Groups of patients with lepromatous and tuberculoid leprosy and hospital staff from six leprosaria in East Africa and 'non-contact' groups of villagers or staff from general hospitals have been skin tested with 10 reagents. These were prepared by ultrasonic disintegration from M. tuberculosis, M. duvalii, M. chelonei and 7 other species identified in the Ugandan environment. Comparisons were made of the percentages of positive reactors in each study group for each reagent. The 'specific' defect of lepromatous patients was found to apply to a variable extent to six of the species tested, but not to M. tuberculosis, M. avium or M. 'A'. The defect applied most noticeably to M. nonchromogenicum and M. vaccae, suggesting that they are more closely related to M. leprae than are the other species tested. The reagent Chelonin produced unexpected and anomalous results in the lepromatous group. It is suggested that this was due to an unusually slow clearing of Arthus' reaction.

A range of new Tuberculins prepared from extracts of living organisms belonging to 12 mycobacterial species has been used to assess the effect of BCG immunization and contact with environmental mycobacteria on Ugandan adults. A total of 2,456 tests were carried out on 562 people, 86% of whom came from three areas selected for special study. These areas were chosen on the basis of occurrence of leprosy and M. ulcerans infection and on data concerning the distribution of environmental mycobacteria. It was found that the effect of BCG was small compared with that previously observed amongst Kenyan schoolchildren, but that the effect of geographical origin was considerable. There was some correlation between the percentages of reactivity to the reagents and the frequency of mycobacteria in the environment.

SUMMARYFour hundred and seventy tuberculosis patients were each skin tested with four of a range of 17 mycobacterial reagents in four countries in all of which tuberculosis and leprosy were endemic. Sixteen of the reagents were new tuberculins prepared from extracts of living mycobacteria disrupted by ultrasonic disintegration and the last was PPD, RT23.The effect that tuberculosis exerted on the delayed-type skin test response to these antigens was assessed by comparing results for tuberculosis patients with those for Tuberculin positive and Tuberculin negative control populations. Tuberculosis patients on Rifampicin therapy showed no difference in their skin test responses to any of the antigens from those patients on other forms of anti-tuberculosis treatment.Amongst the normal population it was found that possession of Tuberculin positivity was associated with an enhanced response to all the other mycobacterial antigens with the exception of A*-in which demonstrated a reciprocal relationship with Tuberculin in Burma. It was also noted, in Burma particularly, that sensitization to mycobacterial species other than Mycobacterium tuberculosis, especially to the slow growers, plays a role in determining responses to different mycobacterial species.In tuberculosis patients enhanced skin test responses were also seen but only in those countries, e.g. Libya, where the prevalence of mycobacterial species was low. Where mycobacteria were common, as in Burma, the converse was true and tuberculosis was associated with a diminished skin test response to each antigen. The high prevalence of A*-in positivity in Burma, its reciprocal relationship with Tuberculin there and the results for all the antigens in the tuberculosis patients indicate that the cell mediated skin test response may have a threshold. If this is exceeded the skin test becomes negative so that non-reactors then include those who have been excessively sensitized as well as those who have not been sensitized. Despite this, a greater percentage of tuberculosis patients in each country responded to the specific reagent Tuberculin than did the control populations and their mean positive induration sizes were consistently larger. Nevertheless, amongst the tuberculosis patients in Burma 13% were complete non-reactors to Tuberculim and this apparent anergy also applied to the other reagents with which these individuals were tested.This differs from lepromatous leprosy where the anergic state pertain exclusively to M. leprae and a few seemingly closely related species. The breadth of anergy in M. ulcerans infection has not been measured but it is known to effect both Burulin and the PPD, RT23.Just as in leprosy and M. ulcerans infection, tuberculosis can be shown to have a disease spectrum here detected by multiple skin testing. The significance of this spectrum and its similarities with and differences from that of the other mycobacterioses is discussed.

The glucose analogue 2-fluoro-2-deoxy-D-glucose (FDG) was used to study chemosensitivity of two human ovarian cancer cell lines and of murine L1210 cells. Cell viability was determined by measuring intracellular adenosine triphosphate (ATP) with a bioluminescence method, which has been shown to correlate closely with trypan blue, stem cell, and [3H]TdR assays. All three cell lines were sensitive to cytostatic drugs, which exerted a parallel decrease in the intracellular FDG and ATP levels. The two measures correlated positively (r = 0.66, P less than 0.001), indicating that FDG uptake is closely linked with ATP production. Relatively low hexokinase (HK)-to-glucose 6-phosphatase (HK/G6-Pase) ratios were measured, which suggests that the metabolic trapping of FDG 6-phosphate within the cytosol is incomplete. Apparently, these cell lines may not depend exclusively on glycolysis for their energy requirement. We conclude that cell killing caused by cytostatic drugs is associated with a decreased ATP content and FDG uptake. This indicates that not only ATP but also FDG may be used to study drug effects in vitro.

SUMMARYThis study on Kenyan schoolchildren aims to elucidate the effect of contact with environmental mycobacteria on the development of specific delayed hypersensitivity. A series of 12 skin test reagents was employed; eleven of them were prepared from extracts of living mycobacteria and the last was the P.P.D. RT 23. Eight of the new tuberculins were prepared from mycobacteria recovered from the East African environment. A total of 8641 tests were carried out on 4320 children between the ages of 6 and 17 years in four townships. Two of these townships were in fertile agricultural areas and two were in the desert. Just over 80 % of the children had received BCG immunization.The results obtained showed that increasing age, geographical locality and BCG immunization all had a profound effect, and socioeconomic background had some effect, on the pattern of reactivity to the various reagents. The rationale behind the use of the series of new tuberculins and the results obtained with them are discussed in relation to the interacting effects of the factors complicating these results.