PubMed Health⌕ Search

Biomedical subjects

D M Weir

Publications and source records attributed to D M Weir.

At least 55 records · Page 3Linked to original sources

Evidence for the role of glycoprotein G of respiratory syncytial virus in binding of Neisseria meningitidis to HEp-2 cells.

Viral glycoproteins G and F are expressed on the surface of cells infected with respiratory syncytial virus (RSV). We investigated the role of these proteins in the previously reported enhanced binding of Neisseria meningitidis to RSV-infected HEp-2 cells. Virus particles attached to bacteria were detected by immunofluorescence with flow cytometry. Binding of FITC-labelled bacteria to RSV-infected cells was significantly inhibited by monoclonal antibody against glycoprotein G. Unlabelled bacteria interfered with binding of the anti-G monoclonal antibody to these cells. These interactions were not found with a monoclonal antibody against glycoprotein F. We propose that glycoprotein G of RSV expressed on the surface of infected cells might act as an additional receptor for meningococci.

Antibodies, Monoclonal↗

Isolation of an adhesin from Staphylococcus aureus that binds Lewis a blood group antigen and its relevance to sudden infant death syndrome.

A 67 kDa protein was isolated from cell membrane preparations of Staphylococcus aureus (NCTC 10655) by affinity adsorption with synthetic Lewis a antigen conjugated to Synsorb beads. Pre-treatment of buccal epithelial cells expressing Lewis a with the purified protein reduced binding of the staphylococcal strain to a greater extent than the material not bound to the Synsorb beads. The significance of this work is discussed with reference to expression of Lewis a antigen in infants and the proposed role of toxigenic strains of staphylococci in some cases of sudden infant death syndrome.

Adhesins, Bacterial↗

Detection of microbial surface antigens that bind Lewis(a) antigen.

There is evidence that the Lewis(a) blood group antigen is one of the receptors for a number of potentially pathogenic microorganisms. To determine how widely distributed the microbial adhesins are that bind this antigen, anti-idiotypic antibodies produced against monoclonal anti-Lewis(a) were used in coagglutination assays to screen a variety of species. The following were agglutinated: 7/7 strains of Staphylococcus aureus; 10/19 (53%) strains of Neisseria meningitidis; 8/13 (62%) strains of Haemophilus influenzae; 1/3 strains of Helicobacter pylori; 1/2 strains of Neisseria gonorrhoeae; 1/2 strains of Candida albicans. The application of the anti-idiotypic antibodies to studies of host cell receptors, isolation of adhesins and development of new epidemiological typing reagents is discussed.

Adhesins, Bacterial↗

The role of infectious agents in sudden infant death syndrome.

Epidemiological factors associated with susceptibility to respiratory infections are similar to those associated with Sudden Infant Death Syndrome. Here we review the evidence that respiratory pathogens might be involved in some cases of Sudden Infant Death Syndrome in the context of factors identified in epidemiological studies of cot deaths: the age range affected; mother' smoking; respiratory viral infections; immunisation status. Both laboratory and epidemiological evidence suggests that vulnerability of infants to infectious agents depends on interactions between genetic, developmental and environmental factors that contribute to colonisation by microorganisms, the inflammatory and specific immune responses and the infants' physiological responses to inflammatory mediators. A model is proposed to explain how microorganisms might trigger a series of events resulting in some of these unexpected deaths and discusses how the the present recommendations regarding child care practices might help reduce the numbers of Sudden Infant Death Syndrome cases associated with infectious agents.

Bacterial Infections↗

Inhibitory effect of saliva from secretors and non-secretors on binding of meningococci to epithelial cells.

Carriage of Neisseria meningitidis B:4:P1.15 was higher among non-secretors during a school outbreak of meningitis; non-secretors had lower levels of anti-meningococcal salivary IgM. Flow cytometry was used to assess effects of secretor and non-secretor saliva on binding of B:4:P1.15 to buccal epithelial cells: (1) to assess inhibition by IgA and IgM; and (2) to assess contributions of salivary antibodies to inhibitory activities. Greater inhibition was obtained with secretor saliva: pooled (P = 0.049); fresh (P = 0.0001). Purified IgA (P = 0.02) and IgM (P = 0.03) were equally inhibitory. After absorption of anti-meningococcal antibodies, there was still significant inhibitory activity in the pools: secretors (P = 0.018); non-secretors (P = 0.005). These results indicate that both secretory immunoglobulins and other factors contribute to protection against colonisation by meningococci and might explain the increased carriage of B:4:1.15 in this population.

Adult↗

The potential role of bacterial toxins in sudden infant death syndrome (SIDS).

Toxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence that Clostridia spp. are associated with SIDS in Britain, strains of Staphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy The pyrogenic toxins, produced by some strains of group A Streptococcus pyogenes as well as staphylococci, are powerful "superantigens" that have significant physiological effects including induction of fever > 38 degrees C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infant's expression of Lewis(a) antigen which acts as a receptor for some microorganisms; viral infections; the effect of mother's smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths.

Bacterial Infections↗

Assessment of Lewis blood group antigens and secretor status in autopsy specimens.

The ability of enzyme linked immunosorbent assays (ELISA) to detect Lewis and H antigens in secretions obtained from 280 autopsies was assessed. The ELISA results were compared with those for matched blood specimens examined by agglutination of erythrocytes by monoclonal anti-Lewis(a) and anti-Lewis(b) antibodies. There was good agreement between the results for the two tests and the ELISAs could be used to determine secretor status of the subject. While determination of ABO group with monoclonal anti-A and anti-B was possible even with lysed blood, the results for Lewis typing by erythrocyte agglutination were poor if the sample was lysed or partially lysed. Detection of the antigens by ELISA was as efficient among elderly subjects as among younger ones and both H and Lewis antigens could be detected on erythrocytes and in secretions up to 127 h after death.

Adolescent↗

Factors enhancing adherence of toxigenic Staphylococcus aureus to epithelial cells and their possible role in sudden infant death syndrome.

Toxigenic strains of Staphylococcus aureus have been suggested to play a role in sudden infant death syndrome (SIDS). In this study we examined two factors that might enhance binding of toxigenic staphylococci to epithelial cells of infants in the age range in which cot deaths are prevalent: expression of the Lewis(a) antigen and infection with respiratory syncytial virus (RSV). By flow cytometry we demonstrated that binding of three toxigenic strains of S. aureus to cells from nonsecretors was significantly greater than to cells of secretors. Pre-treatment of epithelial cells with monoclonal anti-Lewis(a) or anti-type-1 precursor significantly reduced bacterial binding (P < 0.01); however, attachment of the bacteria correlated only with the amount of Lewis(a) antigen detected on the cells (P < 0.01). HEp-2 cells infected with RSV bound significantly more bacteria than uninfected cells. These findings are discussed in context of factors previously associated with SIDS (mother's smoking, bottle feeding and the prone sleeping position) and a hypothesis proposed to explain some cases of SIDS.

Antibodies, Monoclonal↗

Effect of respiratory syncytial virus infection on binding of Neisseria meningitidis and Haemophilus influenzae type b to a human epithelial cell line (HEp-2).

It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virus-infected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0.001) and Hib (P < 0.01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.

Bacterial Adhesion↗

Serogroups, serotypes and subtypes of Neisseria meningitidis isolated from patients and carriers in Greece.

The increase in the number of cases of meningococcal disease reported to the Ministry of Health in Athens since 1989 prompted the present study to determine if isolates from patients or carriers expressed the same phenotypic characters as those in other parts of Europe. None of the isolates from patients (31) or carriers (547) expressed the antigenic combinations associated with outbreaks in northern Europe, i.e., B:15:P1.16 or B:4:P1.15. The majority of the Greek isolates did not react with any of the six monoclonal serotype reagents tested; however, most reacted with one or more of the 11 monoclonal subtype antibodies. The results suggest that additional serotype reagents are needed for epidemiological studies in southeastern Europe and that vaccines based on serotype antigens developed against outbreak strains in northern Europe would not be effective in Greece.

Adolescent↗

The effect of Mycoplasma arthritidis infection on the kinetics of colloidal carbon clearance in mice.

The activity of phagocytes from A/J mice was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. Phagocytic activity was significantly depressed 12 h post-infection (P = 0.001) and returned to normal values at 24 h. For animals examined 2 and 7 days post-infection, the overall phagocytic activity increased significantly (P < 10(-4). Phagocytic activity gradually decreased and returned to that of the control group by the end of the fourth week. The relative weights of liver and spleen were significantly increased from the 2nd day post infection (P = 0.0028 and P = 0.0014 respectively) and remained increased until the end of the experiment. The early depressive effect on phagocytic activity may be related to superantigen activity with the production of mediators such as macrophage deactivating factor. The later expansion of the macrophage population might bring about the stimulation of autoreactive clones of T and B cells and be responsible for the chronic arthritis that developed in the mycoplasma treated mice.

Animals↗

Factors affecting carriage of Neisseria meningitidis among Greek military recruits.

Greek military recruits (993) were examined for carriage of meningococci during July 1990. Blood, saliva and throat swab specimens were obtained and each recruit answered a questionnaire providing information on age, education (a measure of socioeconomic level), place of residence, smoking habits and recent infections. The overall carriage rate was 25% but differed between the two camps: 79/432 (18%) in Camp A and 168/561 (30%) in Camp B (P less than 0.0005). In Camp B, there were significantly higher proportions of recruits who were non-secretors (P less than 0.0005), and/or heavy smokers (P less than 0.0005). They were also younger (less than 19 years old) (P less than 0.001), and on the whole had fewer years of education (P less than 0.0005). By univariate analysis, carriage was significantly associated with smoking. By multiple logistic regression analysis, carriage was associated with smoking (P less than 0.001), age (P less than 0.01) and the camp in which the recruits were based (P less than 0.01). Among recruits in Camp B, 15/38 (40%) of those with recent viral infections were carriers compared with 30% for the camp in general.

Adolescent↗

Antibiotic sensitivities of Neisseria meningitidis isolates from patients and carriers in Greece.

Usage of antibiotics in southern Europe is less well regulated than in northern countries. The proportion (48%) of meningococci in Spain insensitive to pencillin (MIC greater than or equal to 0.1 mg/l) prompted this investigation of antibiotic sensitivities of isolates from Greek patients with meningitis (31) and carriers (47 school-children and 472 recruits). The agar dilution method was used to determine MIC to penicillin G (PN), sulphamethoxazole (SU), rifampicin (RF), cefaclor (CF) and ciprofloxacin (CP). The proportion of isolates insensitive to PN was 48% for isolates from patients, 19% from school-children and 36.6% from recruits. Resistance to SU (MIC greater than or equal to 16 mg/l) was found in 16% of those from patients, 10.6% from children and 40% from recruits. None of the isolates from patients was resistant to RF (greater than or equal to 1 mg/l) but 6% of those from carriers were. Resistance to CF (greater than or equal to 4 mg/l) was found in 9.2% of patient isolates, 6.4% from children and 23.7% from recruits. All isolates except one were sensitive to CP (MIC range less than 0.0015-0.125 mg/l). Resistances to PN, SU and RF were analysed by serogroup, serotype and subtype of the bacteria. The proportion of resistant isolates showed some variation between different areas of Greece, but it was not statistically significant.

Adolescent↗

Secretor status and humoral immune responses to Neisseria lactamica and Neisseria meningitidis.

Non-secretors of ABO blood group antigens are over-represented among patients with meningococcal diseases. Lower levels of secretory IgA reported for non-secretors have been suggested to compromise mucosal defences. Total serum and salivary IgG, IgA and IgM and levels of these isotypes specific for Neisseria lactamica and five isolates of meningococci were determined by ELISA for 357 pupils and staff of a secondary school in which an outbreak of meningitis occurred. There were no differences in total or specific levels of serum IgG, IgA or IgM or salivary IgG or IgA of secretors compared with non-secretors. Non-secretors had significantly lower levels of salivary IgM (P = 0.022). A similar pattern was observed for levels of IgM specific for N. lactamica and five meningococcal isolates. The significance of these results is discussed with reference to the role of secretory IgM in protection of mucosal surfaces in infants.

Adolescent↗

Factors influencing oral carriage of yeasts among individuals with diabetes mellitus.

A total of 439 individuals with diabetes mellitus were examined for carriage of yeasts by the oral rinse and palatal swab techniques. Eighteen genetic or environment variables were assessed for their contribution to carriage of yeasts. The factor contributing to palatal and oral carriage of yeasts among individuals with insulin dependent diabetes mellitus (IDDM) was age (P < 0.01). The factor contributing to palatal carriage of yeasts among individuals with non-insulin dependent diabetes mellitus (NIDDM) was poor glycaemic control (glycosuria P < 0.01); carriage in the oral cavity as a whole was influenced additionally by non-secretion of ABH blood group antigens (P < 0.05). Introduction of a denture altered the above risk factors. For individuals with IDDM, oral carriage was associated with the presence of retinopathy (P < 0.05); palatal carriage was influenced by poor glycaemic control (HbA1P < 0.01, plasma glucose levels P < 0.05) and age (P < 0.05). For those with NIDDM, palatal carriage was associated with continuous presence of the denture in the mouth (P < 0.01); oral carriage was associated with plasma glucose levels (P < 0.05).

Adult↗

Susceptibility to infection in relation to SIDS.

Because there is little evidence that invasive bacterial diseases contribute to cot deaths, most studies on infectious causes of SIDS have focused on viruses or toxin producing bacteria. Although epidemiological studies found marginally significant associations between influenza virus and SIDS, respiratory syncytial virus (RSV) was isolated from 90% of older infants with SIDS. There are conflicting reports that some toxigenic bacteria (Clostridium botulinum, Clostridium difficle, enterotoxigenic Escherichia coli and Staphylococcus aureus) might be implicated in cot deaths. S aureus are common micro-organisms and their toxins are very powerful. As the pyrogenic toxic shock syndrome toxin of S aureus can kill a previously healthy adult, it might easily kill a small infant. Based on our studies on susceptibility of infants to other infections, we suggest the following might be factors leading to colonisation of infants by toxin producing S aureus: The Lewis blood group antigen appears to act as a receptor for some micro-organisms. Epithelial cells expressing high concentrations of Lewis bound appreciably more toxin producing S aureus than cells expressing low concentrations of the antigen. Lewis is expressed in secretions of nearly 90% of infants aged 3 months, the peak age for SIDS. RSV infects about 50% of infants by the first year of life and it is often isolated from infants with SIDS. Studies in our laboratory indicate that RSV infected HEp-2 cells bind more toxin producing S aureus than uninfected controls.

ABO Blood-Group System↗

Association between secretor status and respiratory viral illness.

OBJECTIVE: To determine whether non-secretion of blood group antigens is associated with respiratory virus diseases. DESIGN: Study of secretor status in patients with respiratory virus diseases determined by an enzyme linked immunosorbent assay (ELISA) developed to identify Lewis (Le) blood group antigen phenotypes (Le(a) non-secretor; Le(b) secretor). SUBJECTS: Patients aged 1 month to 90 years in hospital with respiratory virus diseases (584 nasal specimens). MAIN OUTCOME MEASURES: Criteria for validation of ELISA (congruence between results on ELISA testing of 1155 saliva samples from a previous study and previously established results on haemagglutination inhibition (HAI) testing, proportions of Le(a), Le(b), and Le- phenotypes in 872 samples of nasal washings from a previous study compared with the normal population). Secretor status of patients determined by ELISA and viruses isolated. RESULTS: Agreement between HAI and ELISA for 1155 saliva samples was 97%. Lewis antigens were detected by ELISA in 854 (97.9%) of nasal washings (Le(a) 233 (26.7%), Le(b) 621 (71.2%), and Le- 18 (2.1%)) in proportions predicted for a northern European population. Secretors were significantly overrepresented among patients from whom influenza viruses A and B (55/64, 86%; p less than 0.025), rhinoviruses (63/72, 88%; p less than 0.01), respiratory syncytial virus (97/109, 89%; p less than 0.0005), and echoviruses (44/44, p less than 0.0005) had been isolated compared with the distribution of secretors in the local population. CONCLUSION: Secretion of blood group antigens is associated with respiratory virus diseases.

Adolescent↗