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Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 199 records · Page 11Linked to original sources

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.

Adenocarcinoma↗

Lower urinary tract dysfunction in the anterior spinal artery syndrome.

Lower urinary tract function was studied in 10 patients with the anterior spinal artery syndrome. In the acute stage all patients had complete urinary retention. Cystometry in 3 patients showed detrusor areflexia. At a neurologically stable stage 9 patients could void and 1 had urinary retention during the preceding 7 years. Cystometric bladder capacities at first and maximum desire to void were decreased in 8 patients and normal in 2. Detrusor hyperreflexia was noted in 8 patients, a normal bladder in 1 and detrusor areflexia in 1. External urethral sphincter electromyography revealed detrusor-sphincter dyssynergia in 4 patients and normal findings in 6. We conclude that the vesicomotor dysfunction in this syndrome is similar to that of traumatic spinal cord injury except that bladder sensation is preserved. The latter finding indicates that at least some of the bladder sensation travels via the posterior columns of the spinal cord.

Electromyography↗

Corneal transplantation with donor corneas stored in moist chamber and chondroitin sulfate-containing medium.

Two donor cornea preservation methods, moist chamber and chondroitin sulfate-containing medium, were prospectively compared clinically. Paired corneas from 11 donors were divided into two groups: moist chamber group (mean preservation time 9.1 h) and Optisol (Chiron Co., Irvine, CA, U.S.A.) group (mean preservation time 70.8 h). They were compared in terms of their clinical course, corneal thickness, and endothelial density. Recipient age, sex, and diseases were matched between the groups. Nine of 11 corneas in the moist chamber group, and 10 in the Optisol group remained clear at 6 months after surgery. Decreases of the endothelial density were 28.4% in the moist chamber group, and 30.1% in the Optisol group at 6 months after surgery. No differences were found in either endothelial density or corneal thickness throughout the observation period. It was shown that the corneoscleral preservation using chondroitin sulfate-containing medium was as useful as the conventional moist chamber preservation. Considering the requirement for longer donor preservation time, corneoscleral preservation should be adopted in areas other than the United States.

Adolescent↗

Progression of androgen-sensitive mouse tumor (Shionogi carcinoma 115) to androgen-insensitive tumor after long-term removal of testosterone.

Shionogi Carcinoma 115 (SC115) is an androgen-sensitive transplantable mouse tumor. To study the mode of progression from androgen-sensitive to -insensitive tumor, cloned SC115 cells were serially cultured without androgen. Shortly after withdrawal of androgen, SC115 cells showed markedly decreased growth, but growth resumed gradually with loss of response to androgen and the cells 60 weeks after androgen removal [A(-)60 cells] grew faster than SC115 cells cultured in the presence of androgen. A(-)60 cells showed malignant phenotype with morphological changes and tumorigenicity in male and female mice. Although mRNA and binding capacity of androgen receptor were maintained, the cells after removal of androgen rapidly lost expression of mouse mammary tumor virus-related gene and the loss was irreversible in A(-)60 cells. The stimulating effect of basic fibroblast growth factor (bFGF) temporarily decreased, then recovered to the initial level after long-term androgen removal. This fluctuation of response to bFGF was accompanied with changes in the number of bFGF receptors and amount of bFGF-like substance(s) secreted. The substance(s) seemed to be an FGF-like growth factor different from known factors. It was concluded that progression of SC115 cells to androgen-insensitive ones under an androgen-deprived condition proceeded with adaptation by means of increases in production of an FGF-like growth factor and in binding capacity to this factor.

Androgens↗

Distribution of autofluorescence in the rabbit corneal epithelium.

Autofluorescence from reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) was measured in order to detect the difference in redox states in rabbit corneal epithelium. The enucleated rabbit eye was mounted in an eye bank eye container with McCarey-Kaufman medium, and the autofluorescence was measured using ocular redox fluorometry as a function of depth. The PN signal distributed evenly whereas the Fp signal was greater in the posterior epithelial region than in the anterior region (p < 0.05). The PN/Fp ratio, a sensitive indicator of tissue redox state, was less in the posterior region. After the application of 1 mM of potassium cyanide in the medium, the ratio increased significantly in each layer (p < 0.001), and the difference between anterior and posterior region diminished. These results indicate that ocular redox fluorometry has the potential to resolve the redox states of the various layers of the corneal epithelium. The posterior region of the epithelium is more active in mitochondrial respiration than the anterior region.

Animals↗

Effect on urapidil on benign prostatic hypertrophy: a multicenter, double-blind study.

In a prospective multicentric double-blind trial, urapidil, an alpha 1-adrenergic antagonist, was investigated for its efficacy in benign prostatic hypertrophy (BPH). After 1 week of baseline on placebo, 214 patients with BPH were randomly assigned to 4 groups; group P was given placebo, group L, 15 mg of urapidil b.i.d. for 3 weeks, group M, 15 mg b.i.d. for 1 week followed by 30 mg b.i.d. for 2 weeks, and group H, 15 mg b.i.d. for 1 week followed by 45 mg b.i.d. for 2 weeks. In all groups, day and night urinary frequency improved significantly (p < 0.01 or p < 0.05) compared to baseline, but the differences were not significant between groups. The residual urine rate was significantly (p < 0.05 vs. group P) decreased in group H. Average and maximum flow rate improved significantly (p < 0.01 or p < 0.05) in group M and group H, but intergroup differences were not noted. Overall impression evaluated by investigators improved significantly (p < 0.01 vs. group P) in group M and group H. More patients in group H (7/55) and group M (4/51) had side effects than in group P (2/54). None of them were severe. In summary, a daily dosage of 60 mg urapidil proved to be the most beneficial in the treatment of patients with BPH.

Adrenergic alpha-Antagonists↗

An inhibitory effect of TZP-4238 on the growth of androgen-sensitive rat prostatic tumor (Dunning R3327).

An inhibitory effect of TZP-4238, a newly synthesized antiandrogen, on the growth of Dunning R3327 rat prostatic tumor was studied and compared with that of chlormadinone acetate (CMA). TZP-4238 markedly suppressed the growth of R3327 tumor. The inhibitory effect of TZP-4238 on the tumor was more potent than that on the prostate. While the inhibitory effect of TZP-4238 on the weight of the ventral prostate was about 6 times as great as that of CMA, the suppressive effect of TZP-4238 on tumor weight was about 40 times as great as that of CMA. Serum levels of testosterone and dihydrotestosterone showed no obvious changes after the administration of either TZP-4238 or CMA. The inhibitory effect of TZP-4238 on the growth of R3327 tumor indicated the application of the compound to human prostatic cancer.

Administration, Oral↗

[Assessment of the quality of life of prostate cancer patients].

Assessing the QOL in cancer clinical trials is becoming increasingly important. However, a suitable device of assessment of QOL has not been developed yet for prostate cancer patients in Japan. We tried to assess the QOL of prostate cancer patients using the EORTC questionnaire translated in Japanese, and examined its validity and reliability. Thirty-six patients filled in a questionnaire. The reliability of this device was confirmed by the results of test-retest reproducibility. Good correlation was shown between the results and patients performance status, and between the results and clinical stages, which support the validity of the device. As for the results of assessment of QOL, these patients were severely damaged in sexuality. Those factors of functional status, physical symptoms and fatigue/malaise were closely related to disease activity and clinical stage.

Aged↗

[A case of prostatic carcinoma with ectopic ACTH syndrome].

A 67-year-old man was admitted to the orthopedic ward, complaining of severe pain in his right greater trochanter. He was diagnosed as spinal cord tumor and underwent laminectomy for extirpation of the tumor. Histological examination revealed bone metastasis of unknown origin. Laboratory data revealed hypokalemia and hyperglycemia. Endocrinological data showed elevation of plasma cortisol and ACTH, and increased excretion of urinary 17-OHCS. Ten specimens needle biopsy of the prostate showed poorly differentiated adenocarcinoma, thus patient was diagnosed as prostate cancer with bone metastasis (stage D2) and perhaps ectopic ACTH production. Castration was performed, however 2 days after the surgery he died suddenly. We suspected that cerebral hemorrhage was the cause of his death. On autopsy ectopic ACTH production in the prostate was confirmed.

ACTH Syndrome, Ectopic↗

[A simple renal cyst].

Incidence of simple renal cysts was calculated in 30,316 patients receiving routine ultrasound examination in one hospital, and 170 cases visiting Chiba University Hospital were further analyzed in terms of their clinical features. Incidence of simple renal cyst was 14% in all populations and ratio of male to female was 1.6:1. Patients age ranged from 8 to 92 years (average age 58.6 years) and number of a renal cyst was increased after fifth decade in both sexes. Patients of Chiba University Hospital were examined on symptoms and clinical courses with maximal follow up to 132 months (average 18 months). Symptoms associated with simple renal cysts were: none (75.3%) pain (14.7%) and gross hematuria (6.4%). Urinalysis of patients without associated urinary diseases, showed microhematuria in 40% and proteinuria in 12%, however, grade of microhematuria and proteinuria was not correlated with size of cysts. Number of cysts tended to increase with age. Size of cysts and rate of enlargement were increasing along with age. In any cases, renal function was not and affected nor occurred malignant tumor during follow-up period. Cyst punctures with sclerosing agent were performed in 16 patients, and most of the cysts remained the same as or exceeded their original size. It is concluded that routine follow-up is sufficient in most cases without symptoms, since simple renal cysts increase slowly, and impairment of renal function and progression to malignant tumors do not occur.

Adolescent↗

[Determination of tumor marker doubling time in the patients with prostate cancer relapsed from endocrine therapy].

Twenty seven patients with endocrine therapy relapsed prostate cancer were studied by measuring their prostatic acid phosphatase (PAP), prostate specific antigen (PSA), gamma-semino-protein (gamma-Sm) and alkaline phosphatase (ALP) serially before change of the treatment, and tumor marker doubling time was calculated. The exponential increase in PAP, PSA and gamma-Sm was observed in all patients and ALP showed a similar pattern in some. The values of PAP doubling time were the same as those of PSA, but gamma-Sm doubling time was slightly longer than the former ones. Tumor marker doubling time correlated with survival after the increase in markers, and also with time between the start of endocrine therapy and the increase in markers. Patients who showed either NC or PR to chemotherapy had a longer tumor marker doubling time than those with PD. In cases showing progression of bone metastasis, patients with exponential increase in ALP showed worse prognosis when compared with those showing other patterns. From these results, it was demonstrated that determination of tumor marker doubling time in patients with endocrine therapy relapsed prostate cancer was a valuable method to measure rate of regrowth, and to assess the prognosis after relapse.

Acid Phosphatase↗

[Nucleolar organizer regions in renal cell carcinoma].

Argyrophilic Nucleolar Organizer Regions (AgNORs) were examined in 96 patients with renal cell carcinoma undergoing nephrectomy at Department of Urology, Chiba University Hospital during 1985-1990. Silver staining was performed with one-step method described by Ploton5), and average numbers of grains in a cell were obtained by counting 100 cells. Numbers of AgNORs were increased along with up grading. When AgNORs were compared in various cell types, the number in pleomorphic and spindle types and that in Bellini duct carcinomas were more than that in common types. The number of AgNORs correlated with pT and pV factors, but no relationship was shown between the number and these factors when compared in the same grade. The tumor size correlated with the number of AgNORs. The number of AgNORs in the primary legion showed a reversed correlation with doubling times calculated from either primary, recurrent or metastatic legions examined in 22 cases. In all cases it tended that the number of AgNORs correlated with survival, however survival in G3 cases was not influenced due to worse prognosis. It was concluded that the number of AgNORs in renal cell carcinoma was an additional factor for estimating the properties of tumor cells.

Adult↗

[Preoperative grading of renal cell carcinoma by plasma immunosuppressive acidic protein level and tumor diameter using discriminant analysis].

To predict histological grade of renal cell carcinoma preoperatively, an equation using plasma immunosuppressive acidic protein (IAP) level and tumor diameter was proposed. Between April 1977 and December 1991, 281 patients, 195 males and 86 females, aged between 20 and 84-year-old, were operated at our institutions. Multivariate analysis was performed to detect relationship between tumor grade and various factors that have continuous quantity. Among plasma components tested, plasma IAP levels showed the best correlation with grade (r value = 0.526, n = 157). Tumor diameter also showed correlation with grade (r value = 0.476, n = 273). Therefore, these two factors were used as variates. Discriminant analysis was applied to differentiate the patients with grade 1 or grade 2 tumor from those with grade 3 ones. From this analysis the linear function was obtained; z = 6.9429 - 0.0048x1 - 0.4118x2 (x1: IAP (micrograms/ml), x2: diameter (cm)). Tumor was assumed to be grade 1 or grade 2 when z value was positive, and it was assumed to be grade 3 when z value was negative. Overall accuracy was 87.7%. Positive predictive value of grade 1 or grade 2 tumor, and grade 3 tumor was 91.7% and 77.8%, respectively. Sensitivity was 90.9% for grade 1 or grade 2 tumor, and 79.5% for grade 3 tumor. As a result, it's possible to estimate tumor grade before operation using discriminant analysis in patients with renal cell carcinoma.

Adult↗

[Renal functions of the patients with long-term catheterization in upper urinary tract].

In order to investigate long-term effects of indwelling urinary catheters on renal functions, in 46 patients (27 male and 19 female) with ureterostomy or nephrostomy serum creatinine values were measured periodically. Average age of the patients was 60.6 years old. Duration of catheterization was more than 3 years (average 8.1 years). Renal dysfunction was defined as an elevation of serum creatinine more than 2 mg/dl. It was found that catheterization used more than 15 years evoked renal insufficiency over 50% of such patients. This period, however, was shorten to 11 years in patients with nephrolithiasis or frequent fever. It was concluded that urolithiasis and symptomatic urinary tract infections were two remarkable risk factors for the deterioration of renal functions, and that these risk factors must be avoided in patients on long-term catheterization in the upper urinary tract.

Aged↗

[Clinical evaluation of a new kit (IMX PA Dainapack) for detection of serum prostate specific antigen].

A study of the clinical utility of the IMx PA Dainapack, a new kit for detection of serum prostate specific antigen (PSA) by a fully automated enzyme immunoassay (EIA) system, was conducted. Results concerning reproducibility, dilution linearity and sensitivity were good. The excellent assay performance of this kit, particularly in terms of its high sensitivity (0.1 ng/ml), was confirmed. The upper limit of normal was determined to be 4.0 ng/ml from the mean +/- 3 S.D. (3.79 ng/ml) in healthy male controls (n = 244). Using 4.0 ng/ml as the upper limit of normal, 6 of 244 healthy male controls (2%) were positive. In various urinary diseases, 173 of 192 prostatic cancer (90%) and 46 of 112 benign prostatic hypertrophy (BPH) (41%) cases were positive. In prostatic cancer, the positive rates increased with the advance in clinical stage and in stage A the positive rate was especially high (8 of 12 (67%) were positive). On the other hand, using the BPH group as a negative control, the maximum accuracy rate for prostatic cancer had a cut-off value of 8.0 ng/ml. Thus, 8.0 ng/ml is an appropriate cut-off value differentiating prostatic cancer from BPH while 4.0 ng/ml is the cut-off value between the normal group and those with prostatic cancer (including stage A) and BPH. In the follow-up patients with prostatic cancer, serum PSA values measured by this kit reflected the effectiveness of treatment. The correlations between values obtained with the IMx PA Dainapack and 6 current kits were good (r = 0.93 to 0.99) but the values differed with the kit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗