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Biomedical subjects

D M Weir

Publications and source records attributed to D M Weir.

At least 37 records · Page 2Linked to original sources
PubMed1999

Infection with respiratory syncytial virus enhances expression of native receptors for non-pilate Neisseria meningitidis on HEp-2 cells.

Respiratory virus infections have been suggested to be predisposing factors for meningococcal disease. Respiratory syncytial virus (RSV) affects young children in the age range at greatest risk of disease caused by Neisseria meningitidis. It has been previously shown that glycoprotein G expressed on the surface of RSV-infected HEp-2 cells (a human epithelial cell line) contributed to higher levels of binding of meningococci compared with uninfected cells. The aim of the present study was to examine the effect of RSV infection on expression of surface molecules native to HEp-2 cells and their role in bacterial binding. Flow cytometry and fluorescence microscopy were used to assess bacterial binding and expression of host cell antigens. Some molecules analysed in this study have not been reported previously on epithelial cells. RSV infection significantly enhanced the expression of CD15 (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01), and the latter two contributed to increased binding of meningococci to cells but not the Gram-positive Streptococcus pneumoniae.

Adhesins, Bacterial↗
PubMed1999

Binding of bacteria to HEp-2 cells infected with influenza A virus.

Epidemiological studies indicate influenza virus infection increases susceptibility to bacterial respiratory pathogens and to meningococcal disease. Because density of colonisation is an important factor in the development of bacterial disease, the objectives of the study were to use flow cytometry methods for assessment of bacterial binding and detection of cell surface antigens to determine: (1) if HEp-2 cells infected with human influenza A virus bind greater numbers of bacteria than uninfected cells; (2) if influenza infection alters expression of cell surface antigens which act as receptors for bacterial binding; (3) if neuraminidase affects binding of bacteria to HEp-2 cells. There was significantly increased binding of all isolates tested regardless of surface antigen characteristics. There were no significant differences between virus-infected and -uninfected Hep-2 cells in binding of monoclonal antibodies to Lewisb, Lewisx or H type 2. There were significant increases in binding of monoclonal antibodies to CD14 (P < 0.05) and CD18 (P < 0.01). Treatment of cells with monoclonal antibodies significantly reduced binding of Neisseria meningitidis strain C:2b:P1.2, CD14 (P < 0.001) and CD18 (P < 0.001). No reduction in binding of a strain of Streptococcus pneumoniae (12F) was observed in these experiments. Neuraminidase treatment of HEp-2 cells increased binding of monoclonal antibodies to CD14 (P < 0.01) and CD18 (P < 0.01). In three experiments, the increase in binding of meningococcal strain C:2b:P1.2 to neuraminidase-treated cells was not significant, but binding of Staphylococcus aureus strain NCTC 10655 was significant (P < 0.05).

Animals↗
PubMed1999

Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica.

Carriage of non-serogroupable Neisseria meningitidis or Neisseria lactamica induces antibodies protective against meningococcal disease. Antibodies directed against outer membrane proteins are bactericidal and the serotype and subtype outer membrane protein antigens are being examined for their value as vaccine candidates for serogroup B disease. The aim of this study was to examine the effect of carriage of these two Neisseria species among children and young adults on induction of antibodies to outer membrane components from strains causing disease in Greece. Among 53 patients with meningococcal disease, IgG or IgM antibodies were detected by ELISA in 9 of 13 (69%) from whom the bacteria were isolated and 27 of 40 (67%) who were culture-negative. For military recruits (n = 604), the proportion of carriers of meningococci with IgM or IgG to outer membrane proteins was higher than non-carriers, P < 0.05 and P = 0.000000, respectively. Among school children (n = 319), the proportion with IgM or IgG to outer membrane proteins for carriers of meningococci was higher compared with non-carriers, P = 0.000000 and P = 0000043, respectively. Carriage of N. lactamica was not associated with the presence of either IgM or IgG to the outer membrane proteins in the children. The higher proportion of children (50%) with IgM to outer membrane proteins compared with recruits (10%) might reflect more recent exposure and primary immune responses to the bacteria. The lack of association between antibodies to outer membrane proteins and carriage of N. lactamica could reflect observations that the majority of N. lactamica isolates from Greece and other countries do not react with monoclonal typing reagents. Bactericidal antibodies to meningococci associated with high levels of IgG to N. lactamica were found in a previous study; these are thought to be directed to antigens other than outer membrane proteins or capsules and imply antigens such as lipo-oligosaccharide are involved in induction of antibodies cross-reactive with meningococci.

Adolescent↗
PubMed1999

The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells.

Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.

Adult↗
PubMed1999

Recent emergence of serogroup C meningococcal disease in Greece.

The number of cases of meningococcal disease reported to the Meningitis Reference Laboratory in Athens rose dramatically in 1996-1997. The aims were (1) to determine if the increase was due to introduction of new strains, (2) to assess the geographic and age distribution of the cases, (3) to compare antibiotic sensitivity patterns of the current isolates with strains from the early 1990s. In 1993-1994, 15/19 (74%) of the cases for which information on age was available were in children < or = 5 years; in 1995-1997, 80/179 (45%) of cases were in children < or = 5 years and 99 (55%) in the older age range (P < 0.02). From 593 cases in 1993 1997, 214 (36%) isolates were available for characterisation. Serogroup B was predominant in the early 1990s, but by 1997, serogroup C accounted for 46/72 (64%) of isolates and serogroup B for 25/72 (35%). Serogroup B was predominant in children < or = 5 years (44/78, 56%) but only 19/99 (18%) of older children and adults (P=0.0000005). Sulfonamide resistance decreased from 10/22 (45%) in 1993-1994 to 27/192 (14%) in 1995-1997 (P<0.01). Multilocus enzyme electrophoresis of 70 strains obtained during this period identified the epidemic ET-15 clone in 24 (34.3)%. The profiles of the Greek ET-15 isolates were identical to C:2a:P1.2(P1.5) strains responsible for the epidemic in the Czech Republic which began in 1993. This genotype was not found in Greek strains isolated prior to 1993. We conclude that the increase in meningococcal disease is due to introduction of the epidemic serogroup C:2a:P1.2(P1.5) strain responsible for disease in the Czech Republic and Canada.

Adolescent↗
PubMed1999

Infection, inflammation and sleep: more pieces to the puzzle of sudden infant death syndrome (SIDS).

Risk factors for sudden infant death syndrome (SIDS) parallel those for respiratory tract infections; however, infectious agents suggested to be involved in SIDS do not fulfil Koch's postulates. No single agent has been identified in all cases and there is no suitable animal model for SIDS which could be used to test the candidate organisms. Based on epidemiological and experimental work by our group and others, we suggested some SIDS deaths are due to pathophysiological responses elicited by combinations of microbial products and/or cigarette smoke during a developmental stage when infants' endocrine responses are less able to "damp down" the effects of inflammatory mediators. Here we review evidence from studies on interactions between developmental and environmental risk factors that could affect 1) mucosal colonization of infants by potentially pathogenic bacteria, and 2) induction and control of infants', inflammatory responses to infectious agents. New evidence suggests that there are genetic factors involved in the induction of inflammatory responses to some bacterial antigens implicated in SIDS. Further investigation of the role of infection, exposure to cigarette smoke and inflammation in infants, particularly differences in ethnic groups at increased risk of SIDS, could lead to new insights into the events leading to a fatal outcome and perhaps to new intervention schemes to reduce further the incidence of these deaths.

Bacterial Infections↗
PubMed1998

Mannan binding lectin and the sudden infant death syndrome.

Mannan binding lectin (MBL) may be important for innate immunity and some cases of sudden infant death syndrome (SIDS) may be preceded by bacterial infection. Therefore, relative MBL deficiency might be associated with susceptibility to SIDS. We measured MBL concentrations in 46 SIDS infants and 26 controls. The proportion of subjects with low MBL values was similar in the two groups. However, the mean for the SIDS group (3 micrograms/ml) was higher than that of the controls (2.2 micrograms/ml; P < 0.05). We interpret this difference as due to acute phase responses and suggest these findings are consistent with the view that some cot deaths are preceded by bacterial infections.

Bacterial Infections↗
PubMed1997

Bacterial toxins and sudden unexpected death in a young child.

The sudden unexpected death of a six year old child following an upper respiratory tract infection is reported. Laboratory investigations revealed the presence of staphylococcal toxic shock syndrome toxin-1 (TSST-1) in samples of brain tissue. The significance of this finding is discussed.

Bacterial Toxins↗
PubMed1997

Isolation of a cell surface component of Helicobacter pylori that binds H type 2, Lewis(a), and Lewis(b) antigens.

BACKGROUND & AIMS: Individuals of blood group O and nonsecretors of ABO blood group antigens are more susceptible to peptic ulcers. The aim of this study was to determine if blood group antigens associated with group O or secretor status are epithelial cell receptors for Helicobacter pylori. METHODS: Bacterial binding and binding of monoclonal antibodies to H type 2, Lewis(a), and Lewis(b) to Kato III, buccal epithelial, and gastric mucosal cells were shown by flow cytometry. Bacterial outer membrane proteins eluted from H type 2, Lewis(a), or Lewis(b) were shown by polyacrylamide gel electrophoresis. RESULTS: Kato III and human epithelial cells bound each monoclonal antibody; O cells bound more anti-H type 2 (P < 0.05). Binding indices for H. pylori correlated with those for anti-H type 2 (P < 0.005) and anti-Lewis(b) (P < 0.001) but not anti-Lewis(a). A 61-kilodalton protein was eluted from H type 2, Lewis(a), or Lewis(b). CONCLUSIONS: Our results indicate that H type 2 is an important receptor for the 61-kilodalton bacterial adhesin, partly explaining increased susceptibility of individuals of blood group O to ulcers. Lewis(b) binds H. pylori more efficiently than Lewis(a). If these interactions occur in vivo, lack of Lewis(b) in mucosal fluids of nonsecretors may contribute to colonization by H. pylori.

Antibodies, Monoclonal↗
PubMed1996

Helicobacter pylori in the mouth--negative isolation from dental plaque and saliva.

OBJECTIVE: To determine the colonization of Helicobacter pylori in dental plaque and saliva of individuals with H. pylori-associated gastritis. PATIENTS AND METHODS: One hundred and twenty adult dyspeptic patients attending for outpatient endoscopy were randomly selected. Saliva, dental plaques and antral biopsies were collected and cultured in Dent's medium. Antral biopsies were also taken for histological confirmation of colonization. RESULTS: Eleven patients were withdrawn owing to poor tolerance of endoscopy. Fifty-two patients (47%) were found to be H. pylori positive on culture from antral biopsies and on antral histology. H. pylori was not isolated from saliva and dental plaques in any of the patients irrespective of their infective status. The H. pylori seropositivity rate was higher in the Japanese (72%) than in the Dutch (33%). CONCLUSION: We failed to isolate H. pylori from saliva and dental plaque in a group of dyspeptic patients with H. pylori-associated gastritis. We believe that our finding strongly suggests that oral to oral route is not an important mode of transmission in the adult population.

Adult↗
PubMed1996

Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS).

Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus, to human epithelial cells: expression of the Lewis(a) antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis(a) (P < 0.05) and Lewis(x) (P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers (P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 (P < 0.001) and 250825 (P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis(x) (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis. Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993-1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.

Antibodies, Monoclonal↗
PubMed1996

Serum bactericidal activity in a secondary school population following an outbreak of meningococcal disease: effects of carriage and secretor status.

Sera obtained from 106 children following an outbreak of Neisseria meningitidis (B:4:P1.15) were screened for bactericidal antibodies against isolates of meningococci and Neisseria lactamica. Most had high titres of antibodies to N. lactamica and N. meningitidis NG:4:- but not to capsulate isolates: B:4:P1.15; B:15:P1.16; B:4:-; C:4:-. Bactericidal activity was higher for both carriers and secretors but the differences were not significant. Bactericidal activity was not associated with total or specific IgA or IgM. Carriers had significantly higher levels of IgG to N. lactamica but not to NG:4:- in sera with bactericidal activity for each of the capsulate strains. Among non-carriers, higher levels of IgG to N. lactamica were associated with killing of B:4:P1.15 and B:4:-. Secretors' sera with bactericidal activity had significantly higher levels of IgG to N. lactamica compared with sera that were not bactericidal. This was not observed among non-secretors. Antibodies to the outbreak strain were adsorbed by all Neisseria isolates tested and absorption of sera with N. lactamica alone completely removed the bactericidal activity against the outbreak strain.

ABO Blood-Group System↗
PubMed1996

Distribution of AB0 and Lewis blood groups in Greece.

The distribution of AB0 blood and Lewis blood group phenotypes in 2988 Greek individuals was determined with monoclonal reagents and the results analysed according to their birthplace or that of their parents when they were born in the same region. Overall, the AB0 blood groups distribution was similar to that reported for Greek soldiers in 1919. The only unusual variation was that 29% of the donors born in Thrace were group B. The proportion of Lewis (a-b-) individuals ranged from 1-3%. The frequency of Le (a+b-) donors (non-secretors) ranged from 16% in Thessaly to 27% in East Macedonia, Epirus and those born abroad; the Le (a-b+) frequency was 71-83%.

ABO Blood-Group System↗
PubMed1995

Increased natural autoantibody activity to cytoskeleton proteins in sera from patients with necrobiosis lipoidica, with or without insulin-dependent diabetes mellitus.

Necrobiosis lipoidica (NL), a skin disease, is associated with insulin-dependent diabetes mellitus (IDDM). Natural autoantibody (NAb) activity in sera from 16 patients suffering from NL, with or without IDDM, was compared to that in sera from 41 patients with IDDM and 43 healthy controls. Isotype-specific enzyme-linked immunosorbent assays (ELISAs) were used to detect NAbs against actin, myosin, keratin, desmin, troponin, tropomyosin, thyroglobulin, insulin, single-stranded DNA and the hapten trinitrophenyl. NAb activity was significantly higher in sera from patients with NL (either with or without IDDM), compared with that detected in sera from patients with IDDM which was similar to that of healthy individuals. High proportion of NL sera exhibited increased IgG anti-tropomyosin (69%), anti-troponin, anti-desmin and anti-keratin (50% each), anti-insulin (44%) and anti-trinitrophenyl (31%) activities, as well as increased IgA and IgM anti-keratin activities (26% and 31%, respectively). The great majority (88%) of positive sera were polyreactive and contained NAbs, polyspecific and monospecific (as demonstrated by immunoadsorption studies), belonging to more than one isotype; there was no predominant serological reactivity pattern. In conclusion, increased NAb activity to cytoskeleton proteins is associated with the dermatological disease NL and not to the overlapping autoimmune disease (IDDM). The origin and significance of these NAbs is discussed.

Adult↗
PubMed1994

Sudden unexpected nocturnal deaths among Thai immigrant workers in Singapore. The possible role of toxigenic bacteria.

Sudden Unexpected Nocturnal Deaths (SUND) occur in young, apparently healthy immigrant workers from Thailand, the Philippines and Bangladesh living among ex-patriot labour forces in countries such as Singapore and Saudi Arabia. Several factors associated with these deaths are similar to those observed for Sudden Infant Death Syndrome (SIDS): sleep related and mainly nocturnal occurrence; no prodromal illnesses other than mild respiratory tract infection; exposure to cigarette smoke; absence of invasive microorganisms at autopsy. The hypotheses proposed to explain these deaths in adults are examined. Based on our studies of the role toxigenic bacteria might play in some cases of SIDS, we suggest a new approach to the investigation of SUND.

Adult↗
PubMed1994

Lewis antigen expression on human monocytes and binding of pyrogenic toxins.

Toxigenic bacteria such as Bordetella pertussis and Staphylococcus aureus have been implicated in some cases of sudden infant death syndrome (SIDS). We have previously demonstrated that the Lewis(a) antigen is an epithelial cell receptor for S. aureus, and this study demonstrated that Lewis(a) on human monocytes is also a receptor for staphylococcal enterotoxin B (SEB). Values obtained in assays for production of TNF-alpha and nitric oxide were greater for monocytes treated with SEB compared with those treated with lipopolysaccharide (LPS). Exposure to LPS increased the expression of Lewis(a) on monocytes. These results are discussed with reference to the reported enhancement of endotoxic shock by pyrogenic toxins.

Antibodies, Monoclonal↗