Nephrotoxicity of antibiotics was investigated to determine the order of these antibiotics according to their toxicity to the kidney. Adequate methods for evaluating renal damage were also studied.
The respiratory activity of renal tissue, the p-aminohippurate uptake by slices of the renal cortex and the activities of alkalinephosphatase, lactic dehydrogenase and leucine aminopeptidase in the organ have been employed as indicators of tissue damages. Histological changes of the renal tissue were also studied.
The following antibiotics were administered to rats by intramuscular injections daily for 5 to 7 days: Kanamycin, Dihydrostreptomycin, Aminobenzylpenicillin, Cephaloridine, Cephalothin, Chloramphenicol (500mg/kg body weight/day), Aminodeoxykanamycin (300mg/kg/day), Dimethylchlortetracycline, Oxytetracycline (200mg/kg/day), Gentamicin (50mg/kg/day), Colistin methansulfonate (15mg/kg/day), and Polymixin B (3mg/kg day). No water was given to the rats in the whole experimental periods. Liver damage caused by the administration of antibiotics was also investigated to compare with renal impairment.
Results
1. Respiratory activity of renal tissue was most remarkably decreased in rats administered with KM, GM, or SM. Modarate reduction of respiratory activity of renal tissue was obtained in rats administered with CL, AKM, PLB, DMCT, or OTC. Administration of CER, CET, ABPC, or CP to rats caused little or no decrease in renal respiratory activity. Reduction in oxygen comsumption of renal tissue was correlated with renal damage due to administration of antibiotics.
2. Decrease in alkalinephosphatase activity of the kidney seemed to be correlated with renal impairment. Alkalinephosphatase activity of the kidney was easily reduced by small change in condition of the kidney, while succinoxidase activity of the kidney was reduced following severe renal impairment.
3. L. A. P. activity of the kidney was not markedly correlated with activity of renal alkalinephosphatase. L. A. P. activity of kidneys showed small reduction in rats administered with KM, AKM, DMCT, or OTC wheras activity of renal alkalinephosphatase decreased markedly.
4. Activity of renal L. D. H. falls to slightly below the control value but there was no remarkable difference among different antibiotics.
5. In general, PAH uptake by slices of the renal cortex was correlated with respiratory activity of the kidney. Moderate reduction of respiratory activity of the kidney was observed in rats administered with CL, PLB, DMCT, or OTC while remarkable reduction of PAH uptake by slices of the renal cortex was obtained in these cases.
6. Oxygen consumption of liver tissue showed remarkable reduction in rats administered with CER or ABPC. There was no descrease in respiratory activity by other antibiotics.
7. Histological findings of the kidneys were correlated to changes of respiratory activities or to those of PAH uptake.

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Mucoproteins were isolated from the normal human urine, using a method of salting out with sodium chloride (Tamm-Horsfall method, 1952) and a method of absorption on benzoic acid (Anderson-Maclagan method, 1955). The biochemical properties of the urinary mucoproteins isolated by these two methods were investigated and compared with each other.
1) The substance isolated from the urine, regardless of the difference of the methods, are similarly proven to contain nearly all kinds of amino-acids which constitute the protein. The content of hexosamine in the mucoproteins is 5.9% by Tamm-Horsfall method and 5.1% by Anderson-Maclagan method.
2) The urinary mucoproteins show a maximum absorption of ultraviolet ray at 277mμ wavelength, and give a peculiar purple color reaction of maximum absorption at 520mμ wavelength with the diphenylamine reagent. This color reaction is suitably applied for quantitative determination of the urinary mucoproteins.
3) The urinary mucoproteins are separated into three fractions by the gel-filtration method. Fraction 1 consists of substances of molecular weight not less than 2×10⁵, fraction 2 of substances of molecular weight approximately corresponding to that of bovin albumin, fraction 3 of substances of lower molecular weight including lysozyme molecules. But the proportional constitution of the fractions differs between the two isolation methods. The mucoproteins obtained by Tamm-Horsfall method are composed almost exclusively of fraction 1, whereas the ones isolated by Anderson-Maclagan method contains relatively larger amounts of fraction 2 and 3.
4) The correlation between the activity of the urinary lysozyme and the amount of fraction 3 contained in the urinary mucoproteins is demonstrated.

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The fine structure of normal and neoplastic prostate before and after the administration of high dose estrogen, has been investigated by the electron histochemistry and the following results were obtained.
1) Acid phosphatase activity can be seen in the lysosomes, as well as in the granules, vesicles and vacuoles within the secretory vacuole, while no activity can be detected within the cisternae of the rough endoplasmic reticulum and Golgi apparatus.
2) Many lysosomes and large secondary lysosomes surrounded by the access of many lysosomes are seen in the normal prostatic and the well differentiated prostatic cancer cells.
3) The large lysosomes having the internal structure are observed in the prostatic cancer cells.
4) The number of usual lysosomes are decreased and the autophagic vacuoles and the residual bodies with the distinct internal structure of myelin are increased in number at the undifferentiated prostatic cancer cells.
5) The lysosomes and large secondary lysosomes surrounded by the access of many lysosomes are also found in the basal cells of the normal prostate.
6) The cytoplasmic vacuolization near lysosome is seen by the gradual release of lysosomal enzymes, and the secretory vacuole is formed. The lysosome itself decreases in its size, and is observed as a granule in the secretory vacuole.
7) For the secretory mechanism in the cells of normal prostate and prostatic cancer: 1) macroapocrine secretion, 2) microapocrine secretion and 3) secretion by reverse pinocytosis are observed. There are two processes in the extracellular secretion of acid phosphatase: 1) by the secretion of the reverse pinocytosis of secretory vacuole and 2) by the secretion of the macroapocrine in which the lysosomes are possesed.
8) Undemarcated granular and fibrillar components are seen in the nucleoli of undifferentiated prostatic cancer cells, and there is a relative increase of granular component. These nucleoli might be thought to be in active state in the production of cytoplasmic free ribosomes.
9) The early changes in the prostatic cancer cells after the administration of high dose of diethyl stilbesterol diphosphate is seen mainly in lysosomes. Namely the limiting membrane of lysosomes is ruptured and the cytoplasmic vacuolization is formed near the lysosomes. In the ruptured lysosome the netted fine structure can be observed. Diethyl stilbesterol diphosphate might be thought to act as a lysosome labilizer in the prostatic cancer cells.
10) The administration of high dose of diethyl stilbesterol diphosphate may be thought to be more effective in the beginning of treatment when, in early stage, high acid phosphatase activity has been kept in the prostatic cancer cells.
11) High acid phosphatazemia would be seen when the well differentiated cancer cells, in which the lysosomes are rich, are increased in number.

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Since our original report of transrectal approach using television fluoloscopy for roentgenographic visualization of benign prostatic hyperplasia, we have continued to apply this technique to the cases of benign hyperplasia, carcinoma, inflammatory disease and normal condition of the prostatic gland.
Anatomy and histology of the prostate were investigated in this study, and the relationship between prostatogram and anatomic structure of the prostate by this technique were discussed. It was found that this method faithfully visualized anatomic findings of the prostate. Normal or pathologic conditions of the prostate showed various contrast changes.
The characteristic prostatogram in normal condition, inflammatory disease and benign prostatic hyperplasia in an early stage-type showed tubulo-alveolar lobules and tubules which made up the external or true gland of the prostate, but the prostatic capsule was not clearly visualized.
The prostatogram of clinically recognized typical carcinoma showed a filling defect corresponding to the location of the carcinoma, and injection of contrast material into the carcinoma tissue needed a very increased presure.
The characteristics of prostatogram of the benign hyperplasia in alate stage-type showed well vascularrich picture and a constant image by lag of exposure time after injection of contrast material into the prostate. Remains of contrast material in the hyperplastic prostate were quickly and completely absorbed into the vena hypogastrica through the venae pudendae interna and venae vesicales inferiores.

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When renal calculi are too large to be easily removed through an incision in the renal pelvis or when the extrarenal part of the renal pelvis is very small, it has been customary to approach the stone through an incision in the renal parenchyma.
Intrarenal pyelolithotomy was performed in 8 patients with renal calculi.
The patients were placed on the usual lateral position with the loin angled over a cushion.
The kidney was approached by the oblique lumbotomy incision parallel with the transverus abdominis muscle and about 1cm below the 12th rib, from 5cm lateral to the spinous processes in back downward and forward to the lateral border of the rectus muscle. The kidney was dissected free from the surrounding adipose tissue by sharp and blunt dissection. The posterior aspect of the renal pelvis was exposed. The renal parenchyma overlying the renal pelvis was gently pushed away with an elevatorium. The edge of the reflected renal parenchyma was grasped with small retractors. If aberrant vessels appear during the dissection of the fatty tissue on the posterior aspect of the extrarenal and intrarenal pelvis, they should be carefully clamped and ligated. Especially, removal of staghorn calculus necessitated dissection of all the renal parenchyma overlying the intrarenal pelvis.
The intrarenal pyelotomy incision was performed in a longitudinal or transverse fashion without any injury to the ureteropelvic junction. Large or multiple renal stones were easily romoved through it. It was closed with interrupted suture of plain 3-zero catgut on an atraumatic needle. When the retracted parenchyma was released, it could cover the suture line. The wound was then closed with a rubber drain at the lumbar space. After removal of the stones, it was sometimes difficult accurately to close the laceration of the intrarenal pelvis, but in these cases there was little post-operative leakage of urine, profably because the renal parenchyma fell over the suture line to seal up it.
Some stones were large, friable and adherent, others were very hard. The exposure of the renal pelvis by this extracapsular approach was technically easy and offered visibility to all the intrarenal portion of the pelvis and to the major calices. Haemorrhage was minimal in all cases. Post-operative leak of urine was present for the first few days, but without any problem.
This type of surgery improved the prognosis for the cases with staghorn and multiple calculi and made total extraction possible without injury to the renal parenchyma and the excretory tract.
The intrarenal pyelotomy incision is applicable not only for intrarenal pyelolithotomy but also for pelviolithotripsy and “renal stone extraction” in the impression material clot.

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The technique of the “our renal stone extraction” in elastic impression material clods is described. This coagulum theoretically incorporated within itself all free calculi or fragments regardless of size or location. They are removed on withdrawal of the perfect mold of the pelvic cavity through the intrarenal pyelotomy incision.
The main points are as follow:
1) The substance is injected into the renal pelvis by standard techniques, coagulates are formed uniformly and completely within a short period of time and visualized by X-ray films.
2) The properties of the elastic impression materials (Surflex F and Flexicon) are chemically and physically inert, non-allergenic and non-carcinogenic, cause no foreign body reaction, and are easily sterilized.
3) After the intrarenal pyelolithotripsy, large stones are removed with forceps and undemonstrable fragments are easily removed without any trauma of the renal parenchym.
4) The elastic impression materials are very cheap and easily obtained.
This method has been utilized in the renal stone extraction on 5 cases of artifical renal stones and two patients with a staghorn calculus. The results were excellent.

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