This study was carried out to elucidate the policy of treatment especially the necessity of surgical treatment for non-cavitary tuberculous cases with negative sputum for less than 6 months based on culture findings of tubercle bacilli from 51 non-cavitary cases which had been resected during the 10 years' period from 1965 to 1974 at Research Institute Sanatorium. Cases used for this study were divided into several groups by the type of chemotherapy, the status of both radiological and bacteriological findings at the start of chemotherapy and the size of lesions on radiogram at the time of operation.
The bacteriological findings obtained from resected lesions were divided into the following 3 categories; culture positive, smear positive-culture negative and smear negative-culture negative for tubercle bacilli.
The positive rate of tubercle bacilli on culture in the resected lesions was 25.5% in all cases and it was much higher comparing with that obtained from cases with negative non-cavitary cases for more than 6 months (2.8%). The rate showed no relation with the duration of negative sputum and the size of lesion at the time of operation. For example, it was 26.7% in cases with 1 to 2 months' negative sputum and 21.9% in cases with 3 to 5 months' negative sputum. It was 26.7% in lesions less than 2.0cm, 23.8% in 2.1 to 3.0cm and 26.7% more than 3.1cm in diameter.
Comparing by several background factors at the start of chemotherapy, such a positive rate showed no significant difference between cavitary cases and non-cavitary cases, and also between cases having both positive sputum and cavity and cases having both negative sputum and non cavitary lesion (Table 3).
The amount of tubercle bacilli cultivated from resected lesions was usually small; 10 among 13 positive cases showed colonies less than 100 and a large amount of tubercle bacilli was found in only 3 cases which showed 2 months' negative sputum.
The proportion of smear positive cases to culture negative cases in resected lesions was 42.1%, and it was 34.6% in originally treated cases and 58.3% in cases with regimens changed. It showed no significant relation with the duration of negative sputum, the type of chemotherapy and background factors at the start of chemotherapy. The amount of tubercle bacilli on smear was large in 50.0%, moderate in 31.3% and small in 18.8% of smear positive-culture negative cases (Table 4).
The following conclusion can be obtained from the above-mentioned findings: the problem whether or not these cases need the operation can not be decided in such a short negative sputum period, so that chemotherapy should be continued further.

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150 patients, who were diagnosed as showing aggravation of pulmonary tuberculosis and admitted to our hospital during the period from March, 1972 to February, 1973 (Table 1), were studied in order to analyze the correlation between the grade of aggravation and the following clinical symptoms:
*cough and sputum continuing for more than 2 weeks
*bloody sputum or hemoptysis
*fever over 38.0°C continuing for more than 3 days
*chest pain
*evident emaciation
The results were as follows:
1) Among 112 cases showing aggravation with a large amount of bacilli discharge and with worsening of chest X-ray findings, cough was found in 80%, sputum in 77.7%, bloody sputum or hemoptysis in 33.3%, fever in 42.0%, chest pain in 25.9%, and emaciation in 72.3% (Table 2).
2) Among 27 cases showing a small amount of bacilli on culture (less than 20 colonies) with worsening of chest X-ray findings, the above symptoms were found in 33.3%, 33.3%, 40.7%, 33.3%, 25.9% and 29.7%, respectively (Table2).
3) No symptom was observed in 11 cases showing smear positive-culture negative bacilli or single isolation of positive bacilli on culture (less than 20 colonies) without radiological worsening except one complicated with bronchial asthma (Table2).
4) Out of 62 cases who live in Osaka Prefecture, 40 had been registered as tuberculosis at some of health centers in Osaka Prefecture. Among these 40 cases, 30 were treated irregularly or defaulted from treatment and the remaining 7 were inactive cases under followup (Table3).
5) Over 85% of aggravated cases in this study were discovered by symptomatic visit to general practitioners (Table 3).
From the standpoint of patients-supervision, it can be said that more emphasis should be given to prevent patients from defaulting during treatment and to recommend symptomatic visit to physicians for inactive cases.

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A survey was made on the newly registered tuberculosis patients during the period from January 1 to December 31, 1972, regarding their background factors, severity of disease, extent of bacteriological examinations and the mode of detection. In 1972, 148 cases of pulmonary tuber culosis were registered at the Nagano Health Centre, and among them, 113 were newly registered cases and the remaining 35 were relapsed cases. The results were summarized as follows:
a. Newly registered patients.
1) The proportion of children below 15 was 29%, which was higher than the national average (9%). This is explained by the fact that many primary infection cases are registered as active tuberculosis in this age group, and these cases should be differentiated into 2 categories in the future.
2) Observing by the type of lesions, cavitary tuberculosis occupied 25%, non-cavitary lesions 67%, and others 8%.
3) Bacteriological examinations were carried out in 59%, and the bacilli positivity was 24%. The bacilli positivity was 52% for cavitary tuberculosis and 8% for non-cavitary tuberculosis.
4) As to the mode of detection, 26% were found by MMR, 72% by symptomatic visit to physicians and 2% by others. In 1969, 37% of new patients were detected by MMR, and the detection rate was 0. 14% to those examined by MMR. Both the proportion of cases found by MMR and the detection rate of MMR have been decreasing, and they were 26% and 0.06%, respectively, in 1971.
5) Out of whole cases, 78% were examined by MMR within 3 years, and 67% were diagnosed as healthy, 11% were refered to detailed examinations and finally diagnosed as healed. Among 76 cases diagnosed as healthy within 3 years, 16 (21%) developed cavitary tuberculosis, and these cases are considered as rapid cases.
b. Relapsed cases.
1) Relapsed cases occupied 24% of registered cases in 1972. The bacteriological examinations were carried out in 86%, and the bacilli positivity was 20%.
2) As to the mode of detection, 26% were found by MMR and 74% by symptomatic visit to physicians. Relapses were found even among cases with old history of tuberculosis before 1955, and the fact indicates the necessity of inviting cured cases including cases omitted from the register to the periodical follow-up.

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It was reported previously by the present group (1-3) that the frequency of isolation of my cobacteria other than tubercle bacilli (‘atypical’ mycobacteria) and the incidence of mycobacterioses due to these mycobacteria are higher in the hospitals locating in the South coast of the Honshu island. It was shown also that more than 90% of the mycobacterioses in this country were due to M. avium-intracellulare complex and that the lung disease due to M. kansasii was found only in the Tokyo area and its neighbourhood. In the present study, the prevalence rate of the “atypical” mycobacterioses was compared among the hospitals locating in various places of this country.
A morning sputum specimen was added with an equal volume of a 4% NaOH solution and dissolved by shaking at room temperature for 15 to 20 minutes. The sputum was inoculated to the Ogawa egg medium. Growing organisms were screened for ‘atypical’ mycobacteria by the use of the PNB medium (4) or the salicylate medium (5). The acid-fastness and the photochromogenicity were also tested in individual hospitals. The organisms that grew on the PNB or salicylate medium were sent to the Chubu hospital and were identified according to the methods previously described (2).
‘Atypical’ mycobacterioses were defined by the following conditions: (a) The excretion of ‘atypical’ mycobacteria more than three times in the period of the first 6 months after hospitalization; (b) presence of lung lesion in the chest X-ray picture; (c) coincidence of the excretion of ‘atypical’ mycobacteria and clinical symptoms.
The location of the 13 participating hospitals are shown in Fig. 1. The prevalence rate was the highest in five hospitals, Tokyo, Chubu, Kinki, Tenryuso, and Kochi, which are located in the Southern Pacific coast of Japan (Table 1).
The species of mycobacteria other than tubercle bacilli which caused lung disease in patients are shown in Table 2.
Furthermore, it was shown that tuberculous patients who were hospitalized for long time were infected with ‘atypical’ mycobacteria (Table 3). All causative organisms which caused ‘secondary’ infection belonged to M. aviurnintracellulare complex.

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It has been reported by Ribi's research group in which the present author is included that intravenous injection of BCG cell wall (CW) attached to minute droplets of light mineral oil and uspended in saline produces pulmonary granuloma in mice that correlated with increased resistance against aerosol challenge with Mycobacterium tuberculosis, strain H₃₇Rv.
The present study was undertaken to examine an involvement of cell-mediated immunity in increased resistance against tuberculosis in mice immunized with BCG CW.
The following results were obtained
1) Lung cells from BCG CW-immunized mice showed macrophage migration inhibition (MIF) activity which are closely related with protection against aerosol challenge with H₃₇Rv.
2) Intravenous injection of specific antigen, PPD or BCG protoplasm, into BCG CW-immunized mice one day before aerosol challenge with Mycobacterium bovis, strain Ravenel, resulted in increased protection against the aerosol challenge.
3) In order to explain the above mentioned phenomenon, various in vitro and in vitro experiments have been done. Results of these experiments are in favour of our assumption that interaction between sensitized lymphocytes and injected specific antigens releases lymphokaine in cluding MIF factor and possible macrophage activating factor into blood circulation which leads to destroy aerosal challenged-tubercle bacilli.
4) Oil droplets containing P₃ (a nonantigenic, nonsensitizing trehalose mycolate isolated from M. tuberculosis) and an antigenically nonrelated protein, such as BAS, produced an extensive pulmonary granuloma 2 weeks after immunization that declined after 4 weeks, wheras at this time the slower acting BCG CW had developed a comparable granuloma. Accordingly, mice immunized with P₃+BSA and challenged 2 weeks later were as well protected 4 weeks after challenge as were mice which had been immunized with BCG CW 4 weeks prior to challenge.
5) We investigated the effect on pulmonary granuloma formation and protection in BCG CWimmunized mice of administration of specific antigens. Results of this experiment showed multiple intravenous injections of BCG protoplasm inhibited the footpad delayed hypersensitivity, MIF activity of lung cells and pulmonary granuloma formation as well as the induction of resistance against aerosol challenge with H₃₇Rv.
These results suggests that pulmonary granuloma formation is mediated by cellular immunity.
In summary, antituberculous immunity induced with BCG CW in mice is closely associated with pulmonary granuloma which are considered to consist of massive activated macrophages resulting from cell-mediated immunity in lung tissue.

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