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Biomedical subjects

S O'Shea

Publications and source records attributed to S O'Shea.

At least 55 records · Page 3Linked to original sources
PubMed1992

Persistence of specific IgM and low avidity specific IgG1 following primary rubella.

Persistence of specific IgM in sera following primary rubella infection was compared with the maturation of the specific IgG1 response. 206 sera, from 171 patients with primary rubella, taken 1 day to 2.5 years after onset of illness, were tested. Rubella-specific IgM was detected by M-antibody capture radioimmunoassay in 100% of sera taken 15-28 days after onset, but in only 9% taken 3-4 months after onset. However, using the diethylamine (DEA) shift value (DSV) method, low avidity specific IgG1 was detected in 91% sera taken at 3-4 months and at 5-7 months 21% of sera remained positive. Using an avidity index method, with urea in the wash buffer, none of the sera were positive for low avidity specific IgG1 beyond 3 months after onset. With DEA in the wash buffer, the number of sera positive rose to 38% at 3-4 months. Thus, the DSV method for detecting low avidity specific IgG1 is a useful additional test for confirming or refuting a diagnosis of primary rubella and is of particular value for assessing pregnant patients.

Antibodies, Viral↗
PubMed1992

Rubella virus strains show no major antigenic differences.

To determine whether antigenic differences occur among rubella virus strains, five wild-type strains of rubella virus isolated in the UK, the USA, and in Japan between 1964 and 1987 and four attenuated vaccine strains were compared employing a panel of 28 monoclonal antibodies in neutralization, haemagglutination-inhibition, enzyme immunoassay, and indirect immunofluorescence assays. No antigenic differences were detected which confirms that rubella vaccines will protect against circulating strains and that rubella antigens used in serological tests for screening and diagnosis will detect antibodies induced by all strains.

Antibodies, Monoclonal↗
PubMed1992

Induction of thrombospondin 1 by retinoic acid is important during differentiation of neuroblastoma cells.

Neuroblastoma, a malignant neoplasm that arises in the adrenal medulla or sympathetic ganglion, is one of the most common solid tumors of childhood. Reports that neuroblastomas spontaneously mature to form benign ganglioneuromas have prompted investigations into the efficacy of using agents that induce neuronal differentiation in the treatment of this malignancy. Retinoic acid is one agent in particular that has been shown to induce growth inhibition and terminal differentiation of neuroblastoma cell lines in vitro. Using the human neuroblastoma cell line SMH-KCNR, we have investigated the role of the extracellular matrix protein thrombospondin in retinoic acid induced neuroblastoma differentiation. Treatment with retinoic acid results in a rapid induction (within 4 h) of thrombospondin (TSP) message which is independent of intervening protein synthesis and superinducible in the presence of cycloheximide. This suggests that TSP functions as a retinoic acid inducible immediate early response gene. A concomitant increase in both cell associated and soluble forms of TSP protein can be detected within 24 h of retinoic acid treatment. A functional role for TSP in SMH-KCNR differentiation was established in experiments which showed that exposure to anti-TSP monoclonal antibodies delay retinoic acid differentiation for 48 h. At the time the cells overcome the effects of TSP inhibition, laminin production becomes maximal. Treatment of the cells with a combination of anti-TSP and antilaminin antibodies results in complete inhibition of differentiation.

Cell Differentiation↗
PubMed1991

Quantitation of HIV: correlation with clinical, virological, and immunological status.

A quantitative assay has been used to measure titres of infectious HIV in peripheral blood of symptomatic and asymptomatic patients. Viral titres were assessed in conjunction with virological and immunological status of patients including measurement of p24 antigen, antibody responses to structural (gp41, p24) and regulatory gene products (NEF, REV, TAT, and VIF), determination of beta 2 microglobulin levels and enumeration of lymphocyte subsets. Titres of HIV were significantly higher among symptomatic than asymptomatic patients. Viral load was closely associated with the number of CD4+ cells, the proportion of these cells harbouring HIV increasing with disease progression. Higher titres of infectious HIV among symptomatic patients was also associated with p24 antigenaemia and decreased antibody responses to NEF.

AIDS-Related Complex↗
PubMed1990

HIV excretion patterns and specific antibody responses in body fluids.

HIV excretion patterns and specific antibody responses were evaluated in blood, semen, female genital secretions, saliva, and crevicular fluid. Samples were examined for infectious virus, viral antigens, viral nucleic acid, HIV specific IgG, IgA, anti-nef, and anti-p24. Viral load in peripheral blood appeared to increase with disease progression. The proportion of patients with antibody responses specific for nef and p24 was also lower among patients with more advanced disease. Infectious virus and viral antigens were detected infrequently and at lower levels in body fluids than in blood, which may reflect the presence of local antibodies. HIV nucleic acid was detected in some semen and saliva samples in the absence of infectious virus.

Female↗
PubMed1990

Laminin in lung development: effects of anti-laminin antibody in murine lung morphogenesis.

The pattern of deposition and the role of laminin, a major glycoprotein constituent of basement membranes, were investigated during lung morphogenesis in the fetal mouse. Lung primordia were removed from Day 13 embryos, right lower lobes were further dissected and placed in filter membrane assemblies. Explants were then cultured at the liquid-air interface for 3 days in the presence of anti-laminin, anti-thrombospondin (another extracellular matrix constituent), preimmune serum, laminin-neutralized anti-laminin, or medium alone. Cultures were monitored by (direct) phase-contrast microscopy, light microscopy, and immunofluorescence. We found that anti-laminin antibodies altered normal lung morphogenesis in a dose-dependent manner. The anti-laminin-treated explants presented a marked inhibition of branching morphogenesis and a distortion of the bronchial tree. A lower rate of growth was also observed in the explants exposed to this antibody. High concentrations of anti-thrombospondin antibodies, normal rabbit serum, or laminin-neutralized anti-laminin antibodies had no effect on lung morphogenesis. These results were not modified by culturing the explants in submersion culture or on Vitrogen 100-coated surfaces.

Animals↗
PubMed1989

Virus-specific and autoreactive T cell lines isolated from cerebrospinal fluid of a patient with chronic rubella panencephalitis.

Using a recently described technique for expanding of human T lymphocyte populations from cerebrospinal fluid (CSF), we investigated the local cellular immune response in a patient with chronic rubella panencephalitis. A total of 328 T cell lines (TCLs) was established by seeding CSF cells at limiting dilution into histoplates in the presence of irradiated feeder cells and phytohemagglutinin (PHA)-containing conditioned medium. 80% of TCLs expressed the CD4+CD8-, 5% the CD4-CD8+ phenotype and 15% of TCLs contained different proportions of CD4+ and CD8+ cells. Of 191 TCLs analyzed, 85 were cytotoxic, as shown by their lectin-dependent cytotoxicity against allogeneic uninfected target cells. Eight of them demonstrated specificity for the autologous, rubella virus-infected target cells. When tested for antigen-specific proliferative activity, 26 TCLs responded to rubella antigen, 16 TCLs reacted to myelin basic protein (MBP), four TCLs to proteolipid protein (PLP), four to galactocerebrosides and two to actin. Fourteen out of 16 MBP-specific TCLs also responded, to a minor degree, to rubella antigen and/or actin. The results showed that the persisting rubella infection had given rise to autoreactive T cells. Virus-induced autoreactivity to brain antigens may be an important pathogenetic mechanism in other chronic inflammatory disorders of the CNS.

Actins↗
PubMed1988

In vivo expression of rubella antigens on human leucocytes: detection by flow cytometry.

Flow cytometry has been used to detect in vivo expression of rubella antigens on human leucocytes. Sequential samples of peripheral blood were obtained from four volunteers with naturally acquired rubella and five persons immunised with RA27/3 rubella vaccine. Leucocytes were stained for rubella antigens using a pool of rubella monoclonal antibodies. Rubella antigens were detected on the leucocytes of all four volunteers with naturally acquired rubella between 1 and 13 days after onset of illness. Viral antigens were expressed more frequently on the monocyte (9-51%) than the lymphocyte (less than 1-4%) and granulocyte (less than 1-3%) populations. Among the vaccines, rubella antigens were detected on the leucocytes of four of the five volunteers between 5 and 12 days after immunisation. The expression of viral antigens was more transient and the proportion of cells exhibiting rubella-specific fluorescence considerably lower following vaccination (1-12%) than natural infection (9-51%). Our results demonstrate that flow cytometry provides a rapid and sensitive analytical technique for detecting viral antigens on leucocytes from infected persons. Leucocytes may play an important role in the pathogenesis of rubella infection.

Adult↗
PubMed1985

Development and persistence of class-specific antibodies in the serum and nasopharyngeal washings of rubella vaccinees.

Serial samples of serum and nasopharyngeal washings were obtained from 43 volunteers given one of four rubella vaccines (HPV77.DE5, RA27/3, To-336, and Cendehill) and from nine naturally infected volunteers. Rubella-specific serum IgG was detected by radioimmunoassay for up to 12 years in all but one vaccinee, and booster responses occurred in 23.3% of vaccinees. Rubella-specific serum IgA was detected in 37 (90.2%) of 41 vaccinees one year after vaccination but in only five (45.5%) of 11 vaccinees tested 10-12 years after vaccination. Low levels of rubella-specific IgM detected by M-antibody capture radioimmunoassay persisted in seven volunteers--four of them HPV77.DE5 vaccinees--four more than one year after vaccination. Rubella-specific nasopharyngeal IgA was detected for up to five years after natural infection or vaccination with RA27/3 but for no longer than three years among Cendehill, HPV77.DE5, and To-336 vaccinees. Nasopharyngeal IgG antibodies were detected less frequently and at lower levels.

Adult↗
PubMed1983

Viremia, virus excretion, and antibody responses after challenge in volunteers with low levels of antibody to rubella virus.

After intranasal challenge of volunteers with rubella virus vaccine, viremia was assayed by inoculation of lymphocytes and whole blood from vaccines into Vero cell cultures. Viremia was detected in one of 19 volunteers with low levels (less than or equal to 15 IU) of preexisting vaccine-induced antibody to rubella virus, in eight of 10 seronegative volunteers, in none of 10 seropositive volunteers (antibody level, greater than 15 IU), and in none of 12 volunteers with low levels of preexisting naturally acquired antibody. Excretion of the virus was detected in four volunteers with preexisting vaccine-induced antibody but in none with naturally acquired antibody; eight of 10 seronegative volunteers excreted virus. After challenge, all volunteers with low levels of preexisting vaccine-induced antibody developed booster antibody responses that were measured by radioimmunoassay, and low levels of rubella-specific IgM were detected in four volunteers by M-antibody capture radioimmunoassay. One seronegative, one seropositive, and five low-titer volunteers developed arthralgia. The risk of viremia after challenge in individuals with low levels of rubella antibody appears to be low but may be higher than usual when immunity is induced by rubella vaccine.

Antibodies, Viral↗
PubMed1982

Rubella vaccination: persistence of antibodies for up to 16 years.

Sera from 123 volunteers vaccinated six to 16 years previously with one of four rubella vaccines (Cendehill, RA27/3, HPV77-DE5, and To-336) were tested for rubella antibodies by single radial haemolysis and radioimmunoassay. By radioimmunoassay 110 (89.4%) of the vaccinees had antibody concentrations greater than the minimum immune titre (that is, greater than 15,000 IU/1), 11 (8.9%) were seropositive but had concentrations less than or equal to 15,000 IU/1, and two (1.6%) were seronegative. Eight (6.5%) were seronegative by single radial haemolysis, of whom five had received Cendehill vaccine. Six to eight years after vaccination subjects who had received Cendehill vaccine had the lowest geometric mean titre of antibody by radioimmunoassay while the subjects who had received HPV77-DE5 vaccine had the highest. Although antibody concentrations less than or equal to 15,000 IU/1 were not detected among subjects given RA27/3 vaccine six to eight years previously, such low levels were detected in two (15.4%) vaccinated 11-16 years previously. These results emphasise the importance of long-term surveillance programmes so that vaccination policies may be reviewed.

Adult↗