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Biomedical subjects

Y Osada

Publications and source records attributed to Y Osada.

At least 91 records · Page 5Linked to original sources

[Urokinase-type plasminogen activator antigen as a prognostic factor in bladder cancer].

The relationship between the urokinase-type plasminogen activator (u-PA) content in extracts of cancer tissues and the histological grade or the extent of the primary tumor as prognostic factors in bladder cancer were examined in 55 cases of bladder cancer. The patients were divided into 2 groups, high u-PA (8 ng/ml of protein and more) and low u-PA (less than 8 ng/mg of protein) groups. The incidence of vascular invasion was 37% in the high u-PA group, and 7.1% in the low u-PA group (p < 0.05). The incidence of high u-PA group increased with the grade of cancer and the extent of the primary tumor. The 3-year survival rates were 87.3% in low u-PA group and 42.6% in high group (p < 0.005). The survival rates of the patients in the high u-PA group were lower than in the low group, by grade or stage. In a multivariate analysis, the prognostic value of u-PA antigen content was the same as that of tumor grade and stage. Therefore, the content of u-PA may be a useful prognostic marker for bladder cancer in addition to tumor grade and stage although the prognosis of the patients with bladder cancer is considered to be determined by many factors.

Adult↗

[The value of an aseptic intermittent catheterization program in the early management of spinal cord injury patients].

From 1979 to 1989, 269 patients with spinal cord injury were managed by an aseptic intermittent catheterization program during the acute phase of their injuries at the Spinal Injuries Center. One hundred fifty one patients with incomplete cord lesion and 36 males with complete tetraplegia were managed by program I, which protects the shocked bladder from overdistention. In contrast, 82 patients with complete cord lesion excluding male tetraplegia were managed by program II, which allows overdistention of the bladder. Of the 187 patients managed by program I, 137 (73.3%) achieved trigger voiding function, 61.3% of whom were completely dry. Of the 82 patients managed by program II, 62 (75.6%) were put to self- or assisted catheterization, 67.7% of whom were dry. The incidence of a grade I, which means normal bladder configuration, was 88.0% for program I and 87.3% for program II during the follow up course. Upper urinary tract deterioration occurred in only one case. Surgical treatment for urinary tract complications was performed in 14 cases (5.2%). These results suggest that the patients with incomplete cord lesion managed by non-distension regimen of the bladder (program I) and those, especially female, with complete cord lesion managed by overdistention regimen of the bladder (program II) achieve urinary continence with excellent urinary prognosis.

Humans↗

The content of urokinase-type plasminogen activator antigen as a prognostic factor in urinary bladder cancer.

Urokinase-type plasminogen activator (u-PA) is thought to be implicated in cancer invasion and metastasis. The aim of this study was to determine whether the u-PA content of cancer tissue is a prognostic factor in bladder cancer. Tissue samples from 46 patients with bladder cancer were assessed for u-PA antigen by a highly sensitive enzyme immunoassay. The relationships between the u-PA level in extracts of bladder cancer and the survival rates of the bladder-cancer patients were examined. Patients with a high u-PA level (8 ng/mg of protein and more) showed a statistically significantly higher rate of survival than those with a low u-PA level (p less than 0.005). The u-PA antigen level in cancer tissue was significantly lower in low-graded and non-invasive cancers than in others (p less than 0.01).

Aged↗

Inhibition of development of Kaposi's sarcoma-related lesions by a bacterial cell wall complex.

In vitro and in vivo model systems for the study of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) were used to evaluate compounds for their potential as therapeutic agents. A sulfated polysaccharide-peptidoglycan compound (SP-PG) produced by bacteria controlled the in vitro growth of acquired immunodeficiency syndrome (AIDS)-associated, KS-derived spindle-shaped cells (AIDS-KS cells) at noncytotoxic concentrations. Angiogenesis induced by AIDS-KS cells in the chicken chorioallantoic membrane assay was blocked by SP-PG, which also inhibited the vascular hyperpermeability response and the angiogenesis associated with the induction of KS-like lesions that develop after subcutaneous inoculation of AIDS-KS cells into nude mice. Suramin, pentosan polysulfate, and interferon alpha, which are currently in use for therapy of KS, were either less effective than SP-PG or much more cytotoxic, or both.

Acquired Immunodeficiency Syndrome↗

The relationship between cardiovascular complications of estrogen therapy and fibrinolysis in patients with prostatic cancer.

To determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis, fibrinolysis parameters plasminogen, urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy. The levels of plasminogen, u-PA, and PAI-1 in the patients treated with the estrogen therapy were significantly higher than those in the patients before the therapy. The t-PA level in the patients during the therapy was significantly lower than that before the treatment. Cardiovascular complications were found in two patients (16.7%) during estrogen therapy. In the two patients, marked elevation of PAI-1 and decreased level of t-PA were observed during the therapy. These results indicate that cardiovascular complications of estrogen therapy in patients with prostatic cancer may be related to hypofibrinolysis resulting from changes of PAI-1 and t-PA.

Aged↗

Adjuvant chemotherapy with early intravesical instillation of adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer. The Kyushu University Urological Oncology Group.

A randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in 275 patients with superficial bladder cancer. All of the patients were randomized into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of Adriamycin alone; Group B received early instillation of Adriamycin with oral administration of 5-fluorouracil; Group C received delayed (7 days after transurethral resection) instillation of Adriamycin alone; and group D received delayed instillation of Adriamycin with oral administration of 5-fluorouracil. All patients subsequently received instillations weekly for 2 weeks and then every 2 weeks for a further 14 weeks. After 4 months, they received monthly instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o. for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up period for determination of non-recurrence rates was 36 months, during which no significant difference was detected among the four groups. Moreover, no statistically significant difference was found between the early- and delayed-instillation groups. However, the non-recurrence rates obtained in the groups undergoing early instillation were higher than those determined in the delayed-instillation groups during the 36-month follow-up period, and this difference was especially significant at 4 and 5 months. In addition, the early-instillation groups showed significantly higher non-recurrence rates than did the delayed-instillation groups in terms of primary cases (P less than 0.01), tumor size of less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01), pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P less than 0.05). Groups B and D, which were treated by intravesical instillation of Adriamycin with oral administration of 5-fluorouracil, showed no significant prophylaxis of recurrence during the 36-month follow-up as compared with groups A and C, which received intravesical instillations alone. The main side effect, which required discontinuation of the treatment, was bladder irritation. However, no significant difference in its incidence was found between the early- and delayed-instillation groups. No severe systemic side effect was encountered in this study. These results suggest that early as well as repeated intravesical instillation of Adriamycin is clinically tolerable and may be effective in preventing the recurrence of superficial bladder cancer.

Administration, Intravesical↗

Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models.

The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46 mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and 38 resulted in significant reductions in the weight of all tumors except Colon 26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal to that of an Escherichia coli-type synthetic lipid A (compound 506), and also to those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil and cisplatin. Furthermore, DT-5461 was more effective than other immunotherapeutics, including picibanil (OK-432) and lentinan. However, its antitumor effects were inferior to those of Adriamycin or OK-432 against the malignant ascites caused by intraperitoneal inoculation with MethA or with MH134 cells; life span was not prolonged by either intraperitoneal or intravenous administration. In addition, although DT-5461 showed direct inhibitory effects on the in vitro growth of MethA or MH134, these were much weaker than those of Adriamycin. These findings clearly indicated that DT-5461 with systemic administration is a highly effective antitumor agent on solid tumors, and suggest that the antitumor effect of DT-5461 with potent necrotizing activity might derive from indirect mechanisms related to the activation of host immune systems and not to the weak direct cytotoxicity.

Animals↗

The prognostic significance of vascular invasion in upper urinary tract transitional cell carcinoma.

The prognostic significance of vascular invasion was evaluated in a retrospective series of 30 patients with upper urinary tract cancer who underwent a potentially curative operation. Vascular invasion was found in 11 patients (36.7%). The incidence of vascular invasion was well correlated with tumor grade and stage. The incidence of metastases postoperatively was significantly higher in the patients with (72.7%) than without (21.1%) vascular invasion (p < 0.01). The survival rate of the patients with vascular invasion was significantly lower than in those without vascular invasion (p < 0.005). In multivariate Cox regression analysis the prognostic value of vascular invasion was independent of tumor stage and grade. These results indicate that vascular invasion should predict a more unfavorable outcome in patients with upper urinary tract cancer as an independent morphological indicator.

Adult↗

Bladder function in elderly men with subclinical brain magnetic resonance imaging lesions.

Among 43 men more than 60 years old who complained of urinary irritative symptoms 40 had subclinical lesions in the brain on magnetic resonance imaging (MRI). Of these 40 patients 23 (57.5%) had detrusor hyperreflexia. The mean age of the patients with and without detrusor hyperreflexia was 75.8 and 68.2 years, respectively, which is a statistically significant difference. Patients with detrusor hyperreflexia were more likely to have lesions of the basal ganglia than patients without detrusor hyperreflexia. This study suggests that detrusor hyperreflexia, subclinical MRI lesions in the brain and aging are intimately interrelated.

Aged↗

Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates.

DU-6859, (-)-7-[(7S)-amino-5-azaspiro(2,4)heptan-5-yl]-8-chloro-6- fluoro-1-[(1R,2R)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinol one-3- carboxylic acid, is a new fluoroquinolone with antibacterial activity which is significantly better than those of currently available quinolones. The MICs for 90% of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates (MIC90s) were 0.1, 3.13, 0.1, and 0.39 microgram/ml, respectively. MIC50s of DU-6859 against quinolone-resistant, methicillin-resistant S. aureus were 8-, 32-, 64-, and 128-fold lower than those of tosufloxacin and sparfloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin, respectively. DU-6859 inhibited the growth of all strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.1 and 0.2 microgram/ml, respectively, and was more active against enterococci than the other quinolones tested. Although the activity of DU-6859 against Pseudomonas aeruginosa was roughly comparable to that of ciprofloxacin at the MIC50 level, it was fourfold more active than ciprofloxacin at the MIC90 level. DU-6859 was also more active against other glucose-nonfermenting bacteria, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, than the other drugs tested. Strains of Bacteroides fragilis and Peptostreptococcus spp. were susceptible to DU-6859; MIC90s were 0.39 and 0.2 microgram/ml, respectively. DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae. The action of DU-6859 against the clinical isolates was bactericidal at concentrations near the MICs. DU-6859 activity was not affected by different media, pH, inoculum size, or human serum but was decreased in human urine.

Anti-Infective Agents↗

Synergistic effect of romurtide with ampicillin against pneumococcal pneumonia in mice.

The anti-infective activity of romurtide, a synthetic muramyl dipeptide (MDP) derivative, was evaluated in experimental pneumococcal pneumonia in mice deficient in the third component of complement (C3). The compound was found to be effective against the pneumonia in combination with subcutaneous ampicillin (ABPC). This synergistic effect of romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before infection. Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent pneumonia. In contrast, the combination treatment of romurtide with ABPC successfully prevented most of the mice from the purulent pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with romurtide in combination with ABPC. Thus, romurtide was suggested to promote recovery of the mice with pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.

Acetylmuramyl-Alanyl-Isoglutamine↗

Effect of probenecid on the pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in humans.

A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration.

Administration, Oral↗

Intravesical therapy with adriamycin plus verapamil in patients with superficial bladder cancer: a pilot study.

Nineteen patients with histologically proven superficial bladder cancer (Ta, T1) were treated with intravesical instillation of 30 mg of adriamycin (ADM) dissolved in 24 ml physiological saline plus 15 mg of verapamil (VR) (6 ml) every day for 10 days. In spite of the short period of treatment, 6 of the 18 evaluable patients (33.3%) showed complete response (CR) and a further 5 (27.8%) showed partial response (PR). Five of the 6 patients with CR were recurrent cases who had previously received prophylactic intravesical instillation chemotherapy including ADM. Irritative urinary symptoms were observed in 11 of the 19 patients (57.9%). However, these symptoms were mild in the majority of patients and the treatment was completed without interruption in all but 1 patient. There was no significant absorption of ADM and VR into the systemic circulation. No clinical evidence of systemic toxicity was observed. These results suggest that combination of ADM and VR has a possibility to be a useful prophylactic intravesical instillation chemotherapy after endoscopic resection of not only primary but also recurrent chemoresistant bladder cancers.

Administration, Intravesical↗

[Studies on vessel invasion by cancer of the renal pelvis and ureter].

The significance of vessel invasion by cancer of the renal pelvis and ureter was estimated with surgical specimens of 45 patients. The vessel invasion by cancer was observed in 25 out of 45 cases (55.6%). The incidence of vessel invasion increased with the grade of cancer and the extent of the primary tumor. The postoperative metastases by cancer was noted in 22 of the 25 patients with vessel invasion (88%) and in 4 of 20 (20%) patients without vessel invasion. The incidence of metastases in patients with vessel invasion was significantly higher than that without it (p < 0.01). The 5-year survival rate was 13.1% in the patients with vessel invasion and 80.6% in the patients without it (p < 0.005). Postoperative chemotherapy had no effect on the unfavorable outcome of the patients with vessel invasion. Therefore, vessel invasion by cancer may be one of the prognostic factors in renal pelvic and ureteral cancer. The patients with vessel invasion should be treated with more aggressive therapy to improve the poor prognosis.

Adult↗

[The effects of autonomic agonists on the female rabbits urethra--in vitro isovolumetric and isometric study].

To investigate the characteristics of adrenoceptors of the proximal urethra in female rabbits, we performed the in vitro isovolumetric urethral pressure study and isometric study with three parts of muscle strips of the proximal urethra (whole layers, inner layers and outer layers). Both alpha-1 and alpha-2 agonist caused dose dependent response in in vitro isovolumetric pressure study as well as in vivo study. However, the response of alpha-2 agonist in in vitro was small in magnitude compared to in vivo study, suggesting the influence of permeability of drugs from serosa to mucosa in in vitro whole urethra study. The response of the strips of inner layers to alpha-1 agonist is almost the same as that of outer layers and whole layers, while the response of inner layers to alpha-2 agonist is almost twice as that of other layers. These findings are suggestive of predominance of alpha-2 adrenoceptors mediating contractions in the inner layers of the proximal urethra in female rabbits. Alpha-2 adrenoceptors which probably are distributed in mucosal and submucosal layers may have an important role in the mechanism of urinary continence in female rabbits.

Adrenergic alpha-Agonists↗

Expression of Hanganutziu-Deicher antigen in activated human T lymphocytes.

Hanganutziu-Deicher (HD) antigen is a heterophile antigen that is widely distributed in many animals other than humans and chickens and is highly immunogenic in humans and chickens. In the present study, we demonstrated expression of HD-antigenic glycoproteins in activated T lymphocytes by SDS-PAGE and immunoblotting. Treatment with IL-2 plus PMA induced 29kD glycoprotein antigen detected under reducing condition. It contained sialic acid epitope of HD antigen because of the expression being neuraminidase-sensitive. Treatment with PMA plus A 23187 or PHA treatment and then PHA plus IL-2 treatment also induced two proteins of Mr 50kD and 70kD. These expressions were not detected in all individuals examined. These results indicate that HD antigen is an activated T cell antigen and expressed as an isoantigen as it is expressed in cancerous tissues from some patients.

Antigens, Heterophile↗

Inhibition of angiogenesis and tumor growth by a synthetic laminin peptide, CDPGYIGSR-NH2.

A laminin-derived synthetic peptide, Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2 (CDPGYIGSR-H2), containing an active site for cell binding inhibited both angiogenesis and solid tumor growth. It potently suppressed both embryonic angiogenesis of the chick chorioallantoic membrane and migration of vascular endothelial cells induced by a tumor-conditioned medium but neither the in vitro proliferation of endothelial cells nor that of tumor cells. Additionally, in in vivo tests, CDPGYIGSR-NH2 markedly inhibited both the growth of s.c. solid tumor of Sarcoma 180 and that of Lewis lung carcinoma (3LL) in the lungs. On the contrary, ascitic tumor growth of Sarcoma 180 was not affected by this peptide, even though the same cell source was used. It was concluded that solid tumor growth inhibition by CDPGYIGSR-NH2 was due not a direct effect on cell growth but to antiangiogenic effect mediated by the inhibition of endothelial cell migration.

Animals↗