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Biomedical subjects

R B Couch

Publications and source records attributed to R B Couch.

At least 109 records · Page 6Linked to original sources

Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly.

This placebo-controlled evaluation in elderly persons of inactivated influenza virus vaccines containing 200 or 400 chicke cell-agglutinating units of both A/New Jersey/76 and A/Victoria/75 antigens revealed mild systemic reactions in 7.8% and moderate reactions in 4.9% of vaccinees. These reactions were more common after administration of whole-virus than subvirion vaccines, more frequent in females than males, and more frequent in persons with low initial titers of antibody to A/New Jersey antigen. Local inflammation occurred in 18.7% of vaccinees (predominantly females) and frequently was seen with systemic reactions, but did not correlate with antibody response. Titers of antibody to A/New Jersey antigen were initially high and 99% of vaccinees had titers of greater than 1:20 after vaccination. Titers of antibody to A/Victoria antigen were initially low, and 56% of vaccinees had titers of greater than 1:20 after vaccination. Fourfold or greater increases in titer occurred in about 50% of vaccinees for each virus, most often concomitantly. Antibody responses to subvirion and whole-virus vaccines were similar, and increased responses with higher doses coincided with increased reactogenicity. Later revaccinations because of low titers of A/Victoria antibody produced negligible antibody responses.

Adult↗

Effects of low- and high-passage influenza virus infection in normal and nude mice.

A human isolate of type A Hong Kong influenza virus (H3N2) was adapted to mice by serial passage. Lung homogenates from mice who received low passage levels contained about the same quantity of virus (10(6.2-6.95) 50% tissue culture infective doses/ml) as those from mice who received high passage levels (10(5.95-6.45) 50% tissue culture infective doses/ml); however, death occurred only in animals given high-passage virus. Passage 3 (P3) and passage 9 (P9) viruses were selected as representative of low-passage and high-passage viruses, respectively. Although minimal differences were detected in infectivity for rhesus monkey kidney tissue cultures and mice, P9 virus was at least 10,000 times more lethal for mice (mean lethal dose = 10(4.2)). Infection with P3 virus was accompanied by minimal bronchitis and bronchiolitis only, whereas P9-infected animals exhibited marked bronchitis, bronchiolitis, and pneumonia. Striking thymic cortical atrophy was also demonstrable in the P9-infected animals and, although virus was more commonly recovered from thymuses from these animals, immunofluorescent studies revealed only a few cells containing influenza virus antigens. To further explore the participation of thymus-derived lymphocytes in influenza, athymic nude mice and furred immunocompetent littermates were given 500 50% mouse infectious doses of P9 virus. Nude mice exhibited an increased survival time and, in contrast to the extensive lung pathology seen in furred littermates, manifested minimal cellular infiltration and no tissue destruction in lungs. Brains from nude mice exhibited encephalomalacia with lymphocytic perivascular cuffing, which was not seen in furred animals. Virus was recovered from brains of 6 of 13 nude mice and 1 of 10 furred animals. The contrasting models suggest that thymus-dependent cells play a significant role in the inflammatory response to influenza virus infection and should prove useful for probing host-virus interactions which characterize influenza virus virulence.

Acute Disease↗

Human nasal epithelial cell culture system: evaluation of response to human interferons.

This report describes the response of human nasal epithelial cells to exogenously applied human interferon (IF). To measure the response, a system developed to study human nasal epithelial cells in vitro was used. Nasal epithelial cells responded equally to both leukocyte and fibroblast IF, with development of resistance to virus replication that was time and dose dependent. Cells required contact with 1,000 U of IF (400 69/19 reference units) for 4 h to produce consistently a significant reduction in virus yield. This in vitro cell cultured system may be useful in predicting the in vivo response of human IF in respiratory viral infections.

Biopsy↗

Maintenance of viability and comparison of identification methods for influenza and other respiratory viruses of humans.

A comparison of Hanks balanced salt solution, veal infusion broth (VIB), and charcoal viral transport medium for maintaining viability of type A influenza virus indicated approximately equal survival of virus on all three media at -70 and 4 degrees C, whereas at 25 degrees C virus survived best in VIB. VIB supplemented with bovine serum albumin was used as transport medium in a community-wide surveillance of febrile respiratory disease for influenza viruses. Unfrozen throat swab specimens were placed in VIB and stored at 4 degrees C for up to 5 days without effect on isolation frequencies of either type A or type B influenza virus or type 1 or type 3 parainfluenza virus. Comparison of indirect immunofluorescence with hemadsorption for detection of type A influenza virus in rhesus monkey kidney cultures revealed a requirement for at least five fluorescing cells to eliminate false positive indirect immunofluorescence tests and at least 3 days of incubation to eliminate false negative tests when compared with hemadsorption at later times. Detection frequencies for the two methods after 2 and 3 days of incubation were not significantly different.

Culture Media↗

Lymphocyte cytotoxicity to influenza virus-infected cells. II. Requirement for antibody and non-T lymphocytes.

Peripheral blood lymphocytes (PBL) obtained from humans were cytotoxic for influenza virus-infected target cells. The PBL were shown to have associated influenza virus anti-hemagglutinin antibody (AHAb) detectable only by radioimmunoassay. This antibody could be removed by incubating PBL at 37 degrees C for 30 min. The lymphocyte population that was effective in this system was nonadherent and nonphagocytic cells. PBL gave comparable levels of cytotoxicity when tested by using either a xenogeneic or allogeneic virus-infected target cell. These results indicate that lymphocyte cytotoxicity to influenza virus infected cells may be mediated by small quantities of antibody and by lymphocytes that possess characteristics of K cells. No evidence for T cell-mediated cytolysis was found with this xenogeneic system.

Adolescent↗

Influenza virus subunit vaccines. II. Immunogenicity and original antigenic sin in humans.

Subunit vaccines containing hemagglutinin, neuraminidase, and nucleocapsids of A/Port Chalmers/1/73 (H3N2) influenza virus were prepared after treatment of purified virus with ammonium deoxycholate. The immunogenicity of these subunits and the response to the common and specific antigenic determinants on the hemagglutinin subunits were studied in man. The subunits were as immunogenic in man as intact inactivated influenza virus vaccine at an equivalent concentration. Booster doses of antigen did not increase the antibody responses. Intact influenza B virus vaccine did not potentiate the immune response to the type A subunits in man. Volunteers responded differently to the common and specific determinants on the hemagglutinin subunits. The predominant antibody response was to the common or cross-reacting determinants present on hemagglutinins of both A/Hong Kong/1/68 (H3N2) and Port Chalmers/73 virus. Some men who failed to produce specific antibodies to the hemagglutinin of Port Chalmers/73 virus responded to the specific determinants on the Hong Kong/68 hemagglutinin. Higher doses of the subunit vaccines (1,400 chick cell-agglutinating units) did induce antibodies to the specific determinants on the Port Chalmers/73 virus hemagglutinin as well as to the common and specific determinants on Hong Kong/68 influenza virus.

Animals↗

Diagnosis of herpes simplex virus infection by immunofluorescence.

The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections.

Brain↗

Effects of rhinovirus infection of pulmonary function of healthy human volunteers.

The effects of experimentally induced rhinovirus and mycoplasmal respiratory tract infections on the pulmonary function of healthy, young, adult volunteers were investigated prospectively. Before inoculation, 12 volunteers were completely normal, whereas 9 had increased frequency dependence of compliance as their only abnormality of pulmonary function. Rhinovirus infection was induced in 8 of the completely normal volunteers, and 5 developed increased frequency dependence of compliance at the time of illness. These changes returned toward normal during the following 2 weeks and were not associated with concomitant changes in any other parameter of pulmonary function, including "closing volume". Three subjects with increased frequency dependence of compliance as their only abnormality before rhinovirus infection developed no significant change in dynamic compliance or any other abnormality in pulmonary function after infection. No changes in pulmonary function were detected in 3 volunteers with experimentally induced mycoplasmal infection. These finding suggest that although rhinovirus infections are associated primarily with upper respiratory illness, they can produce transient peripheral airway abnormalities in previously normal young adults; however, closing volumes, as well as routine pulmonary function studies, may not detect these changes.

Adult↗

Antigenicity of licensed whole virion and subvirion influenza vaccines in "high risk" persons.

The frequency and magnitude of serum antibody response to type A and B influenza virus induced by whole virion and subvirion vaccines were essentially comparable. Immunization was followed in vaccinated individuals by an antihemagglutinin antibody response to the common antigenic determinant shared by the type A H3N2 viruses. Relatively few individuals developed antibody to the type-specific determinant.

Adult↗

Assessment of immunity to influenza using artifical challenge of normal volunteers with influenza virus.

The candidate humoral mediators of protection against influenza include antibody (Ab) to the viral hemagglutinin (H) or neuraminidase (N) in serum or respiratory secretions. In the present studies these mediators were evaluated principally by low dose live virus challenge of previously vaccinated volunteers. Following IM vaccination with H3N2 virus, Ab appeared in both serum and secretions and direct quantitative relationship between the two was noted. Among individuals vaccinated intranasally with comparable doses, the serum and secretion Ab responses were similar to those after IM vaccination. Irrespective of immunization method, there was a better correlation between protection and titers of serum Ab than titers of Ab in nasal secretions. After vaccination with an N-specific vaccine, an inverse correlation between titer of serum anti-neuraminidase Ab and quantity of virus in secretions occurred. This was reflected in occurrence of illness in those with low Ab titers, infection only in those with intermediate Av titers and no evidence of infection in those with high Av titers. In a naturally occurring outbreak with the England variant, a similar pattern of infection responses occurred among persons with varying titers of serum anti-hemagglutinin Ab. This suggests that, in man, Ab to the H and to the N results in similar host responses to infection and that the extent of infection is determined by magnitude ofAb present.

Administration, Intranasal↗