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Biomedical subjects

Tetsuya Fujimura

Publications and source records attributed to Tetsuya Fujimura.

9 recordsLinked to original sources

Oncofetal protein glypican-3 in testicular germ-cell tumor.

The expression of an oncofetal protein, the glypican-3 (GPC3), was immunohistochemically evaluated in a wide variety of primary testicular germ-cell tumors (GCTs) in comparison with other markers, alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG)-beta, and OCT3/4. Eighty-nine cases of GCT including 22 cases of mixed GCT were evaluated with reference to each tumor component. GPC3 expression was observed in neoplastic cells of yolk-sac tumor (YST) (25/25), teratoma (2/10), components of syncytiotrophoblastic giant cells (STGCs) (10/14), and choriocarcinoma (1/3), but none in intratubular germ-cell neoplasias, unclassified type (0/33), seminomas (0/61), or embryonal carcinoma (0/19). All cases of YST showed diffuse labeling of neoplastic cells in cytoplasmic and membranous patterns, and the positive area of GPC3 was much larger than that of AFP. Glandular structures in teratomas showed GPC3 immunostaining as well as AFP. Although the number of GPC3-positive cells was smaller in STGC components and choriocarcinoma, there was no diffusion artifact in GPC3 immunostaining, as was frequently encountered in hCG-beta staining. Thus, GPC3 is a unique oncofetal protein, which is useful as an immunohistochemical marker for GCT differentiated to extraembryonic tissue, especially YST.

Antigens, Neoplasm↗

Periurethral injection of sustained release basic fibroblast growth factor improves sphincteric contractility of the rat urethra denervated by botulinum-a toxin.

PURPOSE: We evaluated the effects of sustained release basic fibroblast growth factor injection in rat urethra denervated by botulinum-A toxin (Wako Life Science, Osaka, Japan). MATERIALS AND METHODS: A total of 30 female Sprague-Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce chemical denervation of the urethral sphincter. Leak point pressure in the waking state was determined and a significant decrease in leak point pressure vs that in control rats was confirmed (mean +/- SD 58.7 +/- 6.2 vs 120.7 +/- 13.0 cm H(2)O, p <0.0001). Two weeks later 0, 50 and 200 microg basic fibroblast growth factor incorporating 200 microl gelatin hydrogels in 10 rats each were injected into the urethral sphincter, enabling sustained release of basic fibroblast growth factor for 2 weeks. Four weeks later injection leak point pressure measurement and histological evaluation of the urethra were performed. RESULTS: Leak point pressure in rats with 50 and 200 microg basic fibroblast growth factor injection was significantly higher than in rats with the 0 microg injection (82.7 +/- 9.0 vs 95.1 +/- 6.2 and 119.3 +/- 8.1 cm H(2)O, p = 0.0021 and <0.0001, respectively). Maximum cross-sectional area of the urethral smooth muscle layer in the 50 and 200 microg groups significantly increased compared with that in the urethra in the 0 micro group, which was considered 100% (114.1% +/- 15.8% and 132.5% +/- 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross-sectional area of the striated sphincter in the 50 and 200 microg groups was greater than the 100% in the 0 microg group (112.3% +/- 15.6% and 124.3% +/- 14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri-atrophic zone in the 50 and 200 microg groups was significantly higher than in the 0 microg group (p = 0.027 and <0.0001, respectively). CONCLUSIONS: Sustained release basic fibroblast growth factor injection in the chemically denervated urethral sphincter facilitates regeneration of the urethral muscles and improves sphincteric contractility. Endoscopic periurethral injection of basic fibroblast growth factor incorporating gelatin hydrogels may be an attractive therapy for stress urinary incontinence.

Animals↗

Acute pericarditis as a result of unusual metastasis of the visceral pleura in a patient with testicular seminoma.

A 30-year-old man with a left testicular swelling was referred to our hospital. We performed a left high orchiectomy based on a diagnosis of clinical stage II testicular cancer. Pathological specimens of the left testis showed seminoma. The patient underwent three courses of combined chemotherapy. The retroperitoneal lymph nodes were dissected and there were no viable cancer cells. Twelve years later a right testicular tumor was discovered. The patient underwent a right high orchiectomy. Pathological specimens of the testis showed seminoma, and the patient was treated with prophylactic irradiation. One year after discharge a metastasis was found at a left supraclavicular fossa. The patient was treated with combined chemotherapy and irradiation. Six months after the treatment he complained of dyspnea. We diagnosed the condition as pleuritis carcimatosa. Two days after irradiation to the left thorax the patient suffered a sudden and fatal cardiac arrest. Autopsy survey revealed pericarditis as a result of a direct invasion of visceral pleural metastasis.

Adult↗

Tubulovillous adenoma developing after urinary reconstruction using ileal segments.

A case of tubulovillous adenoma arising in an augmented bladder is described. Ureteroileal substitution and ileocystoplasty was performed when the patient was 18 years old. She noticed gross hematuria 44 years after the surgery. Cystoscopy revealed a non-papillary multiple tumor at the site of ileovesical anastomosis and transurethral resection biopsy was performed. Histopathological examination revealed a tubulovillous adenoma. A tubulovillous adenoma developing at the augmented bladder is rare. To our knowledge, this is the second case in which a tubulovillous adenoma developed in an augmented bladder.

Adenoma, Villous↗

Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor.

PURPOSE: alpha1-Adrenoceptor (AR) blockers are known to relieve not only voiding symptoms, but also storage symptoms in elderly men. We investigated lower urinary tract function in mice lacking alpha1d-AR using frequency/volume analysis and filling cystometry. MATERIALS AND METHODS: A total of 10, 12-week-old female alpha1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were studied. Each mouse was placed in a metabolic cage connected to a digital scale and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency and volume were recorded for 48 hours. After frequency/volume analysis filling cystometry was performed with the mice awake and without restraint. The expression of alpha1-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction. RESULTS: Mean daily voiding frequency +/- SD in alpha1d-KO mice was 9.0 +/- 2.1, significantly lower than 15.9 +/- 5.2 in WT mice (p = 0.0048). Mean volume per void in alpha1d-KO mice was significantly larger than in WT mice (0.24 +/- 0.02 vs 0.16 +/- 0.03 ml, p = 0.0096). Similarly cystometric analysis demonstrated larger bladder capacity (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in alpha1d-KO mice compared with those in WT mice. No significant difference in maximum pressure at void was observed between the 2 groups. In WT mice the amount of alpha1a, alpha1b and alpha1d-AR subtype mRNA in the bladder was 5.2 +/- 0.7, 1.0 +/- 0.1 and 6.3 +/- 0.7 gene copies per ng total RNA, respectively. In contrast, alpha1d-AR transcript was not detectable in alpha1d-KO mice but alpha1a and alpha1b-AR expression was similar to that in WT mice. CONCLUSIONS: The results demonstrate that the alpha1d-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that alpha1-blockers with significant affinity for alpha1d-AR are effective for treating storage symptoms associated with benign prostatic obstruction.

Animals↗

Hemiresective reconstruction of a redundant ileal conduit with severe bilateral ileal conduit-ureteral re fl ux.

A 58-year-old man was referred to our hospital with high fever and anuria. Since undergoing a total pelvic exenteration due to bladder-invasive sigmoid colon cancer, urinary tract infections had frequently occurred. We treated with the construction of a bilateral percutaneous nephrostomy (PCN), and chemotherapy. Although we replaced the PCN with a single J ureteral catheter after an improvement of infection, urinary infection recurred because of an obstruction of the catheter. Urological examinations showed that an ileal conduit-ureteral reflux caused by kinking of the ileal loop was the reason why frequent pyelonephritis occurred. We decided to resect the proximal segment to improve conduit-ureteral reflux for the resistant pyelonephritis. After the surgery, the excretory urogram showed improvement and the urinary retention at the ileal conduit disappeared. Three years after the operation, renal function has been stable without episodes of pyelonephritis. Here we report a case of open repair surgery of an ileal conduit in a patient with severe urinary infection.

Humans↗

14-3-3sigma is down-regulated in human prostate cancer.

The 14-3-3sigma is a negative regulator of the cell cycle, which is induced by p53 in response to DNA damage. It has been characterized as an epithelium-specific marker and down-regulation of the protein has been shown in breast cancers, suggesting its tumor-suppressive activity in epithelial cells. Here we demonstrate that 14-3-3sigma protein is down-regulated in human prostate cancer cell lines, LNCaP, PC3, and DU145 compared with normal prostate epithelial cells. Immunohistochemical analysis of primary prostate cells shows that the expression of 14-3-3sigma protein is epithelial cell-specific. Among prostate pathological specimens, > 95% of benign hyperplasia samples show significant and diffuse immunostaining of 14-3-3sigma in the cytoplasm whereas < 20% of carcinoma samples show positive staining. In terms of mechanisms for the down-regulation of 14-3-3sigma in prostate cancer cells, hypermethylation of the gene promoter plays a causal role in LNCaP cells as 14-3-3sigma mRNA level was elevated by 5-aza-2'-deoxycytidine demethylating treatment. Intriguingly, the proteasome-mediated proteolysis is responsible for 14-3-3sigma reduction in DU145 and PC3 cells, as 14-3-3sigma protein expression was increased by treatment with a proteasome inhibitor MG132. Furthermore, tumor necrosis factor-related apoptosis-inducing ligand enhances 14-3-3sigma gene and protein expression in DU145 and PC3 cells. These data suggest that 14-3-3sigma expression is down-regulated during the neoplastic transition of prostate epithelial cells.

14-3-3 Proteins↗

EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer.

Estrogen receptor-binding fragment-associated gene 9 (EBAG9) has been identified as a primary estrogen-responsive gene from MCF-7 human breast cancer cells (Watanabe T, et al., Mol Cell Biol 1998;18:442-9). EBAG9 is identical with RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), which has been reported as a cancer cell surface antigen implicated in immune escape (Nakashima M, et al., Nat Med 1999;5:938-42). In our present study, we examined EBAG9 expression in human prostatic tissues and investigated its prognostic significance in patients with prostatic cancer. EBAG9 expression in normal prostatic epithelial cells and PC-3, DU145 and LNCaP cancer cells was determined by Western blot analysis. Immunohistochemic analysis was performed in 21 benign and 81 malignant prostatic specimens, and patients' charts were reviewed for clinical, pathologic and survival data. EBAG9 was abundantly expressed in the prostate cancer cells compared to the normal epithelial cells. Strong and diffuse immunostaining in the cytoplasm of EBAG9 was found in 44 of 81 (54%) cancerous tissue samples. EBAG9 expression significantly correlated with advanced pathologic stages and high Gleason score (p = 0.0305 and < 0.0001, respectively). EBAG9 was more frequently expressed at sites of capsular penetration (79%) and lymph node metastasis (100%) compared to intracapsular primary tumors (54%) (p = 0.0264 and 0.0048, respectively). Positive EBAG9 immunoreactivity significantly correlated with poor PSA failure-free survival (p = 0.0059). EBAG9/RCAS1 may play a significant role in cancer progression via an immune escape system. Immunodetection of EBAG9/RCAS1 expression can be a negative prognostic indicator for patients with prostatic cancer.

Aged↗

Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma.

We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing's or subclinical Cushing's syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5-69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas.

Acetic Acid↗