 % among those younger than 1 year. Among children younger than 1 year, annual bronchiolitis hospitalization rates increased 2.4-fold, from 12.9 per 1000 in 1980 to 31.2 per 1000 in 1996. During 1988-1996, infant hospitalization rates for bronchiolitis increased significantly (P for trend <.001), while hospitalization rates for lower respiratory tract diseases excluding bronchiolitis did not vary significantly (P for trend = .20). The proportion of hospitalizations for lower respiratory tract illnesses among children younger than 1 year associated with bronchiolitis increased from 22.2% in 1980 to 47.4% in 1996; among total hospitalizations, this proportion increased from 5.4% to 16.4%. Averaging bronchiolitis hospitalizations during 1994-1996 and assuming that RSV was the etiologic agent in 50% to 80% of November through April hospitalizations, an estimated 51, 240 to 81, 985 annual bronchiolitis hospitalizations among children younger than 1 year were related to RSV infection. CONCLUSIONS: During 1980-1996, rates of hospitalization of infants with bronchiolitis increased substantially, as did the proportion of total and lower respiratory tract hospitalizations associated with bronchiolitis. Annual bronchiolitis hospitalizations associated with RSV infection among infants may be greater than previous estimates for RSV bronchiolitis and pneumonia hospitalizations combined.

Bronchiolitis↗

PubMed1999

Genetic variability in envelope-associated protein genes of closely related group A strains of respiratory syncytial virus.

The genetic and antigenic diversity present in respiratory syncytial virus (RSV) strains may in part be explained by genetic drift similar to that which occurs with influenza virus B. To study drift in RSV strains, we sequenced the five membrane-associated genes, M, SH, G, F, and M2, from three sets of RSV isolates: one set of seven closely related isolates obtained over 5 years in St. Louis, MO, and two sets of four closely related RSV isolates from other communities. We found nucleotide-variable and conserved regions in all five genes, and the greatest diversity in the SH and G genes. We did not find clear evidence of genetic drift in the seven isolates from St. Louis for any of the five genes. Although the relationships between strains were usually maintained independent of the genes studied, for several isolates there was a dramatic shift in genetic relationships for one of the five genes. Our inability to demonstrate genetic drift and the dramatic shift in genetic relationships between some strains for some genes suggest that we need to better define the mechanisms and rate of change in this virus to accurately define phylogenetic relationships between strains.

Base Sequence↗

PubMed1999

Respiratory syncytial virus pneumonia among the elderly: an assessment of disease burden.

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease among the elderly, but national estimates of the burden of this disease have not been made. To estimate the morbidity, mortality, and medical costs of RSV-associated pneumonia among US elderly, national hospital discharge data, vital statistics, etiologic studies of adult pneumonia hospitalizations, and Medicare cost data were reviewed. In the United States, 687,000 hospitalizations and 74,000 deaths caused by pneumonia occur annually among the elderly; approximately 2%-9% of these are caused by RSV. At a cost of $11,000 per RSV pneumonia hospitalization, the estimated annual cost of RSV pneumonia hospitalizations is $150-$680 million. Exacerbations of congestive heart failure and other chronic conditions may also contribute substantially to RSV disease burden among the elderly. The total RSV disease burden is probably great enough to justify development of an RSV vaccine for use in this group.

Adult↗

PubMed1999

Prevalence of antibodies to human parvovirus B19 nonstructural protein in persons with various clinical outcomes following B19 infection.

Persistent infections with human parvovirus B19 (B19) associated with debilitating chronic disease have been described, although evidence linking B19 to these more unusual clinical outcomes has been inconclusive. Recent reports have suggested that the development of antibodies to the B19 nonstructural protein (NS1) following B19 infection might be linked to development of severe arthropathy and chronic infection. To confirm these findings, the C-terminal region of the NS1 protein was expressed for use in Western blot assays for detection of anti-NS1 IgG antibodies in human serum. Among 91 persons tested, 0 of 20 not previously infected with B19, 9(36%) of 25 with past B19 infection, and 5 (12.5%) of 40 with recent B19 infection, had detectable anti-NS1 antibodies. Of 6 persons with chronic B19 infection, 2 had detectable antibodies to NS1. The presence of anti-NS1 antibodies did not appear to correlate with unusual clinical outcomes or chronic B19 infection.

Animals↗

PubMed1999

Molecular characterization of a nosocomial outbreak of human respiratory syncytial virus on an adult leukemia/lymphoma ward.

Although nosocomial transmission of human respiratory syncytial virus (HRSV) and its effect on morbidity and mortality among immunocompromised adults are well recognized, few studies have applied molecular techniques to differentiate nosocomial from community-acquired infections. Between January and April 1997, an outbreak of HRSV occurred among adult patients in a leukemia/lymphoma ward. Among 45 hospitalized patients undergoing bronchoscopy for investigation of acute respiratory illness, 8 were identified with HRSV infection. One infected patient developed symptoms before admission and was thought to be the index case. However, subsequent sequencing of 7 HRSV isolates identified 2 distinct genotypes, GA5 (1 case) and GB3 (6 cases). The 6 GB3 isolates could be further differentiated into 2 strains with identical nucleotide sequences that differed from each other and from 14 community HRSV isolates. Instead of a single nosocomial outbreak of HRSV, multiple introductions of HRSV likely occurred with distinct lines of nosocomial transmission.

Adult↗

PubMed1999

Parainfluenza virus infection among adults hospitalized for lower respiratory tract infection.

To better define the contribution of human parainfluenza viruses (HPIVs) to lower respiratory tract infection in adults, we tested acute- and convalescent-phase serum specimens from hospitalized adults participating in a population-based prospective study of lower respiratory tract infection during 1991-1992. We tested all available specimens from the epidemic seasons for each virus and approximately 300 randomly selected specimens from the corresponding off-seasons for antibodies to HPIV-1, HPIV-2, or HPIV-3. During the respective epidemic season, HPIV-1 infection was detected in 18 (2.5%) of 721 and HPIV-3 infection in 22 (3.1%) of 705 patients with lower respiratory tract infection. Only 2 (0.2%) of 1,057 patients tested positive for HPIV-2 infection. No HPIV-1 infections and only 2 (0.7% of 281 patients tested) HPIV-3 infections were detected during the off-seasons. HPIV-1 and HPIV-3 were among the four most frequently identified infections associated with lower respiratory tract infection during their respective outbreak seasons.

Adult↗