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Biomedical subjects

Y Katsuoka

Publications and source records attributed to Y Katsuoka.

At least 19 recordsLinked to original sources

The mechanism of hypoglycemia caused by hemodialysis.

BACKGROUND: Although it is well-known that plasma glucose concentration ((G)p) decreases during hemodialysis, the precise mechanism underlying this decrease has not yet been fully elucidated. The aim of the present study was to investigate the mechanism underlying hemodialysis-induced decrease (HID) in (G)p during the dialysis in vivo or in vitro. METHODS: Using high CO2/ HCO3- dialysate, we measured (G)p by a hexose kinase method ((G)pHK) and concentrations of electrolytes, as well as pH, PCO2 and PO2 for both plasma and dialysate samples at pre- and postdialyzer sites obtained from hemodialysis patients with nondiabetic chronic renal failure (CRF). Furthermore, we studied the effect of PCO2 and acetazolamide (ACZ) on the changes in (G)pHK during the dialysis in vitro. RESULTS: After the first dialysis of CRF patients, the (G)pHK decreased from 118.3 +/- 18.0 to 98.6 +/- 5.7 mg/dl (p < 0.05), the latter value being significantly lower than glucose concentration in dialysate samples (approximately 105 mg/dl) at predialyzer sites. In the experiments of blood samples from healthy volunteers, (G)pHK decreased significantly after elevating or lowering CO2 level in the dialysates. In contrast, when the difference in PCO2 between the blood and dialysate was reduced, the HID in (G)pHK was abolished during hemodialysis. The addition of 10(-4) M ACZ to the blood samples completely prevented the development of HID in (G)pHK caused by the perfusion of high or low CO2/HCO3- dialysates. CONCLUSIONS: During hemodialysis using high CO2/HCO3- dialysate, the HID in (G)p results from the diffusion of glucose from plasma into erythrocytes, probably due to the consumption of glucose resulting from the accelerated anaerobic metabolism induced by the changes in the cytoplasmic pH of erythrocytes.

Acetazolamide↗

Transfection of NFkappaB-decoy oligodeoxynucleotides using efficient ultrasound-mediated gene transfer into donor kidneys prolonged survival of rat renal allografts.

Nuclear factor kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of a series of genes of cytokines and adhesion molecules that are highly involved in the onset of acute rejection in organ transplantation. We previously developed decoy cis-elements oligo deoxyribonucleic acid against NFkappaB (NFkappaB-decoy) that effectively inhibited the activation of major inflammatory mediators in vitro and in vivo. Accordingly, we hypothesized that transfection of NFkappaB-decoy into the donor kidney would prevent acute rejection and prolong graft survival, and thus provide effective therapy for renal acute rejection. To transfect NFkappaB-decoy, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison, and clearly demonstrated successful transfection of NFkappaB-decoy into renal tissue. The therapeutic effect of NFkappaB-decoy on renal allografts was then evaluated in a rat renal allograft model (Wistar-Lewis). In the control group, graft function significantly deteriorated with marked destruction of renal tissue, accompanied by increased production of major inflammatory mediators, and all animals died of renal failure by 9 days. In contrast, graft function (serum creatinine on day 2, NFkappaB-treated: 0.97+/-0.16 versus control: 1.84+/-0.23 mg/dl, P<0.01) and histological structure were well preserved with significantly decreased expression of NFkappaB-regulated cytokines and adhesion molecules, including IL-1, iNOS, MCP-1, TNF-alpha, and ICAM-1, in allografts transfected with NFkappaB-decoy. As a result, animal survival was significantly prolonged in this group as compared to controls (14.2+/-5.2 versus 7.1+/-1.2 days, P<0.01). Thus, we established a novel ultrasound-Optison-mediated gene transfection approach and demonstrated the significant prolongation of graft survival by the successful transfection of NFkappaB-decoy into the donor kidney in a rat renal allograft model.

Albumins↗

The effect of sildenafil on electrostimulation-induced erection in the rat model.

This study was conducted to show the effect of sildenafil on electrostimulation-induced erection in the rat model. Fifteen 12-week-old male Wistar Kyoto rats were used. The intracavernous pressure and arterial blood pressure were simultaneously monitored through electric cavernous nerve stimulation before and after the administration of sildenafil (2 mg/kg). Statistical analysis was performed on maximal intracavernous pressure (MIP), mean arterial blood pressure (MAP), the MIP/MAP and detumescence time. MAP decreased significantly by about 20 mmHg after sildenafil administration. The MIP/MAP increased significantly after sildenafil administration. The effect of sildenafil on the MIP/MAP was marked especially at lower (2-3 Hz) frequencies. The detumescence time significantly increased after sildenafil administration. We have shown that sildenafil is effective for enhancing erection at lower frequencies and prolonging penile erection in rats. After the administration of sildenafil, penile erection would be induced by weak stimuli that will not cause penile erection under normal conditions.

Animals↗

Expression of three extracellular matrix degradative enzymes in bladder cancer.

The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase-2, -9 and heparanase) and microvessel formation were examined in 40 resected bladder cancer specimens by immunohistostochemic staining, and then the association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular invasive or lymph-node metastatic cancer was significantly higher than in superficial or nonmetastatic cancer, respectively (69% vs. 8%, p < 0.001, and 80% vs. 40%, p = 0.028, respectively). Interestingly, heparanase was expressed at much higher levels than matrix metalloproteinase-2 and -9. The mean microvessel count in cancers with heparanase expression was significantly higher than that in cancers without heparanase expression (32.3 +/- 18.2 vs. 5.5 +/- 6.1, p = 0.0008). The microvessel formation was not associated with the expression of matrix metalloproteinase-2 and -9. The cancer-specific and overall survival rates of patients with heparanase expression were significantly lower than those of patients without it (p = 0.0001 and p = 0.0008, respectively). Multivariate analysis showed that heparanase expression was a significantly independent prognostic factor for both cancer-specific (p = 0.0047) and overall survival (p = 0.0200). Our study suggested that heparanase plays important roles in invasion, angiogenesis and metastasis of bladder cancer, and thus, this molecule could be a new molecule to inhibit invasion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease.

Adult↗

Phosphorylation of mitogen-activated protein kinase is inhibited by calcitonin in DU145 prostate cancer cells.

One of the causes of insensitivity to androgen ablation therapy in prostate cancer is thought to be attributable to elevated neuropeptides secreted by neuroendocrine cells in the tumor mass. Calcitonin (CT), one of these neuropeptides, is reported to be associated with the growth of prostate cancer. There is an increase in mitogen-activated protein (MAP) kinase activation as prostate cancer progresses to a more advanced and androgen-independent disease. We examined the effect of CT on signal transduction and the relation between CT and early-response genes in the human androgen-insensitive prostate cancer cell line, DU145. The basal phosphorylation level of extracellular signal-regulated kinase 1/2, which is a key kinase in the mediation of growth factor-induced mitogenesis in prostate cancer cells, was constitutively up-regulated. N-[2-(4-bromocinnamyl) aminoethyl]-5-isoquinoline-sulfonamide (H89), a specific inhibitor of protein kinase A, potentiated the effects of more increased phosphorylation of extracellular signal-regulated kinase 1/2. CT induced the inhibition of this MAP kinase phosphorylation, and this effect was completely abolished by pretreatment with H89. Our findings demonstrate that CT caused the inhibition of constitutive MAP kinase phosphorylation in a protein kinase A-dependent manner in DU145. The transient increase of c-fos expression was detected after CT treatment, whereas expression of c-jun RNA was down-regulated after CT treatment. These results suggest that CT may regulate early-response genes, c-fos and c-jun, via a MAP kinase cascade. In conclusion, these findings suggest that DU145 might be a useful model as a therapeutic approach of neuropeptides in androgen-independent prostatic carcinoma.

Calcitonin↗

Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer.

Androgen, acting via the androgen receptor (AR), is associated with the development and progression of prostate cancer. Anti-androgen therapy is widely used to manage prostate cancer. However, the conversion of the tumor from a hormone-sensitive to a hormone-insensitive status causes such therapy to fail. Several mechanisms have now been put forward for this conversion, including neuroendocrine (NE) differentiation of the tumor cells. In this study, we evaluated the prognostic significance of tumor-cell proliferation activity, NE differentiation and AR expression. Formalin-fixed, paraffin-embedded sections were prepared from 42 patients with adenocarcinoma of the prostate. Using antibodies to AR, the Ki-67 antigen (MIB-1), chromogranin A and synaptophysin, immunohistochemical expression of AR, tumor proliferation activity and NE differentiation were analyzed. Our study revealed that AR expression was significantly lower in adenocarcinoma (52.2 +/- 27.1%) than in non-tumorous prostate tissue (68.3 +/- 18.3%; P < 0.001). NE differentiation was found in 50% of the tumors, which was correlated with the Gleason score (P < 0.05). An univariate analysis revealed a significant correlation between progression-free survival with both AR expression (P < 0.01) and proliferation activity (P < 0.001). NE differentiation was not a prognostic factor in this study.

Adenocarcinoma↗

Metastases to the penis from carcinoma of the prostate.

A 58-year-old man presented with dysuria at the Osaka Medical College Hospital in November 1996. Laboratory examination revealed elevated serum prostate-specific antigen (PSA) to > 100 ng/mL. Adenocarcinoma of the prostate with metastasis to the bone was diagnosed after a biopsy of the prostate and bone scintigraphy; hormonal therapy was administered. Although bone metastasis was well controlled and the serum PSA level declined to within normal levels (2.0 ng/mL), several painless nodules were found on the penile glans. Biopsy of the nodules showed that the penile tumor was a metastasis from the prostate cancer. The patient underwent partial penectomy for relief from penile pain. The serum PSA level showed no elevation 3 months after the partial penectomy, suggesting that careful observation of prostate cancer patients is necessary, even when oseous metastasis is well controlled and serum PSA levels are kept within normal ranges by hormonal therapy. The case also indicates that urologists should consider the possibility of metastasis to the penis from prostate cancer.

Adenocarcinoma↗

Embryonal carcinoma of the testis associated with prostate cancer in a 72-year-old man.

A 72-year-old Japanese man presented with a painless swollen left scrotal mass with elevated levels of serum alpha-fetoprotein and prostate specific antigen. The patient underwent high orchiectomy under diagnosis and a final pathological examination revealed embryonal carcinoma of the left testis. A systematic needle prostate biopsy under guidance of transrectal ultrasound revealed prostate cancer (Gleason score, 8) on the left lobe (T2aN0M0). Systemic chemotherapy was given for retroperitoneal lymph node metastasis of testicular cancer and hormonal therapy (LH-RH analog) was given for prostate cancer. The patient was well with no evidence of metastasis from the testicular cancer or prostate cancer and with no elevation of serum alpha-fetoprotein or prostate specific antigen 26 months after the orchiectomy.

Aged↗

Expression of endothelin receptor a associated with prostate cancer progression.

PURPOSE: We determined the role of endothelin receptors in prostate cancer progression. MATERIALS AND METHODS: We examined 51 prostate cancer specimens obtained at surgery or biopsy for the relationship of endothelin receptor expression determined by immunohistochemical staining with malignant potential. RESULTS: The positive staining rate of endothelin receptor A in the 51 specimens was significantly higher than of endothelin B (71% versus 24%, p <0.0001). The staining rate of receptor A in Gleason score 5 to 10 disease was significantly higher than in Gleason 2 to 4 disease (91% versus 29%, p <0.0001). The overall staining rate of endothelin receptor A in nonorgan confined disease without bone metastasis but with extraprostatic disease was 87% in 23 cases, including 16 of 19 stage T3 (84%) and all 4 stage T4 (100%) cases. This rate was significantly higher than that of organ confined cancer (29%, p = 0.0003). All patients with bone metastasis had positive staining for endothelin receptor A. An especially high rate of intensely positive staining was observed for endothelin receptor A in biopsy specimens with bone metastasis or Gleason sum 8 to 10. Moreover, positive staining was stronger in cancer cells penetrating the prostatic capsule than in those at the primary foci. However, the positive staining rate of endothelin receptor B was not significantly different in organ and nonorgan confined cancer without bone metastasis (12% versus 26%, p = 0.4284), bone metastatic and nonmetastatic cancer (20% versus 36%, p = 0.2619) or the Gleason sum groups (p = 0.0874). CONCLUSIONS: Our results indicate that endothelin receptor A expression may serve as a marker for and have an important role in prostate cancer progression.

Aged↗

Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.

Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 +/- 1.7 mU/mg of protein, mean +/- S.E.M., n = 8) and chymase-like enzyme (4.0 +/- 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 x 10(-7) M) induced a tension of 0.17 +/- 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10(-6) M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10(-4) M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and 125I-[Sar1, Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10(-6) M), markedly displaced 125I-[Sar1, Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.

Angiotensin I↗

[Von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis: a case report].

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.

Adult↗

Heparanase protein and gene expression in bladder cancer.

PURPOSE: We determined the association of heparanase protein and messenger (m)RNA expression with bladder cancer invasion and metastasis. MATERIALS AND METHODS: The expression of heparanase protein and mRNA was assessed by immunohistochemical staining and in situ hybridization, respectively, in 67 bladder cancer specimens resected at various stages of disease. To our knowledge this is the first systematic study of heparanase protein and mRNA expression in human bladder cancer. RESULTS: The expression of heparanase protein in muscular invasive bladder cancer was significantly higher than in superficial cancer (68% versus 19%, p = 0.0001). It was higher in the primary tumor of patients with lymph node metastatic cancer than those with nonmetastatic cancer (80% versus 37%, p = 0.0006). In high grade disease it was significantly higher than in low grade disease (79% versus 29%, p = 0.0001). The expression of heparanase mRNA was also significantly higher in stage pT3 or greater than in stage pT2 or less bladder cancer (96% versus 33%, p = 0.0003). In metastatic N+ cases it was significantly higher than in nonmetastatic bladder cancer (93% versus 46%, p = 0.0037). The heparanase gene and protein showed similar patterns of expression in bladder cancer. CONCLUSIONS: Our study implies that the expression of heparanase protein and mRNA is associated with bladder cancer invasion and metastasis, and heparanase may have a role in disease progression.

Adult↗

Disinfection potential of electrolyzed solutions containing sodium chloride at low concentrations.

Electrolyzed products of sodium chloride solution were examined for their disinfection potential against hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in vitro. Electrolysis of 0.05% NaCl in tap water was carried out for 45 min at room temperature using a 3 A electric current in separate wells installed with positive and negative electrodes. The electrolyzed products were obtained from the positive well. The oxidation reduction potential (ORP), pH and free chlorine content of the product were 1053 mV, pH 2.34 and 4.20 ppm, respectively. The products modified the antigenicity of the surface protein of HBV as well as the infectivity of HIV in time- and concentration-dependent manner. Although the inactivating potential was decreased by the addition of contaminating protein, recycling of the product or continuous addition of fresh product may restore the complete disinfection against bloodborne pathogens.

Acids↗

Ruptured cerebral aneurysm not detected by magnetic resonance angiography in juvenile autosomal dominant polycystic kidney.

Recently, it has been reported that magnetic resonance angiography (MRA) is useful for screening and following up cerebral aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD). However, a patient was encountered with a ruptured cerebral aneurysm that was not detected by routine MRA. The patient, a 29-year-old man with ADPKD, was followed up at our hospital for more than 5 years. Ten months after an MRA examination, he suddenly developed severe headache. Brain computed tomography revealed subarachnoid hemorrhage. Digital subtraction angiography detected an aneurysm with a diameter of approximately 2 mm in the anterior communicating artery. Clipping of the aneurysm was immediately performed and he recovered without sequela after operation. Magnetic resonance angiography is useful to detect cerebral aneurysms, but it can not detect aneurysms measuring less than 4 mm.

Adult↗

Effect of a novel immunosuppressant, FTY720, on allograft survival after renal transplant in rats.

FTY720 was developed by chemical modification of ISP-1 which was purified from culture filtrates of an ascomycete, Isaria sinclairii. We evaluated the effect of FTY720 on allograft survival using a rat renal transplantation model in which Wistar King Aptekman Hokkaido rats (WKAH, RT1(K)) served as the organ donor and Lewis rats (LEW, RT1(l)) as the recipient. WKAH renal allografts were acutely rejected by the untreated LEW recipients at a mean graft survival +/- SD of 7.2 +/- 0.4 days (n = 5). Consecutive oral administration of FTY720 following transplantation significantly prolonged allograft survival in a dose-dependent manner over the range of 0. 05-3 mg/kg/day. The mean allograft survival of the recipients treated with FTY720 at a doses of 0.05, 0.1, 0.5, 1, and 3 mg/kg/day was 12.2 +/- 3.3 (n = 5, p < 0.05, vs. untreated host), 11.2 +/- 2.4 (n = 5, p < 0.05, vs. untreated host), 13.6 +/- 0.9 (n = 5, p < 0.01, vs. untreated host), 14.6 +/- 1.7 (n = 5, p < 0.01, vs. untreated host) and 20.2 +/- 0.8 days (n = 5, p < 0.01, vs. untreated host). In the recipients treated with FTY720 (3 mg/kg/day), the number of peripheral blood lymphocytes significantly decreased. From the results of the flow cytometric study, FTY720 significantly diminished the percentage of interleukin-2 receptor (IL-2R)-positive cells in the allografts (6.34 +/- 0.81% in the untreated recipients vs. 3.10 +/- 0.86% in the recipients treated with FTY720, p < 0.05). As to the CD4/CD8 ratio of splenic cells and graft infiltrate, there was no significant difference between the untreated hosts and the recipients treated with FTY720. In conclusion, FTY720 significantly extended rat renal allograft survival and the immunosuppressive effects of FTY720 may be due to a reduction in not only the number of peripheral lymphocytes but also the percentage of IL-2R-positive cells in the allografts.

Animals↗

Independent prognostic value of serum hepatocyte growth factor in bladder cancer.

PURPOSE: We retrospectively investigated whether the level of serum hepatocyte growth factor could predict the prognosis and extent of transitional-cell carcinoma of the urinary bladder. PATIENTS AND METHODS: Serum samples were collected from 113 patients with bladder cancer and from 200 healthy controls. Of the 113 patients, 59 had superficial bladder cancer and 54 had muscle-invasive cancer. Thirteen bladder cancer tissues (eight superficial and five muscle-invasive) were also collected. The levels of hepatocyte growth factor in the serum and tissues of these individuals were measured by enzyme-linked immunoadsorbent assay using hepatocyte growth factor antibodies. RESULTS: The levels of hepatocyte growth factor in the serum and tissues of patients with muscle-invasive cancer were significantly higher than those of patients with superficial bladder cancer (P <.0001 and P =.0054, respectively). The degree of elevation above the normal level of serum hepatocyte growth factor of the former (61.1%) was significantly higher than that of the latter (8.4%; P <.0001). The elevation was highest in patients with visceral metastasis (93.3%). Among patients with superficial bladder cancer, the overall survival rate of those with low levels of serum hepatocyte growth factor was significantly greater than that of those with high levels (P =.005). Among patients with minimally invasive bladder cancer, the disease-free and overall survival rates of those with high levels of serum hepatocyte growth factor were significantly lower than the same rates of those with low levels (P <.001 and P =.0028, respectively). CONCLUSION: Our study suggests that the level of hepatocyte growth factor in serum could be a predictor of patient survival and extent of bladder cancer.

Aged↗

[A case of xanthogranulomatous pyelonephritis presenting with the flank subcutaneous mass].

A 51-year-old female exhibited fever, left flank pain and left flank mass in March, 1993. Drip infusion pyelography (DIP) revealed a non-functioning left kidney with shadows of calculi, and abdominal computerized tomography (CT) showed renal calculi and multilocular cystic lesions in the left kidney extending through the perinephric space into the mass on the left flank. Percutaneous nephrostomy and percutaneous drainage were performed, followed by left nephrectomy. Histopathological findings revealed xanthogranulomatous pyelonephritis. There have been a few case reports of xanthogranulomatous pyelonephritis forming nephrocutaneous fistula in the back.

Cutaneous Fistula↗