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Biomedical subjects

S Ozono

Publications and source records attributed to S Ozono.

At least 109 records · Page 6Linked to original sources

[Experimental bladder tumor].

Experimental bladder tumor was reviewed in this paper. Many investigators have been studying on the bladder carcinogenesis since occupational bladder cancers were reported. Main object in research for bladder cancer was to identify and remove environmental causes and various factors related to the development of bladder cancer. Human bladder cancers can be classified into papillary non-invasive and nodular invasive cancer. The establishment of an animal model of bladder cancer similar to human bladder cancer is important to clarify the natural history of this disease and obtain basic data on its clinical diagnosis and treatment. Bladder carcinogenesis has been known to occur in a two-stage process: initiation and promotion. Recently inhibitory effects on the bladder carcinogenesis were also studied. In this paper we described the results that have been obtained in our laboratory concerning animal bladder carcinomas.

Animals↗

The molecular mechanism underlying pentylenetetrazole-induced bursting activity in Euhadra neurons: involvement of protein phosphorylation.

1. The involvement of protein phosphorylation in the pentylenetetrazole (PTZ)-induced bursting activity (BA) was evaluated in identified neurons of the snail. Euhadra peliomphala by examining the effect of various protein kinases and their inhibitors on the membrane properties induced by PTZ. 2. In neurons which normally exhibited spontaneous regular firing, PTZ elicited BA, the negative slope resistance (NSR) in the steady-state current (I)-voltage (V) relationship and a reduction of the delayed potassium current (IKD) in a dose-dependent manner. These were inhibited by the cAMP-dependent protein kinase inhibitors, protein kinase inhibitor isolated from rabbit muscle and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide. 3. Intracellular injection of catalytic subunit (CS) of cAMP-dependent protein kinase enhanced PTZ-induced NSR and reduction of IKD, as well as a conversion of the BA to a long-lasting depolarization of the membrane, whereas a saturating dose of the CS occluded PTZ action on the NSR and IKD. 4. Ca2+/calmodulin-dependent protein kinase II (CaMKII), when intracellularly injected during the depolarizing phase of PTZ-induced bursting cycle, changed to a prolonged hyperpolarization of the membrane. This kinase also restored the PTZ-suppressed IKD nearly to the pre-PTZ level. However, when intracellular injection of CaMKII and application of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin inhibitor, to the inside and outside of the neuron were simultaneously carried out, neither post-burst hyperpolarization nor restoration of the IKD was observed. 5. Intracellular injection of calmodulin, together with calcium chloride, had little effect on both the BA and reduction of IKD induced by PTZ. 6. Simultaneous application of 40 microM 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, which selectively suppressed the phosphatidylserine-dependent protein phosphorylation in extracts from Euhadra ganglia, to both the inside and outside of the neuron, did not produce any significant change in the membrane properties induced by PTX. Intracellular injection of protein kinase C also brought about no effect. 7. These findings suggest that PTZ stimulates cAMP-dependent protein phosphorylation which, in turn, is involved in the development of NSR and reduction of IKD, leading to the depolarization of the membrane. In addition, we propose that the Ca2+ ions, increased during the depolarizing phase of the BA cycle, form a Ca2+/calmodulin complex and subsequent protein phosphorylation, coupled with the opening of potassium channels, leading to the membrane hyperpolarization.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Chemotherapy of prostatic cancer].

CDDP combined chemotherapy was performed in 55 cases out of 229 prostatic cancer patients who were treated in Nara Medical University and Nara Prefectural Nara Hospital between January 1979 and August 1989. The previously untreated 33 patients received chemotherapy with anti-androgen treatment as an initial treatment, as well as 7 cases of unresponsive to antiandrogen treatment, 14 relapsing cases and one case with recurrence after total prostatectomy. The major regimens of chemotherapy were cis-diammine dichloroplatinum (CDDP) alone in 16 cases, PVB regimen (bleomycin or peplomycin + vincristine + CDDP) in 19 cases, and CAP regimen (cyclophosphamide + adriamycin + CDDP) in 16 cases. Complete response was not achieved or partial response was observed in 20 cases (34%), no change was seen in 20 cases (34%), and progression was seen in 19 cases (32%). Among each evaluable lesion, effects (CR + PR) were observed in 40% in the prostate, in 18% in the bone lesions, in 44% in the soft tissue lesions, and in 42% in the prostatic tumor marker. The 7-year survival rate of the chemotherapy group (35.6%) was better than that of the antiandrogen treatment group (26.6%) in stage D patients, but was not significant statistically When evaluated by the regimen, a partial response was observed in 56% of CDDP alone, in 21% of PVB regimen, and in 38% of the CAP regimen. However, there was no significant difference in survival rate among the regimens. As an adverse effect, myelosuppression and renal toxicity seemed to be dose limiting factors of CDDP combined chemotherapy for advanced prostatic cancer patients.

Aged↗

Renal cell carcinoma extending into the vena cava: a multi-institute study.

The present paper reports the clinical results from cases of renal cell carcinoma with vena caval tumor thrombus. Fifty patients were entered into the study between 1980 and 1989. The primary tumor and vena caval tumor thrombus were completely removed in 39 (78%) patients, and 41 (82%) received postoperative treatment. The overall 12-, 36-, 60- and 90-month actuarial survival rates were 72, 41, 19 and 10%, respectively. Only tumor stage affected survival, however, other factors such as tumor grade, nodal status, metastatic status and level of vena caval involvement not affecting it. Postoperative interferon (IFN) treatment affected survival, whereas degree of curative surgery did not. The results of our study were, however, examined retrospectively in several institutes. Further investigation of the postoperative treatment for renal cell carcinoma with vena caval tumor thrombus will be necessary.

Actuarial Analysis↗

Tumor thrombus and microvascular invasion as prognostic factors in renal cell carcinoma.

The significance of two types of vascular invasion (macroscopic tumor thrombus into the renal vein or vena cava inferior and microvascular invasion) as prognostic factors in renal cell carcinoma is analyzed in 121 patients treated at the Department of Urology, Nara Medical University. The data indicate there to be close correlations between tumor thrombus, microvascular invasion and distant metastasis. In patients with tumor thrombus, however, the prognosis is not as poor when surgical removal of the tumor thrombus is successfully performed as when it is not. In contrast, the prognosis of patients with positive microvascular invasion is significantly worse than that of those with a negative finding. Microvascular invasion appears to be a significant prognostic factor in renal cell carcinoma in addition to well-known factors such as tumor stage, tumor grade, tumor thrombus and distant metastasis. To detect microvascular invasion, the histological examination should be extended to give as much detail as possible.

Adult↗

[Current status of adjuvant chemotherapy of invasive bladder cancer].

The current status of adjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder is reported. Since 1986, a prospective randomized study has been conducted to examine the effects of neoadjuvant cyclophosphamide + doxorubicin + cisplatin (CAP) and radiation therapy for T2-3N0-3M0. A total of 47 patients were entered. However, 4 patients were excluded from the study. All eligible patients were randomized into two groups: neoadjuvant CAP plus radiation and control group. In the neoadjuvant treated-group, a 55% complete response plus partial response rate and a 88% downstaging were noted. Both the 12- and 36-month disease-free survival rates of neoadjuvant treated-group were 94.7%, and were higher than those of the control group (p less than 0.1). As for T4N0-3M0 cases, a total of 6 patients were treated with neoadjuvant methotrexate + vinblastine + doxorubicin + cisplatin (M-VAC) therapy. Favorable results were not obtained in this study at this point, because full dose M-VAC and planned recycling were not performed sufficiently. These findings suggests that neoadjuvant CAP plus radiation therapy would be useful for T2-3 invasive cancer of the bladder. Methods to administer full dose M-VAC; such as developments of new chemotherapeutic agents and of new anti-toxic agents, should be developed. In addition, a more successful regimen than M-VAC should be considered for T4 localized invasive bladder cancer.

Aged↗

[A case of retroperitoneal ganglioneuroma].

A 41-year-old female patient with a right retroperitoneal tumor for more than thirty years was referred to our department. Exploration was done through a transperitoneal approach and the tumor was removed. A ganglioneuroma was diagnosed histopathologically. There have been 99 reported cases with retroperitoneal ganglioneuroma including our present case in Japan and we discuss the pathogenesis and treatment of this rare disease.

Adult↗

[A case of retroperitoneal pleomorphic lipoma].

A 71-year-old male patient was referred to our department for further examination for right retroperitoneal tumor. Exploration was done through a flank approach and the tumor with right adrenal gland was removed. A pleomorphic lipoma was diagnosed histopathologically. There have been 8 reported cases of pleomorphic lipoma including our present case in Japan and we discuss the pathogenesis and treatment of this rare disease.

Aged↗

[A case of squamous cell carcinoma of the urinary bladder associated with bladder calculi].

A case of squamous cell carcinoma of the urinary bladder associated with a bladder stone in a 43-year-old man is reported. Because a 1 cm x 1 cm sized mass was found in the right lateral side of the dome at the time of vesicolithotomy, partial cystectomy was performed. The weight of the stone was 285 g and the tumor was histologically diagnosed as squamous cell carcinoma, grade 2, pT2. Radical cystectomy with ileal conduit was sandwiched by a total of 6 cycles of chemotherapy with PVB. Twelve cases of squamous cell carcinoma of the urinary bladder associated with a bladder stone(s) from the Japanese literature are reviewed, and the relationship between bladder stone, leukoplakia and squamous cell carcinoma discussed.

Adult↗

The 70-kDa epileptic cortical protein elicits bursting activity accompanied by a reduction of outward current in Euhadra neurons which is inhibited by an antibody against this protein.

The effect on membrane properties of 70-kDa protein (namely P70), a specific protein found in cobalt-induced epileptic cortex of rats, was examined electrophysiologically in identified neurons of the snail, Euhadra peliomphala. Injection of P70 into the neurons elicited a bursting activity resembling the paroxysmal depolarization shift seen in mammalian epileptic neurons and a reduction of the outward current, which were suppressed by Ca2(+)-free saline or tetraethylammonium. The injection of P70-antibody into neurons, preceding the P70 injection, markedly inhibited the bursting activity and the reduced outward current elicited by P70. These findings suggest that P70 causes a reduction of Ca2(+)-dependent potassium conductance which may be one of the mechanisms generating epileptic bursting activity.

Animals↗

A specific 70 kDa protein induced in the epileptogenic cortex of rats elicits bursting activity and inactivation of potassium current in snail neurons.

The capability of a specific 70 kDa (P70) protein produced in cobalt-induced epileptogenic cortex of rat cerebrum in promoting epileptic bursting activity was examined in snail neurons, using the voltage clamp method in combination with the pressure injection technique. Injection of P70 into the neurons elicited bursting activity with paroxysmal depolarization shift together with a reduction in the delayed outward current which was suppressed by tetraethylammonium. These changes of membrane properties induced by P70 were dose-dependently inhibited by prior treatment with the anticonvulsant phenytoin. These findings indicate that P70 causes an inactivation of potassium conductance which may generate epileptic bursting activity.

Animals↗

Rat urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and N-methyl-N-nitrosourea.

The present investigation was conducted to examine the combination effect of N-butyl-N-(4-hydroxy-butyl)nitrosamine(BBN) and N-methyl-N-nitrosourea(MNU) in rat urinary bladder carcinogenesis. Experiment 1 was performed in the groups treated by oral BBN administration in combination with MNU intravesical instillation and their control groups. In the groups given both BBN and MNU, the ratio of rats with the nonpapillary type to carcinoma-bearing rats was significantly higher than in the controls. Since most of the carcinomas were non-invasive, the observation period was prolonged in the groups given both BBN and MNU in experiment 2. However, even after a longer observation period, no invasive carcinoma was observed. These results suggest that high-grade and invasive carcinomas similar to those induced by BBN and MNU in the heterotopically transplanted rat bladder cannot be induced in the natural bladder of the rat.

Animals↗

Effects of bestatin on the host immunity in patients treated for urogenital cancer.

To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity ('invasive treatment') while the other one received other types of basic treatment ('non-invasive treatment'). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the 'invasive' treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the 'non-invasive' group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn.

Adjuvants, Immunologic↗

Production of monoclonal antibody against human prostatic adenocarcinoma and its immunohistochemical properties.

We have generated a monoclonal antibody against prostatic adenocarcinoma, PC-Ab (IgM) was derived from a fusion using the fresh prostatic tissue of adenocarcinoma as the immunogen. Initial screening was performed by enzyme-linked immunosorbent assay (ELISA) on the soluble fraction of the immunogen. The specific analysis was performed by the avidin-biotin-complex immunoperoxidase method on paraffin-embedded sections of normal, benign and malignant neoplastic tissues from the prostate and various organs. PC-Ab reacted with well differentiated adenocarcinoma (83.3%), moderately differentiated adenocarcinoma (92.2%), and poorly differentiated adenocarcinoma (90.2%), respectively. According to classification by stage, the reaction rates with stage T0, T1, T2, T3 and T4 were 77.3%, 80.0%, 95.2%, 91.3% and 92.9%, respectively but no significant differences in the stages were seen among these groups. PC-Ab reacted with the epithelium of the normal prostate and benign prostatic adenoma, and human fetal tissues. Molecular weight and isoelectric point of the antigen recognized by this PC-Ab was estimated to be 57,000 daltons and 7.0, respectively. These results indicate that PC-Ab reacts with the antigen associated with human prostatic adenocarcinoma.

Adenocarcinoma↗

[Diagnostic evaluation of plasma free gamma-carboxyglutamic acid in maintenance hemodialytic patients with renal osteodystrophy].

The levels of serum Bone Gla Protein (BGP) and plasma free gamma-carboxyglutamic acid (free gamma-Gla) were measured in 36 patients on maintenance hemodialysis and compared with conventional parameters of renal osteodystrophy (ROD), such as C-PTH, intact PTH, Al-PIII and hydroxyproline levels in serum, and sigma GS/D. Even though the values of BGP were significantly elevated in patients group, 64.5 +/- 1.74 ng/ml, but the low values within normal range could be found in 3 of 36 patients, also. On the other hand, plasma levels of free gamma-Gla were markedly elevated in all cases as high as 10.40 +/- 3.10 nmol/ml in average compared to 1.29 +/- 0.37 nmol/ml (n = 15) in healthy controls. Comparative analysis of BGP with other parameters showed exclusively significant correlation as follows, C-PTH: r = 0.833 (p less than 0.01), intact PTH: r = 0.702 (p less than 0.01), Al-PIII: r = 0.771 (p less than 0.01), hydroxyproline: r = 0.462 (p less than 0.01), sigma GS/D: r = -0.407 (p less than 0.05). Respective for its higher levels, comparative analysis of plasma levels of free gamma-Gla with other parameters failed to show a significant correlation except for correlation with C-PTH (r = 0.459, p less than 0.01). Based upon these results, we could confirm a marked elevation in plasma levels of free gamma-Gla in all patients, but couldn't point out its clinical value in ROD in this study.

1-Carboxyglutamic Acid↗

[A case of metastatic renal tumor: review of 74 cases reported in Japan].

A 76-year-old man, who had undergone surgery for lung cancer, was referred to our department for further examination for left renal mass. Exploration was done through a transperitoneal approach and the left kidney was removed. A metastatic renal tumor originating from a pulmonary squamous cell carcinoma was diagnosed histologically. There have been 73 reported cases with metastatic renal tumor in Japanese literature and we reviewed the pathogenesis and treatment of this rare entity.

Aged↗

[The diagnostic critical value in DFO low dose loading test on patient with aluminum accumulation compared to each parameter of ROD].

One hundred two hemodialyzed patients were examined to determine the standard level of delta Al value which is the difference of serum Al concentrations between pre and post DFO loading test. We applied low dose of DFO 15 mg/kg in this loading test. Some significant negative correlations were found between delta Al and MCI, sigma GS/D, osteocalcin, free-Hydroxyproline (dialysate) and free-gamma-Carboxyglutamic acid (dialysate). Each correlation rate was -0.58, -0.44, -0.76, -0.57 and -0.51 respectively. In addition tendencies of correlation were found between delta Al and ALP and between delta Al and %QCT (QCT/mean QCT in patient's age x 100). And statistical significant differences were found between (0 less than delta Al less than or equal to 150 micrograms/l) group and (150 micrograms/l less than delta Al) group in each osteobiochemical parameter. These results indicate that 150 micrograms/l is the lower diagnostic standard level of delta Al in 15 mg/kg DFO loading test.

Adolescent↗

[Effect of pulse therapy using 1 alpha(OH)D on secondary hyperparathyroidism in patients on maintenance hemodialysis].

The effect of pulse therapy on severe secondary hyperparathyroidism related to chronic renal failure has been examined in 11 patients on maintenance hemodialysis by using an oral administration of 8 micrograms of 1 alpha(OH)D maximum per week. Throughout the 10 months of this treatment, the serum levels of intact-PTH, HS-PTH, and C-PTH were followed up. Additionally, to estimate the peak level of 1,25(OH)2D, its serum concentration at 10 hours after the 1 alpha (OH)D ingestion was measured. Results have shown that the serum levels of the intact-PTH, HS-PTH, and C-PTH were lowered in 9 of these 11 patients, two of this number especially showing a marked suppression of the serum intact-PTH to a low that was near to the normal upper limit level. In the two other cases of these 11 patients, no suppression was seen in any of serum PTH levels throughout the 10 months. In the cases that showed a good response, the 1,25(OH)2D serum concentration elevated significantly, to more than 100 pg/ml at 10 hours after the 1 alpha (OH)D intake. In contrast, in the 2 cases that showed no response, no appreciable elevation in the serum concentrations was noted. Thus, since the pulse therapy using 1 alpha (OH)D decreased the serum levels of the intact-PTH, HS-PTH, and C-PTH in 9 out of the 11 cases, we have concluded that pulse therapy using 1 alpha(OH)D is a valid therapy for secondary hyperparathyroidism in patients on maintenance hemodialysis.

25-Hydroxyvitamin D 2↗