Hidenobu Miura

Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cell line DU145 through tumor-stromal interaction

In prostate cancer, several growth factors derived from stromal cells regulate tumor cell growth. Hepatocyte growth factor (HGF) possesses biological activities that promote cancer proliferation and invasion through tumor‐stromal interaction. We examined how prostate stromal cell‐derived HGF affects invasion of prostate cancer cells through this interaction.

Ejaculated spermatozoa in patients with non-mosaic Klinefelter's syndrome.

Background : Non‐mosaic Klinefelter patients are generally azoospermic and there is no therapy to improve the spermatogenesis. Some patients have a few spermatozoa in their ejaculates, which can be used for intracytoplasmic sperm injection (ICSI), but only a few cases resulting in a successful birth have been reported.

EFFECTS OF HEPATOCYTE GROWTH FACTOR ON E-CADHERIN-MEDIATED CELL-CELL ADHESION IN DU145 PROSTATE CANCER CELLS

OBJECTIVES To examine how hepatocyte growth factor (HGF) affects cell-cell adhesion junctions on scattering in prostate cancer cells. HGF is known to induce scattering (dispersion of clustered cells into single cells) in various epithelial cells, including prostate cancer cells, but the mechanisms surrounding this action are not fully understood. Cell-cell adhesion junctions are composed of E-cadherin and its associated intracellular catenins and play important roles in the maintenance of cell integrity. METHODS The human prostate cancer cell line DU145 was used in this study. The associations and changes of various adhesion molecules with HGF treatment were investigated by inhibition assays, Western blot analysis, and immunofluorescence staining. RESULTS In the inhibition assay, anti-E-cadherin neutralizing monoclonal antibody caused the dissociation of DU145 cells similar to the scattering with HGF treatment. The expression of E-cadherin decreased with HGF, and the expression of alpha-catenin and beta-catenin did not change by Western blot analysis. In immunofluorescence staining, HGF caused the translocation of E-cadherin from cell-cell adhesion junctions to the cytoplasm. CONCLUSIONS These results indicate that HGF induces scattering by decreasing the expression of E-cadherin and causes its translocation to the cytoplasm of DU145 cells.

Effect of Renal Transplantation on Sexual Function

This investigation was conducted to determine whether renal transplantation can improve sexual function in male patients with chronic renal failure. The authors retrospectively studied 121 men undergoing renal transplantation who complained of any type or degree of sexual dysfunction pre-operatively. Sexual function was evaluated by questionnaire which included erectile, ejaculative, and orgasmic functions. Pre- and postoperative frequency of sexual intercourse was also recorded. Patient characteristics, laboratory data, and endocrinologic profiles were analyzed to identify factors that might influence sexual function. In patients with hormonal determinations, results essentially normalized after transplantation. However, only 43 patients (35.5%) reported improvement of overall sexual function after renal transplantation, while 34 (28.1%) reported worsening. Although frequency of sexual intercourse was unaffected by transplantation, 15 of 20 patients who had no intercourse before transplantation initiated intercourse afterward. These 15 patients all underwent transplantation before 40 years of age. Comparisons of variables by sexual function showed significant differences for type of immunosuppressive treatment, interval after renal transplantation, and serum concentration of hemoglobin A1c. It is concluded that renal transplantation cannot improve sexual function in allpatients, although hormonal profiles were largely normalized, and that renal transplantation should be encouraged at a younger age.

SUSCEPTIBILITY TO IDIOPATHIC AZOOSPERMIA IN JAPANESE MEN IS LINKED TO HLA CLASS I ANTIGEN

PURPOSE Approximately 15 to 20% of infertile men have azoospermia. In the Y chromosome a deletion, termed the azoospermic factor, has been found in some cases of idiopathic azoospermia. We investigate the relationship of factors in autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in idiopathic azoospermia. MATERIALS AND METHODS We evaluated 65 infertile Japanese men with idiopathic azoospermia. The frequency of the HLA allele reported in 1,216 healthy Japanese men was used as a control. HLA class I typing was performed by the National Institutes of Health standard serological method or polymerase chain reaction-sequence specific primer analysis. Allele frequencies were calculated. We determined statistical significance in the frequency of each allele in patients and controls using the chi-square test. The relationship of HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44 was significantly increased compared with controls. The relative risk of HLA-B44 was 8.4, an extremely high value compared with that of other diseases and HLA antigens. CONCLUSIONS We suggest that HLA class I antigens are important genetic markers that represent a risk factor for idiopathic azoospermia.

Survey of Overactive Bladder Symptoms Influencing Bother Before and After Treatment With Tamsulosin Hydrochloride in Japanese Patients With Benign Prostatic Hyperplasia

OBJECTIVE To evaluate the relation between bother and overactive bladder (OAB) symptoms in patients with benign prostatic hyperplasia (BPH) patients using questionnaires: the BPH Impact Index (BII) and the OAB symptom score (OABSS). Annoyance from BPH usually provides the basis for a patients decision to seek medical treatment. However, a study investigating the bother caused by OAB symptoms in patients with BPH and OAB has not been fully conducted. METHODS The present study included 100 male patients who were diagnosed with BPH and OAB according to questionnaire criteria. All patients were instructed to take tamsulosin for 28 days. The relation between the BII and OABSS was assessed to determine the factors influencing OAB symptoms on the BII before and after treatment. RESULTS The BII correlated positively with the OABSS, and multivariate analysis showed that the subscore of urgency was the only independent factor influencing the BII. Even after treatment, lower urinary tract symptoms were diagnosed as OAB using the OABSS criteria in 45 (45.0%) of the 100 patients. In these patients, the BII still correlated positively with the OABSS. However, multivariate analysis showed that the subscore of urgency incontinence, not urgency, was the only independent factor influencing the BII, although the subscore of urgency incontinence was significantly decreased with tamsulosin treatment. CONCLUSION The degree of bother correlated with the degree of OAB symptoms in patients with BPH and OAB at baseline and after treatment with tamsulosin. The OAB symptom causing the bother was altered by treatment with tamsulosin in these patients.

BROMOCRIPTINE FOR INFERTILE MALES WITH MILD HYPERPROLACTINEMIA: HORMONAL AND SPERMATOGENIC EFFECTS

To clarify the influence of hyperprolactinemia on spermatogenesis and steroidogenesis in infertile male patients, the serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol concentrations were and the effect of bromocriptine treatment on spermatogenesis was examined. A total of 1234 patients were evaluated and 147 men had hyperprolactinemia. Of these, only 30 had PRL concentrations more than twice the upper limit of normal and most of them had a little excess over the upper limit. For 10 of these 30, serum hormone concentrations were measured and semen was analyzed before and after bromocriptine administration. No relationship between the PRL and other hormone concentrations was found. No changes were noted in the LH, FSH, testosterone, or estradiol concentrations, or in the sperm density and motility after treatment. The mean PRL decreased from 26.5 +/- 4.5 to 1.4 +/- 1.8 ng/mL. In infertile men who are mildly hyperprolactinemic, bromocriptine administration does not improve semen analysis, although it does normalize the PRL.

[Predictive factor for TESE (testicular sperm extraction)--ICSI (intracytoplasmic sperm injection) for non-obstructive azoospermia].

BACKGROUND TESE-ICSI has been used very successfully in the treatment of the patients with non-obstructive azoospermia but its indication is still controversial. We performed retrospective study concerning parameters to predict successful recovery of testicular sperm from the patients and outcomes of ICSI. PATIENTS AND METHODS 44 patients with non-obstructive azoospermia who underwent TESE-ICSI from July, 1997 to September 1999 were studied retrospectively. RESULTS 1) Testicular sperm were retrieved from 32 patients (72.7%). ICSI was performed in 29 patients and the partner of 15 patients (46.9%) got pregnant. From 10 patients with histology of Sertoli-cell-only, we could retrieve sperm in 3 patients (30%). 2) Testicular volume, Johnsens score count (JSC), and FSH were significant parameter to predict the recovery of testicular sperm from the patients, but if we see only the patients with JSC less than 7, there were no significant parameter. Chromosomal abnormality was not a significant parameter. 3) The partners age, motility of recovered sperm and testicular volume correlated with fertilization rate. Chromosomal abnormality was not significant parameter to predict fertilization. CONCLUSIONS There was no absolute parameter to predict the recovery of testicular sperm from the patients with non-obstructive azoospermia. All patients with non-obstructive azoospermia can be the indication of TESE-ICSI.

OUTCOME OF SURGICAL TREATMENT FOR OBSTRUCTIVE AZOOSPERMIA

The efficacy of reanastomosis was evaluated in 30 patients with obstructive azoospermia, including 19 postvasectomy cases; 7 cases complicating inguinal herniorrhaphy; 2 cases with a characterized isolated congenital anomaly; 1 case of Youngs syndrome; and 1 case with an unknown, possibly congenital cause. In the postvasectomy group, successful vasovasostomy was achieved in 15 of 18 cases (83.3%; 1 postvasectomy patient dropped out of the study prior to analysis). Duration of obstruction in the 3 cases where anastomosis failed was 6, 9, and 20 years. In the group where obstruction followed inguinal herniorrhaphy, unilateral vasovasostomy was performed in 6 cases, and transepididymovasostomy was performed in 1 case. Success was achieved in 3 of 6 cases (50%; 1 case was not included because failure of spermatogenesis was detected postoperatively). In all 4 remaining cases, microsurgical epididymovasostomy or transepididymovasostomy was performed, but success was achieved only in the case of Youngs syndrome. Although mailed questionnaires and telephone interviews indicated occurrence of natural pregnancy in only 4 affected couples, postoperative sperm counts were relatively satisfactory as in previous reports.

[Intravesical bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the urinary bladder and prediction of effects by urinary cytologic examination].

PURPOSE We investigated the effects of intravesical BCG instillations for carcinoma in situ (CIS) of the urinary bladder. And we have retrospectively analyzed the prediction of effects by fresh urinary cytologic examinations before instillation. MATERIAL AND METHODS 33 patients were treated for bladder CIS (1991-1997) with a median follow-up of 30 months (range from 9 to 90 months). The patients (27 males and 6 females) ranged in age from 46 to 91 (average 71 years) and received 6 to 12 weekly BCG Tokyo 172 strain 80 mg instillations. They were divided into 3 groups based on tumor history: primary (9), secondary (15), concurrent (9). The prediction of effects were analyzed by scoring fresh urinary cytologic examinations before instillation. RESULTS 22 cases (67%) were responded and they have remained free of disease for follow-up period. The statistic evaluation proved to show the significance between the effects of treatment and the sum of scoring (cellular appearance and existence of large nuclear cells). CONCLUSION We confirmed the effects of this treatment. The prediction of effect of this treatment seemed to be indicative by fresh urinary cytologic examinations before instillation, especially cellular appearance and existence of large nuclear cells.