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Biomedical subjects

G A Rook

Publications and source records attributed to G A Rook.

At least 163 records · Page 9Linked to original sources
PubMed1985

The effect of lymphokines on the ability of macrophages to protect mycobacteria from a bactericidal antibiotic.

Murine peritoneal macrophages protect Mycobacterium intracellular from amoxycillin added to the culture medium. This protective effect is enhanced by the addition of macrophage-activating lymphokines, although in the absence of amoxycillin these lymphokines cause macrophage-mediated inhibition of the organisms. Thus about 10 times more organisms survive exposure to 100 microgram/ml of amoxycillin for 3 days in the presence of lymphokine-activated macrophages than in their absence, whereas without amoxycillin the reverse is true. These findings suggest that in this in vitro system lymphokines cause stasis rather than kill of the organisms. The possibility that lymphokine-induced bacteriostasis protects mycobacteria from antibiotics in vivo is discussed.

Amoxicillin↗
PubMed1985

Changes in circulating antibody levels to the major phenolic glycolipid during erythema nodosum leprosum in leprosy patients.

Circulating antibody levels to the phenolic glycolipid from Mycobacterium leprae and soluble M. leprae antigens were monitored before, during and following ENL episodes in 12 patients. It was observed that during ENL reaction, there was a fall in circulating antibody levels to the phenolic glycolipid but not to the soluble antigens from M. leprae. When the patients had recovered from their ENL reactions, the anti-glycolipid antibody levels usually increased again to levels similar to those observed before the ENL reaction.

Antibodies, Bacterial↗
PubMed1985

I-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages.

Tuberculosis and leprosy remain two of the world's most significant diseases. Immunity involves the activation of macrophages by lymphokines but the details are unknown because there has been no objective assay for the relevant effector function using human pathogens. We previously reported the use of tritiated-uracil uptake by surviving mycobacteria as a measure of the anti-mycobacterial effect of human monocytes. We describe here the use of a modification of this assay to measure control of the proliferation of Mycobacterium tuberculosis in murine peritoneal macrophages. A bacteriostatic effect can be induced in macrophages infected with M. tuberculosis, by adding small numbers of Ly 1 +2- T cells from in vitro lines derived from immunized mice. The phenomenon is dependent on compatibility at the I-A locus of the major histocompatibility complex (MHC) and mediated by soluble factors. Such T cells also recognise and activate macrophages infected with other mycobacterial pathogens. Thus, T cells recognising shared mycobacterial antigens are active. The findings have implications for MHC linked susceptibility to mycobacterioses and the hypothesized ability of cross-reactive environmental mycobacteria to abrogate or pre-empt the protective efficacy of subsequent BCG vaccination.

Animals↗
PubMed1985

Absence from sera from normal individuals or from rifampin-treated leprosy patients (THELEP trials) of antibody to rifamycin-protein or rifamycin-membrane conjugates.

It has been reported that normal individuals have precipitating antibody which binds to rifamycin-conjugated proteins. An enzyme-linked immunosorbent assay has failed to confirm this claim, although antibodies demonstrable in a solid-phase binding assay are easily raised in mice if complete adjuvant is used. Moreover, no antibodies to rifamycin-protein conjugates were found in sera from the patients included in THELEP trials of six rifampin-containing regimens. Similarly, there was no antibody by the indirect Coombs test performed in another laboratory. Further studies using rifamycin-membrane conjugates regarded as more likely to be immunogenic in vivo also failed to reveal antibody in patients' sera, although this technique revealed an interesting antibody in one of four control sera known to be positive by the indirect Coombs test.

Animals↗
PubMed1983

HLA-DR3 associated genetic control of response to multiple skin tests with new tuberculins.

Multiple skin testing with mycobacterial antigenic preparations reveals distinct reaction patterns, which might be relevant to the development of mycobacterial disease in man. Previous work has shown that HLA-DR associated factors correlate with the position of a leprosy patient in the immunopathological spectrum of leprosy. This study was undertaken to see whether these skin test patterns in healthy persons do show any association with HLA-DR types. Out of a group of 74 healthy Caucasoid individuals HLA-DR3 was observed to be absent from the 16 individuals who did not respond to any of the mycobacterial antigens tested. This is a striking difference from the distribution of HLA-DR3 both among the 17 individuals who responded to all mycobacterial antigens tested (P = 0.005) and the 41 individuals who responded to some but not all antigens (P = 0.015). These data show that an HLA-DR3 associated genetic factor controls, albeit indirectly, skin test responsiveness to mycobacterial antigens. It may be significant that this same HLA-DR determinant is implicated in deciding the type of disease to be developed by a leprosy patient.

Genes, MHC Class II↗
PubMed1982

T-cell-dependent polyclonal activation by soluble mycobacterial extracts of B cells in peripheral blood mononuclear cell populations from leprosy patients and normal donors.

Soluble extracts of ultrasonically disrupted mycobacteria (including Mycobacterium leprae) cause strong T-cell-dependent, Cyclosporin A-sensitive, polyclonal B-cell activation, in human peripheral blood mononuclear cell preparations. It is not enhanced by cortisol. Cells from cases of lepromatous leprosy show no polyclonal B-cell activation in the presence of extracts of M. leprae, although they respond normally to other mycobacterial species. The polyclonal B-cell activation response to the M. leprae extract, of a small group of normal leprosy contacts, was reduced relative to that of non-contacts.

Adult↗
PubMed1982

Absence of antibodies to muramyl dipeptide in patients with tuberculosis or leprosy.

The enzyme-linked immunosorbent assay (ELisa) was used to detect the presence of antibodies to muramyl dipeptide (MDP) in serum of patients with leprosy or tuberculosis. Using a conjugate of MDP-lysine to horse radish peroxidase, no such antibodies could be detected in sera of either patients or controls. Antibodies to a sonicate antigen of Mycobacterium tuberculosis were found in sera of all individuals tested and the binding of these antibodies to the M. tuberculosis antigen could not be inhibited by MDP. On the other hand, binding of MDP to anti-MDP antibodies, raised in rabbits, was largely inhibited by free MDP, slightly inhibited by M. tuberculosis antigen and was not inhibited by the patients' sera.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

An inexpensive, portable, battery-operated photometer for the reading of ELISA tests in microtitration plates.

We described an inexpensive, portable, battery-operated photometer which can read the enzyme-linked immunosorbent assay in 96-well microtitre trays. An example is given of its use to measure IgG antibody to human collagen type II in a serum sample from a rheumatoid arthritis patient known to have a high titre of antibody to cartilage by immunofluorescence. When the same samples were read first with the portable photometer and then in a spectrophotometer (Unicam SP 1800), the accuracy of the two devices was comparable, but the readings were obtained far more quickly in the photometer.

Adolescent↗
PubMed1981

How environmental mycobacteria may predetermine the protective efficacy of BCG.

A proposal is made that there are 2 mechanisms of cell mediated response to mycobacteria, both of which produce positive tuberculin tests and that one of them is more protective against mycobacterial infection than is the other. These are referred to respectively as the Listeria-type and the Koch-type of responses. Contact with environmental mycobacteria will induce one or other of these types of response and BCG vaccination will enhance it. Thus in those places where the environmental species prime for the Listeria-type of response subsequent BCG vaccination will afford good protection from both tuberculosis and leprosy. Where the Koch-type of response frequently results from environmental contact BCG will be ineffective. Evidence if presented that a large contact with Mycobacterium scrofulaceum is prejudicial to at least one marker of BCG efficacy in Burma.

Adolescent↗
PubMed1981

The effect of two distinct forms of cell-mediated response to mycobacteria on the protective efficacy of BCG.

The previous paper presents evidence that prior exposure to some environmental mycobacteria enhances the protective efficacy of BCG, whereas exposure to other species opposes it, and suggests that these different species act by evoking one of two types of cell-mediated response of different protective efficacy. This paper reviews past evidence for the existence of these two types of response, and suggests that both can be demonstrated in mice. The type of response evoked in mice by environmental species correlates with their effect on the efficacy of BCG in man, and with the type of proliferative response evoked in human peripheral blood lymphocytes by their soluble antigens in vitro. Preimmunisation of mice to give one type of response can block subsequent induction of the other. We therefore present a model, based on this principle, for the interaction of contact with environmental mycobacteria with subsequent BCG vaccination.

Animals↗
PubMed1981

Inhibition of the proliferative response of peripheral blood lymphocytes to mycobacterial or fungal antigens by co-stimulation with antigens from various mycobacterial species.

Soluble antigen preparations from Mycobacterium leprae are reported to inhibit the response to other stimuli, of peripheral blood mononuclear cells from lepromatous leprosy cases (BL/LL) and also from tuberculoid cases (TT/BL) and normal donors. We confirm these findings and in addition, report that a similar suppressive effect is exerted by antigen from Mycobacterium vaccae, Mycobacterium nonchromogenicum and, to a lesser extent, Mycobacterium tuberculosis and Mycobactyerium kansasii. Moreover, suppression is seen using peripheral blood mononuclear cells from individuals unlikely to have encountered the organism used. The suppression is not due to toxicity of the antigen preparation, and is not indomethacin sensitive. It involves a cell found in the E-rosetting population, which loses its ability to suppress or be suppressed, after 48 hr in culture. Possible explanations include a pharmacological effect of cell wall peptidoglycolipids, or the triggering of suppressor cells specific for common mycobacterial antigens.

Antigens, Bacterial↗