Anti-human lymphocyte sera (AHLS) were produced by immunization of the horse with human spleen cells, peripheral lymphocytes, lymphocyte membrane components and cultured lymphoblasts as the antigens. The method of immunization and blood collection and the antibody titer of AHLS were discussed.
The anti-lymphocyte antibody was tested in vitro by leukoagglutination, lymphocyte cytotoxicity and rosette formation inhibition test. The other antibodies (hemagglutinin, antiplatelet antibody and antihuman-serum-protein antibody) were also assayed.
In AHLS produced by subcutaneous immunization with spleen cells or peripheral lymphocytes high anti-lymphocyte activities were developed but antibodies against platelet and human serum proteins also made appearance.
In AHLS induced by intravenous immunization with spleen cells and lymphocyte membrane components lower antilymphocyte activities were developed.
AHLS produced by subcutaneous and intravenous immunization with cultured lymphoblasts had a high lymphocyte cytotoxicity and rosette formation inhibition titer without development of antibodies against platelet, human serum protein, and glomerular basement membrane. The antilymphocyte globulin (AHLG) purified from this AHLS can be administered intravenously without development of anemia, thrombocytopenia or allergic reaction and furthermore has a favorable immunosuppressive effect for clinical use in kidney transplantations.

View full abstract

The ¹⁴C-leucine incorporation into monolayer culture was applied to the evaluation of cell damage in immune reactions. The cell viability meassured by dye exclusion was compared with the ¹⁴C-leucine incorporation into the target cells (T24 cell) after the incubation with phytohemagglutinine (PHA) and lymphocytes. The results showed that the cytotoxicity of lymphocytes was dependent on the concentration of PHA and the number of effector cells, and the ¹⁴C-leucine incorporation was correlated well with the viable cell number. The results of the present work indicate that ¹⁴C-leucine incoporation into the target cells can be used as a senitive and reliable measure for the determination of cell-mediated cytotoxicity.

View full abstract

Cytotoxicity of lymphocytes from normal persons against 3 established cell lines was determined by the ¹⁴C-leucine incorporation method. The cytotoxicity expressed by MRT (Mean Reduction per Titer) was 37.9±3.7% against HeLa cells, 21.3±4.8% against T24 cells and 10.6±4.8% against MGH-Ul cells. The percent target cell reduction was correlated well with the number of the effector cells, when T24 cells were used as the target cells.
Prednisolone was demonstrated to inhibit the cytotoxicity of lymphocytes from normal persons against T24 cells and HeLa cells. Prednisolone at a concentration of 10^-4M remarkably inhibited the cytotoxicity against T24 cells in 91.7±6.2% and yet at a concentration as low as 10^-7M produced a significant inhibition of the cytotoxicity in 39.7±11.9%, as compared with the prednisolone-untreated control. The result indicated that the inhibitory effect was closely dose-dependent. A lower concentration (10^-7M) of prednisolone exerted a significant inhibition of the cytotoxicity against HeLa cells as well as T24 cells, but the dose-dependant effect of prednisolone was not so clearly demonstrated in HeLa cells as in T24 cells.
The effect of adding 10^-5M of prednisolone during the 72hr cytotoxicity test using T24 cells as the target cells was as follows. Prednisolone added immediately after the cytotoxicity test (0h) almost completely abolished the subsequent development of cytotoxicity (94.6%). Prednisolone added after 12 and 24hr of the culture also exerted the inhibitory effect (93.2 and 83.7%, respectively). Considerable inhibitions occurred on adding prednisolone after 36 and 48hr (48.0 and 46.6%), while prednisolone added after 60hr was without significant effect on the cytotoxicity.
The present data indicated that the immune responses of lymphocytes from normal persons may be inhibited by the immunosuppressive effect of prednisolone. Such an inhibitory effect of prednisolone suggests the presence of an antigen recognition phase in the cytotoxic reaction of normal persons. Moreover it may be ruled out that the suppresive effect of Prednisolone occurred predominantly on an early step of immune response, since the inhibitory effect decreased progressively 36hr after the initiation of the cytotoxic reaction and no significant effect was seen during the last 24hr.

View full abstract

A clinical study of 73 patients with vesicoureteral reflux is presented. Between 1968 and 1977, we saw 73 patients, ranging in age from 4 months old to 73 years old, with vesicoureteral reflux (24 males and 49 females), which formed 2.1% of the total number of inpatients admitted to Urology service during the same period. Of the 73 patients, 46 had primary vesicoureteral reflux and the remaining 27 had secondary vesicoureteral reflux. Of the 46 patients with primary vesicoureteral reflux, 35 patients were female and 11 were male (female/male=3:1). The age distribution of the female patients showed a high incidence in patients less than 10 years of age and in their twenties and thirties, whereas that of male patients showed a high incidence in patients less than 10 years of age. Primary vesicoureteral reflux was relatively uncommon in male adults, the age of the oldest patients being 33 years old.
The operation for affected ureters was performed on 37 patients (51ureters) with primary vesicoureteral reflux and 7 patients (7 ureters) with secondary vesicoureteral reflux. As a surgical operation for patients with primary vesicoureteral reflux, Politano-Leadbetter procedure was performed in 26 patients (36 ureters), Paquin procedure in 8 patients (12 ureters), and nephrectomy in 2 patients. Also there was a uretero-ureterostomy in one patient who had a unilateral complete double ureter and the refluxing ureter was united to its party. Of the patients with primary vesicoureteral reflux who underwent either Politano-Leadbetter or Paquin procedure and were followed more than one year, 23 patients had no radiological evidence of vesicoureteral reflux (satisfactory operative result) and one had a poor result with formation of a ureteral stricture at the site of repair, making the success rate 97.3%. Both Politano-Leadbetter and Paquin procedure seemed to be epually good in terms of the ease with which the procedure could be performed and the effectiveness to eliminate vesicoureteral reflex. There was no occurrence of vesicoureteral reflux on contralateral ureters after unilateral operation.
Of the 7 patients with secondary vesicoureteral reflux, Politano-Leadbetter procedure and Paquin procedure were performed in epual number, of patients (3 patients) and nephrectomy in one patient.
Based on our experiences as well as review of the literature, it is our rule to consider primarily surgical correction for all adult primary vesicoureteral reflux, including sterile vesicoureteral reflux.

View full abstract

In a retrospective study a total of 83 cases (138 ureters) of anti-reflux ureteroneocystostomy performed by us at the Department of Urology, Hokkaido University School of Medicine during a 6-year period from 1971 to 1977 were reviewed.
1) This series comprised 57 cases of primary VUR, 14 cases of non-refluxing megaloureter and 12 cases of other congenital anomalies of the ureter (e. g. ureterocele and ectopic ureter). They consisted of 56 children and 2 7 adults or 36 males and 47 females.
2) The operation was performed by a modified method of Paquin in 72 cases, by Politano-Leadbetter's procedure in 9 cases and by other procedures in 2 cases.
3) Therapeutic success was achieved in 92% of cases, including 76 cases of success with reoperation. The success rate was 96.5% for primary VUR (including refluxing megaloureter) as against less than 50% for nonrefluxing megaloureter.
4) In 12 cases the initial operation proved to be unsuccessful. These failures were caused by a stenosis of the anastomosed site in 4 cases by VUR or its recurrence in 8 cases. The latter 8 cases were all children. The incidence of postoperative VUR was particularly high among those infantile cases of megaloureter where the narrowing suture had not been done.
5) Postoperative urinary infection was successfully controlled in 61 of 65 cases. The duration of postoperative chemotherapy in these 61 cases ranged from 1 month to 2 years with an average of 6 months.
6) As postoperative complication a transient pyeloureterectasis occurred in 48 of 71 cases. These changes disappeared spontaneously within 3 months in 20 cases, within 6 months in 26 cases and in 1 year in 2 cases.
7) Contralateral VUR occurred in 7 of 41 cases after unilateral operation. This disorder disappeared spontaneously in 2 to 9 months in 3 of these 7 while persisted in the other 4. Those cases in which preoperative examination revealed malformation and malposition of the orifice of the contralateral ureter along with abnormalities in pyeloureterogram had a higher incidence of contralateral VUR with a lower frepuency with which VUR disappeared spontaneously.
8) Nineteen of 41 cases undergoing bilateral operation had residual urine and difficulty of urination over a transient postoperative period. These disorders disappeared completely in 1 to 12 months in all cases but one.
9) In 17 of 41 cases treated by Paquin's procedure unilaterally postoperative voiding cystourethrography demonstrated asymmetric vesical contraction, probably due to insufficient contractility of the ipsilateral bladder walls. In 4 cases this bladder deformity was found to disappear in 1 to 3 years postoperatively.

View full abstract

Anatomical and functional study was performed on the sphincteric system located distally in the sphincteric urethra.
1) The mechanism of urinary continence after the prostatectomy was attributed to the true external sphincter which is anatomically defined as intrinsic striated muscle of the urethra, and functions under the primary influence of α-adrenergics of the short neuron system.
2) The direct innervation of α-adrenergics to this unique striated muscle was postulated from its electromyographic response to the α-adrenergic drugs, and discussion was made on the role of catecholamine in the contraction of skeletal muscle.
3) Clinical experiences in the management of neurogenic vesical dysfunction with α-blocker and α-agonist by relaxing and constricting the external sphincter, respectively, were presented.
Plea was made to pay attention to this revised concept of the external sphincter in understanding various pathophysiology of the lower urinary tract.

View full abstract

Serum CEA and urine CEA were determined by the one-step sandwich method (DINABOT CEA-RIAKIT) in 200 serum and 110 urine samples collected from 108 cases.
The serum CEA level is of little diagnostic value in determining the malignancy, since there was no significant difference in the serum CEA value between the group of patients in early stage of malignant tumors (n=30, X±S. D.=1.7±0.7ng/ml) and the groups of patients without tumors or with nonmalignant disease (n=49, X±S.D.=1.6±1.1ng/ml).
The urine CEA level is also of little use, if the upper limit of normal CEA level is 16.8ng/ml in infected urine and 3.2ng/ml in non-infected urine. It was proved statistically by our measurements, too.
No significant correlation was found between serum CEA and urine CEA with the correlation coefficients 0.34 in infected urine and 0.26 in non-infected urine.
However, it appeared to be possible in certain cases to evaluate the growth and regression of cancers on the basis of the serum CEA value.

View full abstract

In this study in fifteen mongrel dogs, the right renal veins were ligated adjacent to its junction to the inferior vena cava in order to determine the course, total renal functions, fluctuations of the blood enzymes levels, renal histological changes, development of venous collateral drainage and the right renal functions after the removal of the left (namely the opposite side) kidney four weeks after ligation.
1. Out of 11 dogs in which the right renal vein had been ligated, 9 dogs survived more than four weeks. This fact indicates that the ligation of the right renal vein of dogs is not always followed by fatal hemorrhage in the perirenal area or high mortality rate but can be tolerated adequately in general.
2. In 5 dogs in which determinations of the serum creatinine levels were carried out for 2 weeks after the ligation of the right renal vein, it was found that all the fluctuations remained within the normal limit.
3. The blood levels of GOT, GPT, alkaline phosphatase, LDH and aldolase were determined in 5 dogs for 2 weeks after the ligation of the right renal vein. All the changes remained within normal limit in 4 dogs. However, in one dog elevations of LDH and alkaline phosphatase were seen, although both of these changes were mild and transitory in nature. From these results it was considered that histological lesions caused by the ligation of the right renal vein were mild.
4. Among histological changes which occurred under the ligation of the right renal vein were pronounced circulatory disturbances such as thickening of glomerular basement membrane, swelling of the proximal tubular epithelium, retention of albumine cast and dilatation of veins. Four weeks after the ligation, all of these lesions were decreased, and no organic changes were seen.
5. The main venous collateral circulation under the ligation of the right renal vein consisted of ureteral and renal capsular veins, and gonadal vein was also found to play role in venous drainage by forming communication with ureteral and renal capsular veins.
6. In 5 dogs in which the left kidney was removed four weeks after the ligation of the right renal vein, the course after the left nephrectomy was observed. Two out of the 5 dogs died as a result of renal dysfunction. However, the remaining 3 dogs survived with good renal function maintained. The measurement of serum creatinine and excretory urogram were normal after 5 months postoperatively.
From these results it was revealed that in dogs with the right renal vein ligated venous collateral drainage consisting chiefly of ureteral, renal capsular and gonadal veins will be established in 4 weeks after the ligation with recovery of histological changes due to circulatory disturbances and that the right kidney can retain good functions.

View full abstract

Turn over of administrated radioactive fibrinogen and uptake to renal allograft were studied in 9 cases of renal allotransplanted patients. In patients with acute rejection crisis biological half-time (T1/2) of ¹³¹I-fibrinogen were shortened and allograft/heart counts ratio of ¹²⁵I-fibrinogen were elevated up to 125-140 percent at 24-48 hours after administration; these parameters seemed to be useful in aid of diagnosis of acute rejection.
It is suggested that deposition of fibrinogen into allograft and increased turn over of plasma fibrinogen occurred in acure rejection.

View full abstract

Fifty-eight cases of cancer of the penis were treated in our clinic between 1955 and 1977.
In our first report, we reported clinicostatistical studies on 58 cases of cancer of the penis, and that the over-all 5-year survival rate of 49 cases was 77.6%.
In this report, we studied side effects and complications of the treatments, and the prognosis of all sorts of treatments.
The results are summarized as follows:
Fifteen out of 50 cases (30.0%) suffered from stricture of the urethra after amputation of the penis. Fourteen out of 48 cases (29.2%) suffered from lymphorrhea after inguinal lymphadenectomy. Four out of 14 cases (28.6%) suffered from late radiation injury after radiotherapy of the penis.
All of 25 cases (100%) suffered from some side effects of Bleomycin, and 2 cases (8.0%) suffered from pulmonary fibrosis, as the most serious side effect.
The over-all 5-year survival rate of 17 cases with Bleomycin treatment was 76.5%, and that of 32 cases without Bleomycin treatment was 78.1%.
And, there was no statistically significant difference (P<0.05) in the prognosis among all sorts of treatments to the penis and the inguinal lymphnodes.
When we examined the prognosis according to Jackson's staging, the prognosis of high stage was poor, and the cases of high stage were very inclined to resist any other treatments.

View full abstract

Four cases of Noonan's syndrome with complaints of bilateral cryptorchidism were investigated for male gonadal function. All had normal chromosomes and normal pedigrees. Both serum testosterone,
LH and FSH values were low and their responses of HCG and LH-RH were poor in three children, suggesting that they had hypogonadism and that normal spontaneous pubertal growth was not to be expected. In the remaining one case (adolescent age) with considerable responses on HCG and LH-RH stimulation was expected, but not enough to become pubertal maturation.

View full abstract

A 58-year old man visited our clinic with complaint of a painless enlargement of the right scrotal contents in July 1976 during the course of IgG-λ type multiple myeloma. The patient had had chemotherapy with Cyclophosphamide and Predonisolone since October 1974. Right orchiectomy was performed on him in July 1976.
The right scrotal mass was proved to be histlogically metastatic plasma cell myeloma of the testis. He died in October 1976, but postmortem autopsy was not performed. Testicular metastasis of myeloma is quite rare. Our case is the third report in Japan.

View full abstract