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Biomedical subjects

R J Rees

Publications and source records attributed to R J Rees.

At least 19 recordsLinked to original sources

Mycobacterium leprae reactive T cell clones from lepromatous leprosy patients after prolonged dapsone chemotherapy.

The proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and BCG were studied in two groups of leprosy patients: a group of 8 lepromatous patients who had been on treatment for more than 20 years (TLL) and a group of 8 untreated lepromatous leprosy patients (ULL). The mean response to M. leprae of the TLL group was 6195 cpm with 5 of the 8 patients responding positively. The mean response to M. leprae of the ULL group was 617 cpm, with only 1 patient showing a positive response. The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group. Thirteen M. leprae reactive clones were established from 2 TLL patients and 5 M. leprae reactive clones were established from 2 tuberculoid leprosy patients. Seven of these clones, 4 from the TLL patients and 3 from the tuberculoid (TT) patients could be studied further. Three of the TLL clones responded specifically to M. leprae, while one of the clones exhibited a broad cross-reactivity to other mycobacteria. All of these clones were of the CD4+CD8- phenotype. Our findings suggest that responsiveness to M. leprae can be detected in vitro in a proportion of LL patients who have undergone prolonged chemotherapy, and that this response involves M. leprae reactive CD8+CD8- T cells, of which some appear to be specific to M. leprae.

Antigens, Bacterial

Rifampicin for lepromatous leprosy: nine years' experience.

Over 100 patients with lepromatous leprosy were treated with rifampicin in a series of pilot, uncontrolled, and controlled trials in 1968-77. The rapid bactericidal effect of rifampicin on Mycobacterium leprae was confirmed. Clinical improvement became apparent sometimes as early as 14 days after the start of treatment. Nevertheless, a few persisting viable M leprae were detected as long as five years after the start of treatment with rifampicin either by itself or in combination with the bacteriostatic drug thiambutosine. Treatment with rifampicin and dapsone for six months reduced the number of persisting leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of treatment in lepromatous leprosy. Therefore initial intensive combined treatment with two or more bactericidal drugs (including rifampicin) warrants further investigation in both untreated leprosy and lepromatous leprosy resistant to dapsone.

Animals

Formation of antibody against Mycobacterium leprae antigen 7 in armadillos.

A radioimmunoassay developed to measure antibody against Mycobacterium leprae antigen 7 in man was applied to the nine-banded armadillo (Dasypus novemcinctus). Normal armadillo sera had low but significant antibody activity in the test. Fourteen of 17 armadillos with systemic mycobacterial infection after inoculation with M. leprae showed increased antibody activity in the assay, and in some instances the activity was higher than in a pool of sera from patients with lepromatous leprosy. Crossed immunoelectrophoresis with armadillo serum in the intermediate gel revealed antibodies against five distinct antigenic components of M. leprae. Development of systemic mycobacterial infection after inoculation with M. leprae is thus associated with a distinct humoral immune response. The use of radioimmunosassay for selection of animals for inoculation and for following the development of the infection is discussed.

Animals

Lymphocyte response of leprosy patients to human-derived and purified armadillo-derived Mycobacterium leprae, BCG and PPD.

The lymphocyte transformation test was applied to compare in vitro lymphocyte responses of tuberculoid (high resistant) and lepromatous (low resistant) leprosy patients to purified Mycobacterium leprae derived from experimentally infected armadillos and crude M. leprae derived from man, as well as to bacille Calmette-Guérin (BCG) and purified protein derivative (PPD). It was found that the purification procedure using enzymic digestion did not affect the immunogenicity of armadillo-derived M. leprae as compared with the crude human-derived preparation, although 2.5-5-fold higher doses of the purified organisms were required to elicitate equivalent lymphocyte responses. The result indicated the suitability of purified armadillo-derived M. leprae as the standard antigen for lymphocytes transformation tests in leprosy. The cross-reactivity studies show a close relationship between PPD and BCG, but not between M. leprae and PPD or BCG.

Adolescent

Experimental lepromatous leprosy in the white-handed gibbon (Hylobatus lar): successful inoculation with leprosy bacilli of human origin.

Leprosy bacilli of human origin were inoculated into a white-handed gibbon by the i.v. and i.p. routes, and also locally into ears, testis and around an ulnar nerve. The animal was observed closely during a period of nearly 15 years and did not exhibit any clinical evidence of cutaneous or neurological disease. At death, a wide range of tissues was taken for bacterial counts and histological examination, and a disseminated and progressive infection was demonstrated. Acid-fast bacilli were found in many sites; their morphological appearance distribution in nerves, and pattern of multiplication in mouse foot-pads, and also the presence of anti-mycobacterial antibody in the serum and the absence of specific lymphocyte transformation were all in keeping with an infection by Mycobacterium leprae, at an early lepromatous stage. This is probably the first fully documented report of experimental lepromatous infection in a primate. The findings are discussed in relation to the long incubation period of le promatous leprosy and the difficulties of diagnosing the disease at an early stage in man.

Animals

Airborne infection with Mycobacterium leprae in mice.

Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.

Aerosols

Evidence for prevention of borderline leprosy reactions by dapsone.

68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.

Adolescent

Transmissible agents from human sarcoid and Crohn's disease tissues.

Mice were inoculated with human sarcoid tissue homogenates or with a first or a second passage homogenate of mouse tissue (including 0.2 mum membrane filtrates) originating from the inoculation of human sarcoid, Crohn's disease, or control tissue homogenates. Epithelioid and giant cell granulomas were present in the footpads and/or viscera of some of the mice given homogenates originating from each sarcoid or Crohn's disease tissue 15 months after inoculation but were not present in mice given control homogenates. Among mice given homogenates originating from human sarcoidosis, granulomas were present in many organs and tissues; in contrast, a pattern of selective dissemination of visceral granulomas was found among mice given homogenates originating from Crohn's disease. This differential distribution of visceral granulomas also followed the inoculation of 0.2 mum membrane filtrates. Granulomatous responses at Kveim test sites in the ear 9-17 months after inoculation of homogenatesoriginating from human sarcoidosis or Crohn's disease were confined to mice showing granulomas in footpads of viscera. The ability of the transmissible agents to induce granulomas in mice was destroyed when sarcoid or Crohn's tissues were autoclaved or when sarcoid homogenates were stored at -20degreesC for 1 week or exposed to 60Co irradiation (2.5 MR).

Animals