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Biomedical subjects

K McIntosh

Publications and source records attributed to K McIntosh.

At least 145 records · Page 8Linked to original sources

Bronchomammary axis in the immune response to respiratory syncytial virus.

The products of lactation from 26 nursing mothers were sequentially examined over several months for the presence or appearance of antibodies directed against respiratory syncytial virus. Antiviral IgM and IgG were rarely identified in either colostrum or milk. RSV-specific IgA was found in 75% (18/24) of specimens of colostrum; 40% (6/15) and 59% (4/7) of milk samples obtained at three and six months still contained specific IgA antibody. The latter increase was felt to represent boosting of exposed individuals when the virus was present in the community. Infection with the virus was documented in two mothers. Both had specific IgG, IgM, and IgA antibody responses in serum and nasopharyngeal secretions, but response in milk was limited to IgA. These data confirm that antibody to a specific respiratory tract pathogen is present in the products of lactation, that the specific activity is mainly of the IgA class, and that booster responses in milk are exclusively of the IgA class. Since RSV appears to replicate only in the respiratory tract, it is suggested that viral specific antibody activity observed in the mammary gland may be derived from the bronchopulmonary lymphoid tissue.

Adult↗

Infections with Legionella pneumophila in children.

To learn the role of Legionella pneumophila, the agent of Legionnaires' disease, in childhood illness, a prospective study was conducted among 52 children younger than four years of age with acute disease of the lower respiratory tract. Viral, mycoplasmal, and bacterial cultures and acute- and convalescent-phase sera were obtained during 64 episodes of acute illness; additional sera were drawn annually for three to five years. On the basis of serologic evidence, none of the acute episodes appeared to be due to L. pneumophila serogroup 1 or 2. However, examination of annual serum specimens showed that 27 (52%) of the children had rises in titer of indirect immunofluorescent antibody (a fourfold or greater rise to a reciprocal titer of greater than or equal to 128). Most rises in titer were in response to the serogroup 2 antigen. These results suggest that L. pneumophila is not a common cause of acute respiratory disease in early childhood in the study area but that children are frequently exposed to the organism. Alternatively, the serologic responses might be to unrelated cross-reacting microorganisms.

Antibodies, Bacterial↗

Activation of complement by cells infected with respiratory syncytial virus.

The ability of respiratory syncytial virus (RSV)-infected HE(p)-2 cells in culture to activate complement was investigated. After incubation of cells with various complement sources and buffer, binding of C3b to surfaces of infected cells was demonstrated by immunofluorescence with a double-staining technique. Nonsyncytial and syncytial (i.e., fused, multinucleated) cells were separately enumerated. Also, lysis of RSV-infected cells was assessed by lactic dehydrogenase release. In this system only RSV-infected cells stained for C3b, and they did so only after incubation with functionally active complement. Blocking of classical pathway activation with ethylenediaminetetraacetic acid diminished the number of infected nonsyncytial cells positively stained for C3b, but had no effect on staining of syncytial cells. Blocking of alternative pathway activation with either zymosan incubation or heat treatment decreased the number of both syncytial and nonsyncytial cells stained for C3b. Decreasing immunoglobulin concentration of the serum used as the complement source also decreased numbers of both cell types stained for C3b. Eliminating specific anti-RSV antibody diminished numbers of both cell types stained for C3b, but staining was not eliminated. Lastly, incubation with functionally active complement markedly increased lactic dehydrogenase release from infected cells. This study demonstrated that RSV-infected nonsyncytial and syncytial cells are able to activate complement by both classical and alternative pathways. Activation of complement by syncytial cells appears to be less dependent on the classical pathway than is activation by nonsyncytial cells, and activation by syncytial cells may require immunoglobulin but not specific antibody. These experiments suggest the possibility of complement activation during respiratory tract infection by RSV. Implications of this are discussed.

Antibodies, Viral↗

In vitro cell-dependent lysis of respiratory syncytial virus-infected cells mediated by antibody from local respiratory secretions.

Respiratory syncytial (RS) virus causes a local infection of the respiratory tract which is frequently severe in infants. We report the development in infected infants of antibodies in respiratory secretions capable of mediating in vitro destruction of RS virus-infected tissue culture cells in conjunction with non-immune lymphoid cells. The cytotoxic antibody activity was not detectable in nasal secretions from infants hospitalized with respiratory infections where RS virus was not identified. The rise in activity occurred concurrently with recovery from infection and the rise in specific IgG, IgM and IgA antibody levels measured by membrane immunofluorescence assay, but was dissociated from the development of plaque-neutralizing activity. In serum it appears that the cytotoxic antibody belongs to the IgG class as shown by its ability to cross the placenta and by neutralization with specific antiserum. These findings are discussed in relationship to secretory antibody responses in RS virus infection with respect to pathogenesis and recovery.

Antibodies, Viral↗

An epidemic of Reye syndrome associated with influenza A (H1N1) in Colorado.

An unusual cluster of Reye syndrome was associated with an outbreak of influenza A (H1N1) infections in the state of Colorado. Two of the 16 affected children had had prior episodes of Reye syndrome following respiratory infections, and one had had transverse myelitis following varicella. A serologic study of patients treated at a children's hospital and serum specimens submitted to the state health department revealed that approximately 59% of children in Colorado had been infected with the H1N1 strain of influenza A over a two-year period. Based upon this serologic survey, the minimum and maximum rates of Reye syndrome associated with H1N1 infections were calculated to be 2.5 and 4.3 cases per 100,000 H1N1 infections, respectively. A retrospective analysis of admissions to four referral hospitals in Denver failed to reveal any unusual clustering of Reye syndrome with outbreaks of influenza A H3N2 infections during 1975-1978. The reason for an association between Reye syndrome and the H1N1 strain but not the H3N2 strains of influenza A remains unclear.

Adolescent↗

Secretory immunological response in infants and children to parainfluenza virus types 1 and 2.

The secretory immunological responses to natural infection with parainfluenza viruses ae not well defined. Nasopharyngeal secretion specimens from 20 infants and children naturally infected with parainfluenza virus type 1 or type 2 were examined for class-specific antibody and virus-neutralizing activity. There was a marked discordance in individual secretions between immunoglobulin A (IgA) antibody (as measured by indirect immunofluorescence) and neutralizing activity (as determined by either hemadsorption plaque or 50% tissue culture infective dose reduction) to the infecting parainfluenza virus type. Many secretions contained neutralizing activity in the absence of detectable IgA antibody; conversely, secretions with measureable IgA antibody frequently lacked neutralizing activity. Moreover, there was no relationship between neutralizing activity and the course of illness. All 11 patients with serial secretion specimens showed a fourfold or greater titer rise in IgA antibody to the homologous parainfluenza virus type. Antibody usually appeared 7 to 10 days after the onset of symptoms and peaked at about 2 weeks. This response did not appear to be related to age or to severity of illness. in general, the secretory responses resembled those seen in infants infected with respiratory syncytial virus.

Antibodies, Heterophile↗

Cryopreservation of virus-infected cells for use in the fluorescent antibody to membrane antigen test.

Tissue culture cells infected with varicella-zoster, respiratory syncytial, para-influenza types 1, 2, and 3, and influenza A/Texas/1/77 and A/USSR/90/77 viruses were exposed to ultraviolet light and frozen in the presence of a final concentration of 20% glycerol. These cells were quick thawed at 37 degrees C and compared with freshly prepared, living infected tissue culture cells in assays of fluorescence antibodies to membrane antigens of the infecting agents in serum, nasal wash secretions, colostrum, and breast milk. Frozen cells performed as efficiently as fresh cells as targets and retained their activity for long periods of time. Cryopreservation combined with photoinactivation of infected target cells allows this useful antibody test to be performed in routine serology laboratories.

Antigens, Viral↗

Recent advances in viral diagnosis.

A number of new methods have been developed for the rapid and sensitive detection of viral antigens in clinical specimens. These methods are similar in sensitivity to traditional viral culture, but are easier, less expensive, and considerably more rapid. It seems likely that clinical pathologists and microbiologists will become increasingly involved in viral diagnosis.

Antigen-Antibody Reactions↗

Chlamydial infection of mothers and their infants.

In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.

Adolescent↗

Detection of respiratory syncytial virus in nasal secretions from infants by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for detection of respiratory syncytial virus (RSV) in nasal secretions from infants with respiratory disease. RSV was detected in 23 of 29 secretions positive for RSV by tissue culture and in one of 36 samples negative for RSV by tissue culture. The ELISA was a simple rapid, and surprisingly sensitive test for identification of RSV infection in infants.

Child, Preschool↗

Cell-free and cell-bound antibody in nasal secretions from infants with respiratory syncytial virus infection.

Twenty-two infants under 9 months of age hospitalized with bronchiolitis or pneumonia due to respiratory syncytial virus (RSV) were serially sampled to determine the pattern of secretory antibody response. Using double labeling techniques, we found several types of immunoglobulin in secretions: cell-free antibody to RSV of the immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) classes; and immunoglobulins of all three classes bound to RSV-infected cells shed from the nasal epithelium (presumably cell-bound antibody to RSV). IgA attached to RSV-infected epithelial cells was almost always detected in the first available nasal sample (day 1 or 2 of hospitalization). In contrast, cell-free anti-RSV IgA first appeared an average of 3.5 days later at a time when virus antigen was disappearing from the secretion. IgG and IgM attached to RSV-infected cells appeared more irregularly. The titer of cell-free anti-RSV IgM was often higher than that of IgA early in the illness and declined as the infection resolved. Cell-free anti-RSV IgG was usually present earlier than IgA and rose during convalescence.

Antibodies, Viral↗

Rapid subtyping of influenza A virus isolates by membrane fluorescence.

During the winter of 1977-1978 three influenza A virus serotypes (A/Vic/3/75, A/Texas/1/77 [both H3N2], and A/USSR/90/77 [H1N1]) circulated in Denver, offering us the opportunity to apply fluorescent antibody techniques to the specific identification of these viruses. Surface antigens of infected, unfixed primary monkey kidney cells were stained in suspension by an indirect immunofluorescence technique with anti-H3N2 and anti-H1N1 antisera. In tests of cells infected with known viruses, the members of the H3N2 family could not be distinguished from one another, but were easily distinguished from H1N1 strains. A total of 101 hemadsorption-positive clinical specimens were evaluated over a 6-month period. Forty-five of 48 influenza A H3N2 and 24 of 29 H1N1 specimens confirmed by hemagglutination inhibition were correctly identified by membrane fluorescence of cultured cells, with no misidentifications among influenza strains and with 1 false positive among 24 non-influenza isolates. The average time to identification by this technique was 4 days compared to 7 days by hemagglutination inhibition. Live cell membrane fluorescence is a simple, rapid, and accurate method for identifying and grouping influenza A viruses.

Adult↗