[Study of primary tumors of the bladder in the Tokai Urological Tumor Registry over a 4-year period].
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Biomedical subjects
Publications and source records attributed to K Obata.
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Serum and tissue concentrations of 5-FU and FT-207 were estimated in 26 patients with bladder tumor or prostatic carcinoma after administration of FT-207 suppositories. The 5-FU concentration in bladder tumor was higher than in normal mucosal bladder tissue. The 5-FU concentration of prostatic cancer was almost equal to that of normal prostatic tissue. Relatively higher concentrations of 5-FU were recognized in bladder tumor of a high stage than of a low stage. There were no differences of serum and tissue 5-FU concentration in bladder tumor between patients more than 65 years old and those under 65 years old. No side-effects occurred in any case during suppository administration.
A phase II study of a new anthracycline anti-cancer antibiotics, epirubicin (EPI), was undertaken in 71 patients with urothelial malignancies; 40 with advanced urothelial malignancies and 31 with superficial bladder cancer. Out of them 32 patients with advanced stage of urothelial cancer were evaluated for the systemic use of EPI, while 30 patients with superficial bladder cancer for intravesical use. Intravenous administration of this new anticancer antibiotic, at a dosage of 60 mg/m2 every three weeks, showed the response rate of 20.0% for advanced bladder cancer and 14.3% for renal pelvic and ureteral tumors. In cases of superficial bladder cancer, at a dosage of 60 mg/30 ml X 3 day every week in principal, the response rate was 66.7%. Eight out of 30 patients showed complete disappearance of the tumor. Twelve patients also showed more than 50% tumor regression. As for adverse effects no serious cardiotoxicity was demonstrated. Anorexia and other gastrointestinal side effects, such as nausea and vomiting, were also seen. Alopecia and myelosuppression were the major adverse effects among patients with systemic EPI administration. With intravesical use of EPI, cystitis syndrome was the major toxicity. However, no systemic side effects were noted in these cases. In conclusion, EPI was assumed to be effective for the treatment of advanced urothelial tumors and superficial bladder cancer.
The new chemotherapeutic agent NFLX was orally administered 600 mg a day for 5 consecutive days in 44 cases having complicated urinary tract infection, and its clinical efficacy was evaluated. They consisted of 8 marked effective cases, 19 moderately effective cases and 17 ineffective cases, and its overall clinical efficacy was 61%. The bacteria disappeared in 10 cases, and decreased in 9 cases. Thirteen cases showed bacterial alternation, and 12 cases remained unchanged. By type of disease group, the efficacy was slightly inferior in the indwelling catheter group compared with that of the nonindwellt group.
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The organization of the olfactory nerve projection to the olfactory bulb was studied immunohistochemically in the rabbit by using monoclonal antibodies (MAbs). Out of 42 MAbs raised against the homogenate of the olfactory bulb, two types of MAbs that strongly stained the olfactory nerve fibers (axons of olfactory receptor cells) were selected and their staining patterns were analysed in detail. MAbs of one type (represented by MAb R2D5) specifically labeled all olfactory receptor cells in the nasal epithelium and all olfactory nerve fibers and their terminal portions in the bulb. The other type of MAbs (represented by MAb R4B12) recognized only a subgroup of olfactory nerve fibers. The R4B12-positive fibers were distributed over the ventrolateral areas but not in the dorsomedial areas of the epithelium. Similarly in the bulb, the R4B12-positive fibers terminated in the glomeruli in the ventrolateral and the caudal regions but not in the dorsomedial region. These results demonstrate for the first time the cellular heterogeneity among olfactory receptor neurons at the molecular level. The segregated distribution of the subtypes of olfactory receptor cell axons both in the epithelium and the bulb indicates a defined topographical organization of the olfactory nerve projection. These results also suggest a functional division between dorsomedial and ventrolateral areas both in the epithelium and the bulb.
Vomeronasal nerve (VNN) fibers and their terminations in the accessory olfactory bulb (AOB) were studied immunohistochemically using 3 monoclonal antibodies (MAbs). One MAb (R2D5) labeled all VNN fibers. Another MAb (R4B12) labeled a subgroup of the VNN fibers which terminated in the rostrolateral glomeruli in the AOB. The third MAb (R5A10) recognized a complementary subgroup of the VNN which terminated in the caudomedial portion of the AOB. These results for the first time show occurrence of subtypes in the VNN axons with segregated terminations in the AOB.
A library of monoclonal antibodies (MAbs) was generated against a homogenate of the rabbit olfactory bulb. One of them immunohistochemically distinguished a subgroup of olfactory nerves. Both in the olfactory bulb and the epithelium, this MAb labeled most olfactory receptor axons in the lateral but only a small fraction in the medial portion. These findings demonstrate a molecular heterogeneity among olfactory receptor cells and suggest a functional division between the lateral and the medial portions of the epithelium and the bulb.
Degeneration of cholinergic neurons from the basal forebrain nuclei is suspected to be the cause of Alzheimer disease. We have developed dissociated cultures of cholinergic neurons from these nuclei (the nucleus basalis of Meynert, the medial septal nucleus, and the diagonal band nuclei). Brain slices of the forebrains were made by a vibratome, and the basal forebrain nuclei were dissected out, dissociated, and cultured. Choline acetyltransferase immunocytochemistry and acetylcholinesterase cytochemistry revealed large cholinergic cells (average diameter, 20-25 micron) in these cultures. About 75% of large neurons (20 micron or larger in diameter) were cholinergic. Electrophysiological experiments were performed on these large neurons. The neurons usually did not show spontaneous firing, but steady depolarizations produced trains of action potentials, which adapted quickly. The neurons responded with depolarization to the application of L-glutamic acid. Substance P produced depolarization (sometimes hyperpolarization), and during the depolarization membrane resistance was increased.
The developmental changes in protein composition of the chick optic tectum were analyzed by two-dimensional gel electrophoresis. Staining with Coomassie Brilliant Blue R revealed 54 major proteins, eight of which remarkably changed their abundance during development: Four of these proteins (S8, S14, S30, and S54) increased and two of them (S7 and S37) decreased in the course of the brain development. The other two proteins (S5 and S6) appeared at specific embryonic stages and were not detected in the adult. The abundance of S5 protein was highest at day 7, and that of S6 protein at days 9-18. The two proteins were present in other regions of the embryonic brain but were not detected in the embryonic liver. The proteins were purified from the soluble fraction of embryonic chick brains by pH 5.5 precipitation, DEAE-Sepharose column chromatography, ammonium sulfate precipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weights of S5 and S6 proteins were 95,000 and 100,000, respectively, and their isoelectric points were about 4.5. They were compared by peptide mapping using V8 protease and found to share 11 common peptides out of 17 distinct ones. This indicates a strong degree of structural homology between these two proteins.
Relations between occupational history and the development of cancer of the lower urinary tract ("bladder cancer") were evaluated in Boston, Massachusetts, USA, Manchester, UK, and Nagoya, Japan. Population-based series of incident cases and controls were identified and interviewed in each area. The present analysis was limited to men and was based on 430 cases and 397 controls in Boston, 399 cases and 493 controls in Manchester, and 226 cases and 443 controls in Nagoya. In Boston, elevated risk of bladder cancer was associated with employment related to dyes (relative risk = 2 X 1; 90% confidence interval, 0 X 9-5 X 1), leather (1 X 7; 1 X 1-2 X 6), paint (1 X 5; 0 X 9-2 X 4), or organic chemicals (1 X 6; 1 X 1-2 X 5). In Manchester, elevated risk was associated with 0 X 9-3 X 6). No clear association was observed between occupation and risk in Nagoya. Elevations in risk related to occupation generally were stronger in men under 65 years of age compared to older men. Differences from place to place in associations between occupation and risk may be the result of differences in the exposures to hazardous agents that jobs with the same title involve.
We conducted a population-based case-control study of patients with bladder cancer and of controls drawn randomly from the general population of Metropolitan Nagoya and interviewed both groups. The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males, respectively. The analysis, based on 293 patients and 589 controls who were frequency matched for age, sex, and residence, provided the following major findings. Age-adjusted relative risks of 1.89 (1.15-3.10) and 3.53 (1.71-7.27) were found in male and female cigarette smokers, respectively. Significant relative risk was also found in males who drank cocoa. Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke, but this risk was insignificant, with the disappearance of a dose-response relationship, when it was adjusted for smoking. Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship. Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking. Intake of alcoholic beverages and cola was insignificantly associated. Reduced risk of significance was suggested for the intake of black tea and matcha (powdered green tea) in females and of fruit juice in males.
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A case of multiple cavernous hemangiomas of the lung is presented. A 61-year-old woman was suffering from mitral stenosis and insufficiency. On the chest roentgenogram, multiple tumor shadows were revealed at all the lobes of the lung. She had been followed up for about 10 years under the diagnosis of the metastatic carcinoma of the lung. But no tumor lesion had been found at any other organs. Throughout this period, the tumor shadows had not changed in size or number. She died of congestive heart failure, and an autopsy was performed. Histologically, the tumors were diagnosed as cavernous hemangiomas and differentiated from arteriovenous fistula or sclerosing hemangioma.
The mechanism of N6,O2'-dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP) induction of pro-vasoactive intestinal polypeptide (VIP)/PHM-27 biosynthesis was investigated in human neuroblastoma cells in culture. When neuroblastoma cells were grown for 48 h in the presence of 1 mM Bt2cAMP, the synthesis of pro-VIP/PHM-27 was stimulated 11-fold. The amount of prepro-VIP/PHM-27 mRNA determined both by hybridization with cloned prepro-VIP/PHM-27 cDNA and a reticulocyte cell-free translation assay was also increased 11-fold in the Bt2cAMP-induced cells. Transcription of prepro-VIP/PHM-27 mRNA in isolated nuclei was observed in induced cells, but not in uninduced cells. Blot hybridization with prepro-VIP/PHM-27 cDNA of total nuclear RNA isolated from neuroblastoma cells revealed an RNA species corresponding to mature prepro-VIP/PHM-27 mRNA, and the amount of the RNA was markedly increased in the induced cells. The quantity of VIP/PHM-27 gene in the DNA of neuroblastoma cells was analyzed after hydrolysis with a restriction endonuclease, EcoRI. However, VIP/PHM-27 gene was not amplified in the induced cells. These results indicate that Bt2cAMP-induced pro-VIP/PHM-27 synthesis is achieved by enhancing the transcription rate of prepro-VIP/PHM-27 mRNA.
The monoclonal antibody technique was used to investigate neuronal heterogeneity and its developmental changes in the chick embryo trunk especially at the thoracic level. We report here four monoclonal antibodies (called SC 1, SC 2, SC 3, and SC 4) that bound to cell surface antigens. These antigens appeared to be proteins or glycoproteins because of their susceptibility to trypsin. In the spinal cord, antibody SC 3 stained all cells, but antibody SC 1 specifically stained motoneurons and ventral epithelial cells. The staining of motoneurons by antibody SC 1 was transient. It appeared at early stages (stage 16-17; Hamburger and Hamilton), but decreased markedly in intensity at older stages (stage 30-31). Antibody SC 2 did not stain cells in the spinal cord. It stained only neurons in the dorsal root and sympathetic ganglia. Antibody SC 4 stained only cells derived from the neural crest at the early stages (stage 16-20). At later stages, it stained a wider population of cells, including sensory neurons, Schwann cells, and cells in the central nervous system. In the dorsal root ganglion, antibodies SC 1 and SC 2 stained only neuronal cells whereas antibodies SC 3 and SC 4 stained both neuronal and glial cells. The dorsal root ganglionic antigens recognized by these antibodies were not expressed concurrently but appeared in a developmental sequence. Staining with antibodies SC 3 and SC 4 appeared first, then SC 1, and finally SC 2. Among these four antigens, the antigens common to both neuronal and glial cells appeared earlier than the neuron specific antigens. Thus, our monoclonal antibodies revealed heterogeneities in cell surface neuronal molecules and their transient and sequential appearance during embryonic development.