Four hundred and twenty four premature infants had been admitted in the premature infant nursery of Pediatric Department, Kansai Medical University for five years from 1968 to 1972. They were studied statistically, especially on mortality and morbidity of respiratory disorders at first and then relationship between arterial blood gas analysis and clinical symptoms was studied mainly on these infants with respiratory disorders and the following results were obtained.
1) Seventy eight cases of 424 admitted infants died of various conditions and the mortality rate in this nursery (all infants were transported out of the hospital) was 18.3 %. Fourty two cases died of idiopathic respiratory distress syndrome, which showed the highest mortality of 9.9%.
2) Arterial blood gas analyses were done on two samples, arterialized blood obtained by heel puncture and radial artery blood. It was confirmed that the arterialized blood from heel puncture could not be used for monitoring PaO₂.
3) Comparing Silverman's retraction score and blood gas analysing results between infants transported in incubator and infants without incubator, the former showed the better data in blood gas analysis. It was emphasized that infants with respiratory distress should be transported in incubator.
4) Silverman's retraction score in IRDS correlates well to results of blood gas analysis, and may be an effective index to show the course of IRDS, if blood gas analysis is not available.
5) Evaluation of high risk infants by means of results of blood gas analysis immediately after admission is very important for an assessment of prognosis and decision of therapeutic regimens. The blood gas analyser, therefore, should be used in the nursery, to check the blood at whenever time necessary.
6) It was reconfirmed that the blood gas analysis is indispensable as a fundamental test to assess the effects of treatments, including oxygen therapy and alkali therapy for high risk infants, especially for IRDS.

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An electrophysiological study was made concerning the effects on photopalpebral reflex (PPR) and visual evoked response (VER) of rabbits by application of contact lens with the use of ATAC-201 (Nihon Kohden).
1. PPR-wave recorded by unipolar lead induced by photic stimulation was composed of such components as PPR₁, PPR₂, PPR₃, PPR₄, PPR₅ and PPR₆. The amplitude of PPR₁, PPR₂, PPR₃, PPR₄ and PPR₅ components showed no significant changes, however, that of PPR₆ decreased by application of contact lens. It was understood that the inhibition of PPR₆ was due to the decrease of excitability of the reticular formation.
2. VER-wave recorded by unipolar lead was composed of such components as VER₁, VER₂, VER₃, VER₄, and VER₅. These components showed no significant changes by application of the contact lens.

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It is well known that various changes have been induced by tumor-host interactions. Patients with advanced cancer often have bleeding or thrombosis. An alteration in fibrinogen metabolism may be associated with malignant tumors. In recent years, patients with malignant tumors have often shown hypercoagulability and hypofibrinolysis. This study was carried out in order to investigate fibrinogen metabolism related to tumor growth.
In the first experiment, to investigate the fibrinogen metabolism of tumor-bearing animals, Yoshida Sarcoma (1×10⁶cells) was inoculated subcutaneously in the backs of Donryu rats. Controls received subcutaneous injections of turpentine or physiological saline. The level of plasma fibrinogen tended to increase with tumor growth until the 15th day after tumor inoculation when it fell as cahexia developed. The incorporation of ¹⁴C-Leucine into plasma fibrinogen also was increased on the 8th day but significantly decreased on the 15th day after inoculation. The level of fibrinogen in the circulation represents, at least to some extent, a balance between production and destruction. Moreover, from the evidence of the shortened survival of radioactive: fibrinogen in tumor-bearing animals, fibrinogen turnover appears to be accelerated. Therefore, the author examined the alterations in fibrinogen metabolism in tumor-bearing rats. The experimental results showed that the blood levels of soluble fibrin monomer complex and of cryofibrinogen were elevated in rats with Yoshida Sarcoma. In addition to paracoagulation, the fibrinolytic system including plasmin and activator were thought to play an important role in fibrinogen metabolism. The results showed that high concentrations of fibrin or fibrinogen degradation products in the serum and high plasminogen activator activity were present in tumor-bearing rats, especially on the 15th day after inoculation. The citrated plasma was fractionated by means of Lysine-Sepharose affinity chromatography and used to determine the inhibitor, activator, plasminogen and plasmin activities. The results obtained in this experiment showed that increased plasmin and decreased plasminogen activities were present in rats with advanced tumors.
In the second experiment, the mechanism of the altered fibrinogen metabolism in rats was investigated. The tissue extract as well as toxohormone was prepared according to Nakahara's method, and the effects of toxohormone on fibrinogen metabolism in vivo and on thromboplastic activity in vitro were examined. The toxohormone injected intraperitoneally caused elevation of plasma fibrinogen levels and increased incorporation of ¹⁴C-Leucine into the plasma fibrinogen fraction in healthy rats. An elevated level of altered fibrinogen was noted in the circulation of rats injected with toxohormone intraperitoneally. Toxhormone also had higher thromboplastic activity than normal tissue extract.

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An electrophysiological study was made in order to clarify the effects of ATP and cytochrome C on the central nervous system of rabbits with the following results.
1. ATP and cytochrome C decreased the threshold of arousal reaction due to the stimulation of the brain stem reticular formation.
2. On the evoked muscular discharge in fore and hind limbs due to the stimulation of the cerebral cortex, cytochrome C showed facilitatory effect stronger than ATP.
3. On the evoked muscular discharge due to the stimulation of the hippocampus, ATP showed facilitatory effect stronger than cytochrome C.
4. On the early components (N₁, N₂) of afferent average evoked potential in the cerebral cortex due to the stimulation of the sciatic nerve, cytochrome C on one hand showed an inhibitory effect, ATP on the other facilitatory effect.

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Attempted was the experimental production of“pseudo-heart-failure cell pigment”so named, because of its iron-negative reaction, by Maeda et al. to ceroid-like pigment found with or without hemosiderin in some of human pulmonary macrophages.
A kind of this pigment could be histochemically identified, although at a lower frequency, in macrophages in both the alveolar walls and spaces of part of the laboratory animals used, that is, rats either fed a vitamin E-deficient diet for 4 months to one year and a half, a diet containing 0.06% butter yellow for 40 days to 10 months, or completely deprived of food for one to two weeks.
It was noticed that fluorescent microscopy proved to be quite effective in detecting relatively small amounts of“pseudo-heart-failure cell pigment”coexisting with large amounts of hemosiderin in the same macrophages by confirming the autofluorescence of the pigment.
On this occasion, it was suggested on the basis of the results of the carmine vital staining etc. that chronic pulmonary edema caused by an increased permeability of the walls of the pulmonary alveolar capillaries as well as increased amounts of plasma protein fractions (probably abnormal glycoprotein) in the blood induced by hemolysis in vitamin E-deficient rats or by prominent consumption of general tissue proteins in rats completely deprived of food for a certain period would participate in the mechanism of the experimental production of“pseudo-heart-failure cell pigment”in pulmonary macrophages.

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In recent years, there have been reports that various protease inhibitors depress the carcinogenesis in mouse skin induced by DMBA and croton oil, and that protease enhances the transformation and proliferation of cultured cells. Thus, it has been shown that protease plays an important role in carcinogenesis.
This study was undertaken to elucidate the effect of Leupeptin, a protease inhibitor isolated from Actinomycetes, on rat mammary carcinogenesis induced by DMBA. Groups of Sprague-Dawley female rats were given the usual laboratory diet (control diet) and others the same diet containing 0.1% Leupeptin (Leupeptin diet).
In the first experiment, all rats were injected intravenously with 3 mg of DMBA at 55 and 58 days of age. Administration of the Leupeptin diet was begun 7 days before DMBA treatment and continued for 120 days after DMBA treatment. Systemic toxicity combined with adrenal damage caused by DMBA treatment led to 41% mortality in the control diet group and 17% mortality in the Leupeptin diet group. The difference was significant (P<0.05). At the end of the experiment, a comparison was made of tumor development in the two groups. Significantly fewer tumors and lower tumor weight per rat were observed and the incubation time was longer in the Leupeptin diet group than in the control diet group.
In the second experiment, rats were injected with 2 mg of DMBA at 55 and 58 days of age. The periods of feeding with the Leupeptin diet were as follows;
L-1 group; the same period as in the first experiment
L-2 group; 40 days after DMBA treatment
L-3 group; 7 days before DMBA treatment The L-2 group showed significant decrease of tumor number and prolongation of incubation time as compared with the control group. Tumor development in the L-3 group was similar to that in the control diet group.
In the third experiment, protease activities of rat mammary fat pads were assayed and compared 3,7,14,21 and 28 days after DMBA treatment. A 2500×g pellet was active for neutral protease digesting Calf thymus histon and the 20000×g supernatant for Cathepsin D and caseinolytic activities. Caseinolytic activity at 3 days and neutral protease activities at 3,7 and 21 days were significantly decreased in the Leupeptin diet group. However, caseinolytic activity was significantly increased only at 21 days in the Leupeptin diet group. No differencein Cathepsin D activities was observed between the control and Leupeptin diet groups.
Microscopic examination of established mammary tumors showed that majority were papillary or tubular adenocarcinoma, and no differences in histological features were observed between the two groups.
The results indicate that the administration of Leupeptin inhibits rat mammary carcinogenesis, especially when Leupeptin is given during DMBA induction of mammary tumor, and further the effect of Leupeptin is considered to be one of promotion rather than initiation. In addition, it seems that proteases which digest casein and Calf thymus histon play an important role in rat mammary carcinogenesis.

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It has recently been shown that certain amino acid imbalances in the diet inhibit the incidence and growth of tumors.
This report describes the effect of excess arginine in the diet of rats with mammary carcinoma induced by 7,12-DMBA. The diets contained equal quantities of carbohydrate, fat, vitamins and minerals and differed only in protein content;
1) MF diet (Oriental Yeast Co. )
2) 20% casein (control)
3) 15% casein supplemented with 5% arginine
4) 12% casein supplemented with 8% arginine
A fat emulsion of 7,12-DMBA (3mg DMBA per rat) was injected intravenously into the tail vein of female Sprague-Dawley rats at 55 and 58 days of age. The animals were examined every day during the experimental period, and the number and size of the palpable tumors were recorded. All rats were sacrificed at 145 days of age and examined grossly and microscopically.
In the first experiment,40 day-old rats were fed on one of the four diets before and after DMBA-injection, respectively. The mean weight gain in the four groups was the same each other, and no side effects of arginine were noted. A decrease in incidence, a delayed onset and a lower number of tumors were observed in the groups fed argininesupplementd diets. Tumor formation in the MF diet group was almost the same as in the 20% casein diet group.
In the second experiment, three groups of 40 day-old rats were fed on control or arginine-supplemented diets before and for 35 days after the injection of DMBA. Then they all received the MF diet. The incidence, incubation time and average number of tumors were the same in all three groups.
In the third experiment, the MF diet was fed to all groups for 15 days before DMBAinjection, and starting 35 days after DMBA-injection, the control or arginine-supplemented diets were substituted. The tumor incidence was lower in the arginine-supplemented diet groups, but the difference was not statistically significant. However, a prolonged incubation time and fewer tumor were observed, as in the first experiment.
The above data indicate that arginine-supplemented diets have little or no effect on the initiating stage of DMBA-induced mammary carcinogenesis, but they distinctly effect on the promoting stage.
Both the urea concentration and arginase activity in rat mammary fat pads and the urea content of mammary tumors induced by DMBA were examined.
Urea concentrations and arginase activities were increased in rats fed arginine-, supplemented diets.
This suggests that urea in mammary tissue may play an important role in rat mammary carcinogenesis.
Further studies will be reported in another paper.

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The experiments described in Part 1 showed that the growth of tumors induced by 7,12-DMBA was decreased in rats fed arginine-supplemented diets.
This paper described the effect of arginine-supplemented diets on the growth of Walker 256 carcinosarcoma.
In the first experiment, female Wistar rats were fed on three different synthetic diets;
1) 20% casein (control)
2) 15% casein supplemented with 5 % arginine
3) 12% casein supplemented with 8 % arginine
Three million cells of Walker 256 carcinosarcoma were inoculated subcutaneously. The experimental diets were given for 10 days after inoculation. All animals had free access to water. The average body weight gains did not differ much from each other in the three groups, but significantly lower tumor weights were observed in the arginine-supplemented diet groups.
In the second experiment, the diets were started 15 days before and continued for 10 days after inoculation.
The effect of the arginine-supplemented diets on tumor growth was even greater than in the first experiment.
In attempt to clarified the mechanism of inhibition of tumor growth by arginine supplementation, the urea content of Walker 256 carcinosarcoma was examined.
An increased urea concentration was found in tumor tissues of rats fed argininesupplemented diets.
Local injections of various concentrations of urea definitely inhibited the growth of Walker 256 carcinosarcoma in proportion to their concentration.
In summary, arginine-supplemented diets inhibited the growth of Walker 256 carcinosarcoma, probably because of the urea produced with in the tissues of these rats.

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Spasm of the major cerebral arteries occurs in more than 35 per cent of patients with subarachnoid hemorrhage due to the ruptured cerebral aneurysms, and the presence of severe spasm is known to affect greatly the prognosis of the patients. Despite extensive clinical and experimental investigations, no satisfactory treatment has been established up to the present.
Experimental studies were performed to find out effective managements for cerebral arterial spasm. Cerebral vasospasm was produced experimentally by injection of autogenous fresh arterial blood into the cisterna magna of adult dogs and the effects of papaverine hydrochloride which was applied in various ways and concentrations, were evaluated.
1. Biphasic cerebral vasospasm could be produced by injection of autogenous fresh arterial blood into the cisterna magna without vascular injuries and this model of experimental vasospasms was thought to be adequate for the present study.
2. Papaverine hydrochloride was a potent vasodilating drug and its effect was found most marked when it was given directly into the cistern. However, duration of action was only transient.
3. Continuous subarachnoid irrigation was found effective in reducing vasospasm. By adding a small amount of papaverine hydrochloride ( 2×10^-3%), which gave far less concentration than those effectively used topically, to the perfusate the effect of relieving vasospasm was enhanced and prolonged spasmolytic effect was obtained.
As a conclusion, it was important to reduce spasmogenic substances liberated from the blood clots in the subarachnoid space in order to get good and long-lasting effect in relieving vasospasm with spasmolytic agents such as papaverine, and continuous irrigation of the subarachnoid space was of value.

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Spontaneous adrenocortical tumors appear to be rare in popular strains of mice, and above all, the development of hormone-producing adrenocortical tumors are extremely seldom. In order to carry out the induction of functional adrenocortical tumors, a total of 94 C₃H/He virgin mice were divided into the following 4 experimental groups; (1) 16 mice of the age of 6-9 weeks were applied to the untreated control group, (2) 18 mice received an intravenous injection of 2.5 mg of 7,12-Dimethylbenz (a) anthracene (DMBA) twice at the ages of 10-12 and 13-14 weeks in the carcinogen-treated group, (3) 17 mice were ovariectomized bilaterally at the age of 6-9 weeks in the ovariectomized group, (4) 43 mice were ovariectomized bilaterally at the age of 6-9 weeks, and then injected intravenously with 2.5mg of DMBA emulsion at the ages of 10-12 and 13-14 weeks, respectively, in the ovariectomized and DMBA-injected (combination-treated) group. The experimental animals survived more than the age of 7 months were determined to be effective for this tumorigenesis.
Adrenocortical tumors were found unilaterally in some treated mice, and their weights were distributed in the range of 20-1600 mg. The incidences of adrenocertical tumors in the effective animals were as follows: 0 /12= 0% on the control group,1 /13=7.7% on the DMBA-injected group,1 /15=6.7% on the ovariectomized group, and 10/21=47.6% on the combination-treated group. Many mammary tumors with few pulmonary metastasis were observed in the non-operated mice, and some ovarian tumors were detected in the injected mice. Few leukemia, thymoma and lung tumors could be seen in the treated groups. In brief, double administrations of DMBA emulsion in several weeks after the bilateral ovariectomy might evoke more often a neoplastic transformation in the adrenocortical cells of C₃H/He virgin mice.

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