Hashigami had studied higher fatty acids in the blood and urine from patients with urogenital diseases by means of Fujii's paper chromatographical method in an attempt to obtain clarification of the relationship between the results and the metachromatic reaction (abbreviated to “MR”) in the urine. The same investigator emphasized that the “MR” was always positive or pubiously positive when higher fatty acids were detected in the urine and that none of these were detected in the urine which presented the negative “MR”. He concluded that higher fatty acids can safely be regarded as “MR”-positive substances. He added, however, that it was impossible to determine by his own method whether the higher fatty acids that could be detected were of a free form or an ester form.
Higher fatty acids of a free form were lisewise studied by the present author in the urine from 109 cases of urosis and from 20 healthy persons who were chosen at random. Furthermore, higher fatty acids of an ester form were detected by the same method as used by Hashigami in order to seek the relationship between both forms and the “MR”. The fat loading test was performed on 2 patients and 1 healthy person, and the urine which was collected before and after the test was similarly examined with results. This paper presents a description of these rasults.
Experimental results:
1) No free higher fatty acids could be detected in the urine from 109 cases of urosis and from 20 healthy persons.
2) Higher fatty acids of an ester form could be detected in 8 of the 15 cases of tuberculous urogenital diseases, 2 of the 3 cases of urogenital tumor, 4 of the 8 cases of idiopathic nephrorrhagia and 1 case of cancerous cystitis,
3) No higher fatty acids of an ester form were to be demonstrated in the urine from healthy persons and from cases of other urogenital diseases.
4) The positive or doubtful positive “MR” was secured from cases, in whose urine higher fatty acids of an ester form were detected, but the negative “MR” took place in the urine from cases where none of them could be found,
5) As a result of the fat loading test, free higher fatty acids could be detected in none of all the cases. Untile 2 hours after the loading, patients with renal tuberculosis showed an increase in the amount of higher fatty acids of an ester form in the urine. However, such a tendency was not perceived in other cases. These cases alone presented the positive “MR”.
6) As Hashigami claimed, the present author concluded that these higher fatty acids might be regarded as substances in the urine which showed the positive or doubtful positive “MR”. All of these proved to be of an ester form.

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The author applied the Y⁹⁰ colloid and Cs¹³⁷ needle as an interstitial and bracky therapy to eradicate the metastatic retroperitoneal lymphnodes in bladder cancer.
1) The amount of Y⁹⁰ colloid distributed to the regional lymphnodes is at most 1-2μc per gr. tissue, when the colloid is injected into the dog's bladder wall. This amount is far below the theoretical tumor lethal dose.
2) The maximum amount of Y⁹⁰ colloid distributed in the regional lymphnodes is 12μc per gr. tissue, when the colloid is sprinkled into the dog's retroperitoneal space.
3) When the colloid is injected directly into the nodes the maximum amount attains to several hundred μc per gr. tissue. The more the amount of colloid, the higher the grade of destruction of lymphnodes.
This method was applied to nine patients without any complications.
4) Bracky therapy with Cs¹³⁷ needles produces remarkable degeneration of the nodes, when the administered dose exceeds 3000r.
Six patients were treated by Cs¹³⁷ needl bracky therapy. No serious complications were noticed.

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The morphogenesis of prostatic hypertrophy has been confirmed in detail to some extent. As for the cause of the disease, various theories have already been reported. Among them, the theory attributing the cause of the disease to abnormality of internal secretion, especially of sex-hormone predominates at present. We have up to date, however, no evidence justifying any of the theories in substance. The tissue of prostatic hypertrophy is distingwished by a very high content of citric acid.
A few facts found out in the process of my research, in relation to the metabolism of citric acid are here reported. In dogs fed with citric acid and fumaric acid, we see the citric acid increase in prostate, resulting from the citric acid regeneration hindered, and the lowering of TCA cycle in gereral. When fed with fumaric acid alone, the citric acid increase is remarkably large. Aconitase activities in prostate, after 2-3 weeks of citric acid and fumaric acid feeding, are increased. After 2 months, however, the activities are remarkably decreased. Therefore it is understood that, in prostatic hypertrophy, there is a vicious circle of citric acid increased and aconitase activities decrease, citric acid increase preceeding. The order of citric acid value, high or low in the prostatic hypertropby, is as follows: glandular type fibroglandular type fibrous type. The average aconitase activities value in prostatic hypertrophy is lower than in normal prostate, the former being 24.4 and the latter is 37.0. The aconitase activities order is as follows: fibrous type, fibroglandulor type, glondulor type……just reverse to the citric acid value order classified by histological findings.
I measured the activities of Transaminase, in order to know the origin of citric acid in prostatic hypertrophy.
Findings:
GOT, in comparison with GPT, is exceedingly high. Oxaloacetic acid value in tissues is also exceedingly high. Consequently the inverse reaction of GOT is proceeding. In conclusion, it is confirmed that the citric acid increase in prostatic hypertrophy has reference to the proceeding of the inverse reaction of GOT and TCA cycle hindered by aconitase activities lowered. I measured the high energy in prostatic hypertrophy and got ratio ADP/ATP, larger than in normal phosphate bound prostate. It is presupposed from this ratio that the energy regeneration in prostatic hypertrophy tissues is hindered.
By Oxygen consumption experiment, adding parotin, it was found out that parotin promotes TCA cycle regeneration in prostatic tissues, especially it increase the activities of aconitase and isocitric dehydrogenase. Further by the experiment of oxygen consumption, very active when both parotin and ATP are used, it was found out that parotin and ATP would have clinical effect when employed in the treatment of the prostatic hypertrophy.

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The pituitary-adrenocortical function, urinary 17-Ketosteroids and their fractionated patterns, in 23 cases of prostatic carcinoma and. 22 cases of prostatic hypertrophy were investigated and the following conclusions were obtained.
1. The values of 17-Ketosteroids in the urine of patients with carcinoma or hypertrophy of the prostate were in the range of values obtained from normal men of the same age level. Neither was there any significant difference in the values between before and after antiandrogenic therapy of the patients with prostatic carcinoma, and those between before and after prostatectomy of the patients with prostatic hypertrophy.
Although assaying the values of urinary 17-Ketosteroids of the patients with prostatic carcinoma does not necessarily afford a powerful clue in the diagnosis and the judgement of effectiveness of treatment and that prognosis of the patients, the values seemed to indicate, with considerable accuracy, the possibility of relapse or recurrence of prostatic carcinoma in those cases where the values continued to maintain a high level, or elevated again following restoration to the normal level even after the radical operation or antiandrogenic therapy.
2. No significant difference was observed between the values of urinary 17-Ketosteroids of the patients with prostatic carcinoma, those with prostatic hypertrophy and those of normal men. This fact should partly be attributed to wide individual difference of the fractionated patterns of 17-Ketosteroids.
In those patients whose prostatic carcinoma improved with antiandrogenic therapy, the fraction of androgen and glucocorticoids metabolites was markedly reduced and that of dehydroisoandrosterone (Fraction III) showed a tendency to rise elevation. No significant effect was, however, observed after the prostatectomy of prostatic hypertrophy.
3. Relapse or recurrence of prostatic carcinoma after the radical operation or following antiandrogenic therapy of the tumor caused an enhancement of the values of urinary 17-Ketosteroids and of those of the fraction of androgen and glucocorticoid metabolites.
4. In respect to the pituitary-adrenocortical function, examined by Thorn's test, of the patients with prostatic carcinoma, there was observed a reduction of this function in about a half of the patients and no marked improvement followed antiandrogenic therapy. Thorn's test of the patients with prostatic hypertrophy showed the function to be in a normal range.
In patients, whether with carcinoma or with hypertrophy of the prostate, the result of whose Thorn's test was normal, an increase of urinary 17-Ketosteroids was encountered followingthe administration of ACTH. In those the result of whose test was abnormal, the administration of ACTH was not followed by an increase of 17-Ketosteroids, but rather was even followed by a reduction in many cases.
A close relationship was recognized between the increase of the fraction glucocorticoids metabolites in the urinary 17-Ketosteroids following the infection of ACTH and the pituitary-adrenocortical function (a decrease of eosinophile leucocytes according to Thorn's test).
5. Antiandrogenic therapy often proved markedly effective against prostatic carcinomajudging from both clinical and pathological findings of the tumor. The therapy, however, sometimes could not be expected to have such a good effect in the case where the tumor consisted of extremely undifferentiated cells. The administration of corticosteroids and carcinostatic drugs sometimes showed a good result in the patients with prostatic carcinoma which was too advanced to be extirpated by a radical operation, but in respect to the fractionated pattern of 17-Ketosteroids, the treatment showed us significant change.
6. Assay of the fractionation of urinary 17-Ketosteroids in the antiandrogenic therapy of prostatic carcinoma affords a powerful clue in the judgement of effectiveness of antiandrogenic therapy, of possible r

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Experimental studies with electron microscope were performed on the prostatic epithelial cells of rats with special reference to the effects of antiandrogenic therapy. These observations may be valuable in analysing hormonal controls of the prostatic gland and mechanisms of antiandrogenic therapy on prostatic carcinoma. Rats were divided into four groups, namely group 1 (control group), group 2 (Hexsuron group), group 3 (castration group) and group 4 (castration plus Hexsuron group). Hexsuron (4, 4′-dihydroxy-γ, δ-diphenyln-hexane) was given continuously 5 mg a day. In group 4 Hexsuron administration was started from the same day on which castration was carried out. The rats were sacrificed on the 1st, 2nd, 5th, 10th, 20th, 30th and 60th days following the experimental procedures. Specimens from the ventral gland of the prostate were taken immediately after death.
In the normal prostatic epithelium of rats there were well developed Golgi components, abundant endoplasmic reticulum and oval mitochondrias of similar size. The mitochondrias showed a regular distribution in cytoplasm and their inner structure exhibited functional changes.
The first electron-microscopic changes were observed on the 1st day following the first experimental procedures in each experimental group. After endoplasmic reticulum had begun to distend, diminition of cellular organules and atrophy of epithelial cells occurred. These changes were more rapid and more intense in groups 3 and 4 than in group 2. On the 2nd day following castration distension and collaps of the endoplasmic reticulum occurred diffuse in group 3, while the changes in group 2 were patchy on the same day. In group 4 endoplasmic reticulum showed collaps rather than distension from the first. Changes on the 20th day in group 3 were accord with that of 30th and 60th days in group 2. It was interesting that some epithelial cells in groups 3 and 4 contained abundant cellular organules in the specimens after Hexsuron administration of 60 days.
Electron-microscopic examination could reveal marked changes of cellular organules 24 hours after antiandrogenic treatment, though histological examination revealed evident changes only after 5 days. Above-mentioned findings suggest that antiandrogenic therapy damages metabolic system of intracellular organules, resulting in degenaration and destruction of the prostatic epithelium. Similarly, antiandrogenic therapy for prostatic carcinoma may act on remnant normal components of cancer cells.

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Experiments were performed to clarify the mechanism of afferent innervation of the urinary bladder. The afferent impulses from the vesical nerve produced by mechanical stimulation of the bladder were recorded by means of an oscilloscope with continuous photography of the oscilloscopic images. All experiments were performed by using the vesical nerve (N. vesicalis, a branch of N. ischiadicus)-bladder preparations and single afferent myelinated nerve fiber (dissected from the vesical nerve)-bladder preparations of toads (Bufo vulgaris japonicus). In addition electron-microscopic study was carried out to examine the distribution of the diameter of the vesical nerve fibers. These experiments led to the following conclusions.
1) Expansile and contractile autonomic movements of the urinary bladder are smooth and regular. The increase of spontaneous afferent impulses can be seen to occur simultaneously with each bladder contraction.
2) One side of the vesical nerve innervates also the other side of the urinary bladder wall.
3) Any single portion of the bladder wall is innervated by several afferent nerve fibers in an over-lapped manner.
4) Any single afferent nerve fiber innervates only a certain limited area of the bladder wall.
5) The mechanism of producing tension of the detrusor muscle is similar to that of the myotatic reflex or tonic muscle stretch reflex of skeletal muscles.
6) At least three or more types of nerve endings could be distinguished. The first group comprises endings which are stimulated by intravesical pressure. The discharges show a very slow adaptation and usually fade away in 2 to 3 hours or slightly more. About 10 per cent of the nerve endings examined behaved in this manner. The second group comprises endings which are stimulated by the stretch stimuli of the detrusor muscle, and the adaptation to the stimuli was slow or moderately slow. The amplitude of discharge is relatively large. About 75 per cent of the endings examined behaved in this manner. Others, the third type, adapt rapidly and are stimulated by rapid changes in conditions of the bladder wall, e. g., the flexion of the bladder wall. These probably bear no relation to micturition.
7) About 250 nerve fibers are contained within the vesical nerve trunk of the toad. Myelinated nerve fibers occupied about 40 per cent of these, and the rest of them were unmyelinated fibers. In regards to the distribution of the diameters of 128 myelinated and 61 unmyelinated fibers a statistical analysis was made. Myelinated fibers very in diameter ranging from 5.2μ to 0.42μ and unmyelinated fibers, from 3.76μ to 0.27μ. These views were based on the electron microphotographs of the vesical nerve trunk.

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