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The effect of distension of the urinary bladder on activity in efferent renal fibres in anaesthetized dogs.

1. To test whether distension of the urinary bladder causes a consistent change in activity in efferent renal nerve fibres, bladder distension was performed in anaesthetized dogs. The carotid sinuses were vascularly isolated and perfused with blood at constant flow. Both ureters were cannulated and the urinary bladder was distended with warm Ringer solution at a steady intravesical pressure. 2. In a first series of experiments all twenty-six renal nerve fibres in eleven dogs which responded to changes in carotid sinus pressure and changes in the nature of the blood perfusing the carotid sinuses also responded to distension of the bladder. 3. In a second series of experiments, graded bladder distension over a range of pressure of 0-9.2 kPa led to a graded increase in activity in thirteen efferent renal fibres in six dogs. The magnitude of the renal nerve response was greater at low than at high carotid sinus pressure. Over a range of carotid sinus pressure of 9-30 kPa, the greatest renal nerve activity was obtained at the lower end of this range in the presence of bladder distension. 4. Thus distension of the urinary bladder resulted in the response of a consistent increase in efferent renal nerve activity, which could be graded according to intravesical pressure. The magnitude of the responses to bladder distension was affected by carotid sinus pressure.

Action Potentials↗

[Development of invasive urinary bladder carcinomas].

In this paper, we report on invasive urinary bladder carcinomas as follows, (1) p53 mutations have an important role in promotion and progression stages of carcinogenesis, (2) invasive bladder carcinomas occur multi-centrically in the bladder, (3) an organic arsenic, dimethylarsinic acid exerts carcinogenicity in the bladder of rats, (4) p53 mutations in carcinomas are caused by different carcinogens, and (5) bladder urothelium of people living in 137Cs-contaminated areas of Ukraine showed chronic proliferative atypical cystitis (so-called Chernobyl cystitis).

Animals↗

Paraganglioma of urinary bladder wall.

A classic case of pheochromocytoma of the urinary bladder is presented. The history of headaches and palpitations during micturition is the result of sudden release of catecholamines into the general circulation. The diagnosis using selective arteriography as well as the medical and surgical management are described.

Adult↗

Dose-dependent promoting effect of trisodium nitrilotriacetate monohydrate on urinary bladder carcinogenesis in Wistar rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The dose-dependent effect of trisodium nitrilotriacetate monohydrate (Na3.NTA.H2O) as a promoter in 2-stage carcinogenesis in the urinary bladder of male Wistar rats was investigated. Carcinogenesis was initiated by administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks, then Na3.NTA.H2O was given at 1%, 0.5% and 0.3% in the diet for 28 weeks, and rats were killed in week 32. The incidences and numbers of preneoplastic lesions [papillary or nodular hyperplasia (PN hyperplasia)] in rats treated with 0.3% to 1% Na3.NTA.H2O increased progressively with increasing concentration of Na3.NTA.H2O. The incidences of papillomas in rats treated with 1% and 0.5% Na3.NTA.H20 in the diet and the incidence of transitional cell carcinoma (TCC) of the urinary bladder in the rats treated with 1% Na3.NTA.H2O (P less than 0.05) were significantly higher than those in rats treated with BBN only. Administration of various doses of Na3.NTA.H2O without BBN did not cause any histological changes (PN hyperplasia, papilloma or TCC) in the urinary bladder. These findings showed that Na3.NTA.H2O is a potent promoter of urinary bladder carcinogenesis initiated by BBN in rats, and that its effect is dose-dependent.

Acetates↗

Identification and initial characterization of a putative neuromedin B-type receptor from rat urinary bladder membranes.

Receptor binding site(s) on the rat urinary bladder membranes were characterized using a biologically active analog of bombesin, [Tyr4,Leu14]bombesin, and a 50,000 x g total particulate preparation. The binding was specific, reversible, saturable, time- and concentration-dependent. A dissociation curve showed that both bombesin and neuromedin B equally displaced the radioligand in the first 10 min after saturation. From the rate constant of association K + 1 = 7.60 x 10(9) M-1 min-1, and the rate constant of dissociation k-1 = 0.050 min-1, the apparent equilibrium dissociation constant Kd = 6.57 +/- 1.09 pM was determined. A linear Scatchard plot of the specific binding of 125I-[Tyr4,Leu14]bombesin to the membranes revealed that the radioligand bound with high affinity, Kd = 6.38 +/- 0.86 pM, to a single class of sites (Bmax = 2.3 fmol/mg protein). The Hill coefficient of the same binding data was 1.05 +/- 0.21, indicating that the radioligand was binding to a single population of noninteracting binding sites. Both bombesin and neuromedin B displaced the radioligand dose dependently (IC50 = 0.3 nM). Neurokinin A and neurokinin B were less potent (IC50 = 20 and 110 nM, respectively). Substance P, or the specific bombesin receptor antagonists [D-Phe6]bombesin-(6-13) methyl ester, [D-F5Phe6,D-Ala11]bombesin-(6-11) methyl ester, [D-Phe6]bombesin-(6-13) propylamide, [D-Phe6,Leu13psi(CH2NH)Leu14]bombesin or [D-Cpa6,Phe14(psi13-14)]bombesin-(6-14) had an IC50 greater than 1 microM. The results presented suggest the presence of neuromedin B receptor sites on the rat urinary bladder membranes that can be occupied also by some other peptides, notably bombesin, neurokinin A and neurokinin B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beta-adrenoceptor subtypes in the detrusor of guinea-pig urinary bladder.

beta-Adrenoceptors have been demonstrated in the urinary bladders of many animals including the guinea pig. However, there is little information on the subtypes involved in the antispasmodic activity of beta-adrenoceptor activation in the guinea-pig detrusor. The present study uses the non-selective beta-agonist isoproterenol, the antagonist nadolol, the beta 2-selective agonists salbutamol and terbutaline, the antagonist ICI 118551, and the beta 1-selective antagonist metoprolol, to demonstrate functionally the subtypes existing in the guinea-pig detrusor. Isoproterenol dose-dependently reduces the myogenic activity in the guinea-pig detrusor induced by mild depolarization with 20 mM potassium in the tissue bath. At the supramaximal concentration of 30 microM, isoproterenol achieves 73 +/- 2% of the reference maximal response. This activity of isoproterenol is reduced to 9 +/- 5, 24 +/- 6 and 54 +/- 1% in the total blockade of beta, beta 1 and beta 2 with nadolol, metoprolol and ICI 118551, respectively. Consistently, salbutamol and terbutaline at the same concentration produce only 35 +/- 1 and 38 +/- 4% of the response, respectively. Thus, both beta 1- and beta 2-adrenoceptors are present in the detrusor of the guinea-pig urinary bladder. Although activation of either subtype results in antispasmodic action, the larger portion of the antispasmodic activity appears to be associated with the activation of the beta 1-subtype.

Adrenergic beta-Agonists↗

Rat urinary bladder epithelial lesions induced by acrolein.

Acrolein, a constituent of cigarette smoke and a metabolite of cyclophosphamide, has been shown to induce acute cytotoxicity of the rat urinary bladder mucosa when instilled directly into the bladder lumen. To evaluate the effects of systemic administration, we examined the rat urinary bladder following intragastric or intraperitoneal administration of acrolein to male F344 rats. In an initial experiment, acrolein was administered at a dose of 25 mg/kg, which proved to be extremely toxic. Five of 12 rats injected intragastrically and 5 of 12 injected intraperitoneally died within 24 hrs. After 2 days, 3 of the 3 surviving rats injected intraperitoneally had focal simple hyperplasia of the urinary bladder. None of the rats injected intragastrically had bladder hyperplasia. In a second experiment, acrolein was administered by intraperitoneal injection at doses of 0.5, 1, 2, 4, and 6 mg/kg. Five days later, the labeling index of the bladder mucosa was evaluated by autoradiography. In rats injected with 6 mg/kg of acrolein, the labeling index was significantly increased compared to the other doses and compared to a vehicle injection control group. These data indicate that sufficient acrolein reaches the urinary bladder to induce a proliferative response following intraperitoneal administration.

Acrolein↗

Fluoride but not phorbol esters stimulate rat urinary bladder prostanoid synthesis: investigations into the roles of G proteins and protein kinase C.

The role of G proteins and protein kinase C in mediating muscarine receptor-linked prostanoid synthesis by the rat urinary bladder was investigated using the G protein activator, sodium fluoride (NaF); the protein kinase C activators, phorbol myristate (PMA) and phorbol dibutyrate (PDBU); the protein kinase C inhibitor, H7, and the parasympathomimetic, carbachol. NaF stimulated in vitro rat urinary bladder prostacyclin (PGI2) synthesis (EC50 = 6 mmol.l-1), an action inhibited by the presence of EDTA (10 mmol.l-1). Carbachol potentiated the stimulatory action of NaF. NaF (10 mmol.l-1)-stimulated PGI2 synthesis was inhibited by the calcium channel blockers verapamil, nifedipine and the protein kinase C inhibitor, H7, in concentration-dependent manners. Carbachol-stimulated PGI2 synthesis was also inhibited by H7. PDBU and PMA were without effect on de novo, NaF- or carbachol-stimulated urinary bladder PGI2 synthesis. Other prostanoids (PGF2 and PGF2 alpha) were stimulated to the ame degree as PGI2 by NaF, and inhibited equally by H7 and calcium channel blockers. Dibutyryl adenosine 3':5'-cyclic monophosphate was without effect on de novo or NaF-stimulated prostanoid synthesis. Since fluoride activates G proteins, these data indicate that: (1) muscarine receptor-prostanoid synthesis coupling is mediated by G proteins in the rat urinary bladder; (2) fluoride action is mediated by protein kinase C and not adenyl cyclase, probably through activation of phospholipase C and therefore the generation of the protein kinase C activator, diacyl glycerol; (3) activated protein kinase C may initiate Ca2++ mobilisation linked to prostanoid synthesis; and (4) the lack of effect of the phorbol esters on urinary bladder PGI2 synthesis, in contrast to that on other smooth muscle, indicates that in different smooth muscle tissues there are varying forms of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[New WHO classification of urothelial carcinoma of the urinary bladder].

The WHO classification of urothelial carcinomas of the urinary bladder (1999) presents the papillary urothelial neoplasia of low malignant potential (PUNLMP) as a new entity in between the papillomas and the papillary urothelial carcinomas. This neoplasia shows a typical basal palisading, a low mitotic rate, and a low MIB-1-proliferation index. The PUNLMP is said to have an increased risk of development of recurrent papillary lesions with the possibility of malignant transformation. At present, there is an intensive discussion on this new entity. The participants of a meeting on the consensus classification on urothelial tumors held in Ancona in 2000 have meanwhile split in two discussion groups. One favors the new WHO classification with the papillary urothelial carcinomas G I, G II, and G III, but without PUNLMP, whereas the other group favors the consensus classification of 1998 with papillomas, papillary urothelial neoplasia of low malignant potential, and non invasive as well as invasive low-grade and high grade papillary urothelial carcinomas. Future long term prospective studies will show the significance of PUNLMP compared to well differentiated non invasive papillary urothelial urinary bladder carcinoma G I (G Ia). Otherwise, there is no significant difference in the classification of carcinomas and non epithelial lesions compared with the previous classification of 1973. The new WHO does however discriminate the minimally invasive papillary urothelial carcinomas in those with infiltration of the lamina propria above the muscularis mucosae (pT1a), the infiltration of the lamina muscularis mucosae (pT1b), and the extension beyond the muscularis mucosae (pT1c). The recurrence rate increases from stage pT1b. This substaging may be of therapeutical relevance.

Adenocarcinoma, Papillary↗

Primary calcified T-cell lymphoma of the urinary bladder: a case report.

Primary malignant lymphoma of the urinary bladder is extremely rare, and to our knowledge, no case described in the radiologic literature has been accompanied by calcification. We report a case in which the condition was associated with calcification, and describe the pelvic CT and MR imaging findings.

Adult↗

Small cell carcinoma of urinary bladder.

A fifty-seven-year-old woman with urinary bladder carcinoma with extensive areas resembling oat cell carcinoma of the lung in whom distant metastases developed, died seven months after diagnosis. Argyrophil cells could not be demonstrated, but electron microscopy demonstrated dense-core, membrane-bound intracytoplasmic granules. We reviewed 12 cases of epithelial neoplasms of the bladder from the literature in which there was ultrastructural evidence of neuroendocrine differentiation. Cases with malignant histologic features, like their pulmonary counterparts, have the potential for widespread dissemination and rapid growth. We support the previous suggestion that these neoplasms may be of considerable incidence and their recognition is important to determine prognosis and selection of therapy.

Carcinoma, Small Cell↗

Reliability of MR imaging-based virtual cystoscopy in the diagnosis of cancer of the urinary bladder.

OBJECTIVE: Our purpose was to evaluate MR imaging-based virtual endoscopy in patients with urinary bladder cancer compared with conventional cystoscopy as the gold standard. SUBJECTS AND METHODS: Twenty-five patients with urinary bladder cancer diagnosed on conventional cystoscopy underwent MR imaging of the pelvis. Patients were examined without external bladder filling or administration of IV contrast medium. No medications were administered. The data obtained by MR imaging were reconstructed for virtual endoscopy on a workstation. The locations and sizes of tumors were individually determined and compared with results of conventional cystoscopy. RESULTS: Twenty-four patients were evaluated; one patient's examination was excluded from analysis because of metallic artifacts. Seventeen patients were diagnosed with a single bladder tumor. Five patients had two tumors each, and two patients had three tumors. Tumor diameter ranged from 0.4 to 6.4 cm. Thirty (90.9%) of 33 tumors detected on cystoscopy were visualized with virtual endoscopy. The detection rate for 23 tumors of 1 cm or greater was 100%. Difficult conditions for conventional cystoscopy, including hematuria, anterior wall involvement, and urethral strictures, had no deleterious impact on virtual cystoscopy. Difficulties in detection on virtual endoscopy were associated with flat bladder tumors with minimal surface elevation. CONCLUSION: The results of this study suggest a high reliability in the diagnosis of urinary bladder cancer by MR imaging-based virtual cystoscopy-a noninvasive method, independent of medication or contrast enhancement, that may be of value for screening, primary diagnosis, and surveillance. Virtual MR cystoscopy may be indicated when conventional cystoscopy cannot be performed or is ineffective.

Aged↗

Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction.

OBJECTIVES: To examine whether the epithelial sodium channel (ENaC) is expressed in the human urinary bladder and how its expression changes in association with outlet obstruction. Detrusor instability occurs in association with bladder outlet obstruction. The increase of afferent activity is one of the possible mechanisms for this detrusor instability. The ENaC expressed in mammals has been implicated in various mechanosensory functions. METHODS: Specimens of urinary bladder mucosa were obtained from 9 controls and 9 patients with bladder outlet obstruction verified by the International Prostate Symptom Score, prostate volume, and urodynamic tests. In 7 patients with outlet obstruction, involuntary detrusor contraction was demonstrated. The expression and localization of ENaC proteins was examined using immunofluorescent staining. The quantification of ENaC gene expression was assessed by real-time reverse transcriptase-polymerase chain reaction. RESULTS: The alpha-ENaC, beta-ENaC, and gamma-ENaC proteins were expressed in human urinary bladder epithelium with outlet obstruction, and the alpha-ENaC and gamma-ENaC proteins were virtually unstained in the control bladders. Alpha-ENaC, beta-ENaC, and gamma-ENaC mRNA were detected in 1, 6, and 4 of 9 control bladders, respectively. Each ENaC mRNA was clearly present in all obstructed bladders. The expression levels of each subunit in the obstructed bladders were significantly greater than those in controls. The quantified ENaC expression correlated significantly with the storage symptom score. CONCLUSIONS: The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction.

Aged↗

The muscularis mucosae of the human urinary bladder. Implications for tumor staging on biopsies.

The human urinary bladder wall is traditionally described as being without a muscularis mucosae. A consecutive one year material of 772 bladder biopsies from 171 patients were examined for the proposed presence of lamina muscularis mucosae (MM). MM was observed in 15% of the biopsies and in 35% of the patients and graded into three patterns according to its continuity. Biopsies with transitional cell carcinomas were reviewed in order to find out whether MM-positive biopsies had been staged correctly. The data are discussed in relation to earlier studies on the subject.

Biopsy↗

Rociverine citrate: a new spasmolytic agent, potentially useful in the treatment of urinary bladder hyperreflexia.

Rociverine citrate was evaluated for its ability to affect the motility of rat urinary bladder, in vitro and in vivo, in comparison with flavoxate hydrochloride. Rociverine counteracted both methacholine- and high K+-induced tonic contractions of bladder strips. In anaesthetized rats, intravenous rociverine inhibited dose-dependently frequency and amplitude of the distension-induced rhythmic contractions (DIRCs) of urinary bladder and counteracted the topical high K+-induced pressure increase in the same organ. Orally administered rociverine produced a dose-related reversal of the reserpine-induced detrusor hyperreflexia in anaesthetized rats. In each of these experimental models rociverine was more effective than flavoxate. These results point to the usefulness of rociverine in the treatment of urinary bladder motility disorders.

Animals↗

Frequency of urination and its effects on metabolism, pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in beagle dogs given the carcinogen 4-aminobiphenyl.

The human urinary bladder carcinogen, 4-aminobiphenyl (ABP), is known to undergo hepatic metabolism to an N-hydroxy arylamine and its corresponding N-glucuronide. It has been proposed that these metabolites are both transported through the blood via renal filtration to the urinary bladder lumen where acidic pH can facilitate the hydrolysis of the N-glucuronide and enhance the conversion of N-hydroxy-4-aminobiphenyl (N-OH-ABP) to a reactive electrophile that will form covalent adducts with urothelial DNA. Blood ABP-hemoglobin adducts, which have been used to monitor human exposure to ABP, are believed to be formed by reactions within the erythrocyte involving N-OH-ABP that has entered the circulation from the liver or from reabsorption across the urothelium. To test these hypotheses directly, experimental data were obtained from female beagles given [3H]ABP (p.o., i.v., or intraurethrally). [3H]N-OH-ABP (i.v. or intraurethrally), or [3H]N-OH-ABP N-glucuronide (i.v.). Analyses included determinations of total ABP in whole blood and plasma, ABP-hemoglobin adducts in blood erythrocytes, ABP and N-OH-ABP levels (free and N-glucuronide) in urine, urine pH, frequency of urination (controlled by urethral catheter), rates of reabsorption of ABP and N-OH-ABP across the urothelium, and apparent volumes of distribution in the blood/tissue compartment. The major ABP-DNA adduct, N-(guan-8-yl)-4-aminobiphenyl, was also measured in urothelial and liver DNA using a sensitive immunochemical method. An analog/digital hybrid computer was then utilized to construct a multicompartmental pharmacokinetic model for ABP and its metabolites that separates: (a) absorption; (b) hepatic metabolism and distribution in blood and tissues; (c) ABP-hemoglobin adduct formation; (d) hydrolysis and reabsorption in the urinary bladder lumen; and (e) excretion. Using this model, cumulative exposure of the urothelium to free N-OH-ABP was simulated from the experimental data and used to predict ABP-DNA adduct formation in the urothelium. The results indicated that exposure to N-OH-ABP and subsequent ABP-DNA adduct formation are directly dependent on voiding frequency and to a lesser extent on urine pH. This was primarily due to the finding that, after p.o. dosing of ABP to dogs, the major portion of the total N-OH-ABP entering the bladder lumen was free N-OH-ABP (0.7% of the dose), with much lower amounts as the acid-labile N-glucuronide (0.3% of the dose).(ABSTRACT TRUNCATED AT 400 WORDS)

Aminobiphenyl Compounds↗

[Combined treatment with CDDP and radiation effective against neuroendocrine carcinoma of the urinary bladder: a case report].

A case of neuroendocrine carcinoma (small cell carcinoma) of the urinary bladder is presented. A 76-year-old man complaining of dysuria visited our clinic on October 31, 1997. On physical examination, a huge mass was palpable in the lower abdomen. Abdominal and pelvic computed tomographic (CT) scan revealed a huge mass, 6.7 x 6.0 cm in size, with extravesical extension in the anterior wall of the urinary bladder and no metastatic lesions. Percutaneous biopsy of the tumor revealed undifferentiated neuroendocrine carcinoma. The value of serum neuron specific enolase (NSE) was 220 ng/ml (normal range: 0-10 ng/ml). Twenty days after the first CT scan, the tumor had grown to be 12.5 x 11.0 cm in size. He was treated with combination therapy of systemic cisplatin and external pelvic radiation and then achieved complete remission on CT scan and biopsy. The value of serum NSE was normalized. Four months later, abdominal CT scan revealed a huge metastastic lesion in the paraaortic and parahepatic regions, but, no local recurrence in the bladder. The value of serum NSE was 240 ng/ml. He was treated with 4 cycles of systemic combination therapy of cisplatin and etoposide. He achieved partial remission (regression rate: 77%) on CT scan after completion of the first 2 cycles, but the tumor showed rapid re-growth and he died of cancer 1 month later despite another 2 cycles. These combination therapies were effective against neuroendocrine carcinoma of the urinary bladder, although, the duration of the effect was short.

Aged↗

Effect of osmotic stress on expression of a putative facilitative urea transporter in the kidney and urinary bladder of the marine toad, Bufo marinus.

Anuran amphibians accumulate a large amount of urea in their extracellular fluids to avoid a severe dehydration under dry and hyper-saline environments. To clarify the mechanisms of urea retention, we examined structure and distribution of the urea transporter (UT) in the kidney of the marine toad (Bufo marinus), and its expression in the kidney and urinary bladder following exposure to dry and hyper-saline conditions by means of cDNA cloning, semi-quantitative RT-PCR, immunoblot analysis and immunohistochemistry. The Bufo UT cDNA cloned from the kidney encodes a 390-amino-acid residue protein, which is 80% identical to Rana esculenta UT with the functional characteristics of a urea transporter. The Bufo UT mRNA was abundantly expressed in the kidney and urinary bladder, but not in the skin. In immunoblot analysis using a specific antibody raised against the Bufo UT, a 52 kDa protein similar to the glycosylated forms of mammalian UT-A2 ( approximately 55 kDa) was detected in extracts from plasma membrane fractions of the kidney and urinary bladder. When toads were acclimated to dry and hyper-saline environments for 7 days, UT mRNA expression was upregulated in the kidney and urinary bladder and there was an elevated plasma urea concentration and osmolality. Immunohistochemistry showed that the UT was specifically localized on the apical membrane of the early distal tubule, known to be the diluting segment, in the kidney and the epithelial cells of urinary bladder. Immunoreactive cells were not detected along the late distal tubule, the connecting tubule or the collecting duct in the kidney. The present findings suggest that the Bufo UT probably contributes to urea transport in the kidney and urinary bladder in response to hyperosmotic stresses such as body fluid hypertonicity and dehydration.

Adaptation, Physiological↗