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Biomedical subjects

R J Rees

Publications and source records attributed to R J Rees.

At least 37 records · Page 2Linked to original sources
PubMed1986

Two potential improvements to BCG and their effect on skin test reactivity in the Lebanon.

An account of an ongoing project to assess the possible benefits of two additives to BCG vaccine is presented. These additives are suspensions of irradiation killed Mycobacterium vaccae in one case, and M. leprae in the other. Groups of children aged 7-17 living in Zgharta and Akkar districts of North Lebanon have received vaccination with BCG alone or with either of the two additives since 1980. This region was chosen since contact with environmental mycobacteria is small, but both leprosy and tuberculosis occur there. So far the effects of the additives have been assessed by annual skin testing of volunteers with Tuberculin, Leprosin A, Vaccin and Scrofulin, and by measuring the size of the vaccine scars. Some children have now been followed up on four occasions, and special attention is paid to them. No complications have been encountered in the 1740 children who have entered the study (by our observation, or by local report on those who have not attended for follow-up) and the mean scar sizes after vaccines with the additives are no larger than those after BCG alone. There is no evidence that the additives have prevented development of Tuberculin positivity after vaccination, or have changed the nature of reaction to it. Incorporation of M. leprae significantly increased Leprosin A positivity and both additives increased Vaccin positivity in comparison with the effects of BCG alone. The results are fitted to a model of the theoretical expectations of the study and may be beginning to show the advantages expected of the additives. The only unexpected finding was a reduction in Scrofulin positivity especially associated with the additives. The very low contact with environmental mycobacteria experienced in the study area has allowed the pattern of post-vaccination decay of skin test positivity to be studied with greater precision than has been reported before, and differences have been detected between the two districts where the study was conducted. Confirmation of the possible advantage of the additives will rest with data to be obtained in longer term follow-ups and in studies being carried out in other countries.

Antigens, Bacterial↗
PubMed1986

Susceptibility of strains of Mycobacterium leprae isolated prior to 1977 from patients with previously untreated lepromatous leprosy.

Because of the recent spate of reports of primary resistance to dapsone among patients with lepromatous leprosy, largely to small concentrations of the drug, a survey was made of the results of dapsone-susceptibility testing of strains of Mycobacterium leprae isolated before 1977 among six laboratories which employed the mouse foot pad technique for this work prior to that time. Data have been found for strains that had been isolated from 73 patients, representing 19 countries and dependencies, with previously untreated lepromatous leprosy; all 73 strains were inhibited from multiplication by dapsone administered to mice in a concentration of 0.0001 g per 100 g mouse diet. These data suggest that the properties of M. leprae isolated from previously untreated patients with respect to susceptibility to dapsone have changed since the years preceding 1977.

Animals↗
PubMed1985

Adoptive cell transfer of resistance to Mycobacterium leprae infections in mice.

Cells were transferred from mice intradermally vaccinated with killed Mycobacterium leprae to sublethally irradiated recipients. Unseparated cells from lymph nodes or spleens of M. leprae vaccinated mice were found to cause significant inhibition of the growth of a subsequent M. leprae challenge in mouse footpads for up to 26 weeks after vaccination. Vaccination with live BCG and cells transferred from BCG-vaccinated mice caused no significant inhibition of M. leprae growth in mouse footpads. Cell separation into fractions containing predominantly B and T lymphocytes showed that the inhibition of growth was due to M. leprae-sensitized T lymphocytes. M. leprae vaccinated mice were also skin tested with soluble M. leprae antigen and showed maximum delayed hypersensitivity responses 4 weeks after vaccination.

Animals↗
PubMed1985

Comparison of radiometric macrophage assay and the mouse foot pad infection for the evaluation of Mycobacterium leprae sensitivity/resistance to dapsone.

Studies were undertaken in three independent centers to compare the newer, in vitro radiometric macrophage (M phi) assay with the conventional mouse foot pad infection for the diagnosis of dapsone resistance. Results obtained on 12 bacilliferous patients showed good concordance in both assays. One strain diagnosed as sensitive in the M phi assay was found to be resistant in the mouse foot pad. Three Mycobacterium leprae strains considered to be partially resistant in the mouse infection behaved as resistant strains in the M phi cultures. Attention is drawn to a rapid in vitro method for the identification of drug-resistant bacilli in leprosy patients.

Adolescent↗
PubMed1983

Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species.

Serum amyloid A protein (SAA) elevation accompanies induction of secondary amyloidosis in mice given Mycobacterium butyricum in Freund adjuvant. The synthesis of SAA by cultured hepatocytes is induced by a macrophage-derived mediator, which has been identified as interleukin 1. In these studies, SAA synthesis has been used as an index of macrophage activation to examine the in vivo response of mice to challenge with seven different mycobacteria and with synthetic analogs of the immunoadjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(L-D)]. SAA synthesis was stimulated by administration (by the intraperitoneal route) of the mycobacteria dissolved in saline, with Mycobacterium vaccae being the most active and Mycobacterium leprae being the least stimulatory. MDP(L-D), which is the minimal structure (molecular weight, 492) able to substitute for mycobacteria in Freund adjuvant, stimulated SAA synthesis, whereas the MDP(D-D) isomer was inactive. The butyl ester of MDP, which induces no detectable pyrogenicity but retains adjuvanticity, required a 100-fold greater dosage than MDP(L-D) in stimulating SAA synthesis. Amyloidosis was detected histologically only when active SAA inducers MDP(L-D), M. vaccae, and M. butyricum, were administered in incomplete Freund adjuvant, with amyloid-enhancing factor. These studies demonstrated that SAA elevation was a sensitive in vivo marker of the capacity of antigens to stimulate macrophages to produce interleukin 1. A point of considerable relevance to the human use of MDP was the observation that repeated injections of the adjuvant MDP in saline did not induce secondary amyloidosis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Serological activity of a characteristic phenolic glycolipid from Mycobacterium leprae in sera from patients with leprosy and tuberculosis.

Serological activity against a purified phenolic glycolipid from Mycobacterium leprae, which may be obtained in large amounts from M. leprae infected armadillo liver, was investigated using immunodiffusion and an enzyme linked immunosorbent assay (ELISA). Generally a good correlation was obtained between these techniques, but the ELISA was more sensitive and convenient. Relatively high IgG and IgM anti-glycolipid antibody levels were found in lepromatous leprosy patients. The antibody titres to the glycolipid were, however, low when compared with antibody titres to crude sonicates. Since the glycolipid is present in large quantities, this suggests that it is not very immunogenic. Antibody against the glycolipid especially of the IgM class, was demonstrable in some tuberculoid leprosy patients, although at much lower titres than in the lepromatous leprosy sera. In lepromatous leprosy patients that were skin smear negative after more than 5 years of treatment the IgG anti-M. leprae derived glycolipid activity had decreased markedly. The anti-IgG and IgM glycolipid antibody levels in tuberculosis patients did not differ significantly from the levels in appropriate normal healthy subjects. The glycolipid antibody levels in patients infected with M. kansasii, M. avium or M. intracellulare also fell within the range of normal healthy individuals.

Animals↗
PubMed1982

The nose in lepromatous leprosy; bacteriological and histopathological studies of patients treated with dapsone monotherapy for varying periods of time.

A clinical, bacteriological and histopathological investigation of 62 patients with lepromatous leprosy attending a hospital in South India is reported, with particular emphasis on the activity of the disease in the nose. Twelve of the patients were from a group of 34 new patients who had been originally examined 5 years previously, and subsequently treated with dapsone (DDS) monotherapy. A further 50 lepromatous patients were also examined, who had been treated for periods ranging from 3 months to 10 years. With a few exceptions, there was good correlation between the clinical and histopathological findings in the skin and nose. Evidence of disease activity was demonstrated among three-quarters of the patients who had been treated for over a year. Failure to achieve quiescence was explained in most of the patients by failure to collect their dapsone treatment or to ingest it regularly as demonstrated by the determination of DDS/creatinine ratios on urine samples collected at the time of their visit to the clinic. Although the compliance of most patients was relatively satisfactory during the first 12 months of treatment, thereafter it deteriorated markedly. In contrast to the clinical, bacteriological, and histopathological evidence of disease activity in the skin and nose of most patients, in only one of the patients treated for more than a year was a positive nose-blow encountered. This suggests that the infectivity of DDS-treated lepromatous patients within this time and this diminished infectivity often persists despite poor drug compliance and continuing disease activity.

Dapsone↗