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Ca2+ entry through the apical membrane reduces antidiuretic hormone-induced hydroosmotic response in toad urinary bladder.

The role of Ca2+ in the regulation of antidiuretic hormone(ADH)-induced water permeability of the apical membrane of the toad urinary bladder was examined. The effects of modifying Ca2+ entry through the apical membrane of toad urinary bladders on the hydroosmotic water flow (phi H2O) and short circuit current (Isc) were measured. In most experiments the bladders were treated with small amounts of Ag+ (10(-7) mol/l) on the apical side. This treatment was used because previous experiments indicate that it markedly increases alkali-earth cation fluxes through an amiloride-insensitive cation channel in the apical membrane of the urinary bladder. Moreover, when Ca2+ is the major cation in the apical solution of these Ag(+)-treated bladders, Isc is mostly due to Ca2+ entry through the apical membrane. Ag+ increased Isc and simultaneously inhibited phi H2O in bladders perfused with Ca2+ solutions on the apical side. Addition of La3+ to the apical solution reversed the stimulation of Isc and the inhibition of phi H2O produced by Ag+. When bladders were perfused with Ca2(+)-free solutions on the apical side, addition of Ag+ did not inhibit phi H2O while the stimulation of cation movements through the amiloride-insensitive cation channel persisted. In bladders perfused with apical Ca2+ solutions and treated with chlorophenyl thio-cyclic adenosine monophosphate (ClPheS-cAMP) the addition of Ag+ did not inhibit phi H2O while it still increased Isc. Finally, addition of Ca2+ to the apical solution of bladders not treated with Ag+ reduced phi H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urinary bladder distention: effect on labor and uterine activity.

To study quantitatively the effect of urinary bladder distention on labor and uterine activity, 68 patients requiring catheterization were studied. All patients were in the active phase of labor and had transcervical intrauterine pressure monitoring. Patients were studied in the same lateral position for 30 minutes before and after a catheterization interval, during which time uterine activity units were quantitated on line and changes were noted in cervical dilation and station and contraction frequency and tonus. Results were analyzed for the entire study group, for individual patients, and by urine volumes (10 to 550 ml) obtained at catheterization. Total uterine activity units increased in 43 patients and decreased in 25 after catheterization, but when compared with expected increases calculated from the slopes of the precatheterization interval in individual patients, there were 36 increases and 32 decreases. Individual slopes of uterine activity increased in 36 and decreased in 31 cases. There were no differences when the data were analyzed by urine volume, parity, or bith weight except possibly at large volumes. Changes in rates of cervical dilation and descent of the presenting part conform to the expected normal labor pattern. Within the limits of this study, emptying the urinary bladder has no effect on the course of labor or uterine activity based on the dynamic model of labor.

Adolescent↗

Inflammatory pseudotumor of the urinary bladder in a child.

The inflammatory pseudotumor of the urinary bladder is rare, especially in children. It is a benign proliferative lesion of the submucosal stroma easily mistaken for a sarcoma clinically, so it should be differentiated from a malignant neoplasm. We report the case of bladder inflammatory pseudotumor in a 7-year-old girl.

Child↗

Muscarinic receptors in isolated urinary bladder smooth muscle from different mouse strains.

1. The pharmacological characteristics of muscarinic receptors in male and female mouse urinary bladder smooth muscle from different strains (C57Bl/6, 129/SvJ and hybrid backcross N1F2) were studied. 2. (+)-Cis-dioxolane, oxotremorine-M, acetylcholine, carbachol and pilocarpine induced concentration-dependent contractions of the urinary bladder smooth muscle (range for pEC(50)=6.4-6.6, 6.2-6.7, 6.2-6.4, 5.4-6.0 and 0.0-5.1, T(max)=1.9-4.7 g, 1.3-3.4 g, 1.0-3.0 g, 1.4-2.4 and 0.0-0.3 g, respectively, n=4-6 depending on the gender and the strain). In females, these contractions were competitively antagonized by a range of muscarinic receptor antagonists (pK(B) value range, depending on the strain): atropine (8.0-8.9), pirenzepine (6.1-6.4), 4-DAMP (7.6-8.4), methoctramine (5.6-6.1), p-F-HHSiD (7.5-7.7), zamifenacin (7.7-8.4) and darifenacin (8.2-8.7). 3. In recontraction studies, in which the muscarinic M(3) receptor population was decreased, and conditions optimized to study M(2) receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M(3) receptors (pK(B)=6.26+/-0.08, pA(2)=6.31+/-0.07; pK(B)=6.09+/-0.22, pA(2)=6.08+/-0.01 for female inbred strain 129/SvJ and hybrid backcross N1F2, respectively) or intermediate between the one expected for this compound at M(2) and M(3) receptors, (pK(B)=6.66+/-0.08, pA(2)=7.00+/-0.27 for female inbred strain C57BL/6). 4. These data study suggest that muscarinic M(3) receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in female mouse urinary bladder smooth muscle, with strain differences.

Animals↗

Lack of preventive efficacy of FK228, a histone deacetylase inhibitor, against N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in p53+/- and p53+/+ mice.

BACKGROUND: The efficacy of FK228, a histone deacetylase inhibitor that is currently under early clinical trials for cancer therapy, against N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN) -induced mouse urinary bladder carcinogenesis was examined. MATERIALS AND METHODS: Heterozygous p53-deficient (p53+/-) and wild-type (p53+/+) mice were given FK228 (0, 0.01 and 0.1 mg/kg i.p., 3 times/week, respectively) after 10 weeks of 0.05% BBN treatment, and were sacrificed at 22 and 24 weeks after the start, respectively. RESULTS: There was no significant difference in the incidence of urinary bladder tumors among groups in the p53+/- or p53+/+ mice, although the high dose of FK228 increased the p21WAF1 mRNA expression in urinary bladder cancers in animals of both genotypes. CONCLUSION: The present data indicate a lack of any inhibitory effects of FK228 on BBN-induced mouse urinary bladder carcinogenesis under the present conditions.

Animals↗

Diffusion-weighted MR imaging for urinary bladder carcinoma: initial results.

The aim of this study was to demonstrate the feasibility of using diffusion-weighted (DW) magnetic resonance (MR) imaging under free breathing for the detection of a urinary bladder carcinoma. In 15 patients with 17 urinary bladder carcinomas, DW images were obtained in the axial plane under free breathing scanning with a multisection spin-echo type single-shot echo planar sequence with a body coil. DW images were evaluated based on cystoscopic findings. Moreover, the apparent diffusion coefficient (ADC) value was measured in a circular region of interest (ROI) within the carcinoma, urine, normal bladder wall, prostate and seminal vesicle. In the results, on the DW images, all 17 carcinomas were clearly shown as high signal intensity relative to the surrounding structure. The ADC value (x10(-3) mm(2)/s) in the carcinoma was 1.18+/-0.19, which was significantly lower compared with that of urine (3.28+/-0.20), the normal bladder wall (2.27+/-0.24), prostate (transition zone: 1.57+/-0.09, peripheral zone:1.85+/-0.22) and seminal vesicle (2.01+/-0.22). In conclusion, DW images under free breathing enabled the clear detection of the urinary bladder carcinoma, whose ADC values were lower compared with those of the surrounding structure. The DW images may be useful in evaluating tumors invading to the surrounding structures.

Aged↗

Brain metastasis from small-cell neuroendocrine carcinoma of the urinary bladder: a case report.

Eight months after radical surgery for small-cell neuroendocrine carcinoma (SCNC) of the urinary bladder, a 69-year-old man was admitted with a brain tumor in the left frontal lobe. The tumor, about 5 cm in diameter, was intensely but heterogeneously enhanced on computed tomography and magnetic resonance imaging. The tumor was subtotally removed, leaving only the portion adjacent to the anterior horn of the left lateral ventricle. Microscopically, the tumor was composed of diffuse sheets of small tumor cells with round to spindle-shaped nuclei, indistinct nucleoli, scant or absent cytoplasm, and indistinct cell margins. Immunohistochemically, the tumor cells were positive for synaptophysin, neuron-specific enolase, chromogranin A, and keratin. Ultrastructurally, the tumor cells showed classic neurosecretory granules and microvilli in the cytoplasm. The tumor was diagnosed as a brain metastasis from SCNC of the urinary bladder. After surgery, whole-brain radiation therapy of 40 Gy was performed, which succeeded in controlling the residual tumor. However, 4 months after surgery, the patient died of meningeal carcinomatosis. To our knowledge, this is the first report focusing on brain metastasis from SCNC of the urinary bladder. The clinicopathological features and pathological diagnosis of this tumor are discussed.

Aged↗

Calcium dependent K-channels in guinea pig and human urinary bladder.

This study provides evidence for the presence of large conductance Ca(2+)-dependent K-channels in guinea pig and human urinary bladder smooth muscle. A23187, a Ca(2+)-ionophore, increased charybdotoxin and iberiatoxin sensitive 42K efflux in human urinary bladder smooth muscle cells, suggesting that large conductance Ca(2+)-dependent K-channels are present in these cells. NS004, a large conductance Ca(2+)-dependent K-channel opener, relaxed guinea pig bladder strips precontracted with 15 mM KCl which is inhibited by iberiatoxin. In addition, NS004 also evoked an iberiatoxin sensitive increase in 86Rb/42K efflux in guinea pig and human urinary bladder smooth muscle cells, demonstrating that NS004 activates large conductance Ca(2+)-dependent K-channels to achieve its relaxation effect in the bladder.

Animals↗

The effect of catecholamines on H+ and NH+4 excretion in toad urinary bladder.

The catecholamines epinephrine and norepinephrine, when placed on the toad urinary bladder in vitro, at a final concentration of 50 microM, caused a significant increase in H+ and NH+4 excretion by the bladder. Isoprenaline in a final concentration of 50 microM also increased H+ and NH+4 excretion in the bladder. Propranolol at a concentration of 50 microM blocked the stimulation of H+ excretion by isoprenaline but propranolol at 100 microM was required to block the stimulation of NH+4 by isoprenaline. The dose-response analysis indicates that the concentration of epinephrine used (50 microM) is at or near the maximal effective dose. These findings indicate that catecholamines stimulate H+ and NH+4 excretion in the toad urinary bladder and evidence suggests this may be mediated via the beta receptor mechanism.

Adrenergic alpha-Antagonists↗

Liver and urinary bladder tumors in dogs from 3,3'-dichlorobenzidine.

Six female beagle dogs were given, by capsule, a daily oral dose of 100 mg of 3,3'-dichlorobenzidine (DCB), 3 times per week for 6 weeks, then 5 times per week continuously for periods up to 7.1 years. The DCB test was terminated after 7.1 years. Six untreated female beagle dogs served as controls for several tests and were sacrificed after 8.3 to 9.0 years on test. All 6 DCB dogs had an elevated plasma glutamic-pyruvic transaminase activity during the first 3 years on test; two dogs showed persistent elevation throughout the test. One DCB dog, sacrificed in extremis after 3.5 years on test, had no tumors. Another DCB dog, sacrificed in extremis after 6.6 years on test, developed an undifferentiated carcinoma of the liver with metastases to many organs; this dog also had a papillary transitional cell carcinoma of the urinary bladder. Of the 4 remaining DCB dogs sacrificed after 7.1 years on test, 3 developed hepatocellular carcinomas and all 4 had papillary transitional cell carcinomas of the urinary bladder. No liver or urinary bladder tumors were found in the 6 control dogs. DCB was found to be carcinogenic for the liver and urinary bladder in dogs under the conditions employed (p less than .025, Fisher's Exact Test, one tail).

3,3'-Dichlorobenzidine↗

Apical material extracted from amphibian urinary bladder epithelium by enzymes and detergent treatment.

The apical plasma membrane of epithelial cells of frog and toad urinary bladder is subject to large modifications during the induction of water permeability by the antidiuretic hormone. A better characterization of the apical membrane is necessary for a clear understanding of the mechanisms of hormone action. Towards this end, apical material was extracted by enzymatic treatment and by incubation with detergent. Proteolytic enzyme alone had little effect under our conditions. A pretreatment with several glycosidases (alpha-mannosidase or endo-beta-N-acetylglucosaminidase H) increased the hydrolytic action of papain, elastase, proteinase K or Staphylococcus aureus V8 protease and allowed the detection of a major 76 kD in SDS gel electrophoresis. The n-octyl-beta-D-glucopyranoside (0.2%) led to the extraction after 150 mn of 1 to 5 micrograms proteins per cm2 of amphibian urinary bladder apical surface. The extracted proteins migrated as several bands on SDS gels. One of them probably corresponds to the 76 kD fragment obtained after proteolysis. The absence of alteration of the water permeability after extraction and the good preservation of the ultrastructure are evidence for the localisation of the 76 kD at the apical membrane surface. This protein may be the best candidate as antigen to raise antibodies against the apical surface of amphibian urinary bladder epithelial cells.

Animals↗

[New methods of urinary bladder cancer detection at the early stage of the disease in patients of various ages].

In the sickness rate's structure of the malignant neoplasms the urological localization take 6.8 per cent (%). Among them 70% is cancer of the urinary organs. The average age of the patients with cancer of the urinary bladder is from 65.2 to 69.7 years old. The use of fluorescent cystoscopy allows to improve the quality of the diagnostics of the urinary bladder's mucous' neoplastic changes. It is illustrated that the fluorescent cystoscopy's sensitivity is 96.9-98.7% and exeeds the sensitivity of simple cystoscopy research method for more than 20%. Carcinoma in situ was found 2 times more often than with the help of traditional cystoscopy and "blind" biopsy. Carrying out urinary bladder's wall transuretral resection under the photodynamic control increases the radical character of the endoscopic operation and allows to reduce the quantity of cancer's relapses by decreasing the amount of residual tumors. The test examination (in a year after the operation) has shown that the tumor's recurrences were registered 2.2 times more seldom in those group of patients, which had the neoplasms extracted under the photodynamic control.

Adult↗

Apical membrane area of rabbit urinary bladder increases by fusion of intracellular vesicles: an electrophysiological study.

Mammalian urinary bladder undergoes, in a 24-hour period, a series of slow fillings and rapid emptying. In part the bladder epithelium accommodates volume increase by stretching the cells so as to eliminate microscopic folds. In this paper we present evidence that once the cells have achieved a smooth apical surface, further cell stretching causes an insertion of cytoplasmic vesicles resulting in an even greater apical surface area per cell and an enhanced storage capacity for the bladder. Vesicle insertion was stimulated by application of a hydrostatic pressure gradient which caused the epithelium to bow into the serosal solution. Using capacitance as a direct and nondestructive measure of area we found that stretching caused a 22% increase in area. Removal of the stretch caused area to return to within 8% of control. An alternate method for vesicle insertion was swelling the cells by reducing mucosal and serosal osmolarity. This perturbation resulted in a 74% increase in area over a 70-min period. Returning to control solutions caused area to decrease as a single exponential with an 11-min time constant. A microtubule blocking agent (colchicine) did not inhibit the capacitance increase induced by hypoosmotic solutions, but did cause an increase in capacitance in the absence of a decreased osmolarity. Microfilament disrupting agent (cytochalasin B, C.B.) inhibited any significant change in capacitance after osmotic challenge. Treatment of bladders during swelling with C.B. and subsequent return to control solutions increased the time constant of the recovery to control values (22 min). The Na+-transporting ability of the vesicles was determined and found to be greater than that of the apical membrane. Aldosterone increased the transport ability of the vesicles. We conclude that some constituent of urine causes a loss of apical membrane permeability. Using electrophysiological methods we estimated that the area of cytoplasmic vesicles is some 3.3 times that of the apical membrane area. We discuss these results in a general model for vesicle translocation in mammalian urinary bladder.

Animals↗

Smooth muscle neoplasms of the urinary bladder: a clinicopathologic comparison of leiomyoma and leiomyosarcoma.

We report the clinicopathologic, immunohistochemical, and DNA ploidy findings of 18 leiomyosarcomas of the urinary bladder. In addition, we compare these malignant smooth muscle tumors with 10 cases of urinary bladder leiomyoma. The 14 male and four female patients with leiomyosarcoma ranged in age from 25 to 88 years (mean 64 years). The tumors ranged from 3.0 to 15.0 cm (mean 7.1 cm) in greatest dimension and were moderately to highly cellular, consisting of interlacing fascicles of spindled cells with mild to marked nuclear atypia. Coagulative tumor necrosis was identified in 14 cases (78%), and mitotic activity ranged from 1 to 42 mitotic figures (MF) per 10 high power fields (HPF) (mean 12 MF/10 HPF). Tumors were classified as either high-grade (12 cases) or low-grade (six cases) based on nuclear atypia, mitotic activity, and tumor necrosis. Actin positivity was present in 15 tumors (83%), and desmin immunoreactivity was present in seven tumors (39%). All cases were negative for epithelial markers and S-100. Proliferative activity, as assessed by MIB-1 staining, ranged from 0.1% to 51.4% (median 9.1%). Seven (39%) of the leiomyosarcomas were DNA aneuploid, eight (44%) were tetraploid, and three (17%) were diploid. Five patients underwent radical cystoprostatectomy, one radical cystectomy, seven had partial cystectomy, two underwent pelvic exenteration, and three patients had transurethral resection only. Follow-up information was available on all 18 cases and ranged from 2 to 68 months (mean 22 months). Of the 12 patients with high-grade tumors, six (50%) died of disease from 2 to 20 months (mean 7 months) after diagnosis and three patients (25%) are alive with metastatic tumor. Two of the six patients with low-grade leiomyosarcoma died of tumor, 61 and 68 months after diagnosis. There were five male and five female patients with leiomyoma ranging in age from 22 to 78 years (mean 61 years). The tumors ranged from 0.5 to 4.5 cm (mean 1.6 cm) in greatest dimension, were well circumscribed, and had low cellularity. Mitotic activity, necrosis, and cellular atypia were absent, and the tumors were strongly positive for both actin and desmin. MIB-1 staining ranged from 0% to 3.8% (median 0.8%). Seven (87.5%) of the leiomyomas were DNA diploid or near-diploid and one (12.5%) was DNA aneuploid. Six patients were treated with transurethral resection and four with partial cystectomy. All 10 patients were alive at the last follow-up (mean follow-up 75 months), and no tumor recurred or metastasized. Our study shows that low-grade leiomyosarcomas are capable of malignant behavior, and high-grade leiomyosarcomas appear to behave more aggressively than low-grade tumors. In addition, the diagnosis of urinary bladder leiomyoma should be reserved for noninfiltrative smooth muscle tumors lacking mitotic activity, cytologic atypia, and necrosis.

Actins↗

Primary carcinoid tumor of the urinary bladder.

A polyp of about 1.0 cm diameter was incidentally found at the center of the posterior wall of the urinary bladder in a 73-year-old man on cystoscopic examination. A polyp was resected through a transurethral route without recurrence for 22 months. A polyp consisted of a tumor covered with mucosa of the bladder. Tumor cells have round or oval nuclei with fine chromatin and one or two nucleoli per nucleus, and finely granular eosinophilic cytoplasm, being arranged in a trabecular or tubular pattern. Furthermore, they showed positive staining for chromogranin-A and with Grimelius stain, indicating that the tumor is a carcinoid tumor. Since there was no evidence of carcinoid tumors in organs other than the urinary bladder, the present case is a primary carcinoid tumor (well differentiated endocrine tumor) of the urinary bladder which is extremely rare.

Aged↗

Permeability of pig urinary bladder wall: the effect of chitosan and the role of calcium.

Chitosan is a cationic polysaccharide widely employed as an absorption enhancer. The aim of this work was to examine the effect of chitosan on the permeability of isolated pig urinary bladder wall as well as to determine the role of calcium ions in this process. Besides permeability studies, scanning electron microscopy and fluorescent microscopy were applied to get an insight into the mechanism by which chitosan increases the permeability of urinary bladder wall. Additionally, the obtained findings were compared to the mechanism proposed for Caco-2 cells. The results show that 0.5% (w/v) chitosan increases the permeability of urinary bladder wall by causing the desquamation of the urothelium. Calcium ions, when applied to the luminal surface of the urinary bladder at the same time as chitosan, decreases the effect of chitosan on permeation of the model drug moxifloxacin into the bladder wall in concentration dependent way. The desquamation of urothelium cells caused by chitosan was reduced in the presence of calcium, but not to such extent as it would be expected from the permeability studies. When present, calcium obviously interferes directly in the interactions between chitosan and the surface of urothelium.

Animals↗

Carcinoma of the urinary bladder associated with schistosomiasis in Egypt: the possible causal relationship.

Carcinoma of the urinary bladder is the most common malignancy in Egyptians. At the National Cancer Institute in Cairo, it accounts for 27.6% of all cancers--38.5% of cancers in the male and 11.3% in the female. This very high frequency is attributed to underlying schistosomiasis. The infection can lead to malignancy through local tissue damage, mechanical irritation, bilharzial toxins or through secondary bacterial infection. Bacterial products include nitrate reductase capable of synthesizing nitrosoamines and beta glucuronidase enzymes, active at pH 7. Through liver involvement and dysfunction, tryptophan metabolism is disturbed, with the excretion of carcinogenic metabolites. Vitamin A deficiency is responsible for the squamous metaplasia and the high frequency of squamous cell carcinoma observed in the bladder. The characteristic clinico-pathological features of cancer of the urinary bladder are outlined, mainly the occurrence at a young age, the male predominance, especially farmers, and the high association with schistosomiasis. The tumors are often first seen in an advanced stage, arising from the posterior bladder wall and vault. The trigone is only affected in 8.5% of the cases. Histologically, squamous cell carcinomas of low grade are the most frequent cell type. Lymph node involvement is low in spite of the advanced stage of the tumor. Therefore, the results of radical surgery are encouraging. The results of a special study correlating the above parameters with the intensity of ova deposition are presented. Patients with heavy infection at a slightly earlier age but other tumor parameters the same are similar to those of egg-negative cases. This study indicates that other factors also play a role in the induction of tumors that are enhanced by the schistosomal infection. In Fayoum Province, schistosomiasis is decreasing while bladder cancer is increasing. Urine cytology as a screening tool is effective in detecting early bladder cancer. Studies are now in progress to detect tumor associated antigens in sera and urine of patients.

Adult↗