Biomedical subjects

Koichiro Nomata

Publications and source records attributed to Koichiro Nomata.

7 recordsLinked to original sources

PubMed2003

Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase.

Sonic hedgehog (Shh) acts as a morphogen in many cell types. Recent studies have shown that hedgehog signaling is involved in vascular development as well as postnatal angiogenesis. However, the direct action of Shh on cultured endothelial cells has not been clearly shown. To address this issue, we examined the effect of Shh on morphological changes by murine brain capillary endothelial cells (IBE cells) and human umbilical endothelial cells (HUVECs). Shh induced capillary morphogenesis by these cells. The effect was inhibited by cyclopamine or pertussis toxin. Shh-induced capillary morphogenesis was also blocked by LY294002, a phosphoinositide 3-kinase (PI3-kinase) inhibitor. Shh rapidly increased PI3-kinase activity in IBE cells and HUVECs; this activity was inhibited by cyclopamine. Nuclear localization of Gli1 was increased in Shh-treated IBE cells, which was not affected by LY294002. Actinomycin D and cycloheximide inhibited Shh-induced capillary morphogenesis. In IBE cells expressing kinase-inactive c-Fes, Shh failed to stimulate PI3-kinase activity and capillary morphogenesis. Considered collectively, Shh induced capillary morphogenesis of endothelial cells through both rapid activation of c-Fes/PI3-kinase pathways and transcriptionally regulated pathways.

Animals↗

PubMed2002

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment.

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for non-muscle-invasive bladder cancer after transurethral resection. We evaluated the optimal duration of EPI instillation in a multi-institution prospective randomized clinical study. METHODS: Between June 1995 and May 1998, a total of 125 patients with superficial bladder cancer (transitional cell carcinoma grade 1 or 2) were enrolled in this study, and 102 patients were fully evaluated for recurrence. Two protocols for intravesical therapy (arm A - 30 mg EPI/30 ml saline 19 times over 1 year; arm B - 30 mg EPI/30 ml 12 times over 5 months) were established. Instillations were given every week for 4 weeks and then every 2 weeks for 4 months in arm B. After 5 months of treatment, maintenance was performed with seven further instillations (one every month for 7 months) in arm A. The analyzed background factors were the therapeutic method, gender, history (primary or recurrent tumor), stage (T classification), grade, number of tumors, and tumor size. RESULTS: There were no significant differences in the analyzed background factors between the two arms, and there were no serious side effects in the study. In an intent-to-treat analysis, the overall 3-year recurrence-free survival rates were 48.5% in arm A and 55.1% in arm B. The difference between the two groups was not significant. CONCLUSIONS: This analysis indicated that extended prophylactic maintenance instillation of EPI was not significantly effective in reducing bladder cancer recurrence.

Administration, Intravesical↗

PubMed2002

Transient decrease in gap junction expression during compensatory renal growth in mice.

OBJECTIVES: To examine gap junction expression during compensatory renal growth. Compensatory renal growth is a normal response to the removal of renal cells. Gap junctional intercellular communication plays important roles in homeostatic regulation, differentiation, and synchronization of cellular electronic and metabolic functions. METHODS: The right ureters of 5-week-old ddy mice were dorsally incised and unilaterally obstructed, and the animals were killed at varying intervals. The control group underwent a sham operation. Freeze-fractured kidney tissue samples were studied using electron microscopy. The amount of proliferative cell nuclear antigen-positive cells and connexin 43 (Cx43) protein was studied by immunohistochemistry and Western blotting, respectively. RESULTS: Proliferative cell nuclear antigen-positive cells in the renal tubules increased on days 1 and 2 after surgery that obstructed the ureter, and decreased to normal levels by day 14. The number of gap junctions significantly decreased on days 1 and 2, and then gradually increased to normal levels from days 3 to 14 after surgery. The amount of Cx43 protein in the renal tubules decreased until day 2 and recovered to the same level as that of the control by day 14 after surgery. Significantly, a hyperphosphorylated band of Cx43 in the control kidney was not detected in the operated kidney. CONCLUSIONS: These data suggest that the gap junctional intercellular communication of renal tubular cells during compensatory renal growth after unilateral ureteral obstruction could be temporarily reduced concomitant with a decrease of the expression of a phosphorylated Cx43 protein in renal cortical tubular cells after unilateral ureteral obstruction of the contralateral kidney.

Adaptation, Physiological↗

PubMed2002

Renal cell carcinoma with solitary metachronous metastasis to the urinary bladder.

We report a case of renal cell carcinoma with solitary metachronous metastasis to the urinary bladder occurring 6 years after radical nephrectomy. The patient was treated with partial cystectomy and survived for 60 months. Other cases like this one were reviewed in published reports, and the 3-year survival rate for patients with this type of cancer with solitary metastasis to the urinary bladder was found to be 80%. The follow-up duration of our case was the longest in the published studies. We suggest that urinary bladder metastasis of renal cell carcinoma should be resected because no effective treatment for metastatic renal cell carcinoma is available. A good prognosis may be expected, especially in patients with solitary metastasis to the urinary bladder.

Aged↗

PubMed2002

Fas-Fas ligand system as a possible mediator of spermatogenic cell apoptosis in human maturation-arrested testes.

To elucidate the mechanism of maturation arrest, known as one of the male infertility, we addressed whether germ cell apoptosis occurs during maturation arrest, and if so, whether Fas and Fas ligand expressions are involved in the apoptosis. By electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), typical apoptotic features were frequently found around the spermatocytic stage in maturation arrest, compared to that in normal testes. When paraffin-embedded sections reacted with anti-Fas antiserum, staining for Fas was found in the plasma membranes of spermatocytes in the maturation-arrested testes, while no positive spermatogenic cells were seen in the normal testes. On the other hand, positive immunostaining for Fas ligand was restricted to Sertoli cells in the maturation-arrested testes as well as in the normal testes, although the intensity of staining for Fas ligand in normal testicular Sertoli cells was much weaker than that of maturation-arrested ones. Thus, these findings demonstrate that "maturation arrest" is characterized by frequent apoptosis of spermatocytes, and that Fas and Fas ligand staining are associated with a high frequency of apoptosis.

Adult↗

PubMed2002

[Feasibility and change in the level of blood paclitaxel concentration after paclitaxel therapy for a hemodialysis patient with cisplatin resistant metastatic transitional cell cancer].

The patient was a 54-year-old woman with recurrent urinary tract cancer. A CT of the lung showed multiple nodules after bil-nephroureterectomy, cystectomy and combination chemotherapy with cisplatin (CDDP) and epirubicin (EPI). As second line chemotherapy for the patient, TXL was administered. She was hemodialized after operation, and there are few reports about paclitaxel (TXL) therapy for hemodialysis (HD) patients. Peak blood TXL concentration, about 1,200 ng/ml, was achieved 6 hours after the administration of TXL. The blood TXL concentration was 41 ng/ml 24 h after the administration of TXL. However, the TXL therapy was not repeated because of unacceptable neurological side effects. An almost 40% shrinkage in the size of the metastatic lung nodule was obtained after 1 cycle of treatment.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Restoration of gap junctional intercellular communication by dibutyryl-cAMP in renal epithelial cells treated with renal carcinogen.

Dimethylnitrosamine(DMN) is an alkylating agent and a known renal carcinogen. A short exposure of renal epithelial cells to cytotoxic concentrations of DMN influences the expression of gap junction proteins. In this study, we examined gap junctional intercellular communication and connexin 43 expression in renal epithelial cells treated with 1% DMN and also examined the effects of dibutyryl-cAMP on preventing gap junctional disturbances. Connexin 43 becomes hypophosphorylated after treatment with 1% DMN for 15 minutes, but this hypophosphorylation is inhibited by pretreatment with dibutyryl-cAMP. These results suggest that changes in gap junction protein expression are early events associated with 1% DMN treatment of renal epithelial cells, and such changes are prevented by dibutyryl-cAMP pretreatment.

Animals↗