Mitsumasa Takeda

GnRH analog, leuprorelin acetate, promotes regeneration of rat spermatogenesis after severe chemical damage

Future fertility is a major concern for cancer patients who undergo intensive chemotherapy. There has been controversy about whether hormonal treatments may have protective effects against the severe spermatogenic damage caused by chemotherapy or irradiation. Recently, it has been proposed that gonadotrophin‐releasing hormone (GnRH) analogs administered after testicular damage stimulate the recovery of spermatogenesis. In this study, we have investigated the effects of GnRH agonist, leuprorelin, on the damage to spermatogenesis induced by busulfan.

CYCLIN D1 PROTEIN OVEREXPRESSION IS RELATED TO TUMOR DIFFERENTIATION, BUT NOT TO TUMOR PROGRESSION OR PROLIFERATIVE ACTIVITY, IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER

PURPOSE We attempted to clarify the significance of cyclin D1 in the development and progression of transitional cell carcinoma of the bladder in humans. MATERIALS AND METHODS Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 163 patients was performed by the labeled streptavidin-biotin-peroxidase method. RESULTS Cyclin D1 protein overexpression was observed in 51 of the 163 specimens (31.3%). Cyclin D1 protein overexpression was showed a highly significant inverse correlation with the histological grade of malignancy (p < 0.01). Grade 3 tumors showed a highly significant low incidence of cyclin D1 protein overexpression as compared with grade 2 tumors (p < 0.01). There was no significant correlation between the overexpression of cyclin D1 protein and tumor stage or the Ki-67 labeling index. CONCLUSION Cyclin D1 in transitional cell bladder carcinoma was closely related to tumor differentiation but not to tumor progression. Transitional cell carcinoma of the bladder may utilize another pathway for proliferation that is independent of cyclin D1.

Enhanced expression in seminoma of human zinc finger genes located on chromosome 19

Six Krüppel-type zinc finger (ZF) genes were cloned from a seminoma cDNA library. One, ZFS-1, showed high sequence homology to the ZNF91 KRAB (Krüppel-associated box) ZF gene family and also the same chromosomal assignment. Interestingly, Northern blot analyses using ZFS-1 and ZNF91 revealed that multiple ZF genes on chromosome 19 were predominantly expressed in seminomas. In addition, the testis and the seminoma showed specific expression of 2.3 kb transcript. Our results suggest that ZF genes on chromosome 19 may be implicated in the development and/or growth of seminomas.

Recovery of spermatogenesis by high dose gonadotropin-releasing hormone analogue treatment in rat cryptorchid testis after orchiopexy

PURPOSE Cryptorchidism is an adverse condition of spermatogenesis in many mammals. Surgical cryptorchidism in rats lasting more than a few weeks is so detrimental that spermatogenesis cannot be completely recovered even after orchiopexy. We evaluated the efficacy of the high dose gonadotropin-releasing hormone (Gn-RH) agonist leuprorelin acetate on damaged spermatogenesis in rat cryptorchid testes. MATERIALS AND METHODS Male Fisher rats were divided into 2 groups of 6 each and bilateral cryptorchidism was artificially produced. Five weeks later all rats underwent bilateral orchiopexy. One group served as the control, while the other received Gn-RH agonist injections at orchiopexy and 4 weeks later. The animals were sacrificed 15 weeks after orchiopexy. The weight of the body, testis and epididymis was measured and the histology of spermatogenesis was examined. For statistical analysis the Student t test was applied. RESULTS Testes in the Gn-RH group rats showed significant recovery of spermatogenesis up to complete spermatozoa formation, while those in control rats remained almost degenerated. The mean incidence of seminiferous tubules with recovered spermatogenesis plus or minus standard deviation was significantly higher in the Gn-RH than in the control group (87.8% +/- 6.0% versus 12.5% +/- 7.7%, p <0.001). CONCLUSIONS Administering the high dose Gn-RH agonist leuprorelin acetate after orchiopexy greatly enhanced the recovery of spermatogenesis in rats. This finding is in accordance with other recent reports that treatment with Gn-RH analogues promotes the regeneration of once damaged spermatogenesis. On the other hand, these findings may cause one to question supplementation therapy now used in regular practice to boys with cryptorchidism.

Viability and function of human sperm in electrolyte-free cold preservation

OBJECTIVE To assess the viability and function of human sperm in electrolyte-free cold preservation. DESIGN Prospective comparative study. SETTING Andrology laboratory of our hospital. PATIENT(S) Ten semen samples obtained from patients attending our infertility clinic. INTERVENTION(S) Ejaculated sperm were washed using the electrolyte-free Percoll gradient and were then preserved in 0.33 M glucose solution, 0.16 M NaCl solution, 0.16 M KCl solution at 4 degrees C for 4 weeks. As a control, TEST (TES and Tris) yolk buffer (TYB) was added to the ejaculated semen and preserved at 4 degrees C. MAIN OUTCOME MEASURE(S) Sperm tail morphology, motility, viability (eosin-Y stain), and the concentration of adenosine triphosphate (ATP) were analyzed. RESULT(S) The number of sperm with normal tail form and the motility of sperm preserved in glucose solution (electrolyte-free cold preservation) were significantly (P < 0.01) higher for 4 weeks than those of sperm preserved in the other three media. The sperm viability in glucose solution was 75.5%, 65.4%, and 51.3%, after 1, 2, and 4 weeks, respectively. The ATP concentration after 1, 2, and 4 weeks remained 64.2%, 53.0%, and 4.3% of the prestorage value, respectively, in the sperm stored in glucose solution. CONCLUSION(S) The morphology, motility, viability, and ATP concentration of sperm in electrolyte-free cold preservation were substantially better than those in NaCl solution, KCl solution, or TYB for 2 weeks.

Serum-free coculture of stromal and epithelial cells from benign prostatic hyperplasia with keratinocyte growth factor

We developed a serum-free coculture model of benign prostatic hyperplasia (BPH) to clarify whether stromal cells stimulate growth of epithelial cells from BPH tissues. Epithelial and stromal cells from freshly isolated BPH tissue were cultured separately in defined serum-free WAJC 404/RPMI 1640 medium supplemented with insulin, transferrin, selenium, hydrocortisone, bovine serum albumin, epidermal growth factor, basic fibroblast growth factor and keratinocyte growth factor. 3H-Tdr incorporation into epithelial cells and stromal cells was used as a measure of proliferation. When epithelial cells were cocultured with stromal cells, 3H-Tdr incorporation into epithelial cells was increased in comparison to that in epithelial cells cultured alone. Dihydrotestosterone significantly increased this effect. It is likely that the in vitro coculture model reported here will be useful for isolating and understanding stromal cell-derived paracrine growth factor(s).

Clinical Significance of Interruption of Therapy with Allylestrenol in Patients with Benign Prostatic Hypertrophy

Background: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH).

A Case of Vesical Paraganglioma Behind the Symphysis Pubis

We report on a 15-year-old boy with a vesical paraganglioma behind the symphysis pubis. Magnetic resonance imaging and transurethral intravesical ultrasonography were helpful in the preoperative localization of the lesion.