Biomedical subjects

N Nishisaka

Publications and source records attributed to N Nishisaka.

At least 19 recordsLinked to original sources

PubMed2001

Microscopic hematuria as a screening marker for urinary tract malignancies.

BACKGROUND: Although a mass screening urinalysis is a widely accepted procedure, it has not yet been shown if microhematuria is an appropriate and useful screening marker for urologic malignancies. METHODS: (1) The incidence of hematuria was studied in 113 patients with renal cell carcinoma (RCC), 185 with bladder carcinoma and 51 with renal pelvic or ureteral carcinoma. The association of the T stage with the intensity of hematuria in each malignancy was also examined. (2) In 823 asymptomatic adults with microhematuria, the prevalence of these malignancies was studied retrospectively to find the positive predictive value (PPV). RESULTS: (1) The incidence of hematuria was 35% for RCC, including gross and microhematuria. Advanced RCC (T3 and T4) were diagnosed more frequently in the gross hematuria group than in the microhematuria and no hematuria groups. In contrast, the incidence of hematuria was 94% for urothelial carcinomas either in the upper urinary tract or in the bladder. There was no significant difference in the T stage nor grade between the gross hematuria group and the microhematuria group. (2) Regarding asymptomatic microhematuria, the PPV was 1.7% (14 cases) for bladder carcinoma, 0.4% (3 cases) for ureteral/renal pelvic carcinoma and 0.2% (2 cases) for RCC. In men aged 50 years or older, PPV was 6.2% for urothelial carcinomas. In 14 cases of bladder carcinoma, 3 cases showed muscle invasion. CONCLUSIONS: Microhematuria is an appropriate screening marker for urothelial carcinomas, particularly in elderly men, but not for RCC. However, it is unlikely that a mass screening urinalysis using a single voided urine sample would contribute to earlier detection of bladder carcinoma.

Adult↗

PubMed2001

Primary retroperitoneal pure yolk-sac tumor in an adult male.

Pure extragonadal tumors are rare in adult males. A 24-year-old male with an extremely high level of serum alpha-fetoprotein (32.795 ng/ml) was diagnosed by abdominal computed tomography as having a retroperitoneal tumor. A case of primary retroperitoneal pure yolk-sac tumor in an adult male is described.

Adult↗

PubMed2001

[Experience with partial nephrectomy for renal cell carcinoma].

From Sept. 1991 to Jan. 1999, we performed partial nephrectomy on 7 patients with renal cell carcinoma. The indication was imperative for 3 patients, and elective for 4 patients. The 3 imperative cases consisted of bilateral renal cell carcinomas, a polycystic kidney disease and a contralateral atrophic kidney. All 4 patients with elective indication revealed renal cell carcinoma with a normal functioning contralateral kidney. The tumor size ranged from 1.3 cm to 6.0 cm (2.7 cm on average). The mean clamping time of renal artery was 22 minutes and mean blood loss was 400 ml. The pathological stage was pT1a in 6 patients and pT1b in one patient. Postoperative follow-up ranged from 4 months to 92 months (mean: 43 months). One patient with bilateral renal cell carcinoma died of metastases to the lungs and brain at 25 months postoperatively. The remaining 6 patients are alive without recurrence and metastasis. We obtained a good postoperative course in our selected patients with low stage. Thus it was considered that partial nephrectomy is effective against small renal cell carcinoma.

Adult↗

PubMed2001

[Effects of cernitin pollen-extract (Cernilton) on inflammatory cytokines in sex-hormone-induced nonbacterial prostatitis rats].

Cernitin pollen-extract (Cernilton, CN) is a preparation made from eight kinds of pollen and has been used for various prostatic diseases in Japan and Europe. We reported previously that CN possessed a recovery action on the sex-hormone-induced nonbacterial prostatitis in rats. To clarify the possible mechanism of action of CN, we investigated the effects of CN on inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the same model. Aged Wistar rats were castrated and injected 17 beta-estradiol (0.25 mg/kg/day, s.c.) for 30 days. CN (630 and 1,260 mg/kg, p.o.) or testosterone (2.5 mg/kg, s.c.) was administered for the last 14 days of the treatment of 17 beta-estradiol. In control rats, prostatic IL-6 and TNF-alpha contents were increased approximately 2-3 fold, and acinar glandular inflammation and stromal proliferation were found histopathologically, as compared with those of intact rats. On the other hand, CN decreased the increased contents of cytokines in a dose-dependent manner. The histopathological changes mentioned above were restored in rats treated with 1,260 mg/kg. Testosterone also ameliorated them significantly. These results indicate that CN has an anti-inflammatory action, and that the inhibitory effect of CN on the prostatic inflammatory cytokine is an important factor in its action.

Animals↗

PubMed2000

Clinical trials of immunotherapy for advanced prostate cancer.

There is a lack of effective therapeutic regimens for advanced hormone-refractory prostate cancer (HRPC). Recent combination regimens of chemotherapy have improved management of HRPC. Neither systemic chemotherapy nor radiation regimens have significantly improved survival. Conventional systemic cytokine therapy has had limited efficacy in the treatment of advanced prostate cancer patients and its toxicity is severe. Combinations of multiple biological response modifiers for treatment of this disease also have limited efficacy. Results from phase II trials have shown that the combination of interferon-alpha and interleukin-2 therapy and the infusion of dendritic cells primed with peptides of prostate specific membrane antigen are promising. The former showed 31% response using the National Prostatic Cancer Project criteria, and the latter showed 27% of objective partial response with a reduction of >50% prostate specific antigen level. The toxicity of these two regimens was tolerated by patients. New approaches with tumor vaccines in conjunction with cytokine gene therapy have also been investigated. The clinical responses of these trials have been limited but promising. Immunotherapy may become an effective modality of prostate cancer treatment in the future.

Journal Article↗

PubMed2000

Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine.

We have previously demonstrated in a murine lung metastasis model that local sublethal radiation of tumors can synergistically enhance their sensitivity to immunotherapy with either systemic high-dose interleukin-2 (IL-2) or vaccination with autologous tumor cells expressing IL-2, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF). Host antitumor activity was mediated in large part by natural killer cells, which can be activated by IFN-alpha. In the present study, we used this lung metastasis model to investigate the efficacy of combined therapy with local tumor radiation and vaccination with IFN-alpha-secreting tumor cells (Renca/IFN-alpha). The in vitro and in vivo growth rates of Renca/IFN-alpha cells were significantly reduced relative to normal controls. Subcutaneous vaccination with Renca/IFN-alpha or selective X-irradiation of the left lung (300 rad) reduced the number of lung tumors by 40% and 27%, respectively. The combination of lung irradiation plus vaccination reduced the number of lung metastases by 60%, and the net tumor volume by 95%. The reductions in tumor volume in both irradiated and non-irradiated lungs were comparable. These results indicate that host antitumor response to subcutaneous vaccination with Renca/IFN-alpha was systemic, and was significantly enhanced by radiation of tumor-bearing lungs. A regimen based on enhancement of IFN-alpha immunotherapy by local tumor radiation may be useful in the treatment of metastatic renal cell carcinoma.

Animals↗

PubMed2000

Extracorporeal shock wave lithotripsy for upper urinary tract stones using the Dornier Lithotripter Compact: an experience in Japan.

Between May 1997 and February 1998, 40 cases of renal stones and 40 cases of ureteral stones in 60 males and 20 females were treated with the Dornier Lithotripter Compact. The size of the stones ranged from 5 mm to 80 mm. Three patients required epidural anesthesia and 4 patients required a ureteral stent. Fragmentation of the stones was observed in all patients. After 1 month, the efficacy and stone free rates were 91% and 54%, respectively. After 3 months, they were 91% and 68%, respectively. There were no serious side effects such as pyelonephritis, perirenal hematomas, and massive hematuria. In conclusion, the Dornier Lithotripter Compact proved to be a safe and highly effective lithotripter for the treatment of renal and ureteral stones.

Adolescent↗

PubMed1999

Molecular cloning of an apoptosis-inducing protein, pierisin, from cabbage butterfly: possible involvement of ADP-ribosylation in its activity.

We have previously reported that the cabbage butterfly, Pieris rapae, contains a 98-kDa protein, named pierisin, that induces apoptosis in a variety of human cancer cell lines. In the present study, sequencing and cloning of a cDNA encoding pierisin was accomplished. PCR-direct sequencing showed that the gene encodes an 850-amino acid protein with a calculated molecular weight of 98,081. An intact clone at the amino acid level encompassing the entire coding region was obtained by recombination of two independent clones, and the molecular mass of its in vitro expressed protein was about 100 kDa on SDS/PAGE, the same as that of purified native pierisin. The expressed protein induced apoptosis in human gastric carcinoma TMK-1 and cervical carcinoma HeLa cells, like the native protein, indicating functional activity. The deduced amino acid sequence of pierisin showed 32% homology with a 100-kDa mosquitocidal toxin from Bacillus sphaericus SSII-1. In addition, pierisin showed regional sequence similarities with ADP-ribosylating toxins, such as the A subunit of cholera toxin. A glutamic acid residue at the putative NAD-binding site, conserved in all ADP-ribosylating toxins, was also found in pierisin. Substitution of another amino acid for glutamic acid 165 resulted in a great decrease in cytotoxicity and induction of apoptosis. Moreover, inhibitors of ADP-ribosylating enzymes reduced pierisin-induced apoptosis. These results suggest that the apoptosis-inducing protein pierisin might possess ADP-ribosylation activity that leads to apoptosis of the cells.

ADP Ribose Transferases↗

PubMed1999

Immunotherapy for lung metastases of murine renal cell carcinoma: synergy between radiation and cytokine-producing tumor vaccines.

We investigated the combination therapy of local radiation of lung metastasis and vaccination with autologous tumor cells that produced interleukin (IL)-2, interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) using the mouse Renca pulmonary metastasis model. Wild-type Renca (W/Renca) were transfected with pEF-BOS vector incorporating cDNAs for IL-2, IFN-gamma, or GM-CSF to express these cytokines. W/Renca, IL-2-producing Renca (Renca/IL-2), and IFN-gamma-producing Renca (Renca/IFN-gamma) produced subcutaneous tumor at the injection site in eight of eight, one of eight, and two of eight mice, respectively. No tumors were found in the GM-CSF-producing Renca (Renca/GM-CSF) group (zero of eight). Renca/IFN-gamma produced subcutaneous (s.c.) tumors in all Balb/c nude mice, but Renca/IL-2 and Renca/GM-CSF did not. To test the elicitation of antitumor activity, Balb/c mice were injected intravenously with 1 x 10(5) W/Renca on day 0, vaccinated, s.c., with 1 x 10(6) cells each of 5,000 rad preirradiated Renca/IL-2, Renca/IFN-gamma, and Renca/GM-CSF or 3 x 10(6) cells of preirradiated W/Renca on days 1, 7, and 14, and radiated with 300 rad to both lungs on day 5. The animals were killed on day 21 and tumor nodules in the lungs were enumerated. Neither local irradiation alone nor the combination of lung radiation and multiple vaccination with irradiated W/Renca significantly reduced the number of lung tumors. In contrast, the combination of lung radiation and the multiple vaccinations with cytokine-producing Renca cells significantly reduced the number of lung tumors. This regimen was more effective than the multiple vaccinations with cytokine-producing Renca cells alone. These studies demonstrate the efficacy of vaccination with autologous tumor cells expressing these cytokines and sensitization of the tumor target with radiation.

Animals↗

PubMed1999

Clinical results of total cystectomy for 92 patients with bladder cancer.

The survival rate of 92 patients with primary bladder cancer who had undergone total cystectomy during a 13-year period from 1984 to 1996 was examined. The mean follow-up period was 1,886 days. The 5-year survival rate was 67.9% and the 10-year survival rate was 55.1%. When survival rates were compared pathohistologically, with 81 patients with transitional cell carcinoma divided into two groups, a high-stage group including T3 and T4 patients and a low-stage group with all other patients, the cancer-specific 5-year survival rate of the low-stage group was 88.9% while that of the high-stage group was 45.4%; this difference was significant (p = 0.0002). There were also significant differences in survival rate between those with and those without regional lymph node metastasis, those with and those without lymphatic infiltration, and those with and those without vascular infiltration. However, there was no significant difference in survival rate for the 34 patients with T3 or T4 disease when those with or without chemotherapy and/or radiation therapy were compared.

Adult↗

PubMed1997

Significance of cyclin D1 overexpression in transitional cell carcinomas of the urinary bladder and its correlation with histopathologic features.

BACKGROUND: Genetic alterations leading to neoplastic transformation of the urothelium are likely to involve the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 has been implicated as a putative protooncogene whereas mutations of the p53 gene occur frequently in invasive transitional cell carcinomas (TCCs) of the urinary bladder. In this study, cyclin D1 overexpression and nuclear accumulation of p53 were evaluated and the results correlated with histopathologic features. METHODS: TCCs of the urinary bladder from 161 surgical procedures were evaluated for cyclin D1 overexpression and nuclear accumulation of p53. Results were correlated with tumor grade, T classification, and papillary status. Topologic distributions of cyclin D1, p53, and proliferating cellular nuclear antigen (PCNA) were evaluated. Northern blot analysis was performed on selected specimens. RESULTS: Overexpression of cyclin D1 was observed in 47% (24 of 51) of Grade 1 TCCs and 20% (13 of 65) of Grade 2 TCCs but in no Grade 3 TCCs. Approximately 34% (14 of 41) of Ta classified TCCs and 21% (13 of 63) of T1 classified TCCs were immunoreactive for cyclin D1 whereas none of the TCCs beyond T1 was immunoreactive. Overexpression of cyclin D1 was observed only in papillary type TCCs. Results of Northern blot analysis for cyclin D1 were comparable to those of immunohistochemistry. CONCLUSIONS: The observed significant relation between cyclin D1 overexpression and tumor grade/T classification suggests that cyclin D1 may be a useful biologic marker for biopsied materials or urine cytology specimens. The prognostic significance of cyclin D1 overexpression in TCCs remains to be determined.

Adult↗

PubMed1997

Is a cystic lesion located at the midline of the prostate a müllerian duct cyst? Analysis of aspirated fluid and histopathological study of the cyst wall.

OBJECTIVE: In 6 patients, ranging in age from 26 to 71 years, we analyzed aspirated fluid and histologically studied cystic lesions located at the midline of the prostate. METHODS: Digital rectal examination, ultrasonography, magnetic resonance imaging, and aspiration of cystic fluid were performed to evaluate size, contents, and location of the cystic lesion. A 22-gauge needle was inserted into the cystic lesion perineally under ultrasound guidance. After extracting fluid for cytology and measurement of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), a specimen from the prostate involving the cystic wall was collected. Hematoxylin-eosin staining and immunohistochemical staining for PSA were performed. RESULTS: All aspirated fluid specimens were yellowish and clear without any sperm or malignant cells. The PSA levels in the fluid ranged between 90 and 670 x 10(4) ng/ml, while the PAP levels were between 168 and 4,000 ng/ml. These levels of PSA and PAP were significantly higher as compared with those in the serum. The cystic wall was lined with cuboidal or columnar epithelium. Some epithelial cells from the cystic wall showed positive immunostaining for PSA. CONCLUSIONS: Not all cystic lesions located at the midline of the prostate are müllerian duct cysts, and there is a high probability that the lesion could be a cystadenoma or a simple cyst of the prostate.

Acid Phosphatase↗

PubMed1997

[Urinary interleukin-6 and interleukin-8 in females with urethral syndrome].

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of an inflammatory response. We measured creatinine-collected urinary levels of IL-6 and IL-8 by an enzyme-linked immunosorbent assay in 21 women with urethritis syndrome as well as 20 age-matched healthy women. Urine samples were collected before treatment and after 7 or 14 days of oral administration of sparfloxacin (100 mg once daily). Urinary IL-6 level was elevated in a patient with urethritis syndrome (41.1 pg/mgCr), while urinary IL-8 levels were elevated in 8 (range 13.3 to 560 pg/mgCr). On the other hand, none of the healthy controls showed any detectable urinary level of IL-6 and IL-8. Of the 9 patients with elevated urinary IL-6 or IL-8, symptomatic improvement was obtained after chemotherapy in 8 and urinary interleukins became undetectable in 7. Urinary IL-6 and IL-8 seem to have some role in the induction of urinary symptoms.

Anti-Infective Agents↗

PubMed1996

[The effectiveness of neoadjuvant chemotherapy for invasive bladder cancer].

BACKGROUND: Sixteen patients with invasive bladder cancer were received neoadjuvant methotrexate, vinblastine, pirarubicin and cisplatin chemotherapy on our planning protocol. METHODS: The tumor was evaluated after 1 course of chemotherapy by radiographic examination, urine cytology, cystoscopy and random biopsy. If the response is CR or PR, one more course of chemotherapy was performed, and cystectomy was carried out. If the response is NC or PD, cystectomy was immediately carried out. Twelve of them were underwent cystectomy and four were preserved bladder. Clinical response was evaluated by echo, CT, MRI, urinary cytology, cystoscopy and random biopsy. RESULTS: Clinical CR was observed in 25% and PR was 37.5%. Pathological CR was observed in 31.3% and PR was 37.5%. The different rate between clinical and pathological evaluations was 31.3% and the result suggests that we should find the method of more accurate staging evaluation. Four patients who were evaluated clinical CR were selected bladder-preserving. However, two of them (50%) had recurred; one had grade 3 tumor was treated by total cystectomy and the other had multiple tumors was treated by one course of M-VAC and TUR-Bt. CONCLUSION: We should consider which cases are possible to preserve bladder by investigating the tumor characteristics.

Aged↗

PubMed1996

[A case of oligozoospermia with marginal hyperprolactinemia due to pituitary microadenoma].

We present an infertility male with prolactin level of 37.5 ng/ml. The patient had pituitary microadenoma detected by Gd-DTPA enhanced magnetic resonance imaging (MRI). After bromocriptine was administrated for 4 months, the size of microadenoma decreased, and sperm density and mortality improved. His wife became pregnant after 6 months. Dynamic MRI is a useful modality for detection of pituitary microadenoma, and bromocriptine is also useful for treatment of oligospermic patients with marginal hyperprolactinemia.

Adenoma↗

PubMed1995

[Seminal plasma cytokines in nonbacterial prostatitis: changes following sparfloxacin treatment].

The detection of various cytokines; interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), was studied in patients with nonbacterial prostatitis (NBP), and the clinical efficacy of sparfloxacin was also reported. The seminal plasma of 11 normal men and 10 patients with NBP were examined for the cytokines. There was no IL-1 beta or IL-6 in the seminal plasma of normal men. TNF-alpha was detected in only one normal man. In the seminal plasma of the patients, IL-1 beta was detected in 2 out of 10, and IL-6 was also detected in 6. TNF-alpha was detected in 6 out of 10 patients with NBP. The rate of detection of IL-6 and TNF-alpha was significantly higher in the patients with NBP than in normal men. The average levels (range) of IL-1 beta, IL-6 and TNF-alpha were 28 pg/ml (27-29), 110 pg/ml (25-476) and 25 pg/ml (6-113), respectively. After treatment with sparfloxacin at a dose of 100 mg to 200 mg per day, their symptoms disappeared. The number of leukocytes in the seminal plasma decreased to the normal level and these cytokines were not detected. The favorable clinical effect was achieved in 13 of the 17 patients (76%). These findings suggested that the cytokines have an important role in the pathogenesis of prostatitis and that the level of the cytokines are useful indicators in patients with prostatitis, particularly with NBP.

Adult↗

PubMed1994

[Evaluation of the results of one session of extracorporeal shock-wave lithotripsy (ESWL) for a single urinary tract stone].

Fourteen hundred seventeen patients with a single stone under either general or epidural anesthesia were treated by one session of ESWL using the Dornier HM3 while 255 cases by one session of ESWL using the Dornier MPL9000 under no anesthesia but only with some analgesics, with 3 months' follow up available in all patients. The ratio of stone location in the kidney vs ureter was 7 to 3 in the Dornier HM3 and 5 vs 6 in the Dornier MPL9000. The overall success rate (stone free and residual stone fragments of less than 4 mm, 3 months after ESWL) was 58% (591 cases/1016 cases) for kidney stones with the Dornier HM3 and 35% (41/117) with the Dornier MPL9000. On the other hand, the overall success rate for ureter stones was 61% (245/401) with the Dornier HM3 and 70% (96/138) with the Dornier MPL9000. The overall success rate for stones of more than 10 mm, was poor when treated by the Dornier MPL9000 compared with the Dornier HM3.

Adolescent↗

PubMed1994

[The effect of TZP-4238, an anti-androgen drug, on renal function].

The effect of TZP-4238, an antiandrogen drug, on renal function was examined. Single administration test: Patients with prostatic hypertrophy were divided according to creatinine clearance (CCr) into group A (CCr < 50 ml/min) and group B (CCr > or = 50 ml/min), and hemodynamics after a single administration of TZP-4238 were compared between the two groups. Groups A and B showed similar TZP-4238 hemodynamics, and there was no significant difference in pharmacokinetic parameters or the rate of serum protein binding between them. There was no difference in the hemodynamics of a major metabolite, 15-OH body, between the two groups. Neither was there any significant difference in the urinary excretion rate of TZP-4238 or 15-OH body. There were no findings of adverse clinical significance, and there were no problems with safety. Consecutive administration test: A 16-week consecutive administration study was performed on patients with prostatic hypertrophy associated with relative renal hypofunction. The blood levels determined in 5 patients were in good accordance with the simulation curve drawn from the results of group A. The rates of efficacy, safety and usefulness were 71.4%, 90% and 71.4%, respectively. Mild side effects were observed in one patient, but the 16-week administration was completed in all patients, and no adverse effects on renal function were observed. Favorable blood levels of TZP-4238 were obtained even in patients with prostatic hypertrophy associated with renal hypofunction, and adequate efficacy and safety were achieved even with consecutive administration. Furthermore, the drug had no apparent adverse effect on renal function.

Aged↗