The inhibitory activity of 6-mercaptopurine and 6-mercaptopurine riboside against Rauscher Leukemia Virus and Leukemia 1210 cells was studied. LD₅₀ of 6-mercaptopurine riboside was 2.5g/kg in mice by intraperitoneal injection and that of 6-mercaptopurine was 380 mg/kg.
6-Mercaptopurine and 6-mercaptopurine-riboside were effective against Rauscher Leukemia Virus. The therapeutic index of 6-mercaptopurine-riboside was 8.3 and that of 6-mercaptopurine was 3. 8. These drugs were effective against Leukemia L-1210 cells too, and the therapeutic index of 6-mercaptopurine-riboside was 135, and that of 6-mercaptopurine was 51. From these results, it may be said that 6-mercaptopurine riboside was effective twice than 6-mercaptopurine.
The development of the resistance of L-1210 cells to 6-mercaptopurine riboside was slower and a little weaker than that of 6-mercaptopurine resistance.
The clear cross-resistance between 6-mercaptopurine resistant cells and 6-mercaptopurine-riboside resistant ones, was observed.

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The blood concentration, the excretion into feces and urine and the body distribution of ³H-6-Mercaptopurine Riboside (6-MPR) administered orally were estimated. 500 mg/kg of 6-MPR was administered. In blood 6-MPR was detected at the 1st hour and reached the maximum amount at the 2 nd hour, and then went down slowly. About 50% of administered 6-MPR was found in feces and about 6% of it was found in urine within 24 hours after administration. In the observation of the body distribution of 6-MPR, the most intersting results were (1) the rapid and high distribution of 6-MPR into spleen and (2) the high amount in brain.

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1) The sensitivities of Cephalexin (CEX) against 55 strains of coagulase positive Staph. aureus were measured by plate dilution method. Fourty-seven out of 55 strains of Staph. aureus were inhibited by 12.5 mcg/ml or less of CEX. The sensitivities of CEX against those 55 strains were from 2 to 16 times inferior than those of CER.
2) The average blood levels at one hour and two hours after an oral administration of 500 mg of CEX were 12.6 mcg/ml and 10.0 mcg/ml respectively. Urinary recoveries in 12 hours were from 85.3 % to 108%.
3) The binding rate of CEX with horse serum protein was measured by equilibrium dialysis method. The binding rate was 39.9%.
4) Twelve patients of various infectious diseases were treated by CEX. Ten patients were improved by CEX treatment. The elevations of GOT and GPT were observed jn one patient of pharyngeal abscess, who received the CEX treatment for 31 days. The liver functions returned to normal range within 2 weeks after the removal of the drug.

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Experimental and clinical studies on cephalexin (Glaxo's and Lilly's), a new oral cephalosporin C derivative, were performed. The results obtained were as follows.
(1) The sensitivity of cephalexin against Staphylococcus aureus was a little inferior to cephaloridine and cephalothin, but it was the same as cephaloglycin.
(2) The sensitivity of cephalexin against E. coli was superior to cephalothin and the same as cephaloglycin, but it was inferior to cephaloridine.
(3) Very high blood levels were obtained by oral administration. There was no difference between Lilly's and Glaxo's. Oral administration of 500 mg produced more than 10 mcg/ml peak blood levels and no detectable levels in the serum after 8 hours. The total amount recovered in the urine were very high.
(4) Excellent clinical response were obtained with Lilly's or Glaxo's. 85% of 12 respiratory tract infections and 7 urinary tract infections and one biliary tract infection showed good response with administration of average daily dose of 1.5 g in divided 3 times.
(5) Any side effects were not observed except one gastric disturbance and one temporal slight numbness which were not necessary to stop the administration. No abnormal findings of renal, liver, and blood function were not observed.

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Cephalexin, a new oral antibiotic of the cephalosporin C, was evaluated through laboratory and clinical investigations and the following results were obtained :
1. The antibacterial activity of cephalexin appeared to be less sensitive than those of other cephalosporins, but there is not yet observed resistant group of E. coli which is isolated from many cases of urinary tract infections. Cephalexin was not sensitive to Pseudomonas aeruginosa and some strains of Proteus species like other many antibiotics. Cephalexin is superior to cephaloglycin, an analogue of the oral cephalosporin, in the point that ten or more times higher concentrations in blood and urine are obtained with cephalexin, which indicates to be a very valuable drug for the treatment of urinary tract infections.
2. Cephalexin was clinically evaluated in uncomplicated acute cystitis on the dosage of 2g and 4g daily for 3 days reatment, and the effectiveness obtained in 38 cases of 2g and 31cases of 4g was 76.4% and 93.6% respectively.
This result indicates that even if spontaneous healing is considered, cephalexin is apparently an effective antibiotic to the infection studied and the dosage of 4 g daily for 3 days is better than that of 2g daily.
3. A short period of treatment was adapted for the evaluation of cephalexin in order to exclude the influence of spontaneous healing as much as possible. This method adapted for the present study is considered to be a better one.
As a considerable rate of spontaneous healing was observed even 3 days observation, however, it still remains how to resolve this problem concerning the criteria of therapeutic response by chemotherapy.

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An oral preparation of synthetic cephalosporin C, cephalexin was studied bacteriologically and clinically, with the results which may be summarized as follows :
1) In a study by the agar plate dilution method on a total of 98 strains of 19 bacterial species, Staphylococci, Pneumococci, β-Hemolytic streptococci, Corynebacterium diphtheriae and Neisseria gonorrhoeae were found to be markedly susceptible to the agent, showing their MICs almost less than 4.4 μg/ml. Gram-negative rods including E. coli, Klebsiella, Salmonella and Shigella were fairly susceptible with the MIC values ranging from 1. 1 to 8. 8, ug/ml. While, Enterococci, Proteus group and Pseudontonas displayed a rather poor susceptibility to the agent ranging in MIC values over 35, μg/ml.
2) With the view of preparing grounds for application of the single-disc method to the sensitivity test in clinical laboratory, graphic analysis of the dose-response data concerning the interrelations between MIC value and diameter of inhibition zone were conducted on each of i) conventional (over-night : about 16 hours) assay, ii) 4-hour rapid assay with heavy inoculum, iii) 6-hour rapid assay with heavy inoculum and iv) delayed (about 24 hours) assay for slowly growing bacteria. Experimental errors of single-disc method inherent was also discussed in comparison with the ones in the dilution method.
3) By the thin-layer cylinder-plate technique using B. subtilis PCI 219 as a test organism, cephalexin was found to be assayable to the lower limit of 0.3 μpg/ml in serum (1 : 2 in phosphate buffer).
Following a single oral administration of 500 mg cephalexin, peak serum levels of 7-20 μg/ml were obtained at 2 hours, with persistence of serum levels of at least 0.5 μg/ml over ensuing 8 hours. And the agent was recovered for the most part from the urine in the microbiologically active form.
4) In comparison with other cephalosporin C derivatives as cephalothin and cephaloridine, cephalexin is hardly inactivated by penicillin-resistant Staphylococci (β-lactamase producer) and consequently cephalosporinase producing ability of Staphylococci would be lower with cephalexin.
5) Treatment with cephalexin was effective in two cases of urinary tract infection caused by the organisms whose sensitivities to the agent were determined as very sensitive by the above mentioned single-disc method.
6) No any side effects were observed in these 2 cases.

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It was commonly believed that there was high incidence of mixed infection with gram-negative bacilli in the patients whose general condition were so poor and postoperative infections were prolonged, and the management of those patients were extremely complicated. In this study, the authors performed basic and clinical experiment on gentamicin, to which gram-negative bacilli showed higher sensitivity as compared with other antibiotics, and it was obtained interesting results as follows :
1. Mean MIC of gentamicin for 104 strains of gram-negative bacilli was 0.84mcg/ml and that of Pseudomonas aeruginosa was 3.4 mcg/ml.
2. The blood level of gentamicin was 3.2mcg/ml at 30 minutes after the intramuscular administration of 40 mg of gentamicin, then it dropped quickly. But the blood level was 0.1-0.5mcg/ml at 12 hours after the administration.
3. The urine excretion of gentamicin was reached to 36.5% in the male of 60 kg, 33.4% in the male of 75 kg, and 10.0% in the male of 90 kg at 6 hours after the intramuscular administration of 40 mg of gentamicin.
4. In 13 clinical cases, the effective rates were evaluated to be 85% and there was not found any remarkable associated effect, especially concerning liver and renal function. Additionally, the authors discussed briefly on indication of gentamicin in the treatment of gram-negative bacilli and Pseudomonas aeruginosa infection in our Department.

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The physiological disposition of TC-17 in tumor-bearing mice, rabbits and normal rats was investigated.
When TC-17 was injected parenterally, various tissue levels increased rapidly and were retained in high levels in the body for 10 days or more. Peak values in various tissue levels in rats receiving TC-17 intraperitoneally in a single does of 100 mg/kg were found at 5 or 10 days after the injection and the drug was concentrated temporarily in lung and kidney. Serum half-life was about 14 days.
Serum half-life in tumor-bearing rabbits receiving 50 mg/kg of the drug intravenously was about 4 days.
Urinary excretion of the drug was almost none in rats and rabbits, and its biliary excretion was a little.
Repeated intraperitoneal injections on tumor-bearing mice showed accumulation of the drug in liver, kidney and testis.
At rabbit serum levels of 100 to 500, μg/ml, about 50% of TC-17 bound with the serum proteins, and TC-17 serum protein complex occurred the ionic dissociation in electrophoreetic process.

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