[Hypogonadism in male infertility due to defective LH molecule caused by a single amino acid substitution in the beta subunit of luteinizing hormone].
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Amino Acid Substitution↗
Biomedical subjects
Koji Shiraishi
Publications and source records attributed to Koji Shiraishi.
[True hermaphroditism].
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Chromosome Aberrations↗
Generation of 4-hydroxy-2-nonenal modified proteins in testes predicts improvement in spermatogenesis after varicocelectomy.
Increasing evidence suggests that testes with varicocele are exposed to oxidative stress (OS) with deterioration in spermatogenesis; however, the relationship between testicular OS and outcome after varicocelectomy is poorly understood. Levels of testicular 4-hydroxy-2-nonenal modified proteins, an OS marker, were significantly higher in responders than in nonresponders, suggesting that varicocelectomy reduces OS in testis.
Adult↗
Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases (ERK1/2).
We show that activation of the recombinant lutropin/choriogonadotropin receptor (LHR) in mouse Leydig tumor cells (MA-10 cells) leads to the tyrosine phosphorylation of Shc (Src homology and collagen homology) and the formation of complexes containing Shc and Sos (Son of sevenless), a guanine nucleotide exchange factor for Ras. Because a dominant-negative mutant of Shc inhibits the LHR-mediated activation of Ras and the phosphorylation of ERK1/2, we conclude that the LHR-mediated phosphorylation of ERK1/2 is mediated, at least partially, by the classical pathway used by growth factor receptors. We also show that the endogenous epidermal growth factor receptor (EGFR) present in MA-10 cells is phosphorylated upon activation of the LHR. The LHR-mediated phosphorylation of the EGFR and Shc, the activation of Ras, and the phosphorylation of ERK1/2 are inhibited by expression of a dominant-negative mutant of Fyn, a member of the Src family kinases (SFKs) expressed in MA-10 cells and by PP2, a pharmacological inhibitor of the SFKs. These are also inhibited, but to a lesser extent, by AG1478, an inhibitor of the EGFR kinase. We conclude that the SFKs are responsible for the LHR-mediated phosphorylation of the EGFR and Shc, the formation of complexes containing Shc and Sos, the activation of Ras, and the phosphorylation of ERK1/2.
Animals↗
Laparoscopic decortication of symptomatic simple renal cysts: 10-year experience from one institution.
OBJECTIVE: To assess the long-term results by symptomatic and radiological outcome of laparoscopic decortication of renal cyst, first reported in 1992. PATIENTS AND METHODS: We retrospectively reviewed the records of 36 patients who had a total of 36 laparoscopic decortications at our institution between December 1993 and March 2004. Of these cysts, 30 were peripheral and six were peripelvic cysts; the patients were asked if they had pain or not. Changes of cyst size after decortication were determined by computed tomography and the serial changes of each cyst were evaluated as the percentage of the diameter before surgery. The relationships between radiological and symptomatic outcome or cyst location were examined. RESULTS: Peri-operative morbidity was satisfactory; with a mean (range) follow-up of 67.2 (13-128) months the symptomatic and radiological success rates were 92% (33 of 36) and 81% (25 of 36), respectively. Peripelvic cysts were significantly correlated with radiological failure. Symptomatic improvement was evident by 3 months, while radiological improvement continued for up to 3-4 years after surgery. Seven asymptomatic patients with radiological failure selected a conservative follow-up. CONCLUSIONS: Laparoscopic decortication is safe and provides long-term satisfactory symptomatic results. The radiological improvement was slower than the symptomatic improvement and several cysts remained large, indicating some reduction in volume that was enough to improve the symptoms. This procedure is still challenging for peripelvic cysts in terms of radiological results, yet feasible for the clinical outcome.
Adult↗
Activation of the lutropin/choriogonadotropin receptor in MA-10 cells leads to the tyrosine phosphorylation of the focal adhesion kinase by a pathway that involves Src family kinases.
We show that activation of the endogenous or recombinant lutropin/choriogonadotropin receptor (LHR) in mouse Leydig tumor cells (MA-10 cells) leads to the tyrosine phosphorylation of the focal adhesion kinase (FAK) and one of its substrates (paxillin). Using specific antibodies to the five tyrosine residues of FAK that become phosphorylated, we show that activation of the LHR increases the phosphorylation of Tyr576 and Tyr577, but it does not affect the phosphorylation of Tyr397, Tyr861, or Tyr925. Because FAK is a prominent substrate for the Src family of tyrosine kinases (SFKs) we tested for their involvement in the LHR-mediated phosphorylation of FAK-Tyr576. Src is not detectable in MA-10 cells, but two other prominent members of this family (Fyn and Yes) are present. The LHR-mediated phosphorylation of FAK-Tyr576 is readily inhibited by PP2 (a pharmacological inhibitor of SFKs) and by dominant-negative mutants of SKFs. Moreover, activation of the LHR in MA-10 cells results in the stimulation of the activity of Fyn and Yes, and overexpression of either of these two tyrosine kinases enhances the LHR-mediated phosphorylation of FAK-Tyr576. Studies involving activation of other G protein-coupled receptors, overexpression of the different Galpha-subunits, and the use of second messenger analogs suggest that the LHR-induced phosphorylation of FAK-Tyr576 in MA-10 cells is mediated by SFKs, and that this family of kinases is, in turn, independently or cooperatively activated by the LHR-induced stimulation of Gs and Gq/11-mediated pathways.
Animals↗
Hand-assisted laparoscopic radical nephrectomy: comparison of the transperitoneal and retroperitoneal approaches.
Transperitoneal and retroperitoneal approaches have been introduced to perform hand-assisted laparoscopic radical nephrectomy. The efficacy and convalescence of both approaches were compared. Of 26 patients with renal cell carcinoma, 14 patients were treated by the transperitoneal approach and 12 by the retroperitoneal approach at the same institution. The mean operative time by transperitoneal approach was significantly shorter than retroperitoneal approach (236.4 and 280.0 minutes, respectively, P < 0.05), but there is a steeper learning in retroperitoneal approach. A significant increase in operative time was required with an increase in specimen weight (r = 0.591, P < 0.05). There were no differences in patient demographic, operative, and convalescence data between the both groups. Hand-assisted laparoscopic radical nephrectomy is safe by either the transperitoneal or the retroperitoneal approach. Making enough retroperitoneal space for the hand and instrument enables us to use the retroperitoneal approach readily. Patients with abundant fatty tissues around the kidney should be treated by the transperitoneal approach.
Aged↗
Torsion of a communicating hydrocele in a child.
Among the diseases presenting as acute scrotum, torsion of a communicating hydrocele is extremely rare. A 5-year-old boy was referred with discomfort and swelling of the left scrotum. Operative findings revealed a torsion of a communicating hydrocele. We report a case of torsion with preoperative findings of ultrasonography and magnetic resonance imaging. We also emphasize the awareness of this disease as a differential diagnosis of the acute scrotum.
Child, Preschool↗
Usefulness and limitation of punched-out orchidometer in testicular volume measurement.
AIM: To determine the limitations of a punched-out orchidometer in practical use, we compared with a scrotal ultrasound (USG). METHODS: A total of 281 testes from 142 males were examined using both a punched-out orchidometer and a USG. The volume differential between both methods was calculated and expressed as orchidometer/USG volume (O/U ratio). Distribution of the O/U ratio was determined and subdivided by clinical or pathological diagnosis. The correlations between the O/U ratio and patient age or orchidometer results were assessed. RESULTS: There was a significant linear relationship between the results of orchidometer and USG (r=0.94, P <0.0001). The relationship between the O/U ratio and age or testicular volumes showed significant inverse correlations (r=0.22, P=0.0002, r=0.45, P <0.0001, respectively). Klinefelter's syndrome, ipsilateral detorted testes and hypogonadotropic hypogonadism comparatively showed a high O/U ratio. No incidental lesion was detected by USG necessitating treatment. CONCLUSION: The punched-out orchidometer gives estimates that correlated well with the USG measurements and provides enough information for routine andrological evaluation. We should be aware that the orchidometer often overestimates the testicular volume, especially for the patients with small testis or adolescents.
Adolescent↗
Recurrent epididymo-orchitis caused by posterior urethral valve associated with imperforate anus.
Epididymo-orchitis is an uncommon complication of imperforate anus. A 14-year-old boy who received surgical repair for imperforate anus was diagnosed with right epididymo-orchitis. Intravenous pyelography showed a right solitary kidney. Posterior urethral valve, reflux of contrast medium to the ejaculatory duct and incomplete duplicate urethra were suspected from voiding cystourethrography. Valve ablation was performed to prevent the recurrence of epididymo-orchitis. Improvement of urinary force was achieved and the patient has been free of recurrence during a 2-year follow up. For the patient with imperforate anus, we should evaluate not only anorectal function, but also the genitourinary tract in order to preserve renal function and fertility.
Abnormalities, Multiple↗
Phyllodes tumor of the prostate: recurrent obstructive symptom and stromal proliferative activity.
We report the case of a 59-year-old man with a metachronous development of phyllodes tumor and adenocarcinoma of the prostate. He complained of urinary obstruction and transurethral resections of the prostate (TUR-P) had been performed six times in 10 years. Microscopic examination showed cystically dilated glands consisting of bizarre cells with pleomorphic, hyperchromatic nuclei in the stroma at the sixth TUR-P. Radical prostatectomy was performed against recurrences and adenocarcinoma was incidentally detected. Apparent up-regulation of proliferative nuclear antigens (PCNA), but not p53, was observed in the prostatectomy specimen by Western blotting. Active proliferation of stromal cells is considered to have caused the recurrent obstructive symptom.
Adenocarcinoma↗
Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells.
Quality-control mechanisms in spermatogenesis are important to eliminate injured or abnormal cells, thereby protecting the organism from abnormal development in the next generation. The processes of spermatogenesis are highly sensitive to high temperatures; however, the mechanisms by which injured germ cells are eliminated remain unclear. Here, we found that heat shock proteins are not induced in male germ cells in response to thermal stress, although heat shock transcription factor 1 (HSF1) is activated. Using HSF1-null mice, we showed that apoptosis of pachytene spermatocytes was markedly inhibited in testes with a single exposure to heat and in the cryptorchid testes, indicating that HSF1 promotes apoptotic cell death of pachytene spermatocytes exposed to thermal stress. In marked contrast, HSF1 acts as a cell-survival factor of more immature germ cells, probably including spermatogonia, in testes exposed to high temperatures. These results demonstrate that HSF1 has two opposite roles in male germ cells independent of the activation of heat shock genes.
Animals↗
Metastatic renal cell carcinoma to the bladder 12 years after radical nephrectomy.
We report, herein, a case of metastatic renal cell carcinoma of the urinary bladder. A 76-year-old man presented to our hospital. He had undergone right radical nephrectomy at 64 years of age. Cystoscopy revealed a solitary, spherical tumor 1.5 cm in size protruding into the urinary bladder. Transurethral resection was performed and the pathological diagnosis of the lesion was clear cell carcinoma. The patient is alive 12 months after recurrence to the bladder, under the administration of interleukin-2.
Adenocarcinoma, Clear Cell↗
Role of ureteroscopic biopsy in the management of upper urinary tract malignancy.
BACKGROUND: The aim of the study presented here was to examine the accuracy of ureteroscopic biopsy in the diagnosis of upper urinary tract transitional cell carcinoma (TCC) and whether nephron-sparing management (holmium YAG laser, transurethral resection or partial ureterectomy) is possible or not based on pathological diagnosis. METHODS: Forty consecutive patients underwent ureteroscopic biopsy with the use of 3-Fr cold cup forceps. Pathological diagnosis of the biopsy sample and grade or stage of surgically resected tumors were compared. In patients with grade 1 or 2 TCC diagnosed by ureteroscopic biopsy, the disease-free and survival rates determined whether nephron-sparing management was performed or not. RESULTS: There were no major complications associated with ureteroscopic biopsy. The pathological grading of the biopsy specimen was almost the same as that of the surgically resected specimen. Eighty five percent of grade 2 or 3 TCC showed muscle invasive disease. There were no significant differences in the disease-free and survival rates between the nephroureterectomy and the nephron-sparing management groups, except for grade 3 or pT3 tumors. CONCLUSION: Ureteroscopic biopsy is safe and accurate if sufficient tissue sample is obtained. Ureteroscopic biopsy should be performed in patients who require nephron-sparing management. Nephroureterectomy can be avoided if the tumor is confirmed as low-grade.
Aged↗
Angiotensin II dependent testicular fibrosis and effects on spermatogenesis after vasectomy in the rat.
PURPOSE: Vasectomy induces testicular interstitial fibrosis in time dependent fashion and inhibits spermatogenesis. We investigated the contribution of angiotensin II (Ang II) to the development of interstitial fibrosis after vasectomy. MATERIALS AND METHODS: Bilateral vasectomy was performed in 8-week-old Wistar rats and the testes were harvested 1 to 24 weeks after vasectomy. Interstitial fibrosis was evaluated by Masson's trichrome staining. Western blotting and immunohistochemistry were done to examine the expressions of heat shock protein 47 (HSP47), HNE (4-hydroxy-2,3-nonenal) and transforming growth factor-beta1 (TGF-beta1). The antioxidative agent N-acetylcysteine (NAC), the Ang II type 1 receptor antagonist losartan or the Ang converting enzyme inhibitor enalapril was given orally for 24 weeks to vasectomized rats. Spermatogenesis was evaluated by testicular weight and the percent of haploid cells was analyzed by flow cytometry. RESULTS: Vasectomy significantly increased interstitial fibrosis (more than 8 weeks) and induced the expression of HSP47, HNE modified protein and TGF-beta1. TGF-beta1 and HSP47 immunoreactivity was localized to Leydig cells and fibroblasts. NAC or losartan but not enalapril inhibited the expression of these molecules induced by vasectomy. Increased interstitial fibrosis and impaired spermatogenesis were partially abrogated by NAC or losartan administration. CONCLUSIONS: There is Ang II type 1 receptor dependent fibrosis after vasectomy. Oxidative condition is considered to trigger and promote these fibrogenic processes. Ang II contributes to the regulation of intratesticular autocrine or paracrine functions after vasectomy.
Acetylcysteine↗
Fertile eunuch syndrome with the mutations (Trp8Arg and Ile15Thr) in the beta subunit of luteinizing hormone.
Fertile eunuch syndrome is caused by isolated LH deficiency, but its pathophysiology still remains controversial. We report a case of fertile eunuch syndrome with homozygous Trp8Arg and Ile15Thr mutations in the LH beta subunit gene. An 18-year-old man was admitted to our hospital for hypogonadism. Examination of genitalia revealed Tanner G1PH1, whereas both testes were elastically palpated and developed up to 18 ml. Endocrinological evaluations revealed normogonadotropic hypogonadism and there were normal responses after GnRH and hCG stimulation. Intratesticular testosterone concentration was almost normal (1.34 x 10(3) ng/g). By PCR direct sequencing, homozygous Trp (8) Arg and Ile (15) Thr mutations in exon 2 of LH beta were detected. Normal virilization and improved semen parameters were achieved after hCG supplementation. To our knowledge, this is the first case of fertile eunuch syndrome with homozygous Trp (8) Arg and Ile (15) Thr mutations in beta subunit of LH gene.
Adolescent↗
Influence of interstitial fibrosis on spermatogenesis after vasectomy and vasovasostomy.
This study focused on the testicular interstitial fibrosis after vasectomy and the intraseminiferous status [i.e., Johnsen's score, proliferative cell nuclear antigen (PCNA) expression] following vasectomy reversal. Testicular biopsy specimens from 21 consecutive men were obtained at vasovasostomy. Percent of interstitial fibrosis was determined quantitatively by NIH-image after Masson Trichrome staining. PCNA-labeling index (LI) was calculated on each testis. The associations between the obstructive interval and each parameter were examined. These parameters were also analyzed on whether patency or pregnancy was achieved or not. Significant decrease in PCNA-LI and increase in interstitial fibrosis were observed along with the obstructive interval (p <0.0001, p = 0.0005, respectively). Interstitial fibrosis of the patients without patency/fertility was significantly greater than that of the patients with patency/fertility (47.5%/39.0% versus 33.4%/32.3%, p = 0.02/0.04, respectively). PCNA-LI and Johnsen's score did not predict the treatment outcome. Interstistial fibrosis, but not the extent of germ cell differentiation or DNA synthesis, reflects the treatment outcome after vasectomy reversal. Interstistial fibrosis contributes to the irreversible damage of vasectomized testes.
Adult↗
Activation of mitogen activated protein kinases and apoptosis of germ cells after vasectomy in the rat.
PURPOSE: Vasectomy induces a large amount of germ cell apoptosis. We examined the activation of mitogen activated protein kinases (MAPKs) in association with the apoptosis and proliferation of germ cells after vasectomy in the rat. MATERIALS AND METHODS: Eight-week-old Wistar rats underwent bilateral vasectomy and the testes were harvested 1 to 9 days after vasectomy. Germ cell apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling and electrophoretic assay of DNA fragmentation. Western blotting and immunohistochemistry were used to examine the temporal and spatial activation of signal regulated kinases 1/2, c-Jun-terminal kinases 1/2 and p38. Phospho-specific MAPK antibodies were used to examine their activations. Proliferation of germ cells was evaluated by proliferative nuclear cell antigen expression. RESULTS: Germ cell apoptosis was detected predominantly in primary spermatocytes with a peak 7 days after vasectomy. Signal regulated kinases 1/2, c-Jun-terminal kinases 1/2 and p38 were constitutively expressed in the control testis. Western blotting and immunohistochemistry showed rapid activation of signal regulated kinases 1/2, followed by activation of c-Jun-terminal kinases 1/2 and p38. Immunohistochemical study demonstrated the temporal and spatial relationships of apoptosis and MAPK activation in primary spermatocytes. On the other hand, proliferating cell nuclear antigen expression was enhanced in tetraploid spermatocyte and spermatogonia maximally 5 days after vasectomy. CONCLUSIONS: MAPKs were rapidly activated after vasectomy and germ cell apoptosis was observed after vasectomy. In contrast to the delayed phase up to 24 weeks after vasectomy, we observed hyperdynamic cellular turnover, spermatocyte loss through apoptosis and enhanced germ cell proliferation transiently at the early phase after vasectomy.
Animals↗