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Biomedical subjects

Kazunori Kihara

Publications and source records attributed to Kazunori Kihara.

At least 19 recordsLinked to original sources

Control of canine membranous urethra, bulbocavernosus and ischiocavernosus muscles by lumbosacral sympathetic pathways.

The membranous urethral muscles, bulbocavernosus muscle (BCM) and ischiocavernosus muscle (ICM) play a significant role on expulsion at ejaculation. Projection of the sympathetic pathways in the retroperitoneum to these muscles was investigated in the dog. Intraluminar pressure of the membranous urethra and contractions of the BCM and ICM to electrical stimulation of the lumbar splanchnic nerve (LSN) or the lumbosacral sympathetic chain (LSC) were examined. Stimulation of the LSN was performed after transection of the unilateral hypogastric nerve (HGN) to clarify its cross-innervation. Stimulation of each of the 2nd to 4th LSNs elicited elevation of the intraluminal pressure of the membranous urethra. In eight dogs whose right HGNs were transected, 15 of the 19 right LSNs, and 12 of the 16 left LSNs examined elicited elevation of the membranous urethral pressure, respectively. In five dogs whose left HGNs were transected, 6 of the 9 right LSNs and 10 of the 12 left LSNs stimulated elicited elevation of the pressure. Stimulation of the HGN caused no detectable contractions of the BCM and ICM in all six dogs examined. Stimulation of the LSC elicited responses of the BCM and ICM in all six dogs examined and the membranous urethra in three of six dogs. The maximum value of the response of the BCM was greater than that of the ICM. After consecutive transection of the ipsilateral pelvic nerve, stimulation of the LSC showed no significant changes in the responses of the BCM and ICM. The above results indicate the following: (1). each of the L2-L4 LSNs sends signals to the membranous urethra via two routes, passing through the ipsilateral or contralateral HGN; (2). the above nerve does not send effective signals to the BCM and ICM; (3). the LSC sends signals to the membranous urethra, BCM and ICM; (4). the signals from the LSC mainly pass through the pudendal nerve to the BCM and ICM; and (5). the signals were dominant to the BCM compared with the ICM.

Animals↗

Successful long-term disease-free survival following multimodal treatments in a patient with a repeatedly recurrent refractory adrenal cortical carcinoma.

A 47-year-old male patient underwent surgery for a 10-cm adrenal cortical carcinoma. A large invasive adrenal mass was surgically removed en bloc with the right kidney and the lower lobe of the liver. Two months postoperatively, a 7-cm recurrent mass developed in the right psoas muscle. After a partial response was achieved by irradiation (40 Gy) and high-dose chemotherapy (carboplatin and etoposide) with peripheral blood stem cell transplantation, the patient underwent surgery with a wide excision of the psoas muscle. Twelve months after the initial surgery, an 8-cm rib metastasis developed and the patient again underwent surgery after a combination of irradiation (50 Gy) and chemotherapy (cisplatin and etoposide). The patient has been doing well without any evidence of recurrence for 5 years. Refractory or metastatic adrenal cortical carcinomas have been thought to be lethal, therefore, the present case provides support for multimodal treatments of refractory adrenocortical cancers.

Adrenocortical Carcinoma↗

Adenocarcinoma arising at the ileoileal anastomotic site of Scheele's ring.

Most tumors arising after augmentation ileocystoplasty have been reported to develop adjacent to the ileovesical anastomosis. Herein, we report a case of adenocarcinoma arising at the ileoileal anastomotic site 33 years after augmentation ileocystoplasty (Scheele's ring plasty) for tuberculous contracted bladder. The present case shows the possibility of late malignancy developing at the ileoileal junction after ileal neobladder.

Adenocarcinoma↗

[Fibroepithelial polyp of the anterior urethra, found during post-operative follow-up of ureteral cancer].

A 52-year-old man underwent nephroureterectomy against left distal ureteral cancer (transitional cell carcinoma, Grade 2, pTa), and was followed up by surveillance alone. Twenty-two months postoperatively, a pedunculated tumor was found in the anterior urethra by cystourethroscopy. Pathological examination of the tumor resected transurethrally revealed a fibroepithelial polyp. There have been only twelve cases of fibroepithelial polyp of the anterior urethra reported in the literature. Since 4 out of 8 adult cases among them were found during the postoperative follow up period of urothelial cancer, mechanical irritation by repeated transurethral procedures might be responsible for the development of fibroepithelial polyp of the anterior urethra in these cases. If anterior urethral tumor is found during follow-up urothelial carcinoma, benign urethral polyp should be considered in the differential diagnosis.

Carcinoma, Transitional Cell↗

[A case of fibroepithelial ureteral polyp in an adult patient].

A 24-year-old man complaining of asymptomatic gross hematuria was referred to our hospital for treatment of bilateral hydronephroses (left > right) diagnosed at a previous clinic. Radiological examinations demonstrated a filling defect at the left uretero-pelvic junction. Cytological examination of the urine was negative. With the diagnosis of suspected benign ureteral polyp, the patient underwent endoscopic-assisted partial ureterectomy and pyeloplasty through a 5 cm flank incision. Histological examination revealed that the villous tumor in the ureter was a fibroepithelial polyp.

Adult↗

p53 gene family p51(p63)-encoded, secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation.

p51(p63), a member of the p53 tumor suppressor gene family, generates multiple isoforms, including the potent and less potent transactivators p51A(TAp63gamma) and p51B(TAp63alpha), respectively, the latter poorly characterized for its protein features and functions. When constitutively expressed in 1-2-3 mouse erythroleukemic cells, p51B(TAp63alpha) appeared as a broad band with an approximate molecular mass of 85 kDa in Western blot. When cells were exposed to genotoxic stress by UV-C irradiation or by DNA-damaging drugs, including actinomycin D, bleomycin, and eptoposide, the protein accumulated intracellularly without an increase in its mRNA. Unlike p53 and p51A(TAp63gamma), however, p51B(TAp63alpha) did not activate p21(waf1) gene expression, nor did it induce apoptosis or hemoglobin production. While wild-type p53 was precipitated by an anti-MDM2 antibody, p51B(TAp63alpha) was not detectable in the MDM2 immunoprecipitates from the producer cells. After treatment with okadaic acid, a Ser/Thr phosphatase inhibitor, p51B(TAp63alpha) increased its apparent molecular mass and protein content. A 26S proteasome inhibitor, MG132 (N-CBZ-Leu-Leu-leu-al), also increased p51B(TAp63alpha) retention in an either transient or constitutive expression system. Without an interaction with MDM2, p51B(TAp63alpha) may be degraded by proteasome under normal cellular circumstances but stabilized under genotoxic stress by a posttranscriptional mechanism which might involve Ser/Thr phosphorylation.

Animals↗

PPARgamma ligands suppress proliferation of human urothelial basal cells in vitro.

Expression of peroxisome proliferator-activated receptor (PPAR) gamma in the human urinary tract through embryonic development suggests its possible roles in the development, proliferation, and differentiation of uroepithelium. Little is known, however, about physiological roles of PPARgamma in the urinary tract. We investigated effects of PPARgamma ligands on the proliferation of normal human urothelial cells and stromal cells cultivated from surgical specimens. Active proliferation in vitro as well as high molecular weight cytokeratin expression indicated that cultured urothelial cells possess basal cell phenotype. PPARgamma protein, expressed predominantly in the epithelial layer of the normal human urinary tract in vivo, was abundantly expressed in urothelial cells but barely detectable in stromal cells in vitro. Natural ligand for PPARgamma, 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), as well as synthetic ones, troglitazone and pioglitazone, suppressed proliferation of the urothelial cells dose-dependently. These effects were PPARgamma specific because clofibrate or PGF(2alpha) did not affect proliferation of urothelial cells. Neither 9-cis retinoic acid or all-trans retinoic acid (ATRA) at 1 microM showed any synergism on the antiproliferative effects of PPARgamma ligands. Urothelial cells treated with PPARgamma ligands showed drastic morphologic changes and cell cycle arrest at G0/G1 phase accompanied with increased mRNA level of a cyclin-dependent kinase inhibitor p21(WAF1/CIP1). Since 15d-PGJ(2) is present in vivo during the resolution phase of inflammation, these results indicated that PPARgamma might be involved in the terminal phase of urothelial re-epithelialization processes.

Cell Cycle↗

Different distribution of nitric oxide synthase and soluble guanylyl cyclase activities in the detrusor and proximal urethra of the rabbit.

PURPOSE: We investigated the different distributions of nitric oxide synthase (NOS) and soluble guanylate cyclase activities in the detrusor and proximal urethra in the rabbit. MATERIALS AND METHODS: The detrusor and proximal urethra were excised, the mucosa and muscularis were separated and each layer was homogenized to measure the activities of NOS as well as baseline and sodium nitroprusside (SNP) activated soluble guanylate cyclase. Isometric tension experiments were performed in detrusor and urethral strips with and without mucosa. RESULTS: In the detrusor NOS and sodium nitroprusside activated soluble guanylate cyclase activities in the mucosa were much higher than in the muscularis. While in the proximal urethra NOS activity in the 2 layers was similar, SNP activated soluble guanylate cyclase activity in the muscularis was 2.8 times higher than in the mucosa. Removing the mucosa reduced nitric oxide (NO) mediated neurogenic relaxation in the proximal urethra, while no relaxation responses could be elicited by electrical field stimulation with or without mucosa in the detrusor. On the other hand, removing the mucosa did not affect SNP or 8-bromo-cyclic guanosine monophosphate induced relaxation in the detrusor and proximal urethra. CONCLUSIONS: In the detrusor NOS and soluble guanylate cyclase activities were mainly detected in the mucosa, while in the urethra these activities were distributed throughout the mucosa and muscularis. Also, the mucosa in the urethra but not in the detrusor contributed to electrical field stimulation induced, NO mediated relaxation. These findings confirm previous studies demonstrating that NO has a different role in the detrusor than in the proximal urethra.

Animals↗

Positive expression of HIF-2alpha/EPAS1 in invasive bladder cancer.

OBJECTIVES: To investigate the expression of hypoxia-inducible factor (HIF)-2alpha/endothelial PAS domain protein 1 (EPAS1) in bladder cancer. METHODS: Two bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF-2alpha/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF-2alpha/EPAS1 protein by Western blot analysis, respectively. Expression of HIF-2alpha/EPAS1 protein was also investigated immunohistochemically on paraffin-embedded sections from 24 patients with bladder cancer. RESULTS: HIF-2alpha/EPAS1 mRNA and protein could be detected in the two bladder cell lines under normoxia. The normal urothelium and all 7 superficial cases (pTis-pTa) were negative for HIF-2alpha/EPAS1. Five of the 8 pT1 cases (62.5%) and all 9 muscle-invasive cases were positive. The invasive compartment showed stronger HIF-2alpha/EPAS1 immunoreactivity compared with the superficial compartment. All the tumor clusters infiltrating to the interstitial tissue among muscle fibers showed moderate to strong positive staining. CONCLUSIONS: HIF-2alpha/EPAS1 is mostly expressed in invasive bladder cancer, which indicates a possible role for HIF-2alpha/EPAS1 in the invasion of bladder cancer.

Aged↗

Intracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinoma.

The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma.

Antineoplastic Agents↗

Endoscopic minilaparotomy radical nephrectomy for chronic dialysis patients.

BACKGROUND: To assess the feasibility of laparoscope-guided minilaparotomy (endoscopic minilaparotomy) for renal cell carcinoma in patients on chronic dialysis. METHODS: Endoscopic retroperitoneal minilaparotomy using a 30 degrees telescope was carried out through single skin incision (5-8 cm) in eight patients with renal cell carcinoma who were on chronic dialysis. Outcomes of the operations were compared to those in eight patients on chronic dialysis with renal cell carcinoma who underwent standard translumbar radical nephrectomy. RESULTS: Resection of the tumor was successfully completed without complication and the postoperative course was uneventful in both of the treatment groups. No significant difference in mean operative time or mean blood loss was observed between the treatment groups. Wound pain was minimal and analgesics were generally not required in the minilaparotomy group. The endoscopic laparotomy group resumed full diet and began walking earlier than the group that underwent standard radical nephrectomy. CONCLUSIONS: Endoscopic minilaparotomy seems to be a valuable alternative treatment for renal cell carcinoma in patients on chronic dialysis.

Aged↗

Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases.

Neuroendocrine differentiation and subsequent excretion of neuropeptides have been demonstrated to be associated with progression of human prostate cancer. Among neuropeptides found to exist in the prostate, bombesin/gastrin-releasing peptide has been shown to upregulate matrix metalloproteinase-9 (MMP-9) in human prostate cancer cell lines. Expression levels of bombesin, MMP-9, and neuron-specific enolase were examined by immunohistochemistry in 41 cases of clinically organ-confined prostate cancers including 9 with microscopic lymph node metastases. Twenty-seven (64%) of the 41 radical prostatectomy specimens were positive for both MMP-9 and bombesin. Expression of these molecules was observed in almost the same population of the cancer cells. The remaining 14 cases were negative for both MMP-9 and bombesin. High-grade tumors (Gleason sum > or = 7) were more likely to express MMP-9 and bombesin (21/24:88%) than low-grade tumors (Gleason sum > or = 6) (7/17:41%). In eight of the nine cases with pathological lymph node metastases, expression of MMP-9 and bombesin was also noted in metastatic sites. Neuron-specific enolase was positive in 16 cases (39%) and not always associated with the expression of bombesin. Expression of bombesin and expression of MMP-9 are common in human prostate cancers and may be related to an aggressive phenotype.

Aged↗

Endoscope-assisted minilaparotomy (endoscopic minilaparotomy) for retroperitoneal Schwannoma: experience with three cases.

We have been applying endoscope-assisted minilaparotomy (endoscopic minilaparotomy) to retroperitoneal operations with favorable outcomes. Here, endoscopic minilaparotomy through a single flank incision (4-7 cm) was performed in three cases of incidentally discovered retroperitoneal Schwannoma. Resection of the tumor was successfully completed. The postoperative course was uneventful. Wound pain was mild and full oral feeding and walk were resumed the day following operation. It is concluded that endoscopic minilaparotomy is applicable to retroperitoneal Schwannoma with excellent postoperative recovery.

Aged↗

Endoscopic minilaparotomy partial nephrectomy for solitary renal cell carcinoma smaller than 4 cm.

BACKGROUND: For small, incidentally discovered renal cell carcinoma, partial nephrectomy is becoming more widely accepted as an alternative to radical nephrectomy and the need for minimally invasive approach is increasing. METHODS: We carried out endoscopic minilaparotomy partial nephrectomy in seven cases of solitary renal cell carcinoma smaller than 4 cm. Five of them were without renal pedicle clamping. All procedures were done through single skin incision (5-8 cm) using a 30 degrees telescope. Hemostasis was achieved with a harmonic scalpel, a microwave tissue coagulator, an argon beam coagulator and autologous fibrin glue. RESULTS: There were no perioperative complications. All patients had negative surgical margins. The operating time was 157-275 min (average 209 min). The blood loss was 20-1200 ml (average 525 ml). Postoperatively, renal function as assessed by serum creatinine was within normal limits. Neither local recurrences nor metastases were observed during a follow-up of 6-15 months. The postoperative course was markedly improved over that expected from standard open surgery. CONCLUSIONS: With minimal morbidity and complications, endoscopic minilaparotomy partial nephrectomy is feasible for small renal cell carcinoma.

Aged↗

Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia.

We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are involved in the impaired cavernosal relaxation with ischemia in rabbits. Two weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium-dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were significantly impaired in the isolated corpus cavernosum. The Ca(2+)-dependent NO synthase (NOS) activity and the basal and stimulated cGMP productions with carbachol or EFS were significantly decreased after ischemia. Supplementation of excess L-arginine partially recovered both of the impaired relaxations. The contents of N(G)-monomethyl-L-arginine (L-NMMA) and asymmetric N(G), N(G)-dimethyl-L-arginine (ADMA) but not L-arginine and symmetric N(G),N'(G)-dimethyl-L-arginine (SDMA) were increased in the cavernosal tissues after ischemia. Authentic L-NMMA and ADMA but not SDMA concentration dependently inhibited both relaxations without affecting the relaxation produced by SNP in the control. Excess L-arginine abolished the inhibition with L-NMMA and ADMA. These results suggest that the impaired NO-mediated cavernosal relaxations after ischemia are closely related to the decreased NOS activity and the increased accumulation of L-NMMA and ADMA.

Animals↗

A case of ACTH-independent bilateral macronodular adrenal hyperplasia successfully treated by subtotal resection of the adrenal glands: four-year follow-up.

We report ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH) seen in a 48-year-old male with a history of rectal and skin cancer. Bilateral multiple adrenal nodular lesions on abdominal CT scans, elevated early morning plasma cortisol levels with undetectable plasma ACTH, increased 24-hour urinary free cortisol excretion, and loss of the normal circadian rhythm in cortisol secretion established the diagnosis of AIMAH. Subtotal resection of the adrenal glands preserving lower one third of the left side was performed, considering the unfavorable effects of total adrenalectomy on future treatment of his malignancies. He has been doing well for four years with normal plasma ACTH and cortisol levels. This case suggests that subtotal resection of the adrenal glands may be applicable to selected patients.

Adrenal Glands↗