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G A Rook

Publications and source records attributed to G A Rook.

190 records · Page 11Linked to original sources
PubMedDate not supplied

Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis?

Serum immunoglobulin (Ig) G responses to a variety of mycobacterial antigens were measured in children from the UK, in children with tuberculosis from Hyderabad, India and Dhaka, Bangladesh, classified according to whether the disease was disseminated or localized, and in non-tuberculous controls. Anti-lipoarabinomannan (LAM) IgG responses in UK children showed a marked trough between 6 months and 3 years coincident with the reported peak incidence of disseminated tuberculosis. Geometric mean IgG responses to sonicates of slow-growing mycobacteria (rich in LAM) in 36 children with disseminated tuberculosis were markedly lower than in 99 children with localized tuberculous lesions (for Mycobacterium scrofulaceum P < 0.01, for M. tuberculosis P < 0.01, and for M. vaccae P < 0.01). Responses to purified LAM were also lower in the disseminated tuberculosis group (P < 0.05) but there was no difference between the groups in their response to mycobacterial 65 kDa protein. Multiple regression analysis showed that the reduced response to sonicated mycobacterial antigens and to LAM in children with disseminated disease was independent of age, nutritional status, skin test reactivity, duration of previous symptoms, and city of origin. There was no evidence for sequestration of antibody to immune complexes. These findings are compatible with the hypothesis that children with low levels of antibody to sonicated mycobacterial antigen and to LAM, or those who cannot mount an antibody response, are predisposed to dissemination. A role for antibody in preventing disseminated forms of tuberculosis in childhood has implications for the development of improved vaccines and for the optimum timing of vaccination with bacille Calmette-Guérin.

Adolescent↗
PubMedDate not supplied

TNF alpha-mediated tissue damage in mouse footpads primed with mycobacterial preparations.

Tissue sites involved in certain types of inflammation become sensitive to the destructive effect of a subsequent injection of tumour necrosis factor alpha (TNF alpha). To try to further delineate the cascade of effector and regulatory events controlling this activity, a new model is described and its main properties characterized. C57BL/GrFa mice received mycobacterial products subcutaneously in the footpads. Recombinant TNF alpha was injected 24 h later into the same sites. To assess the tissue-destructive effect of TNF alpha in these "primed" footpads, swelling and haemoglobin content of injected footpads were measured, 16 h and 20 h respectively after the injection of TNF alpha. When loaded with either Escherichia coli LPS (10 micrograms) or Mycobacterium vaccae soluble sonicate (17 micrograms), footpads were reactive to the subsequent injection of 1 microgram recombinant TNF alpha, as assessed by both swelling and haemoglobin content. When C57BL/GrFa mice received 10(9) autoclaved M. vaccae subcutaneously in the back 10 days before the footpad was "primed" with soluble M. vaccae sonicate, the destructive effect of TNF alpha was significantly enhanced, becoming 5-10-fold greater than that seen in sites "primed" with an optimal dose of LPS. This higher reactivity was abrogated by a single dose of anti-CD4 given just before the injection of TNF alpha. This local reactivity to TNF alpha of skin sites loaded with mycobacterial products is compared to the local LPS-dependent Shwartzman reaction, and the relevance of this assay as a model with which to delineate the mechanisms of tissue damage in tuberculosis is discussed.

Animals↗
PubMedDate not supplied

Raised levels of agalactosyl IgG in childhood tuberculosis.

Raised levels of agalactosyl immunoglobulin G (IgG) have been found in adults with tuberculosis, Crohn's disease and rheumatoid arthritis, and recent evidence, both circumstantial and experimental, suggests that it has distinct functional properties that play a role in pathogenesis. Since tuberculosis in infants is strikingly different from the disease seen in adults, but switches to the adult form at adrenarche or puberty, we documented the association of agalactosyl IgG with tuberculosis in childhood between the ages of 0 and 16 years. Sera were collected from 99 children diagnosed as cases of tuberculosis in Istanbul, Turkey, and compared with levels in non-tuberculous controls. The percentage of agalactosyl IgG was significantly raised in children with tuberculosis overall (P < 0.001, Mann-Whitney U test) and in all age groups except for children over 12 years old, whose numbers were too small to be meaningful. Therefore the differences between adult and childhood tuberculosis are not due to a difference in the tendency for agalactosyl IgG to be produced at different ages. The percentage of agalactosyl IgG may be useful for monitoring the progress of individual complicated cases.

Adolescent↗
PubMedDate not supplied

Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection.

BACKGROUND: A third of the world's population has latent infection with Mycobacterium tuberculosis, and in areas of low endemicity, most cases of active tuberculosis arise as a result of reactivation of latent bacilli. We sought to establish the cellular location of these latent organisms to facilitate their elimination. METHODS: We applied in-situ PCR to sections of macroscopically normal lung tissue from 13 individuals from Ethiopia and 34 from Mexico who had died from causes other than tuberculosis. Sections of lung tissue from six Norwegian individuals (ie, individuals from a non-endemic population) acted as negative controls, and six Ethiopian tuberculosis cases acted as positive controls. FINDINGS: Control necropsy samples from the Norwegian individuals were all negative by in-situ PCR and conventional PCR, whereas all samples from known Ethiopian tuberculosis cases were positive by both methods. However, in macroscopically normal lung tissue from Ethiopian and Mexican individuals without tuberculous lesions, the in-situ PCR revealed five of 13 and ten of 34 positive individuals, respectively. These results were confirmed by conventional PCR with extracted DNA. Positive cells included alveolar and interstitial macrophages, type II pneumocytes, endothelial cells, and fibroblasts. INTERPRETATION: M. tuberculosis can persist intracellularly in lung tissue without histological evidence of tuberculous lesions. M. tuberculosis DNA is situated not only in macrophages but also in other non-professional phagocytic cells. These findings contradict the dominant view that latent organisms exist in old classic tuberculous lesions, and have important implications for strategies aimed at the elimination of latent and persistent bacilli.

Adolescent↗
PubMedDate not supplied

Antibodies to heat shock protein 65 kD in type 1 diabetes mellitus.

To determine whether antibodies to mycobacterial heat shock protein of 65 kD molecular weight (hsp 65) could be important in the pathogenesis of Type 1 diabetes we tested patients before and at diagnosis of diabetes, as well as patients with rheumatoid arthritis. Using ELISA, increased hsp 65 antibodies were detected in 2 of 8 pre-diabetic twins, 1 of 13 newly diagnosed untreated diabetic patients and 3 of 10 rheumatoid arthritis patients. Levels of hsp 65 antibodies in pre-diabetic twins, median (range), 0.25 (0.104-1.904) and newly diagnosed diabetic patients (mean +/- SD) (0.299 +/- 0.220), did not differ significantly either from each other or from their control subjects (0.134 +/- 0.123). In contrast, levels of hsp 65 antibodies in rheumatoid patients (0.59 +/- 0.42) were significantly higher than in their control subjects (0.21 +/- 0.18; p = 0.02). Of twins studied prospectively before diagnosis, at diagnosis but before insulin treatment, and soon after diagnosis, three of four had hsp 65 antibodies at some stage. We conclude that serological immunity to mycobacterial hsp 65 can occur in Type 1 diabetes, but it is neither a characteristic nor a specific feature of the disease.

Adult↗
PubMedDate not supplied

Immunity to heat shock proteins in rheumatoid arthritis.

Heat shock proteins (hsp) or "stress proteins" are a group of highly conserved proteins which are important in the day to day function of all cells. Early studies by others have indicated that immunity to the 65 kDa hsp of mycobacteria is important in the development of arthritis in the adjuvant arthritis model in rats. In this paper, we review the evidence suggesting that, as for the rat model, immune reactivity to hsp is of importance in the human disease. Elevated levels of IgG antibodies to the 65 kDa hsp of mycobacteria are characteristic of rheumatoid arthritis (RA) patients. Much of this antibody cross-reacts with human 65 kDa hsp and is therefore autoreactive. The 65 kDa hsp is found in synovial fluid and is therefore a potential target for antibody. Antibodies to the 70 kDa hsp (both of mycobacterial and human origin) are elevated, but not specifically, in RA. Increased T cell responses to the 65 kDa hsp are also found in synovial fluid of RA patients. Although gamma delta T cells are present in the synovial joint of RA patients, they do not appear to be particularly increased in frequency although the subset distribution of these cells is clearly different from that seen in the circulation. In fact, the synovium looks like the "gut" with regard to these subsets!

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