Tadayuki Miyamoto

Prostatic carcinosarcoma: A case report and review of literature

Abstract A unique case of carcinosarcoma of the prostate detected in a 71‐year‐old man is presented. Pelvic exenteration was performed, and the resected prostatic mass was found to consist of two histologically distinct elements; adenocarcinoma and sarcoma with focal osteosarcomatous element. The patient is still alive with neither metastasis nor recurrence. This is the 42nd case of carcinosarcoma of the prostate to be reported in the literature.

Immunohistochemical presence of 5 α-reductase rat type I -containing cells in the rat brain

Abstract We showed immunohistochemically the localization of 5 α-reductase-containing cells in the rat brain, using a rabbit antibody generated against 5α-reductase rat type 1. The antibody was produced by injecting the synthetic peptide corresponding to the amino acids 38–53 of 5α-reductase rat type 1, conjugated to keyhole limpet hemocyanin with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride. Western blot analysis revealed that this antiserum recognized the protein with a molecular weight of 29 000 Da. The inununoreactive cells were distributed throughout the brain and they were preferentially located in the white matter rather than in the grey matter. These cells were mostly small and round and had a few fine processes. The immunoreaction was confined to the cytoplasm and processes. These findings indicate that 5α-reductase rat type 1-containing cells are widely distributed in the rat brain and are located preferentially in the white matter rather than in the grey matter.

Immunocytochemical localization of 5α-reductase type 1 in the prostate of normal and castrated rats

We immunohistochemically studied the localization of 5α-reductase type 1 in combination with androgen receptor (AR) expression in individual lobes of the prostates of intact and castrated rats. In the normal rat prostate, 5α-reductase was localized in the cytoplasm of most epithelial cells in the ventral, dorsal, and lateral type 1 (L1) lobes. Epithelial cells of lateral type 2 (L2) lobes were negative for 5α-reductase. AR was present in the nuclei of all epithelial and stromal cells throughout the prostate. The number of 5α-reductase-immunoreactive cells rapidly decreased in the ventral and L1 lobes after castration, whereas many positive cells remained in the dorsal lobe even at 4 weeks after castration. AR immunostaining was lost in the ventral, dorsal, and L1 lobes at 1 week after castration, but remained in the L2 lobe of 4-week-castrated rats. Electron microscopic immunocytochemistry showed that 5α-reductase was exclusively localized in the rough endoplasmic reticulum membranes and that there were no distinct structural differences between the positively and negatively stained epithelial cells. These findings suggested that the expression of 5α-reductase type 1 in the epithelial cell is heterogeneous within and among the individual lobes of the rat prostate, and does not correspond to AR expression.

Steroid 5α-reductase type 1 immunolocalized in the adrenal gland of normal, gonadectomized, and sex hormone-supplemented rats

Abstract Steroid 5α-reductase in the rat adrenal gland is supposed to play a role in the catabolism of adrenal steroids. We showed immunohistochemically the cellular and subcellular localization of 5α-reductase in the rat adrenal gland, using a polyclonal antibody against 5α-reductase rat type 1. In the adrenal cortex, positive immunoreaction was found in the cells of the zonae fasciculata and reticularis but was absent in those of the zona glomerulosa. The positive staining was restricted to the cytoplasm but not to the nucleus, Golgi complexes or mitochondria. The staining intensity showed a marked change depending on the steroidal milieu. Gonadectomy for 6 weeks increased the immunoreaction, regardless of the sex. Testosterone replacement for the last 2 weeks considerably reduced the immunoreaction in 6-week-castrated males, and estradiol supplement for the last 2 weeks also resulted in the marked reduction of immunostaining in 6-week-gonadectomized females. In the adrenal medulla, the immunoreaction was localized in the supporting cells and the Schwann cells but not in the chromaffin cells. In these cells, the immunoreaction was not affected by steroidal treatments. These findings suggest that the expression of 5α-reductase in the rat adrenal cortex is regulated by sex hormones from the gonads, and the enzyme may participate in the conversion of adrenal steroids depending on the steroidal environment, although the functional significance of the enzyme in the adrenal medulla remains unclarified.

Steroid 5α-reductase type 1 immunolocalized in the anterior pituitary of intact and castrated male rats

The localization of 5α-reductase was immunohistochemically studied in the anterior pituitary of male rats, using a polyclonal antibody against 5α-reductase rat type 1. The immunoreactive cells were concentrated in the central region and on the border of the intermediate lobe in the anterior pituitary, but not in the intermediate or posterior lobe. The immunoreaction was located mostly in the cytoplasm and occasionally in the cell nuclei. The immunoreactive cells showed alterations in size and number and in the intensity of the immunoreaction after gonadectomy. One week after castration, the cells became larger and the immunoreactivity increased. Two weeks after castration, the number of immunoreactive cells increased. Double immunostaining using antiluteinizing hormone β-subunit or anti-follicle stimulating hormone β-subunit antibody revealed that most of the cells containing 5α-reductase were gonadotrophs. Electron microscopically, the immunoreactive cells showed lamelliform rough endoplasmic reticulum and a depletion of secretory granules 1 week after castration. One week later, the rough endoplasmic reticulum was developed and dilated and the number of secretory granules increased. These results suggest that 5α-reductase is located in the gonadotrophs of rat anterior pituitary and that it is involved in the feedback regulation of gonadotropin secretion by androgens.

Immunolocalization of Steroid 5α-Reductase Type 2 in Human Prostate, Seminal Vesicle and Vas Deferens

Localization of steroid 5a-reductase type 2 in human prostate, seminal vesicle and vas deferens was investigated by light and electron microscopic immunohistochemistry using a rabbit polyclonal antiserum raised against a synthetic peptide fragment representing amino acids 225-240 of the human 5a-reductase type 2 enzyme. Under light microscope, the enzyme was localized in the cytoplasm of basal epithelial and stromal cells of the prostate. Secretory epithelial cells were negative. There was no immunoreaction in cell nuclei. Double immunostaining for 5ƒ¿-reductase and muscle specific actin indicated that all smooth muscle cells had 5ƒ¿-reductase type 2. However, a few type 2-positive cells did not react with a muscle specific actin antibody. Electron microscopic immunocytochemistry revealed that the cytoplasm of smooth muscle cells and of a few fibroblasts had immunoreaction products for this enzyme. In the seminal vesicle and vas deferens, basal and smooth muscle cells were positive for the type 2 enzyme. These findings indicate that the major sites of the DHT production are basal epithelial cells and stromal smooth muscle cells in human prostate, seminal vesicle and vas deferens. These cells may play a role in maintaining the functional activity of these male accessory sex organs through the production of DHT.

Study of recombinant human erthropoietin administration for anemia in hemodialysis patients. Clinical study of dose determination.

目的: 腎性貧血に対するリコンビナント・ヒト・エリスロポエチン (r-HuEPO) の至適投与量を明らかにするため多施設共同試験を実施した. 対象と方法: 慢性腎不全血液透析患者でHt値25%以下の症例273例を対象とした. 初期投与を3群 (1,500IU×3/W, 1,500IU×2/W, 3,000×2/W) に分類し, Ht値が27-33%に達した時点より維持投与に移行し, Ht値を30%前後に維持するように投与量を変更もしくは休薬した. 結果: 初期投与では投与後4週後のHt値は3群とも有意な上昇を示し, 3群間では3,000×2/Wが有意に高値であり, その効果は用量依存性であった. 12週目では3群間に差がなく, 貧血改善を緩徐に行うためには1,500IU×2/Wで十分であった. 維持投与量は, 低用量に移行し, 4,500IU/W以下が約80%を占めた. しかしながらHt値30%を維持するためには25%の症例で6,000IU/Wの投与が必要であった. 副作用は34例 (12.5%) に認められ, 主要な副作用は血圧上昇で, 投与量が増えるに従い, その発生頻度が増加した. 6,000IU/W投与する場合, 血圧の上昇を懸念する必要があると思われた.