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Biomedical subjects

T Ishibe

Publications and source records attributed to T Ishibe.

At least 37 records · Page 2Linked to original sources

Estramustine-binding protein in carcinoma and benign hyperplasia of the human prostate.

For the purpose of elucidating whether the biological characteristics of estramustine-binding protein (EMBP) are different in benign prostatic hypertrophy (BPH) and prostatic carcinoma (PC) and also to determine the clinical value of EMBP in the tissue, the EMBP concentration in 19 patients with BPH and 26 with untreated PC was measured by means of radioimmunoassay (RIA) using an antibody raised against EMBP obtained from the rat ventral prostate and compared simultaneously with the dihydrotestosterone (DHT) level in the same tissue. The level of serum prostate-specific antigen (PSA) was also measured in these patients. The EMBP concentration was significantly correlated with the tissue DHT level in BPH and well-differentiated PC (r = 0.745, p < 0.0001), whereas it did not correlate in moderately and poorly differentiated PC (r = -0.159, p = 0.542). By comparing well-differentiated PC with moderately and poorly differentiated PC, the EMBP concentration was significantly lower in the former than in the latter two conditions (p < 0.005) in spite of the highest tissue DHT level in well-differentiated PC. The ratio of the EMBP concentration to the DHT level in moderately and poorly differentiated PC was significantly higher when compared with that observed in either BPH or well-differentiated PC (p < 0.005, respectively). However, the level of serum PSA did not reflect the histological differentiation of PC. These results suggest that: (i) the correlation of the EMBP concentration to the DHT level changed with the progression of the histological grade, and (ii) the ratio of the EMBP concentration to the DHT level in the tissue is clinically valuable in elucidating the biological potential of individual tumors.

Aged↗

Relationship of genetic instability with immunoreactivities for p53 protein and proliferating cell nuclear antigen in transitional cell carcinoma of the bladder.

OBJECTIVE: To elucidate the relationship between genetic instability and tumor development in transitional cell carcinoma (TCC) of the bladder. METHODS: The genetic instability as assessed by 2c deviation index (2cDI) and 5c exceeding rate (5cER) was compared with immunoreactivities for p53 protein and proliferating cell nuclear antigen (PCNA) in specimens obtained from 65 patients with primary untreated TCCs. RESULTS: Both p53 and PCNA immunoreactivities significantly correlated with histological grade as well as stage. The immunoreactivity of p53 significantly correlated with that of PCNA, while a dissociation of the positive correlation between p53 immunoreactivity and PCNA expression was noted in the TCCs with high 2cDI value (> or = 2.0) and/or high 5cER (> or = 10%). In addition, PCNA expression became higher as the genetic instability increased, however, the p53 immunoreactivity was not parallel with the change of genetic instability. Moreover, some TCCs with high genetic instability (2cDI > or = 2.0 and 5cER > or = 10%) showed concomitant expression of high PCNA and low p53 protein, whose clinical outcome was poor in general. CONCLUSIONS: The inactivation of p53 may represent a rather early event in the development of TCC of the bladder. However, the proliferative activity in itself rather than the effect due to a specific alteration in p53 plays an important role in the development and progression in TCC of the bladder.

Carcinoma, Transitional Cell↗

Association of nm23 protein levels in human prostates with proliferating cell nuclear antigen expression at autopsy.

OBJECTIVE: To investigate nm23-H1 gene expression in the human prostate. METHODS: The nm23-H1 protein levels of normal prostatic tissues, latent cancers of the prostate and primary and metastatic sites of clinical prostate cancers from autopsied men were evaluated using immunohistochemical analysis. Cell proliferation in serial sections using proliferating cell nuclear antigen immunoreactivity was also estimated. RESULTS: Intense nm23-H1 staining was observed in metastatic sites of clinical prostate cancers. The incidence of intense nm23-H1 staining cells in primary sites of clinical prostate cancers was significantly higher than that found in latent cancers and normal prostates (p < 0.01). The staining pattern of nm23-H1 was heterogeneous in latent cancers of the prostate. A significant relationship was observed between nm23-H1 staining and positive proliferating cell nuclear antigen staining (p < 0.01). CONCLUSIONS: These results seem to indicate that the nm23-H1 gene expression is related to cell proliferation and tumor metastatic potential, and appear to show the existence of a biologically different population of cells within the latent cancer.

Aged↗

Absorption of nitrogen dioxide and nitric oxide by soda lime.

Inhaled nitric oxide (NO) is used for the treatment of pulmonary hypertension as a selective pulmonary vasodilator. However, NO is oxidized rapidly to the more toxic nitrogen dioxide (NO2). Elimination of NO2 from inspired gas is essential for safe clinical use NO. We therefore investigated the efficacy of soda lime in absorbing NO2 from NO2-containing gases. Commercially available soda limes (Soda sorb and Wako lime-A), were exposed to the following six gas mixtures containing NO and NO2 in a hypoxic carrier gas for 20 min: No. 1: NO 40 ppm; No. 2: NO 35 ppm and NO2 5 ppm; No. 3: NO 30 ppm and NO2 10 ppm; No. 4: NO 20 ppm and NO2 20 ppm; No. 5: NO 10 ppm and NO2 30 ppm; and No. 6: NO2 40 ppm. Both types of soda lime completely absorbed the NO2 in all samples when it was present (Nos 2-6). NO concentration in these gas mixtures was reduced by an amount equal to the NO2 absorbed by soda lime. NO was absorbed minimally when NO2 was not present in the mixture. Nitrite was detected from the Wako lime-A granules exposed to the test gas by the chemical analysis. These findings suggest that soda lime completely absorbs NO2 by chemical neutralization, but NO is absorbed as simultaneously absorbed NO2 only where NO and NO2 coexist. Therefore, we conclude that soda lime is useful for NO2 absorption during NO inhalation therapy but NO monitoring from a point distal to the soda lime is required for precise control of inspired NO concentration.

Absorption↗

Immunohistochemical analysis of nm23 protein in transitional cell carcinoma of the bladder.

OBJECTIVES: To elucidate the clinical significance of the nm23 gene product in transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: The immunoreactivity of nm23 protein and proliferating cell nuclear antigen (PCNA) were evaluated in paraffin-embedded tumour samples obtained from 74 patients with TCC of the bladder who underwent total cystectomy between 1981 and 1993 and compared with the histological findings and clinical outcome. RESULTS: The immunoreactivity of nm23 protein was positive near basement membrane in normal transitional epithelium and superficial TCCs; it could also be positive at the invasive front of TCCs. The immunoreactivity of nm23 protein in TCCs was significantly higher than that in normal transitional epithelium and correlated significantly with the expression of PCNA and with histological grade. Similarly, immunoreactivity was significantly higher in invasive TCCs than in superficial TCCs; however, there was no significant difference between superficial TCCs and normal transitional epithelium. Immunoreactivity of nm23 protein was not associated with the early development of metastasis after radical surgery or with a favorable clinical outcome. CONCLUSION: Immunoreactivity of nm23 protein appeared to be associated with the proliferation and progression of TCC of the bladder. The potential role of nm23 as a suppressor of the metastatic activity of tumours was less prominent, partly because of mutations of nm23 in TCCs of the bladder.

Adult↗

Long-term results with M-VAC for advanced urothelial cancer: high relapse rate and low survival in patients with a complete response.

OBJECTIVE: To describe the long-term results of treating patients with advanced urothelial cancer using a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). PATIENTS AND METHODS: Fifty-one patients (37 men and 14 women, median age 66 years, range 41-82) with inoperable or metastatic carcinoma of the bladder, ureter or renal pelvis were treated with M-VAC and their responses evaluated for up to 7 years. Relative dose intensity (RDI) was calculated by dividing the actual dose intensity by the projected total dose intensity and related to outcome. Overall survival was assessed from the date of initiation of treatment with M-VAC, using the Kaplan-Meier method. RESULTS: Of the 51 patients. 10 (20%) had a complete and 18 (35%) had a partial response, giving an overall response rate of 55% (95% CI, 41-68%). There was no significant difference in the median values of RDIs with response to the M-VAC regimen. The median duration of response was 11.9 months for the 10 patients with a complete response and of these, eight relapsed at a median of 10 months after treatment and died at a median of 8.5 months from the time of disease recurrence. Survival of patients with a complete response differed significantly from those with no response at 1 year after the start of treatment, but not subsequently. CONCLUSION: Long-term follow-up revealed a high relapse rate and poor prognosis in patients with a complete response who received the M-VAC as induction therapy. Therefore, new adjunctive therapies are needed for patients with locally unresectable or metastatic urothelial cancer.

Adult↗

Clinical value of argyrophilic organizer region in bladder transitional cell carcinoma.

For the purpose of elucidating whether or not argyrophilic organizer regions (AgNORs) predict the biological behaviors of bladder tumors, the AgNOR was analyzed in 80 primary bladder transitional cell carcinomas (TCCs), using the computer-assisted image analyzer. The AgNOR parameters used were the mean AgNOR count (C-AgNOR) and the percentage of cells exhibiting more than 3 AgNOR dots or 4 AgNOR dots within nuclei (3P-AgNOR and 4P-AgNOR, respectively). The correlation of C-AgNOR with 3P-AgNOR and 4P-AgNOR reached a high statistical significance (p < 0.0001, respectively). All of these three AgNOR parameters correlated with histological grade, whereas the difference between grade I and II proved to be higher in 3P-AgNOR and in 4P-AgNOR (p < 0.01, respectively) as compared with that in C-AgNOR (p < 0.05). Similarly, these three parameters correlated with histological stage, whereas the statistical significance of the correlation was less prominent in C-AgNOR. Moreover, the prognostic relevance was noted in C-AgNOR (p = 0.041), whereas it was indicative in 3P-AgNOR as well as in 4P-AgNOR (p = 0.090 and p = 0.061, respectively). These results suggest that 3P-AgNOR and 4P-AgNOR reflect the difference in the proliferative activity of individual TCCs more precisely than C-AgNOR. Since the biological behaviors of individual TCCs cannot be predicted by the proliferative activity alone, the AgNOR in TCCs has a rather limited value regarding the prediction of survival.

Adult↗

Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract.

Cisplatin-based multiple-drug chemotherapy is currently considered the most effective treatment for advanced and metastatic urothelial cancers. We treated 15 patients with locally advanced urothelial cancers of the upper urinary tract using the cisplatin-based multiple-drug regimen in a neoadjuvant setting. The regimens administered were: M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin); MEC (methotrexate, etoposide and cisplatin), or M-VEC (methotrexate, vinblastine, epirubicin and cisplatin). Total nephroureterectomy was performed in all patients and response was evaluated pathologically Of 15 patients 2 (13%) achieved a pathological complete response, 6 (40%) a pathological partial response, for an overall response rate of 53% (95% confidence limits 29-77%). The median durations of response were 54 months for patients with a pathological complete response and 15.5 months for patients with a pathological partial response. One of six patients with a pathological partial response and 4 of 7 with no remission died of cancer. While a positive relationship between the pathological response and prognosis was observed, adequate follow-up is needed to assess the ability of neoadjuvant chemotherapy to improve the prognosis of patients with locally advanced urothelial cancer of the upper urinary tract.

Adenocarcinoma↗

[Acid phosphatase (ACP)].

The acid phosphatases are a group of enzymes capable of hydrolyzing esters of orthophosphoric acid in an acid medium. Acid phosphatase activity is widely distributed in human tissues and acid phosphatases represent a heterogeneous group of enzymes containing many isoenzymes, each specific for one type of tissue. The human prostate is particularly rich in this enzyme (PAP) and serum enzyme levels have been used as a tumor marker of prostate cancer. While PAP was markedly increased in patients with bone metastases of prostate cancer, it is unable to detect earlier stage tumors reliably. The sensitivity and specificity of serum acid phosphatases and PAP are low in diagnosing, staging and following patients with prostate cancer. Presently, prostate-specific antigen (PSA) is superior to PAP for diagnosis, screening, and monitoring prostate cancer. PAP may have an adjuvant value in the management of prostate cancer because a combination of PSA and PAP testing has revealed a high sensitivity and specificity in detecting prostate cancer.

Acid Phosphatase↗

[Acid phosphatase].

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Acid Phosphatase↗

A mapping of histology and cell proliferation in human bladder cancer: an immunohistochemical study.

Transitional cell carcinoma of the urinary bladder is a multifocal disease and the whole bladder mucosa is more or less involved in the neoplastic process. A mapping study of 5 cystectomy specimens was performed, and cell proliferation was evaluated immunohistochemically using anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. A correlation between the pathological findings and the rates of PCNA-positive cells was observed in both the tumor and the surrounding mucosa in 4 of the 5 cases. The rates of PCNA-positive cells increased in areas with normal mucosa adjacent to those with dysplasia or transitional cell carcinoma, and in areas with normal mucosa or dysplasia adjacent to those with carcinoma in situ or transitional cell carcinoma in 2 cases. These features may indicate that a field change observed in the mapping study of a bladder with cancer is a manifestation of a stepwise progression of the mucosal disease.

Aged↗

Factors related to the outcome of M-VAC in 101 patients with advanced urothelial cancer.

The objective of this study is to identify factors related to the results of intravenous methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for 101 patients with advanced urothelial cancer. The effects of various factors on response and survival were evaluated using univariate and multivariate analyses. The factors included in the analyses were sex, age, performance status (PS), primary site, histological type, grade, T category, N category, M category, prior chemotherapy, prior radiotherapy, and dose of chemotherapeutic drugs. Univariate analysis revealed that M category and prior chemotherapy had a significant correlation with the response, and that factors significantly related to survival were PS, primary site, N category, M category, prior chemotherapy and prior radiotherapy. A multiple logistic regression model showed that N category, M category and prior chemotherapy were related to response. The response rates of patients with N1-4 or M1 or prior chemotherapy were lower than those with N0 or M0 or without prior chemotherapy. A Cox regression model demonstrated that PS and M category independently contributed to survival. Patients with high grade PS or distant metastases showed a lower survival rate than those with low grade PS or localized diseases. M category was the most important factor related to response and survival. These results seem to indicate the low effectiveness of M-VAC for distant metastases, and the inability of this regimen to improve the outcome of patients with advanced urothelial cancer.

Adolescent↗

Study of estramustine binding protein: its relationship to androgen dependency and histological differentiation in human prostatic carcinoma tissue.

For the purpose of elucidating the clinical significance of estramustine binding protein (EMBP), EMBP concentration in human prostatic carcinoma (PC) tissue was measured by radioimmunoassay (RIA) using an antibody raised against rat EMBP and was compared with dihydrotestosterone (DHT) level and histological differentiation in the same tissue. The mean concentrations of EMBP in 20 untreated and 6 hormonally refractory PC were 112.6 +/- 120.7 and 218.0 +/- 102.3 ng/g tissue, respectively. In the 20 untreated PC, the EMBP concentration was not significantly different between the high and low tissue DHT groups. On the other hand, the EMBP concentration was significantly higher in moderately and poorly differentiated PCs as compared with well-differentiated PC, whereas the DHT level was highest in well-differentiated and lowest in poorly differentiated PC. Furthermore, in the 6 hormonally refractory PC, the EMBP concentration was higher in spite of a lower tissue DHT level in comparison with untreated PC. These results suggest that the EMBP concentration does not reflect androgen status in PC tissue but might reflect the malignant potential of the tumor.

Aged↗

Vesicourethral function after surgery for uterine cancer: predictive value of postoperative maximum urethral closure pressure on residual urine.

Using a urodynamic technique, vesicourethral function was evaluated in 30 patients who had undergone surgery for uterine cancer. In all 28 patients treated with radical hysterectomy, detrusor function was damaged irrespective of the use of the Cavitron ultrasonic surgical aspirator (CUSA), whereas, in 2 patients treated with semiradical hysterectomy, the function was preserved. Vesicourethral functions 3 weeks after the operation in all 28 patients treated with radical hysterectomy showed underactive detrusor function with low compliance. In 10 out of these 28 patients, postoperative maximum urethral closure pressure (MUCP) did not decrease, without relation to the use of CUSA nor to the presence of detrusor sphincter dyssynergia, and more than 5 weeks were required to reduce residual urine to less than 50 ml. On the other hand, in the remaining 18 patients, postoperative MUCP decreased, and residual urine decreased to less than 50 ml by 5 weeks after the operation. From the results obtained here, we can conclude that the evaluation of MUCP at an early phase after the operation is a useful tool to predict complications caused by residual urine, such as urinary tract infection, irreversible alteration of detrusor function or deterioration in renal function.

Female↗

Beta adrenergic receptor inhibitory factor in serum of patients with nasal allergy.

Sera obtained from patients with perennial mite nasal allergy and Japanese cedar pollinosis were examined to identify "beta receptor inhibitory factor". This was done by evaluating the inhibition of 3H-dihydroalprenolol binding to guinea pig cerebral membrane. beta receptor binding was inhibited by preincubation with sera from 8 of 44 (18.1%) perennial allergy patients, whereas sera from 2 of 41 (4.9%) controls showed this inhibition. Sera from 6 of 41 pollenosis patients (14.6%) showed this inhibitory effect in the pollen season but not in other seasons. Serum from one such patient (2.4%) demonstrated this effect both in and out of the pollen season. Sera from 2 pollenosis patients inhibited the beta receptor function not in the pollen season, but in the off season. This inhibitory effect was eliminated by immunodepletion from the positive-inhibition serum. These findings identified circulating beta receptor inhibitory factor in a limited population of patients with nasal allergy indicating the possible pathogenetic role of this factor in the disturbance of the sympathetic nerve function. This beta receptor inhibitory effect may correspond to the anti beta receptor autoantibody which Venter postulated in 1980.

Animals↗

[Cryptorchism].

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Cryptorchidism↗