Takayoshi Demura

Androgen receptor abnormality in X‐linked spinal and bulbar muscular atrophy

X-linked spinal and bulbar muscular atrophy (SBMA) is usually associated with feminization and hypogonadism. We were unable to find androgen receptor (AR) in the scrota) skin of three patients with SBMA, and propose that AR abnormality is the cause of the disease.

Measurement of Prostate Specific Antigen and γ-Seminoprotein Ratio: A New Means of Distinguishing Benign Prostatic Hyperplasia and Prostate Cancer

We measured a ratio of serum prostate specific antigen (PSA) and gamma-seminoprotein concentrations (referred to as the PSA/gamma-seminoprotein ratio) and evaluated its usefulness for the diagnosis of prostate cancer. Between April 1988 and October 1992, 214 men underwent prostatic biopsy and/or transurethral resection of the prostate, and the disease was diagnosed pathologically. Of 214 patients 127 were diagnosed as having benign prostatic hyperplasia, prostatitis or a normal prostate (no cancer), while 87 had prostate cancer. Of 61 patients with a serum PSA level greater than 10 ng./ml. 50 (82.0%) had prostate cancer, compared to 31 of 84 (36.9%) with a serum PSA level of 3.0 to 10 ng./ml. Of 113 patients with a serum gamma-seminoprotein level greater than 4.0 ng./ml. 52 (46.0%) had prostate cancer. The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratio for 127 patients without cancer was 0.942 +/- 0.564, while that for 87 prostate cancer patients was 12.840 +/- 45.327 (Wilcoxon p < 0.0001). The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratios for 37 prostate cancer patients with a PSA level of 10 ng./ml. or less and for 50 prostate cancer patients with a PSA level of more than 10 ng./ml. were 2.044 +/- 0.767 and 20.829 +/- 58.757, respectively. Even the mean PSA/gamma-seminoprotein ratio for prostate cancer patients with a PSA level of 10 ng./ml. or less was significantly greater than that for patients without cancer (Wilcoxon p < 0.0001). The sensitivities for PSA (cutoff value 3.0 ng./ml.), gamma-seminoprotein (cutoff value 4.0 ng./ml.) and PSA/gamma-seminoprotein ratio (cutoff value 1.45) were 93.1%, 59.8% and 92.0%, respectively, and the specificities were 49.6%, 52.0% and 91.3%, respectively. Of 91 patients with a PSA/gamma-seminoprotein ratio of 1.45 or more 80 (87.9%) had prostate cancer, while 116 of 123 (94.3%) with a PSA/gamma-seminoprotein ratio of less than 1.45, had no cancer. These results suggest that PSA/gamma-seminoprotein ratio yields the same sensitivity as PSA and more specificity than PSA levels, offering significant advantage over PSA in detecting prostate cancer. The mean plus or minus standard deviations of PSA/gamma-seminoprotein ratios for stages A, B, C and D prostate cancer were 1.847 +/- 0.786 (11 patients), 2.740 +/- 1.536 (30), 7.626 +/- 9.140 (12) and 27.149 +/- 70.500 (34), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of androgen receptor in the rat spinal motoneurons. Immunohistochemical and immunoblotting analyses with monoclonal antibody

Androgens play an important role in motoneuron growth, development and regeneration. We proved the existence of androgen receptor (AR) in the motoneurons of the rat spinal cord by the immunohistochemical stain and Western blotting. The possibility that AR protein in spinal cord is expressed in tissue-specific form is proposed, being different from other androgen-dependent tissues. AR abnormality in X-linked spinal and bulbar muscular atrophy (SBMA) among a variety of motor neuron diseases were reported recently. Our study may give some clue to the AR abnormality leading to the degeneration of motoneurons.

Establishment of monoclonal antibody to human androgen receptor and its clinical application for prostatic cancers.

Hybrid cell lines were prepared by the fusion of BALES/ c myeloma NS-1 cells with the lymphocytes of BALB/c mice that were immunized with partially purified androgen receptor (AR) from human prostates. One of the clones. 5F4, was chosen for detailed specificity analysis. The avidin-biotin-peroxidase complex (ABC) procedure was used for immunohistochemical staining of the 5F4 monoclonal antibody. In human benign prostatic hypertrophy (BPH) tissues, cytoplasm and nuclei were stained. Of 16 prostatic cancer tissues. 2 were composed of AR-positive cells exclusively. 7 were composed of AR-negative cells, and 7 contained both AR-positive cells and AR-negative cells (mixed). Of nine cases that were AR-positive or mixed, seven cases responded to the hormone therapy, and two were not determined for responsiveness because the patients died early of other diseases. Of seven AR-negative cases, all but one inestimable case had no response to the hormone therapy. Immunohistochemical analysis of AR by using the monoclonal antibody 5F4. was a useful tool for determining androgen dependency of prostatic cancers.

Autoradiographic localization of α1-adrenoceptors in human prostate : special reference to zonal difference

Using autoradiography, localization of alpha 1-adrenoceptor in human prostate was examined with particular reference to zonal difference. Prostatic tissues were obtained from total cystoprostatectomy specimens of six male bladder tumor patients. Peripheral zone (PZ), central zone (CZ) and preprostatic region which contained preprostatic sphincter and periurethral gland were dissected from the tissues. [125I]-HEAT was used as radioligand for autoradiography. Autoradiographic distribution of alpha 1-adrenoceptor was quantitated by grain counting using a light microscope equipped with a micrometer. Specific binding was demonstrated predominantly in fibromuscular stroma of PZ, fibromuscular stroma of CZ and preprostatic sphincter. No specific binding was demonstrated in glandular epithelium of PZ and periurethral gland. Glandular epithelium of CZ showed a few specific bindings. Among fibromuscular portion, specific bindings in both CZ and preprostatic sphincter were significantly higher than in PZ. Specific binding in glandular epithelium of CZ was significantly less than in fibromuscular stroma of PZ. These results show that the human prostate has a zonal difference in the distribution of alpha 1-adrenoceptors, probably reflecting some functional difference in these regions.

5-fluorouracil and low-dose recombinant interferon-α-2a in patients with hormone-refractory adenocarcinoma of the prostate

The effectiveness of a chemotherapy regimen including 5‐fluorouracil (5‐FU) and recombinant interferon‐α‐2a (rIFN‐α‐2a) was evaluated in hormone‐refractory prostate cancer patients.

Androgen binding activity in the spongy tissue of mammalian penis

The binding of [3H]R1881 to cytosol fractions was determined for the spongy tissues of horse, porcine and human penis. Binding of [3H]R1881 to cytosol fractions from these spongy tissues was found to be specific with high affinities (mean of Kd; 1.8 X 10(-10) M) but with equally low binding capacities (mean of 4.66 fmol/mg. protein). Saturation analysis revealed that the binding capacity was similar for both corpus cavernosum and corpus spongiosum of horse penis. We conclude that a trace amount of androgen receptor is present in spongy tissue of the penis and that there is no difference in cytosolic receptors between corpus cavernosum and corpus spongiosum in adult mammalian penis.

Treatment of Metastatic Nonseminomatous Germ Cell Tumors of the Testis: Significance of the International Consensus Prognostic Classification as a Prognostic Factor-Based Staging System

Background: We reviewed treatment results in patients with metastatic nonseminomatous germ cell tumors of the testis and examined the significance of the International Consensus Prognostic Classification to make appropriate risk‐based decisions concerning induction chemotherapy.

Mechanism underlying the negative effect of prostate volume on the outcome of extensive transperineal ultrasound-guided template prostate biopsy

Previous studies have indicated a possible relationship between increased prostate volume (PV) and decreased biopsy yield, although the mechanism involved is unclear. We evaluated 1650 patients who underwent template biopsy. The distribution of 993 cancer lesions in 302 prostatectomy specimens was compared with the biopsy data to determine whether each lesion was detected. A receiver operating characteristic (ROC) model was used to determine the diagnostic accuracy of prostate‐specific antigen (PSA) and related markers. A medical record number (MRN) was used as a negative control. The cancer positive rate did not change as PSA increased in patients with PV ≥50 mL (P = 0.466), although it increased as PSA increased in patients with PV<50 mL (P = 0.001). The detection rate of cancer lesions decreased as the diameter of the lesions decreased (P = 0.018), but remained unchanged with respect to PV. The diameters of the maximum lesions in patients with PV ≥ 50 mL were significantly smaller than those in patients with PV<50 mL (P = 0.003). In patients with PV ≥ 50 mL, the areas under the ROC curves for PSA‐related markers did not differ significantly from that for MRN, although they were significantly greater than that for MRN in patients with PV<50 mL (P < 0.001). These results suggest that an increase in PV is associated with a decrease in size and detectability of cancer lesions resulting in a decrease in biopsy yield. Loss of diagnostic accuracy of markers in patients with PV ≥ 50 mL indicates a decrease in serum levels of PSA produced by prostate cancer, which suggests growth inhibition of the cancer.

A case of epididymal sarcoidosis

We reported a case of epididymal sarcoidosis. The patient was a 13-year-old boy with a chief complaint of right scrotal mass. On physical examination, a firm, nontender 7 mm mass was palpable in the right hemiscrotum and appeared to involve the head of the epididymis. Ultrasonography showed a highly echogenic mass in the epididymis. A routine chest X-ray revealed lymphadenopathy of the mediastinum and reticular shadows in bilateral lung fields. Because the lesion might be confined to the epididymis, a partial epididymectomy was performed. The histopathologic specimen showed noncaseating granulomas consistent with sarcoidosis. Lung biopsies also revealed noncaseating granulomas. Subsequent pulmonary function studies revealed a mild obstructing ventiratory defect, therefore therapy was instituted with systemic steroids. There were no further recurrent scrotal masses. Although sarcoidosis is known to affect many organs, involvement of the genital system is relatively rare. Most of the patients with intrascrotal sarcoid lesions have an abnormal chest X-ray. We need to differentiate these lesions from advanced testicular cancer. This is the 5th case of intrascrotal sarcoidosis in Japanese literature.