Motoyuki Masai

Androgen receptor gene mutations in human prostate cancer

To investigate the structural abnormality of the androgen receptor (AR) in human prostate cancers, exons B-H encoding DNA- and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products using originally designed oligoprimers. Tissues from 7 cases of untreated stage B prostate cancer surgically removed and from 8 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Two different mutations were identified in exons D and H in the different cancer foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu to His) was detected in the prostate, and the other in exon H (at codon 877, Thr to Ala) was found in metastatic tissues. In untreated cancer tissues and the other autopsy samples, no mutations were detected. The mutation in exon H was identical to that reported in LNCaP cells. These results indicate that AR gene mutations occur in relation to endocrine therapy-resistance, although the mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.

Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma

Patients with prostate carcinoma generally respond to androgen withdrawal therapy, but subsequent progression to androgen‐independence is frequently observed. Since androgen receptors play a key role in androgen action, the ratio of androgen receptor‐containing cells in cancerous tissues was determined by immunohistochemical staining of prostate biopsy specimens for comparison with the outcome.

Tumor marker doubling time in patients with prostate cancer : determination of prostate-specific antigen and prostatic acid phosphatase doubling time

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

Histochemical examination of expression of ras p21 protein and R 1881-binding protein in human prostatic cancers.

Expression of ras p21 was examined with monoclonal antibody RASK-3 in normal, benign hyperplasic, and cancerous prostates. In patients with stage D2 disease who received endocrine therapy, the relation between ras p21 expression, response to therapy, and prognosis was studied. In these patients, R 1881-binding protein (androgen receptor and progestin-binding protein) was also examined. Non-cancerous cells and most cancer cells from stage A patients did not express ras p21, while expression increased with both higher staging and grading. Staging pelvic lymphadenectomy was done in some stage A2-C cases, and presence of nodal metastasis was correlated with ras p21 expressions in the primary tumours. In stage D2, there was no correlation between ras p21 expression and R 1881-binding protein. Response to therapy and survival did not correlate with expression of ras p21, but was influenced by presence of R 1881-binding protein.

Clinical Course of Bone Metastasis from Prostatic Cancer Following Endocrine Therapy: Examination with Bone X-Ray

X-ray findings of bone metastatic lesions from 81 cases of stage D2 prostatic cancer were examined before and following endocrine therapy. Untreated lesions were classified into five types; osteoblastic (15%), mixed, but mainly osteoblastic (31%), mixed, but mainly osteolytic (17%), osteolytic (10%), and undetermined with a positive bone scan (27%). Patients with two mixed types had a tendency of widely speeded areas of metastasis and elevated serum prostatic acid phosphatase. Temporal enlargement of sclerotic lesion immediately after the start of therapy did not indicate disease progression. In many cases, changes from osteolytic to osteoblastic patterns were noticed in the same lesion regardless of the effects of endocrine therapy. Remodeling to the sclerotic pattern appeared as curative changes. From these findings, it was concluded that the natural course of bone lesions showed a tendency to change from the osteolytic to osteoblastic type and relapse was often accompanied by an increase of the osteolytic type lesion. Evaluation of therapeutic effects based on remodeling, changes in number and areas of lesions, and the appearance of new lesion correlated well with prognosis.

Endoscopic Re-Establishment of Membranous Urethral Disruption

A total of 17 patients with traumatic membranous urethral disruption underwent urethral reconstruction via a core-through technique. Followup was 1 to 8 years (mean 3.7 years) postoperatively, and included 6 weeks with an indwelling catheter, periodic dilation for 6 months and occasional sounding. Within 1 year postoperatively, 6 patients required additional scar incision, including 3 who underwent scar resection. At 1 to 8 years postoperatively 6 patients had complications: 3 had stricture requiring periodic dilation (including 2 who underwent scar incision), while 2 had mild stress incontinence and 1 had nocturnal enuresis. Traumatic impotence was noted in 7 patients but the operation was not the cause in any. This method of endoscopic management was found to be an acceptable alternative to urethroplasty in cases of membranous urethral disruption.

Relationship between diurnal rhythm of serum testosterone and two prostatic markers (PSA and PAP) in untreated prostate cancer

OBJECTIVE To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). METHODS Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer. RESULTS Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were observed in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients. CONCLUSIONS Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

Clinical and biochemical features of uric acid nephrolithiasis

A clinical investigation was carried out on patients with uric acid stones in order to study the frequency and pathogenesis of uric acid nephrolithiasis. Of 652 patients with stones in the upper urinary tract in whom the stone composition could be examined, 36 patients and uric acid stones (5.5%). The male to female ratio was 11:1. The average age of the 33 male subjects was 49 +/- 11 years (mean +/- SD), and the 3 females were 22, 37 and 42 years old, respectively. Two of the females showed hypouricemia. With regard to stone composition, pure uric acid stones were present in 26 cases (72%), a mixed uric acid and calcium oxalate stones were found in 6 cases (17%), both pure uric acid and mixed uric acid and calcium oxalate stones were observed in 3 cases (8%), and a mixed uric acid and sodium acid urate stone in 1 (3%). Biochemical studies on male patients showed that the blood uric acid level was higher in the uric acid stone group and the pure uric acid stone group compared to the calcium stone group. The blood uric acid levels of the former 2 groups did not differ from the control group. With respect to urine chemistry, the excretion of calcium in the uric acid stone group was significantly lower than that in the control group. In the uric acid stone group and the pure uric acid stone group the excretion of calcium tended to be lower than that in the calcium stone group. The amounts of oxalic acid excreted in the uric acid stone group and in the pure uric acid stone group were low compared to the calcium stone group. Oxalic acid elimination in these 2 groups did not differ from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties.

Purpose: To examine the influence of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties.Patients and Methods: Dietary intake was recorded by using the dietary–record method in 58 idiopathic stone formers in their forties. The patients collected their urine for 24 h at home and their urinary oxalate excretion was measured. The relationship between the dietary intake of various nutrients and urinary oxalate excretion was examined by mono– and multivariate analysis.Results: The intake of animal fat was correlated with urinary oxalate excretion by monovariate analysis, but that of total protein, animal protein, calcium and carbohydrate were not. By multivariate analysis, the intake of animal fat was correlated with urinary oxalate excretion and the intake of calcium was inversely correlated with urinary oxalate excretion.Conclusion: The intake of animal fat was positively and the intake of calcium was negatively correlated with the urinary oxalate excretion in stone formers in their forties. It was shown that animal fat plays an important role in urinary oxalate excretion.

Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.