(1) Experiments in guinea pigs
Guinea pigs were inoculated with 1mg and 10mg of the Terai strain subcutaneously andwere sacrificed after 2, 4, 6 and 8 weeks, one animal at each time. Comparison was madewith guinea pigs inoculated with 0.01mg of virulent human tubercle bacilli, Kurono strain.
Skin reaction to 100 fold dilution of old tuberculin were positive after 4 to 6 weeks in bothgroups and it was more marked in the group inoculated with than that inoculated with 0.1mg, although still weaker than in the group inoculated 10mg with Kurono strain. The weight ofspleen was heavier in the Terai strain group than in the Kurono strain group, being morethan twice heavier 8 weeks after the inoculation. There were complications of pleurisy andperitonitis in many of the Terai strain group but no such compliations in the Kurono straingroup. The macroscopic pathological findings in lymph nodes and other organs were muchmore marked in the Kurono strain group. But microscopically the tubercles were seen in allthe organs examined, i.e. spleen, liver and lung, regardless of the amount of inoculation, andthe time of sacrifice. The number of tubercles was generally the most in spleen, then in liverand the least in lung. Colony counts per 1mg of the organs, were less in the group inoculatedwith 1mg than that with 10mg and were more in spleen and liver than in lung. With thelapse of time, colonies became less in mumber but were still present 8 weeks after the inoculation. This tendency was the same in the Kurono strain group.
The Terai strain is considered to possess considerable virulence to the guinea pig.
(2) Experiments in rabbits and hens.
Both rabbits and hens were inoculated with 10mg of the bacteria subcutaneously and weresacrificed 8 and 12 weeks after the inoculation.
The rabbits revealed tubercles only in the regional lymph nodes and no lesion in otherorgans macroscopically. Histological examination proved these results, i.e. only tubercles inthe regional lymph nodes and no tupercles in other organs. Cultures yielded colonies from theinoculated site, the regional lymph nodes, and mesenteric lymph nodes but only a few colonies from the liver at 8 weeks after the inoculation. Other organs faild to yiels the bacteria.These results are coincident with the pathological findings.
In hens, there were no macroscopical lesions seen but microscopically many tubercles wereseen at the inoculated site and a few in the liver. Cultures yielded many colonies from theinoculated site and a few from the spleen, liver and lung.
Consequently the Terai strain seems to have no or only a slight, virulence to rabbits andhens.
Summary of the first, second and the third reports.
The Terai strain which was isolated from a patient appears to be a strain of non-photochromogen type of the nuclassified mycobacteria from the clinical data and the various in-vitroexperiments. The pathogenicity of the strain to animals was investigated.
The results show that the strain possess approximately the same degree of virulence to themouse as virulent human tubercle bacilli, Kurono strain, with intravenous inoculation. Thevirulence was less to the guinea pig than that of the Kurono strain with subcutaneous inoculation.It seems to have no or slight virulence to the rabbit and the hen, with subcutaneous inoculation.

View full abstract

The following results were obtained from the experiments of lathyrogenic effect by injectingINAH to fertilized hens eggs:
1) 7.5mg of INAH were injected into fertilized eggs placed in the inculator for 2 weeks, and at the 17th day the fragility was measured and dydroxyproline as well as rel. η in thelong bone extract were measured, and a remarkable collagen solubility was found.
2) The collagen solubility increased as the injected INAH was increased in quantity, butwhen it was 30mg or more, the number of death cases was increased and collagen solubilitywas obscure.
3) When 7.5mg of INAH were injected into eggs incubated for 5, 8 and 11 days respectively, the earlier the time of injection, the greater the number of death cases. All died when injectedat 5 days, and when injected at 11 days, only one of 10 cases breathed faintly but instantlydied when taken out of the shell. Its growth was apparently poor as compared with the control.
4) Embryos damaged by the INAH injection were recovered when the period from theinjection to the examination was long.
5) INAH derivatives, like INAH, had lathrogenic effect.
6) Equimolar amount of INAH vitamin B6 was injected into the both ends of the egg at14 days and examined at 17 days. No death was observed in the pyridoxine group with orwithout INAH. All was dead in the pyridoxal group, irrespective of whether INAH was addedor not, and hard haemorrhage was observed.
7) Pyridoxine somewhat decreased collagen solubility caused by INAH. On the other hand, pyridoxal could almost prevent the solubility, but since all cases died in this group, a furtherresearch is necessary to determine whether the time for INAH to achieve the effect was longenough or not.
8) FKI hydrochloride (Furyl-2-methylketone isonicotinyl hydrazone) in high concentrationis hard to dissolve unless it is warmed. The diversity in FKI data seems to be due to theuncertain amount of FKI caused by the difficult dissolution. And examining paperchromatograph, two unknown compounds are found through sterilization, and thesecompounds may influence the data considerably.

View full abstract

A number of studies on the in vitro activity of ethambutol (EMB) against M. tuberculosishave been reported, while only a few roports concerning atypical acid-fast bacilli are noted. In thispaper, the authors present their studies on the susceptibility in vitro of twenty-three strainsof atypical mycobacteria and ten strains of acid-fast bacilli isolated from natural sources toEMB and to commonly used antituberculosis drugs, using 1% Ogawa egg medium and modifiedkirchiner's agar medium (KYOKUTO product).
Nine out of ten strains of atypical mycobacteria pathogenic for man were inhibited completely in the concentrations of one to ten mcg per ml. of EMB. However, only five out ofthirteen strains of casual isolates and five out of ten strains isolated from natural sourceswere inhibited in their macroscopic growth at the concentrations of five to ten mcg per ml.and one to ten mcg per ml. of EMB, respectively.
The number of the strains inhibited their growth in the concentrations of less than tenmcg per ml. of eight kinds of anti-tuberculosis drugs including EMB was in the followingorder:
INH>EMB>SM=Kanamycin (KM) >PAS> Cycloserine (CS) >Ethionamide (TH) =Tibione (TBI) in atypical mycobacteria pathogenic for man, KM>EMB>SM>INH>PAS=TH>CS>TBI in casual isolates, and EMB>SM=KM>INH among the acid-fast bacilli isolated fromnatural sources. None of the strains isolated from natural sources were inhibited their growthin the concentrations of less than ten mcg per ml. of PAS, CS, TH or TBI.
Thus, the inhibitry effect of EMB on atypical mycobacteria was much stronger than thoseof PAS, CS, TH, and TBI, and comparable to those of INH, SM and KM.
The slowly growing strains were more susceptible to anti-tuberculosis drugs, generally, than did the rapidly growing ones.

View full abstract

Clinical effects of synthetic protein anabolic steroid (HMD) upon advanced cases of pulmonarytuberculosis positive of resistant acid fast bacilli were studied from the pharmacological aspect.
1) 15 cases of advanced pulmonary tuberculosis with positive resistant strain of acid fast: bacilli but without complication were continued of the basic medication with PAS and INH, and in addition, they were administered with 15 mg/day of HMD for more than a year for thepurpose of studying its effect on body weight, sedimentation rate of erythrocyte, liver function, findings of the blood, pulmonary lesions and bacteriological findings.
2) In the humans administered with HMD, acetylating capacity for sulfa preparation, and, NEFA (nonesterified fatty acid) of the serum obtained while fasting were measured.
3) In the healthy rabbit administered with HMD, the decrease of blood sugar by theadministration of BZ 55 and the effect of HMD on the acetylation capacity of BZ 55 were.examined. Also NEFA uptake of the heart muscle in vitro was estimated from its change in, the medium.
4) Normal male rats or those treated with HMD, thyroxine or estradiol were investigated, of the isocitrate dehydrogenase activity of the 40% ammonium sulfate fraction of liver homogenatewith the addition of DPN, TPN or TPN plus DPN. The estimation was made from theincrease of the absorption spectrum at 340 mμ.
Results
1) No roentgenological and bacteriological aggravation (according to the Gakkenclassification of pulmonary tuberculosis) was observed. Gain in body weight and improvementin sedimentation rate were seen in some cases.
2) The number of red blood cells tended to increase but hemoglobin was not changed.
3) BSP showed a transient retention but returned to the normal state in the course of theobservation.
4) Acetylation capacity for sulfa preparation was decreased.
5) NEFA in the serum obtained while fasting was decreased.
6) NEFA uptake of the heart muscle of rabbit was accelerated.
7) As to the liver isocitrate dehydrogenase, DPN specific ICDH activity showed a tendency of elevation by treating with thyroxine, but no apparent difference of activity from the controlwas seen by treating with estradiol. By the treatment with HMD, both TPN specific ICDHactivity and DPN specific ICDH activity were observed to decrease, and also there was seensome effect on the transdehydrogenase activity.
Conclusion
The combined use of HMD has its significance both in suppressing the acetylation and inkeeping PAS and INH longer in effective form in the body possibly resulting in better antibacterial action.
The suppressive effect of the acetylating capacity of the drug does not seem to be causedby liver disturbance but by the changes in the matabolic patterns related to the enzymaticactivities of the liver.

View full abstract