Biomedical subjects
Publications and source records attributed to C S Easmon.
The interaction of Pneumocystis carinii purified from rat lungs with rat peritoneal macrophages and human circulating polymorphonuclear leucocytes was studied by amplified chemiluminescence and examination of stained cytospin preparations. A polyclonal rat antiserum to P. carinii was opsonic with both types of phagocyte. Complement had no opsonic properties alone but produced a synergic effect in combination with antibody.
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OBJECTIVE: To study the epidemiology of antibiotic resistant strains of Neisseria gonorrhoeae from sexually transmitted disease clinics in The Gambia. MATERIALS AND METHODS: One hundred and sixty five strains of N gonorrhoeae were tested for their antibiotic susceptibility, auxotype, serotype, and plasmid content. RESULTS: Of the total population 84 (51%) were non-penicillinase producing (nonPPNG) and 81 (49%) penicillinase-producing N gonorrhoeae (PPNG). There were 16 serovars, five auxotypes and 33 auxotype/serovar (A/S) classes in the total population and the nonPPNG. Among PPNG only five serovars, two auxotypes and nine A/S classes were found. One A/S class predominated, NR/IB-7 (86 isolates), of which 66 (77%) were PPNG and the remainder were chromosomally-mediated resistant N gonorrhoeae (CMRNG). These strains also showed reduced susceptibility to ciprofloxacin, ceftriaxone and tetracycline and were evenly distributed among patient groups. CONCLUSION: We have identified a relatively homogeneous gonococcal population with a core group of isolates exhibiting high levels of antibiotic resistance.
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One hundred and forty-seven isolates (128 strains) of Mycobacterium avium-intracellulare (MAI) were screened by agarose gel electrophoresis for the presence of plasmids. Plasmids were characterised according to size and by Southern hybridisation analysis of intact and restriction endonuclease-digested DNA. Two cloned MAI plasmids, pLR7 and pLR20, were used as probes. There was no significant difference in the rate of plasmid carriage in MAI strains isolated from patients with the acquired immuno-deficiency syndrome (AIDS) and from non-AIDS patients in the UK, but a higher rate of plasmid carriage was observed in a panel of American strains from AIDS patients. Plasmids were grouped into two broad categories: small (mostly 14-30 kb) and large (greater than 150 kb). Southern blot analysis identified two distinct groups of small plasmids, the majority of which showed homology with pLR7. Plasmids from this group were significantly more common in strains of serotypes 4 and 8 which are particularly associated with AIDS.
The interaction of Pneumocystis carinii purified from rat lung with human polymorphonuclear leukocytes (PMN) was studied using amplified chemiluminescence. Pre-incubation of PMN with granulocyte-macrophage stimulating factor or gamma interferon resulted in phagocyte stimulation.
OBJECTIVE: To study the epidemiology of Neisseria gonorrhoeae that exhibit both chromosomal and plasmid-mediated resistance to penicillin. MATERIALS AND METHODS: A total of 1589 strains of N gonorrhoeae isolated from patients attending St Mary's Hospital, London were tested for both their susceptibility to penicillin and for their auxotype and serotype. RESULTS: Of the 940 non-penicillinase producing N gonorrhoeae, 840 were considered penicillin sensitive (MIC less than or equal to 0.5 mg/l) and 100 were chromosomally-mediated resistant N gonorrhoeae (CMRNG), (MIC greater than or equal to 1.0 mg/l). Of the 649 penicillinase producing N gonorrhoeae (PPNG), 429 carried the 4.4 megadalton (MDa) penicillinase encoding plasmid and 220 carried the 3.2 MDa plasmid. CMRNG were predominantly serogroup IB (90%). PPNG with 3.2 MDa plasmid were the only group more often serogroup IA (58%) than IB (42%). Serovar IA-1/2 and requirement for arginine, hypoxanthine and uracil (AHU) were associated with increased susceptibility to penicillin whereas serovar IB-5/7 was associated with decreased susceptibility in nonPPNG. There was a significant difference in the distribution of the IA and IB serovars between PPNG carrying either the 4.4 MDa or 3.2 MDa plasmid. AHU and PAOU requiring strains were not found among PPNG and were uncommon among CMRNG. CONCLUSION: Some clear associations have been found but the pattern among PPNG appears more complex and in most instances could be related to clusters of a single strain over a short time span.
Pneumocystis carinii pneumonia was induced in rats by chronic corticosteroid immunosuppression. The parasite was separated from virtually all contaminating host cells using the technique of unit gravity sedimentation. Cellular contamination was routinely below 0.02%. The same technique allowed partial separation of the cyst from the trophozoite stage.
This review concentrates on two aspects of the pathogenesis of septicaemia. Firstly, those factors that enable bacteria to resist or avoid host defence mechanisms, including opsonization, phagocytosis, intracellular killing and terminal complement lysis of bacterial cell walls, are described. Secondly, the complication of septicaemia by septic shock with reference to the role played by lipopolysaccharide and tumour necrosis factor is reviewed, as are the possible implications for therapy.
Murine monoclonal antibodies (MAbs) and immune rabbit serum were raised against the rough mutant of Salmonella minnesota strain R595. These antibodies were tested for their ability to inhibit LPS-induced B-cell mitogenicity and neutralise LPS toxicity in chick embryos. Immune rabbit serum inhibited both mitogenicity and LPS lethality. None of the MAbs or a cocktail of antibodies were able to neutralise LPS lethality in chick embryos. However, they were able to inhibit mitogenicity by varying degrees.
Rabbit antiserum and murine monoclonal antibodies were raised against a strain of Haemophilus ducreyi. The antiserum gave high immunofluorescence titres and strong dot blot reactions with all H. ducreyi strains tested and the only cross reaction was with Bordetella pertussis. Three monoclonal antibodies, all of isotype IgG2a, also gave high immunofluorescence titres with H. ducreyi but did not cross react with any other species tested. Immunoblotting showed the monoclonal antibodies to react with a single polypeptide band of mol. wt 29,000 in the outer-membrane fraction of H. ducreyi. These antibodies have potential for use as diagnostic reagents and for investigating the pathogenicity of H. ducreyi.
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Non-penicillinase producing Neisseria gonorrhoeae isolated at St Mary's Hospital, London were examined for the prevalence of resistance to penicillin and for decreased susceptibility to cefuroxime. Of the 941 non-PPNG tested 100 (10.6%) were resistant to penicillin (minimum inhibitory concentration, MIC, greater than or equal to 1 mg/l) and were considered to be chromosomally-resistant N gonorrhoeae (CMRNG). Decreased susceptibility to cefuroxime (MIC, greater than or equal to 0.5 mg/l) was detected in 79% of the CMRNG. The CMRNG were also more often prototrophic and of serogroup IB than the remaining non-PPNG. The correlation coefficient for resistance to penicillin and cefuroxime was high, 0.79. Transformation experiments with both genetically-defined strains and transformants obtained using DNA from clinical isolates, showed that increased resistance to cephalosporins was acquired in three steps in close association with penicillin. We think this suggests that the loci controlling resistance to the cephalosporins are identical or closely linked to those controlling penicillin resistance.
Meropenem and imipenem were compared for their capacity to kill intracellular Staphylococcus aureus, to alter the pattern of lysis of serum-sensitive or resistant Escherichia coli, and to affect the uptake and intracellular killing of opsonized S. aureus by human neutrophils and mouse peritoneal macrophages. Meropenem killed intracellular S. aureus at concentrations equal to eight times the MBC while imipenem did not. Neither antibiotic had any significant effect on any of the other interactions studied.
Monoclonal antibodies were raised to the anaerobic curved rods, Mobiluncus curtisii subsp. curtisii NCTC 11656, M. curtisii subsp. holmesii NCTC 11657 and M. mulieris NCTC 11658. Three antibodies reacted with the two subspecies of M. curtisii and, when used in combination against clinical isolates, showed 100% sensitivity and specificity in immunofluorescence studies. Immunoblotting showed that two of these antibodies reacted with an epitope on a protein which had an electrophoretic mobility corresponding to a Mr of 75 Kda in the absence of a reducing agent and 82 Kda in its presence in both type strains and in clinical isolates. The third antibody reacted with an epitope in type strains which had a mobility corresponding to 75 Kda and was unaffected by a reducing agent. However, in clinical isolates the epitope was present on a protein of 75 Kda or 71 Kda, or on both. A fourth antibody showed reactivity with M. mulieris NCTC 11658 alone, but only 6 (24%) of 25 clinical isolates gave positive results by immunofluorescence. The epitope is believed to be present on a protein of greater than 90 Kda. All four antibodies were shown by immunogold staining to be directed against epitopes exposed on the cell surface.
To investigate changes in the gonococcal population over time, the plasmid content, serotype and auxotype have been determined for strains of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolated from patients attending the Praed Street Clinic for Sexually Transmitted Diseases between 1978 and 1987. Three distinct changes have been identified: (i) in the main plasmid type, from PPNG with the 3.2-Mda plasmid before 1982 to strains with the 4.4-Mda plasmid between 1982 and 1985; (ii) the decline during this time of strains also carrying the 24.5-Mda conjugal plasmid; (iii) the re-emergence of PPNG with the 3.2-Mda plasmid in 1986. The three typing methods used have identified eight clusters of strains which have been prevalent in different years between 1978 and 1987.
A serological classification scheme for Neisseria gonorrhoeae was used to investigate the epidemiological associations between gonococcal serotype and other bacterial and host characters. Six hundred and fifty clinical isolates of non-penicillinase producing N gonorrhoeae from the Praed Street Clinic, St Mary's Hospital, were included in this study. The strains collected represented 41 serovars, although 485 (75%) of the 650 strains belonged to five serovars. Strains of serovar IA-1/2 were commonly isolated from the cervix and tended to be sensitive to penicillin and moderately resistant to erythromycin. Strains of serovar IB-1 showed bimodal patterns of susceptibility to both penicillin and erythromycin and were obtained equally from all anatomical sites. Strains of serovar IB-2 were isolated more often from the rectum and were associated with homosexually acquired infections, whereas those of serovar IB-3 were sensitive to erythromycin and were rarely isolated from the rectum. Strains of IB-5/7 were more resistant to penicillin and erythromycin than strains of other serovars. The serological classification of N gonorrhoeae is thus a powerful tool that may be used to study biological characteristics of the gonococcus, such as susceptibility to antimicrobials and site tropism.
A monoclonal antibody raised against Haemophilus ducreyi was tested for its sensitivity and specificity as an immunofluorescence (IF) reagent using simulated vaginal smears containing H. ducreyi, smears taken from skin lesions of mice infected with H. ducreyi and patients from South Africa, Thailand and Malaysia with clinically diagnosed chancroid. The IF test was more sensitive than culture or Gram staining in the simulated smears, theoretically detecting less than 4 organisms/sample. It detected H. ducreyi in 95% of the animal lesions compared with 14% detected by culture. Immunofluorescence testing identified over 90% of culture-positive cases of chancroid but also detected organisms in some culture-negative cases where clinical evidence for the diagnosis was strong. These results suggest that this antibody may provide a simple, rapid and sensitive means of detecting H. ducreyi in cases of chancroid.