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A reinvestigation of the function of the mammalian urinary bladder.

The function of adult mammalian urinary bladder is evaluated in light of recent in vitro experiments. The discrepancy between in vivo and in vitro experimental results is examined and a possible solution proposed. Techniques for eliminating edge damage and measuring apical membrane surface area are described. A new chamber design for microelectrode studies is illustrated. The possibility of apical cell membrane damage caused by microelectrodes is critically examined and tested using the polyene antibiotic Nystatin. Using data from transepithelial and microelectrode experiments, a model for net Na+ transport across the bladder is proposed and then critically analyzed. The possible clinical implications of the in vitro experiments are briefly discussed.

Amiloride↗

Histogenesis of nonurothelial carcinomas in the human and rat urinary bladder.

The histogenesis of nonurothelial carcinomas (squamous cell carcinoma, common adenocarcinoma, clear cell adenocarcinoma, signet ring cell adenocarcinoma and undifferentiated carcinomas) of the urinary bladder is difficult to understand, since the bladder is normally lined exclusively by transitional cell epithelium and contains no otherwise specified epithelia. In the present study we analysed the morphology and development of nontransitional cell carcinomas of the human and comparatively of the rat urinary bladder in an attempt to elucidate their histogenetic derivation. There is strong evidence that the underlying histogenetic principle consists in the well-known pluripotent metaplastic potency (squamous, columnar, goblet and signet ring cell, glandular and so-called nephrogenic metaplasia) of the normal and neoplastic urothelium as well, due to the complex embryologic origin of the bladder. Our findings indicate that squamous cell carcinomas, common and clear cell adenocarcinomas, and signet ring cell adenocarcinomas mainly arise secondarily from preexisting, predominantly solid transitional cell carcinomas by focally beginning and diffusely progressing metaplastic changes of various types. The second histogenetic pathway consists in the formation from primary metaplasias of the transitional cell epithelium in situ. Undifferentiated carcinomas (small, large and sarcomatoid subtypes) develop from preexistent solid urothelial carcinomas by a cellular dedifferentiation. Recognition of transitional cell carcinomas characterised by focal metaplastic processes or cellular dedifferentiation seems to be important from a clinical point of view, because of their probably more malignant biologic behaviour compared with uniformly differentiated pure urothelial carcinomas. Our comparative morphologic analysis of nonurothelial carcinomas and their histogenesis has demonstrated that the findings in the human and rat urinary bladder are largely identical. The experimental models used permit reliable extrapolation of the results obtained to the situation in man.

Adenocarcinoma, Clear Cell↗

Morphologic changes in the urinary bladder and stomach after long-term administration of sodium saccharin in F344 rats.

The effects of long-term administration of sodium saccharin on the urinary bladder and stomach of F344 rats were investigated. Sixty-eight male F344 rats, aged 7 weeks at the beginning of the experiment, were maintained on diet supplemented with 5% sodium saccharin for 112 weeks. Animals were killed periodically and investigated for gross and microscopic lesions in the urinary bladder and stomach. Papillary or nodular hyperplasia was evident in the urinary bladder epithelium from 8 weeks onwards although no papillomas or transitional cell carcinomas developed. Lesions observed in the bladders of control animals fed the basal diet without the saccharin supplement were limited throughout the experiment to a few areas of simple hyperplasia. While no changes were apparent in the stomach of control animals, a 100% incidence of hyperkeratosis at the limiting ridge of the forestomach was observed after 80 weeks administration of saccharin, 5 of 20 animals also having papillomas. Furthermore, erosion was pronounced in the glandular stomach of saccharin-treated animals with 4 cases of atypical gland being observed. No histopathological lesions were apparent in the liver, kidneys or spleen of either control or experimental groups.

Animals↗

[Innervation of the rat urinary bladder. II. Effects of prostaglandins on the denervated detrusor muscle after bilateral pelvic ganglionectomy].

The effects of prostaglandin (PG) F2 alpha and E2 on the denervated smooth muscle of the urinary bladder in female rats were studied in vivo by histochemistry and electron microscopy. The urinary bladder denervated by bilateral removal of the pelvic ganglion was markedly distended, being filled with urine. Daily intravenous administration of PGF2 alpha or PGE2 for 6 days following the operation showed that rats receiving PGE2 urinated remarkably more than those receiving PGF2 alpha. But the ultrastructural changes on the smooth muscle cells, such as dilated tubules of rough endoplasmic reticulum and large Golgi vacuoles, were more prominent in the PGF2 alpha administrated urinary bladders than in PGE2 administrated ones. On occasion, cholinergic ganglion cells happened to be encountered in the muscular layer of a rat urinary bladder. These intramural ganglion cells and the cholinergic nerve fibers surrounding the cells displayed strong acetylcholinesterase activity, unaffected by bilateral pelvic ganglionectomy.

Animals↗

Inverted papillary carcinoma of the urinary bladder.

A 47-year-old man presented with an inverted papillary carcinoma of the urinary bladder. Cystoscopy revealed an approximately 2 cm mass, with a small stalk and smooth surface, which was situated just medial to the right ureteral orifice. Transurethral resection of the tumor was performed on July 25, 1983. Malignant changes were recognized in the epithelial cords in the resected specimen. This is in contrast to the general view that inverted papilloma of the urinary bladder is benign in nature. The authors believe that careful pathologic examination should be done when an inverted type tumor of the urinary tracts is found. No recurrence has been recognized as of September 11, 1987.

Carcinoma, Papillary↗

Higher DNA adduct levels in urinary bladder and prostate of slow acetylator inbred rats administered 3,2'-dimethyl-4-aminobiphenyl.

Human epidemiological studies suggest associations between acetylator phenotype and aromatic amine-induced tumors. The aromatic amine carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMABP) induces colon, prostate, and urinary bladder tumors in the rat, and a rapid and slow acetylator rat model has been characterized. The formation of DNA adducts has been used as a valuable biomarker in tumorigenesis. In order to examine the relationship between the acetylation polymorphism and aromatic amine-induced cancer, DNA adducts were measured in three target organs (colon, prostate, and urinary bladder) and two nontarget organs (liver and heart) of male rapid (F344) and slow (WKY) acetylator inbred rats administered DMABP. Two DMABP-DNA adducts, N-(deoxyguanosin-8-yl)-DMABP (C8-DMABP) and 5-(deoxyguanosin-N2-yl)-DMABP (N2-DMABP), were identified in each target and nontarget organ examined. C8-DMABP-DNA adduct levels were highest in liver and were dose related in liver, colon, urinary bladder, and prostate. DMABP-DNA adduct levels were significantly higher in the prostate and urinary bladder of slow acetylator vs rapid acetylator rats. These studies suggest that DMABP-induced DNA damage is acetylator phenotype-dependent in urinary bladder and prostate, two target organs for DMABP-induced tumorigenesis in the rat.

Acetylation↗

Effects of promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in the rat.

It has been shown that the occurrence of the preneoplastic lesion, papillary or nodular hyperplasia (PN hyperplasia) in rat urinary bladder induced by carcinogens is correlated with that of cancer. Therefore, the promoting effects of chemicals in two-stage bladder carcinogenesis were judged by measuring their ability to induce PN hyperplasia in rats. Male rats were given N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then one of 16 test chemicals for 32 to 34 weeks. Saccharin, ascorbate, DL-tryptophan, allopurinol, and diphenyl promoted development of PN hyperplasia. The dose-response of the promoters were examined in both sexes of rats by administration of saccharin at doses of 0.04, 0.2, 1.0 and 5.0% for 32 weeks after BBN treatment. The occurrence of PN hyperplasia was significantly increased in the group given 5% saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 0.2 to 5% saccharin. The organ specificities of promoters were studied in rats initiated with BBN or 2-acetylamino-fluorene (2-AAF) followed by phenobarbital or saccharin for 32 weeks. Phenobarbital greatly enhanced hepatocarcinogenesis. Saccharin significantly enhanced the occurrence of both BBN-induced and 2-AAF-induced PN hyperplasia. However, there was no effect of phenobarbital on the urinary bladder or of saccharin on the liver. The rats showed a strain difference in susceptibility of the urinary bladder to saccharin; ACI rats were most susceptible and Sprague Dawley rats were most resistant to saccharin. The membrane potential of superficial epithelial cells in the urinary bladder of rats treated with saccharin was measured with an intracellular microelectrode and found to be higher than that of controls.

2-Acetylaminofluorene↗

A comparative study on the contraction induced by high K+/Na+ deficient solution in rat uterus or urinary bladder.

In the present paper, effects of high K+/Na+ deficient solution on the rat uterus were examined on the mechanical response, wet weight of the tissue or rate of oxygen consumption, and they were compared with those in rat urinary bladder. In the uterus, isosmotic substitution of K+ for Na+ in a physiological salt solution (PSS) induced a contraction followed by a small sustained contraction, while hyperosmotic addition of KCl to PSS induced a sustained contraction. The hyperosmotic KCl addition increased the rate of oxygen consumption in comparison with that in PSS, and the substituted high K+/Na+ deficient solution decreased it as compared with that in the hyperosmotic KCl addition. Similar results were shown in the urinary bladder. At 120 min after application of the substituted high K+/Na+ deficient solution, the relative wet weight increased in the uterus, but did not change in the urinary bladder. Both the decrease in the developed tension and the increase in the wet weight of the uterus were prevented by the hyperosmotic addition of sucrose. In the urinary bladder, the decreased tension was significantly prevented by the hyperosmotic addition of NaCl to the PSS or substitution of pyruvate or oxalacetate for glucose, whereas it was slightly prevented by the hyperosmotic addition of sucrose. From these results, it is suggested that the decrease of the developed tension in isosmotically substituted high K+/Na+ deficient solution in rat uterus is probably due to cell swelling and that the inhibition of contraction in urinary bladder is mainly caused by the inhibition of glucose utilization by Na+ deficiency in the medium.

Animals↗

Superimposed histologic and genetic mapping of chromosome 17 alterations in human urinary bladder neoplasia.

Multistep alterations of chromosome 17 in the progression of human urinary bladder neoplasia were studied by superimposed histologic and genetic mapping. The p53 gene was included in the analysis as a model tumor suppressor gene that is frequently involved in urothelial carcinogenesis. The strategy provided a systematic approach to the study of multistep genomic alterations that occur as neoplasia progresses from precursor intraurothelial conditions to invasive cancer. This was accomplished by sampling the entire mucosa of the organ and displaying microscopically identified invasive cancer and precursor conditions in the form of a histologic map. Subsequent isolation of DNA provided a set of samples in which the search for genetic alterations was performed and superimposed on the histologic map. This approach disclosed multifocal allelic losses of chromosome 17 in the early preinvasive phases of urothelial neoplasia. The alterations were predominantly confined to the p12-13, q22-11 and q24-25 regions. Mutations and allelic losses of the p53 gene were mapped to early preinvasive phases of urothelial neoplasia. The data provide detailed analysis of chromosome 17 allelic losses that occur in the development and progression of urothelial neoplasia and represent the first step for genome-wide modeling of multistep human urothelial carcinogenesis.

Alleles↗

Increase of S-100 immunoreactivity in the urinary bladder from patients with multiple sclerosis, an indication of peripheral neuronal lesion.

The Schwann cells in urinary bladder biopsies from multiple sclerosis patients and controls were examined by immunocytochemistry with an antiserum to S-100. S-100 immunoreactivity was found to be markedly increased in these tissues as compared with the controls, indicating a Schwann cell hyperplasia in the urinary bladder in multiple sclerosis. This finding suggests that local neuronal damage exists in the urinary bladder of patients with multiple sclerosis. Therefore, the concept of multiple sclerosis as a disease wholly of the central nervous system should be reexamined.

Animals↗

[Radiogenic alterations following telecobalt irradiation of urinary bladder tumors].

The investigation reports on the frequency of radiogenic changes after high dosage radiotherapy of carcinomata of the urinary bladder carried out on 109 patients. Severe changes on urinary bladders and rectum were established in ca. 15% of the patients, 61.5% were clinically without any complaints. The importance of the single focus dose for the complication rate is proved and an adequate radiotherapy regime for the reduction of late sequelae is recommended. With regard to the necessity of the telecobalt irradiation one must cope with smaller lesions.

Cobalt Radioisotopes↗

5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder.

The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M) caused contractions of strips of the urinary bladder, in a concentration dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while granisetron and SB204070 antagonized the contractions induced by high concentrations of 5-HT. Atropine inhibited the contractions induced by high concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the presence of atropine, but granisetron and SB204070 did not affect the contractions under such a condition. 5-HT enhanced the electrically-stimulated (5 Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline, and the enhancement was antagonized by granisetron and SB204070. Thus, the contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5-HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a property of low affinity to 5-HT and located on the cholinergic neurons.

Animals↗

Effects of sensitization on the permeability of urothelium in guinea pig urinary bladder.

Permeability of the guinea pig urinary bladder was investigated in a model of experimental cystitis induced by intravesical antigen challenge following sensitization. Guinea pigs were sensitized by intraperitoneal injections of ovalbumin (10 mg./kg.) given on days 1, 3, and 5. The studies described were done four weeks after the last injection. Controls (injected with saline) were used at the same time as sensitized animals. Each group (control and sensitized), was divided into two subgroups; guinea pigs challenged with intravesical ovalbumin (10 mg./ml., one ml.) and those receiving one ml. saline intravesically. Immediately following the antigen (or saline) challenge, one ml. of 14C-urea urea was placed into the bladder for two hours. We examined the peripheral blood concentrations of 14C-urea at periods of time up to 120 minutes. There was a progressive increase in the blood level of 14C-urea with time only in the sensitized group challenged with antigen (ovalbumin). There was no 14C-urea present in the blood of the sensitized group without antigen challenge, or in either unsensitized group. We also measured isotope concentration in the bladders and found a significantly higher concentration of isotope in the bladders from ovalbumin-treated sensitized guinea pigs. We believe that this animal model of cystitis is an improvement over previous models because of its physiological relevance. In this model, cystitis is produced without mechanical or chemical damage to the bladder mucosa. A discussion of the model in relation to interstitial cystitis is presented.

Animals↗

Nomograms of total renal volume, urinary bladder volume and bladder wall thickness index in 3,376 children with a normal urinary tract.

BACKGROUND: We have previously shown that urinary bladder volume index (BVI = length x width x depth of bladder) and bladder volume wall thickness index (BVWI = BVI at full bladder/average bladder wall thickness) are useful indicators of bladder dysfunction in children with enuresis and urinary tract infection. These indices show a good correlation with urodynamic studies. We have expanded the study to include normal paediatric subjects with a wide age range. We illustrate a simple sonography protocol with nomograms of different parameters, which provide useful references for functional assessment in children with urological abnormalities. OBJECTIVE: To construct nomograms of total renal volume, maximum BVI and BVWI based on a Chinese paediatric population with age range from newborn to adolescence. MATERIALS AND METHODS: Sonography was performed in consecutive children with normal urinary tracts on imaging, using a standardized protocol. Data were collected for construction of nomograms for different parameters. RESULTS: Nomograms of total renal volume, BVI and BVWI were constructed based on 3,376 consecutive paediatric subjects. All parameters consistently increased with age. CONCLUSION: Nomograms of total renal volume, BVI and BVWI could provide useful references for studying bladder dysfunction in children using noninvasive dynamic sonography.

Adolescent↗

Enhancing effect of thiabendazole on urinary bladder carcinogenesis induced by sodium o-phenylphenate in F344 rats.

Sodium o-phenylphenate (OPP-Na), a urinary bladder carcinogen in rats, and another fungicide, thiabendazole (TBZ) were fed separately or simultaneously to F344/DuCrj rats of both sexes. The rats were fed one of six diets, either the basal (control) diet or basal diet containing 0.2% TBZ (group T), 1% OPP-Na (1% SO), 2% OPP-Na (2% SO), 1% OPP-Na plus 0.2% TBZ (1% SO-T) or 2% OPP-Na plus 0.2% TBZ (2% SO-T) for 13 or 65 wk. In the 13-wk study, in which groups of ten rats of each sex were used, urinary bladder tumours appeared in 8/10 males in each of three groups--the 2% SO, 1% SO-T and 2% SO-T groups--but not in the remaining animals. Of these tumours, carcinoma accounted for 3/8 tumours in the 2% SO group, 2/8 in the 1% SO-T group and 8/8 in the 2% SO-T group. In the 65-wk study, in which groups of 15 rats were used, the tumour incidence in males was 1/15 in the T group and 15/15, 12/15 and 14/15 in the 2% SO, 1% SO-T and 2% SO-T groups, respectively, while in the females, tumours were found in 2/15, 1/15 and 12/15 animals in the 2% SO, 1% SO-T and 2% SO-T groups, respectively. Of these tumours, carcinoma accounted for 10/15, 11/12 and 10/14 in the males of the 2% SO, 1% SO-T and 2% SO-T groups, respectively, and for 1/2 and 6/12 in the 2% SO and 2% SO-T females, respectively. The tumour incidences in the 1% SO-T males in the two studies and in the 2% SO-T females in the 65-wk study showed a statistically significant increase over those in the 1% SO males or the 2% SO females. Thus, TBZ apparently enhanced the carcinogenic effects of OPP-Na in the rat urinary bladder.

Animals↗

[A new way of preventing urinary bladder tumors].

An experimental study of urinary bladder tumor in rats has demonstrated that their development is suppressed and latency period is increased as a result of a prolonged inhibition of a urine enzyme, beta-glucuronidase by treatment with poglucar.

Animals↗