(-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

Antimalarial activity of a riboflavin analog against Plasmodium vinckei in vivo and Plasmodium falciparum in vitro.

The riboflavin analog 10-(4'-chlorophenyl)-3-methylflavin was found to have significant activity against Plasmodium vinckei vinckei when administered orally and parenterally; it was active against P. falciparum in culture. It inhibited mouse erythrocyte glutathione reductase in a dose-dependent manner. When administered orally, 5-deazariboflavin was not active in vivo although it has been shown to have activity against P. falciparum in vitro.

Further studies on specificity of red cell adherence test: nonmalignant bladder lesions.

Specific red cell adherence test for blood group antigens was utilized in 32 nonmalignant bladder lesions, none of which was associated with bladder cancer, to determine the specificity of this test. All of the 14 lesions of cystitis cystica, cystitis glandularis, and chronic cystitis retained their antigens. Of the 18 lesions of squamous metaplasia, 13 (72%) were antigen positive. Testing for blood group antigens showed an overall 84 per cent specific rate in 27 of the 32 nonmalignant bladder lesions.

(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release.

"Catecholaminergic and serotoninergic activity enhancer" effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP HCl], a compound with selective and potent "catecholaminergic and serotoninergic activity enhancer" effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (-)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3-10 mg/kg). (-)-BPAP HCl (1-3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (-)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390), suggesting that the effects of (-)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (-)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (-)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (-)-BPAP HCl significantly improved ptosis. These findings suggested that a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.

On the conversion of thymidine phosphate bromohydrins to thymidine phosphates: a model reaction for the repair of oxidized nucleotides.

Bromohydrins (12, 13, and 14), which were oxidatively damaged products of thymidine nucleotides, were repaired by the action of sunlight (2700 lux) or heat via a radical mechanism to regenerate the original nucleotides (8,9, and 10). A significant effect of 3',5'-phosphate linkage on the repair reactions to natural type of thymidine nucleotide was proposed.

[Clinical studies on cases of suprapubic prostatectomy].

The results of the operation were analyzed statistically in 68 patients who underwent suprapubic prostatectomy for benign prostatic hypertrophy from 1979 to 1985. The patients were between 59 and 86 years old with a mean age of 72.0 years. The average operation time was 63 minutes and average blood loss during the operation was 292 g. The average weight of enucleated prostate was 32.6 g. Acute epididymitis and urine leakage from the wound were the most frequent postoperative complications. There were no postoperative deaths. The average postoperative admission period was 25.6 days. Histological examination of the specimens revealed occult carcinoma in 2.9% of the patients.

[A clinical study on renal cell carcinoma].

One hundred and thirty-two patients with renal cell carcinoma, treated by the TEKK Group, during the period from 1962 to 1983 were clinically reviewed. The patients ranged in age from 13 to 77 years with a mean age of 57.3 years, and were 89 men and 44 women, with a sex ratio of 2.07 to 1. The most common symptom was hematuria (55.4%), followed by palpable mass (19.2%), pain (13.8%) and fever (6.9%). The distant metastasis was observed in 26 patients (19.7%), mostly in the lung (54%) and the bone (19%). Overall estimated survival rates at 1,3 and 5 year were 83.0%, 58.2% and 56.9% respectively. The prognosis of the patients with renal cell carcinoma was dependent upon affected site, age, ESR, CRP, alpha 2-globulin and distant metastasis.

[Clinicopathological observation on renal cell carcinoma. "The relationship between the histological and clinical findings"].

The relationship between the histological and clinical findings of 128 cases of renal cell carcinoma operated on during the past 17 years were analyzed. With elevation of tumor grading, the elevated ESR and CRP-positive cases were increased with a significant difference. The serum alpha 2-globulin was elevated in the grade 3 group significantly, but not in the grade 1 or 2 group. Seven of the eight spindle cell type cases showed an elevation of ESR, CRP-positive and an elevation of alpha 2-globulin. There was no difference in clinical findings between well circumscribed border and poorly demarcated margin. A high percentage of quick type cases of renal cell carcinoma were found in high grade cases with a significant difference.

[Inverted papilloma of the ureter].

Two cases of ureteral inverted papilloma are reported. Case 1: A 48-year-old male had asymptomatic gross hematuria and filling defect of left middle ureter on intravenous pyelography. Segmental resection of ureter was performed. The specimen was a 1 cm polypoid lesion with histologic features resembling "multifocal bud-like proliferation", which was reported as the initial stage of the inverted urothelial tumor by Kunze et al. Case 2: A 64-year-old female with asymptomatic gross hematuria and complete obstruction of left middle ureter on ante- and retrograde pyelograms. Total nephroureterectomy was performed. A 4 cm lobulated and pedunculated lesion with histologic features of typical inverted urothelial papilloma was resected. Twenty-one cases of ureteral inverted papilloma in the literature, including our cases, are analyzed.

[A clinicopathological study on tumor of the renal pelvis and ureter].

We report 42 patients with urothelial tumors in upper tract admitted to our hospital between August, 1969 and August, 1988. The patients consisted of 33 males and 9 females; their ages ranged from 42 to 85 years with a mean of 66.2 years. Total nephroureterectomy with bladder cuff resection was employed as the surgical method in 24 cases, total nephroureterectomy without bladder cuff resection in 11 cases, total nephroureterectomy with total cystectomy in 2 cases and partial ureterectomy only in 2 cases. Tumor lesions had a positive correlation with grade and stage. The survival rate for all the patients at 1, 3 and 5 years was 76.0, 58.8 and 54.6%, respectively, as measured by the Kaplan-Meier's method. The prognosis of the patients with renal pelvic tumor and ureter tumor was dependent upon grade, stage and intravascular tumor-emboli. Vesical recurrence was observed in 10 cases and found frequently in low grade tumor and/or low stage tumor cases. The frequency of vesical recurrence was not positively correlated with cuff resection The 5-year survival rate was not different between the patients with vesical recurrence and those without vesical recurrence.

[Prognostic factors for muscle-invasive bladder cancer treated with a combination of intra-arterial chemotherapy and low-dose radiotherapy].

Clinical and pathological factors that affect short-term responses and long-term prognosis of muscle-invasive bladder cancer were studied in 73 patients who underwent a combination of intra-arterial chemotherapy and low-dose radiotherapy. Complete Response (CR) was observed in 41 (56%) of the 73 patients. The frequency of CR was significantly different according to the sex (males 64%, females 29%; p = 0.0239), clinical stage (T2 74%, T3 64%, T4 20%; p = 0.0005), tumor size (< 3 cm 81%. > or = 3 cm 31%; p < 0.0001), and tumor grade (G3 72%, G2 41%, p = 0.0127). By multivariate analysis, a significant difference was observed only in the tumor grade. The 5-year survival rate after bladder-preserving operations (median duration of follow-up 69 months) was significantly different according to the sex (males 75.2%, females 57.1%; p = 0.0427), clinical stage (T2 86.3%, T3 82.3%, T4 33.8%; T2 vs T4, p = 0.0005; T3 vs T4, p = 0.0107), tumor size (< 3 cm 89.6%, > or = 3 cm 47.2%; p = 0.0012), and tumor response (CR 95.0%, non-CR 38.6%; p < 0.0001). By multivariate analysis, a significant difference was observed only in the tumor response. The combination therapy of intra-arterial infusion and irradiation produced excellent short-term effects and prolonged the survival of the patients. Preservation of the bladder is considered to be possible in patients who obtained CR.