On the occasion of the centenary of Koch's discovery of tubercle bacilli, the Japanese Society for Tuberculosis decided to make series of general review on tuberculosis science and publish them monthly on “KEKKAKU”. As the magnitude of tuberculosis problem is underestimated not only in techni cally developed countries but also in developing countries and the misunderstanding that all problems of tuberculosis were already solved scientifically is commonly seen, the objectives of these serial review were 1) to review scientific achievements obtained during the past 100 years, 2) how to utilize these lessons for the future fight against tuberculosis and other diseases, and 3) to find out scientific topics which should be investigated in the future.
As the top of serial review, the author made a general introductory review on the problem. WHO set a global target “Health for All by the Year 2000”, but this target could not be achieved if a disease like tuberculosis with known technology how to control the disease would not be brought under control in the coming two decades.
Short historical review was made on the development of techniques used for controlling tuber culosis and their application to the tuberculosis control programme. Some peculiar topics in tuber culosis research were discussed briefly, such as the mechanisms of tuberculosis immunity and delayed type hypersensitivity, methods of case-finding, chemotherapy including combination therapy, con trolled trial and importance of regular drug-taking, and epidemiology.
Major research topics which should be investigated in the future were also discussed briefly. Last but most important problem is why we failed to control tuberculosis in developing countries and how to intensify the tuberculosis control programme. These problems were discussed too.

View full abstract

Mycolic acids, an α-alkyl β-hydroxy very long chain (C_20-40) fatty acids are well known to be the most characteristic cell wall lipid, component in Actinomycetales and to contribute to the physiological characteristic of cell walls in acid-fast bacteria. In order to investigate the biosynthetic mechanism and physiological roles of such type of fatty acids, we have developed the powerful analytical method for mycolic acid composition from various species of Mycobacteria and related microorganisms using gas chromatography-mass spectrometry. The results showed, the first, M. phlei possessed α-mycolic acids (M₁) ranging from C₇₀ to C₈₀ (dienoic monocarboxylic acids) and dicarboxy mycolic acids (M₃) ranging from C₅₂ to C₆₄ (monoenoic dicarboxylic acids) with C₂₀ or C₂₂ alkyl chain at α position, as major components of both the extractable and cell wall bound lipids. The second, with using this method, the changes in mycolic acid composition upon the growth inhibition by the antituberculous drug, isoniazid (INH), were examined and the synthesis of longer chain mycolic acids in both sub classes were shown to be strongly inhibited with the increase in the concentration of INH. Changes in acid-fastness (the disappearing of acid fastness) or surface structure of the cells were also observed, paralelled with the inhibition of mycolic acid synthesis. The third, the adaptive changes in mycolic acid composition were also demonstrated in response to the shift of growth temperature. Increasing the growth temperature from 20°C to 50°C resulted in an increase in longer chain species of both my colic acid subclasses with a concomitant decrease in shorter chain homologues. The most abundant species were C₇₆ of M₁ and C₅₈ of M₃ in the 20°C grown cells, while the 50°C grown cells contained C₈₀ in M₁ and C₆₂ in M₃, most abundantly. Mass fragmentographic analysis revealed an increase in total carbon numbers of mycolic acids was caused by the elongation of straight chain alkyl unit, without any change in α-branch. In vitro incorporation studies of 1-¹⁴C-acetate into long chain fatty acids by the ammonium sulfate precipitated enzyme fraction obtained from sonicated M. phlei extracts showed the radioactivity was incorporated actively into wide ranges of long chain even and odd num bered fatty acids ranging from C₂₄ to C₅₀, which could be precursors of straight chain alkyl unit of my colic acids. The ¹⁴C incorporation pattern on radio gas chromatogram was profoundly affected by the incubation temperature, the shorter acids were labelled at the lower temperature and the longer acids were labelled at the higher temperature, this indicating the adaptative change in mycolic acid molecule appeared again to occur at the straight alkyl chain, exclusively.
From the results obtained above, it was demonstrated the structure of mycolic acid are not only characteristic in the species of mycobacteria, but also vary by the environmental condition, such as the growth temperature or the presence of antituberculous isoniazid, followed by the changes in the cell wall surface structure.

View full abstract

Killer (K) activity was determined by the microplate method in 12 patients with pulmonary tuber culosis and natural killer (NK) activity by 51Cr release assay in 6 patients.
The results were as follows:
1. In the control group, K activity was independent of the donors' age and sex, whereas NK activity was only independent of the donors' age. NK activity of the male in the control group was higher than that of the female, but satistically not significant.
2. K activity in patients with pulmonary tuberculosis was significantly higher than that of healthy controls. The absolute number of K cells, however, remained within normal range.
3. NK activity in patients with pulmonary tuberculosis was significantly higher than that of healthy controls.

View full abstract

From data obtained in 1980, the incidence rate of the lung disease due to atypical mycobacteria in Japan was estimated as 1.5 per 105 population per year. The incidence rate during the period from 1976 to 1980 ranged from 1.3 to 1.9 per 105 population per year, and the rate seemed almost constant.
When observed on individual diseases, however, the incidence rate of the lung disease due to M. avium-M. intracellulare, which occupies a majority of all atypical mycobacteriosis, ranged from 1.2 to 1.7 per 105 population per year and seemed to be almost constant, whereas the prevalence rate of the lung disease due to M. kansasii increased from 0.04-0.1 in 1975-1976 to 0.25 in 1980. In accordance with the increase of the incidence rate of the M. kansasii disease, the location where the disease was found has spread from Tokyo area to several prefectures, Osaka, Fukuoka, Shizuoka and Kochi. To explain this phenomenon, a hypothesis has been presented that the increase of the incidence correlates to decrease of tuberculosis. In a circumstance where the prevalence of tuberculosis is still high, persons with attenuated resistance may be infected by tubercle bacilli and develop tuberculosis, but in a cir cumstance where the prevalence of tuberculosis is low, such persons may become infected by M. kansasii which originates from the environment.
In the past one decade, 35, 696 patients were hospitalized to our tuberculosis departments. Out of these patients, 632 (1.8%) of the patients with atypical mycobacteriosis were found; M. kansasii disease, 59 (9.3%); M. szulgai disease, 3 (0.5%); M. avium-M. intracellulare disease, 558 (88.3%); M. fortuitum disease, 7 (1.1%); M. chelonei disease, 3 (0.5%); others, 2 (0.3%).

View full abstract