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R A Wall

Publications and source records attributed to R A Wall.

At least 37 records · Page 2Linked to original sources
PubMed1990

Immunogenicity and cross-reactivity of the 70-Kda iron-regulated protein of Neisseria meningitidis in man and animals.

The immune response to different serogroups and serotypes of N. meningitidis has been examined in acute and convalescent sera from patients with meningococcal diseases. The focus of the study was the c. 70-Kda iron-regulated outer-membrane protein (FeRP-70). FeRP-70 was demonstrated on all strains of different serogroups and serotypes examined by sodium dodecylsulphate-polyacrylamide gel electrophoresis or Western blots of outer-membrane proteins (OMPs). Immunoblotting experiments demonstrated the presence of considerable amounts of anti-FeRP-70 IgG antibodies in the acute and convalescent sera of six patients; the antibodies reacted with homologous and heterologous strains. However, sera from two patients who died of severe meningococcal septicaemia had no antibodies against FeRP-70 or any other OMPs demonstrable by immunoblotting. Absorbed rabbit hyperimmune sera reacted with FeRP-70 of their homologous strains, but, unlike human sera, with only a few of the heterologous strains. We believe that FeRP-70 is strongly immunogenic in vivo, cross-reactive amongst different strains, and that man and animals differ considerably in their response to similar meningococcal antigens. The functional attribution of human antibody response against this protein requires further exploration.

Animals↗
PubMed1989

Epitopes of serogroup B Neisseria meningitidis analysed in vitro and directly from cerebrospinal fluid.

Two type B15 P1.16 strains of Neisseria meningitidis were examined by immunogold electron microscopy for accessibility of two outer membrane protein (OMPs) to monoclonal antibodies. Both strains exhibited cell-to-cell variation of one epitope of the Class 3 OMP (P3.15) and one of the Class 1 OMPs (P1.16) when grown in vitro. One strain, a nasopharyngeal isolate revealed this variation to be growth-phase independent and double labelling of both epitopes showed independent variation. CSF containing N. meningitidis was stored in liquid nitrogen without laboratory processing at the time of isolation of the second strain. Direct analysis of the organisms showed no cell-to-cell variation and immunoglobulin G on the surface. However, while there were similar labelling densities of the Class 1 epitope in vivo compared with either strain grown in vitro, there was a lower labelling density of the Class 3 epitope in vivo that was not caused by freeze-thawing. This reduction may be due to decreased expression of this epitope in vivo which casts doubts on the use of the Class 2/3 OMP as a vaccine candidate.

Adult↗
PubMed1989

Clonal and variable properties of Neisseria meningitidis isolated from cases and carriers during and after an epidemic in The Gambia, West Africa.

A representative collection of meningococci was isolated from cases and healthy carriers in The Gambia between 1982 and 1988, during and after an epidemic of meningococcal meningitis. These bacteria were subjected to a clonal analysis. All serogroup A bacteria from both cases and carriers were of one clone (A IV-1). Several unrelated clones were observed among serogroup 29E and serogroup Y carrier strains. The serogroup A strains were uniform for serotype and subtype antigens (serotype 4, subtype P1.7) and antibiotic sensitivity pattern. Occasional strains varied in their lipopolysaccharide (LPS), DNA fingerprint pattern, and/or the quantitative expression of the class 1 protein. A high degree of strain-specific variation was found for the expression of class 5 proteins, pili, and sulfonamide sensitivity. The frequency of strains expressing reduced amounts of the class 1 protein, altered LPS, and/or increased amounts of capsular polysaccharide rose among case strains obtained after the epidemic had ceased. These strains seem to be generally resistant to antibody-mediated bactericidal activity.

Antibodies, Monoclonal↗
PubMed1988

2-Phenylpyridine and 3-phenylpyridine, constituents of tea, are unlikely to cause idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (PD) is likely to be caused by one or more unidentified neurotoxins, present in the environment or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in lower primates and mice and in humans inadvertently exposed to it that closely resemble those found in PD. 2-Phenylpyridine (2-PP) and 3-phenylpyridine (3-PP), both of them present in tea, are the only MPTP analogues that are known to be present in the human diet. We exposed C57 black mice, animals very sensitive to the dopaminergic neurotoxicity of MPTP, to prolonged parenteral and oral administration of large doses of 2-PP, and to prolonged parenteral administration of the N-methylated tetrahydro derivatives of 2-PP and 3-PP. The latter are closer chemical analogues of MPTP than are 2-PP and 3-PP themselves. None of these MPTP analogues lowered the contents of dopamine and its metabolites in the striatum of mice. We speculate that the neurotoxins which cause PD are unlikely to resemble MPTP structurally, and we suggest that the search for chemical causes of PD should be directed to a wider variety of compounds encountered by humans.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Sequelae of epidemic meningococcal meningitis in Africa.

Audiological and other long-term neurological sequelae were determined in 157 cases and their controls matched for age, sex and village 6 to 12 months after an epidemic of group A meningococcal meningitis in rural West Africa. 19 cases (12.1%) and 3 controls (1.9%) had moderate or severe neurological sequelae of any type (P less than 0.001); 6 cases (3.9%) and no controls had severe or profound sensorineural hearing loss (P = 0.03). There was no difference in conductive hearing loss between cases and controls. Other cranial nerve sequelae (except visual defects) and generalized neurological and motor and co-ordination sequelae were also significantly increased in cases. Sensorineural hearing loss and other cranial nerve sequelae occurred significantly more frequently in males than in females, and co-ordination sequelae more frequently in cases aged 10 years or more than in younger cases. Sensorineural hearing loss and loss of visual acuity were found significantly more frequently in cases whose treatment was delayed for 4 d or more, compared with those who received treatment sooner.

Adolescent↗
PubMed1988

Comparison of clonal analysis and DNA restriction analysis for typing of Neisseria meningitidis.

We have formerly described a clonal analysis of 423 serogroup A isolates of Neisseria meningitidis which distinguished 21 clones and 34 electrophoretic types. The clones were found to be uniform within distinct epidemiological situations and distinct between different sets of epidemics. Strains representative of the 34 electrophoretic types have now been analyzed by restriction endonuclease digestion of their genomic DNA's. The results correlated partially with the clonal assignments; the discrepancies were epidemiologically more consistent with the interpretation of the clonal analysis than with that of the restriction endonuclease analysis.

Bacterial Typing Techniques↗
PubMed1988

Meningococcal carriage, meningococcal disease and vaccination.

Group A meningococcal carriage rates were determined 6 months before and 6 and 18 months after a mass vaccination campaign with a combined group A and group C meningococcal polysaccharide vaccine in a rural area of The Gambia. During the first pre-vaccination survey, performed during an outbreak of meningococcal disease, the carriage rate was high (16%). The carriage rate remained high during a second survey made 6 months after a vaccination campaign that covered approximately 90% of the study population. A year later very few group A meningococcal carriers were found. Membrane protein patterns of isolates obtained before and after vaccination were similar. We conclude that vaccination had little influence on the carriage rate of group A meningococci but that this was influenced by changes in herd immunity or by other unidentified factors.

Bacterial Outer Membrane Proteins↗
PubMed1988

The comparative in-vitro activity of ofloxacin.

The antibacterial activity of ofloxacin, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with that of nalidixic acid, norfloxacin, enoxacin, pefloxacin and ciprofloxacin by determination of minimum inhibitory concentrations (MICs). Ofloxacin was very active against nalidixic acid-susceptible isolates of the Enterobacteriaceae (MIC less than or equal to 0.12 mg/l) and was also active against strains resistant to nalidixic acid (MIC less than or equal to 2 mg/l). The activity was similar to norfloxacin, enoxacin and pefloxacin but some four-fold less than that of ciprofloxacin. All of the fluoroquinolones were highly active against Vibrio cholerae (MIC less than or equal to 0.015 mg/l), V. parahaemolyticus (MIC less than or equal to 0.12 mg/l) Aeromonas hydrophila (MIC less than or equal to 0.03 mg/l), Plesiomonas shigelloides (MIC less than or equal to 0.015 mg/l), Campylobacter jejuni (MIC less than or equal to 0.5 mg/l), Neisseria spp., Haemophilus influenzae, H. ducreyi, Bordetella pertussis and Legionella pneumophila (MIC less than or equal to 0.06 mg/l for all species). Ofloxacin, ciprofloxacin and pefloxacin (MIC less than or equal to 1, 2 and 2 mg/l, respectively) showed similar activity against Staphylococcus spp. and were somewhat more active than enoxacin (MIC less than or equal to 4 mg/l) and norfloxacin (MIC less than or equal to 8 mg/l). Ofloxacin was moderately active against beta-haemolytic Streptococcus spp. (MIC less than or equal to 2 mg/l), Corynebacterium diphtheriae (MIC less than or equal to 1 mg/l) and Cory. jeikeium (MIC less than or equal to 2 mg/l) and somewhat less active against alpha- and non-haemolytic Streptococcus spp., Str. pneumoniae and Listeria monocytogenes (MIC less than or equal to 4 mg/l for all species) and Str. faecalis (MIC less than or equal to 8 mg/l). The activity of ofloxacin, against these species, was similar to ciprofloxacin and four to eight times greater than norfloxacin, enoxacin and pefloxacin. Ofloxacin, and all of the fluoroquinolones, were less active against anaerobic than aerobic bacteria. Clostridium perfringens (MIC less than or equal to 1 mg/l) was more susceptible to ofloxacin than were other anaerobic species and Cl. difficile (MIC less than or equal to 16 mg/l) was more resistant. Ofloxacin was the most active compound tested against Chlamydia trachomatis SA2f (MIC less than or equal to 0.5 mg/l) with only ciprofloxacin (MIC less than or equal to 1 mg/l) approaching similar activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria, Anaerobic↗
PubMed1987

4-phenylpyridine and three other analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lack dopaminergic nigrostriatal neurotoxicity in mice and marmosets.

C57 black mice were injected repeatedly with maximal tolerated doses of 2 chemical analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); 4-phenylpyridine and 4-phenyl-1,2,3,6-tetrahydropyridine. Although both compounds were clearly acutely toxic to mice, neither caused any reduction in striatal dopamine content after chronic exposure. Two MPTP analogues which may be formed endogenously during the metabolism of brain monoamines, 2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydro-beta-carboline, were injected repeatedly into common marmosets. Again, although both compounds appeared highly toxic, neither caused any reduction in striatal dopamine content. It appears unlikely that any of these 4 MPTP analogues causes idiopathic Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Mortality from meningococcal disease during an epidemic in The Gambia, West Africa.

Mortality from meningococcal disease was determined during an epidemic in a rural area of The Gambia with few medical resources, but where a system of registration of births and deaths had been established before the introduction of a primary health care programme. 33 deaths were recorded among 127 patients, a case mortality rate of 26%. 84% of deaths occurred within the first 24 h of illness and many patients died before they could reach any source of treatment. Previous studies, based on regional statistics or on hospital series, may have underestimated mortality from epidemic meningitis in Africa. Mortality from this infection will be reduced only if treatment can be made readily accessible to patients early in the course of their illness.

Adolescent↗
PubMed1987

Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West Africa.

A study was made of factors that influenced susceptibility to group A meningococcal disease during an epidemic that affected The Gambia, West Africa during the dry season of 1982-83. No explanations were found for the distribution of cases between villages or within affected villages. Socio-economic status, crowding, nutrition and previous exposure to meningococcal disease all appeared to be unimportant. Examination of serum samples obtained before the outbreak from a few children who subsequently became patients and from an equal number of age-matched controls from the same village showed a higher mean serum IgA value in children who became patients than in controls. There were not, however, any significant differences found in the concentrations of IgG, IgM, complement or meningococcal antibody between the two groups. Four children who developed culture-proven group A meningococcal disease had raised titres of bactericidal antibody to the epidemic strain 2-3 months before their illnesses. Our findings suggest that some important risk factors for group A meningococcal disease remain to be identified.

Adolescent↗
PubMed1987

Plasmid content, auxotype and protein-I serovar of gonococci isolated in the Gambia.

Twenty-nine strains of penicillinase-producing Neisseria gonorrhoeae (PPNG) and 30 non-penicillinase-producing strains, all isolated in the Gambia, were characterized in terms of their plasmid content, auxotype and protein-I serovar. Sixty-two per cent of the PPNG strains contained the 3.2 MDa penicillinase-coding plasmid, and 38% had the 4.4 MDa plasmid. All the PPNG strains contained the 2.6 MDa cryptic plasmid but lacked the 24.4 MDa conjugative plasmid. In contrast, 46.7% of the non-PPNG strains harboured only the cryptic plasmid while 16.7% contained both the cryptic and conjugative plasmids. Seventeen per cent of the non-PPNG strains contained the conjugative plasmid only and 20% lacked plasmids. The PPNG and non-PPNG strains also differed in terms of their protein-I serovar. Eighty-six per cent of the PPNG strains belonged to serogroup 1 A, whereas the majority (60%) of non-PPNG strains belonged to serogroup 1 B. There was no significant difference in the auxotypes of the PPNG and non-PPNG strains, with both groups consisting predominantly of prototrophic and proline-requiring strains, with a minority of strains requiring arginine. When the 59 strains were each characterized in terms of their combined plasmid profile, auxotype and serovar, 39 different combinations were noted, which indicates the heterogeneous nature of the gonococcal population found in the Gambia.

Gambia↗
PubMed1987

Aetiology of genital ulceration in the Gambia.

The aetiology of genital ulceration was studied in 104 unselected patients (94 men, 10 women) attending a sexually transmitted disease (STD) clinic in the Gambia. Chancroid was diagnosed in 54 (52%), syphilis in 23 (22%), lymphogranuloma venereum (LGV) in seven (7%), and herpes in six (6%). In 28 (27%) patients no diagnosis was reached. Ten (10%) patients were found to have both chancroid and syphilis, three (3%) had both LGV and syphilis, and one (1%) had both herpes and syphilis. Trimethoprim 160 mg and sulphamethoxazole 800 mg twice daily for one week was found to be effective in the treatment of chancroid. This regimen with a single intramuscular injection of benzathine penicillin 2.4 MIU is recommended for the treatment of genital ulcers in Gambian health centres without laboratory facilities.

Adolescent↗
PubMed1987

Comparative metabolism of E-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in herpes simplex virus-infected cells.

The antiviral activities and metabolic fates of E-5-(2-bromovinyl)-2'-deoxyuridine (BrVdUrd) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BrVaraUra) were compared in a dThd kinase-deficient human fibroblast cell line, infected with parental strains of herpes simplex virus, and other strains expressing no viral dThd kinase activity. Metabolic experiments were performed at concentrations well above the ID50 for each compound because radiolabeled agents were not available. BrVaraUra and its nucleotides qualitatively displayed chromatographic and anabolic characteristics which closely paralleled those of BrVdUrd and its nucleotides. Monophosphorylation of both drugs was dependent upon the presence of viral dThd kinase activity except in the case of one dThd kinase-negative type 1 mutant (SC16R5C1) which retained BrVdUrd/BrVaraUra kinase activity. Intracellular uptake of either parent compound was absent during mock-infection and minimal in the cases of infection with mutants unable to phosphorylate the parent compound. Parental type 1 strains were able to induce diphosphorylation and triphosphorylation of both compounds to a similar, dose-dependent degree. Extracts of type 2-infected cells contained greater quantities of BrVdUrd and its monophosphate compared with BrVaraUra and its monophosphate, after identical drug exposure and infection conditions. As previously observed for BrVdUrd, diphosphorylated and triphosphorylated nucleotides of BrVaraUra were not detected after type 2 infection. BrVdUrd and BrVaraUra metabolic breakdown pathways differed, however, as evidenced by the formation of E-5-(2-bromovinyl)uracil (BrVUra). Unlike BrVdUrd, BrVaraUra formed no BrVUra in infected cells, suggesting that replacement of 2'-deoxyribose with arabinose makes the compound biologically more stable, presumably because of resistance to enzymatic breakdown by pyrimidine nucleoside phosphorylases. In this dThd kinase-negative cell line, BrVdUrd and BrVaraUra displayed qualitatively similar susceptibility profiles in that activities were type 1 selective and dThd kinase dependent. Antiviral activities against dThd kinase-positive type 1 strains were similar with both compounds. These data would suggest that BrVdUrd and BrVaraUra have identical type-specific dThd-dTMP kinase-dependent mechanisms of cellular uptake and phosphorylation, but that the latter is not subjected to phosphorolysis and resultant formation of an inactive metabolite. Furthermore, the absence of presence of phosphorolysis of the parent nucleoside does not apparently adversely affect in vitro antiviral activity.

Arabinofuranosyluracil↗
PubMed1987

Oral and cutaneous features of acute human immunodeficiency virus infection.

Acute infection with human immunodeficiency virus (HIV-1) may give rise to a febrile illness with distinctive clinical features. Oral and cutaneous involvement may be prominent. Two cases are reported that illustrate this syndrome, and the importance of its early recognition is emphasized.

Acquired Immunodeficiency Syndrome↗