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The role of M(2)-muscarinic receptors in mediating contraction of the pig urinary bladder in vitro.

1. In urinary bladder, M(2)-muscarinic receptors predominate, but it is the smaller population of M(3)-receptors which mediate detrusor contraction. This study examines the M(2) : M(3) ratio and the role of M(2)-receptors in contraction of pig urinary bladder. 2. Competition experiments with [(3)H]-QNB determined the ratio of M(2) : M(3). In functional studies, affinity values (pK(B)) for 4-DAMP, darifenacin and methoctramine were calculated. Similar experiments were performed on tissues following selective M(3)-inactivation (incubation with 40 nM 4-DAMP mustard in the presence of 1 microM methoctramine to protect M(2)-receptors), precontraction with 50 mM KCl and relaxation with isoprenaline (30 microM) or forskolin (1 microM). 3. In competition binding, displacement of [(3)H]-QNB by 4-DAMP, darifenacin and methoctramine best fitted a two-site model suggesting a predominant (70 - 80%) population of M(2)-receptors. 4. On normal detrusor in vitro, 4-DAMP and methoctramine caused surmountable antagonism of responses to carbachol with pK(B) values of 9.37+/-0.07 and 6.05+/-0.05 respectively. Darifenacin caused unsurmountable antagonism, the apparent pK(B) value being 8.61+/-0.10. 5. In tissues where the M(3)-receptors had been inactivated and cyclic AMP levels elevated, 4-DAMP and darifenacin were less potent, with apparent pK(B) values of 8.72+/-0.08 and 6.74+/-0.07. In contrast, methoctramine was more potent, the apparent pK(B) value increasing significantly to 6.86+/-0.06. 6. se data suggest that the pig bladder possesses a similar muscarinic receptor population to the human bladder and that the M(3)-receptor subtype mediates contraction of the normal detrusor muscle. However an involvement of M(2)-receptors in contraction can be observed following pharmacological manipulation of the receptor population.

Animals↗

Computed tomography of nephrogenic adenoma of the urinary bladder.

Nephrogenic adenoma of the urinary bladder is a rare benign tumor. It is generally accepted that the tumor represents metaplasia of the urothelium in response to chronic inflammation or injury. Its CT appearance can be similar to that of carcinoma of the bladder.

Adenoma↗

Xenon-133 resorption in urinary bladder: functional diagnosis of bladder epithelium.

The examination of resorption from the urinary bladder had previously been restricted almost exclusively to animal research, since, as a rule, a separation of the bladder from the urinary tract is required. If this is not done, the resorbed test substance quickly finds its way back into the bladder. More than 95 per cent of the xenon which has been resorbed from the bladder becomes eliminated through the lungs. The detection and measurement of xenon in the exhaled air enables one to conduct, in a relatively simple fashion, urinary bladder resorption research using human subjects. Studies based on 141 patients showed that the xenon exhalation tests currently represent the most sensitive and exact method for detecting and determining the nature of inflammatory diseases of the urinary bladder. With a number of so-called "irritable bladder" cases it became clear that functional disorders of the bladder epithelium could be present without any evidence of associated morphologic changes. With radiogenic treatment of tumors in the lower pelvic region one experiences an increase in bladder resorption with increased exposure to radiation. There exists, as it were, a linear correlation between the radiation dosage and the degree of resorption from the urinary bladder. Three months after terminating radiotherapy one can detect, as a rule, only a negligible increase in resorption. If at this time the rate of xenon resorption still remains clearly high, one must reckon with permanent radiation damage of the bladder, insofar as it proves unsuccessful to eliminate the cause of cystitis.

Cystitis↗

Chromosomal abnormalities in inflammatory pseudotumor of the urinary bladder.

Inflammatory pseudotumors of the urinary bladder are rare, benign, nonepithelial tumors. Fewer than 30 have been reported, and no data are available on their karyotypic characteristics and/or the molecular mechanisms of pathogenesis. We performed short-term culturing and cytogenetic analysis of an inflammatory pseudotumor of the bladder, finding a der(20)t(12;20)(q13 approximately q15;q13) as the only cytogenetic aberration. The detection of a 12q13 approximately q15 rearrangement in the inflammatory pseudotumor indicates that this lesion is pathogenetically related to other benign mesenchymal tumors displaying, for example, lipogenic or leiomyomatous differentiation, something that is in sharp contrast to the karyotypic profile of epithelial tumors of the urinary bladder mucosa.

Chromosome Aberrations↗

[Pseudo-tumoral colic metaplasia of the urinary bladder].

Colic metaplasia of the urinary bladder is a rare disease, secondary to a chronic irritative factor. In its minor form, it has the same clinical features as simple cystitis, but its major pseudoneoplastic form may be mistaken for bladder tumor. The diagnosis is essentially histological. Treatment is based on eradication of the irritative factor and of the resection of pseudoneoplastic form. Surgery is performed in the case of complications of this disease. The clinical course is unclear, requiring long-term surveillance. We report one case of colic-type glandular metaplasia of the urinary bladder in a 50 years-old patient. The clinical symptomatology was dominated by hematuria and pollakuria. A bladder neoplasm was highly suspected in ultrasound and endoscopic findings. The patient underwent a transurethral resection of the bladder tumor. Histological examination of of resection shavings revealed a colic-type glandular metaplasia.

Granuloma, Plasma Cell↗

[A case of metachronous adenocarcinoma of the urinary bladder and the right upper urinary tract].

Bilateral hydronephrosis identified by a local physician brought a 65-year-old man to our hospital. Emergency percutaneous nephrostomy was bilaterally established for obstructive renal failure. After recovering renal function, the patient underwent radical cystectomy under the diagnosis of invasive bladder cancer and the construction of an ileal conduit. The pathology reported well differentiated adenocarcinoma (pT2, pL1, pV1). Five years after the surgery, gross hematuria developed. A computed tomographic scan revealed right hydronephrosis with a solid mass in the upper calyx. The urinary cytology was negative. The patient underwent right nephrectomy in May, 1999. The pathology then revealed well differentiated adenocarcinoma in the renal pelvis and ureter (pT3, pL0, pV0 and pT1, pL0, pV0, respectively). He is alive with mild chronic renal insufficiency with evidence of tumor at ten months after surgery. To our knowledge, this is the first case of metachronous adenocarcinoma of the urinary bladder and the upper urinary tract reported in the Japanese literature.

Adenocarcinoma↗

In vitro comparison of isometric and stop-test contractility parameters for the urinary bladder.

Contractility parameters in the urinary bladder can be calculated from isometric contractions (no extra patient load as compared to routine cystometry) or from stop-tests (more accurate, simpler analysis). A stop-test involves a voluntarily interrupted micturition with pressure and flow measurement. In a series of measurements in vitro on pig urinary bladder strips, parameters of the first type, obtained either by analyzing isometric contractions in terms of the Hill model, or by making phase plots, were compared to parameters of the second type. A good correlation was found. Th parameter correlating best with the maximal contraction velocity of the bladder, normalized for differences in initial muscle length, as obtained from stop-test, is the isometric contraction force, which can be obtained from an isometric contraction by either of the two analysis techniques. Clinically, making phase plots seems more promising than analyzing contractions in terms of the Hill model.

Animals↗

Hemangioma of the urinary bladder.

A hemangioma of the urinary bladder occurring in a 66-year-old man is described. Although hemangioma is a common lesion in many parts of the body, it remains a very rare primary tumor in the bladder. Clinically the patient usually presents with recurrent hematuria, control of which may necessitate a segmental cystectomy.

Aged↗

Protection of urinary bladder function by grape suspension.

Urinary bladder dysfunction secondary to BPH is a major affliction of aging men. A rabbit model of partial outlet obstruction was used to evaluate the ability of a standardized grape suspension to protect the bladder against obstructive bladder dysfunction.Twenty-four New Zealand White rabbits were separated into four groups of six rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with a standardized grape suspension suspended in water; groups 2 and 4 were treated with vehicle. Groups 1 and 3 received sham operations after 3 weeks of treatment; groups 2 and 4 received partial outlet obstruction by surgically placing a silk ligature loosely around the urethra. At 3 weeks following surgery, in vivo and in vitro bladder functions were evaluated. Based on both in vivo and in vitro studies, the grape suspension significantly reduced the severity of obstructed bladder dysfunction. This is consistent with the hypothesis that ischemia is a major etiological factor in obstructive dysfunction, and treatment with antioxidants and membrane stabilization compounds such as those in the grape suspension can be effective in the treatment of obstructive bladder pathology.

Adrenergic alpha-Antagonists↗

Localization of the FA-CHIP water channel in frog urinary bladder.

Like mammalian kidney collecting duct, the water permeability of frog urinary bladder epithelial cells is antidiuretic hormone (ADH)-sensitive. In kidney, this permeability is mediated by water channels named aquaporins. We recently reported the cloning of the frog aquaporin CHIP (FA-CHIP), a water channel from frog urinary bladder. FA-CHIP has 79% identity with rat Aquaporin 1 (AQP1) and only 42% identity with the kidney collecting duct Aquaporin 2 (AQP2). The purpose of this study was to examine the localization of FA-CHIP in frog urinary bladder. We raised antibodies against peptides of 15 to 17 residues, encompassing the N-ter and C-ter regions of FA-CHIP. Anti-FA-CHIP antibodies were used for Western blotting, indirect immunofluorescence microscopy and gold labeling electron microscopy in urinary bladder and other frog tissues. By Western blotting of frog urinary bladder total homogenate, the antibodies recognized a band of 29 kDa and glycosylated forms of the protein between 40 and 70 kDa. No signal was found on membrane preparations from epithelial cell homogenate. FA-CHIP was also found in frog skin, brain, gall bladder, and lung. In immunofluorescence microscopy on urinary bladder sections, FA-CHIP was localized to endothelial cells of blood capillaries and on mesothelial cells of the serosal face. Red blood cells, epithelial and basal cells were unstained. The localization of FA-CHIP in cell plasma membranes was confirmed by gold labeling electron microscopy. In other positive tissues, FA-CHIP was also localized to capillaries. In brain, plasma membranes of epithelial cells were also stained. In conclusion, like its mammalian homologue AQP1, FA-CHIP appears to be localized to constitutively water permeable cells of frog. Therefore, it belongs to the AQP1 family of proteins although unlike AQP1, FA-CHIP is absent from red blood cells and kidney. In frog urinary bladder and skin, FA-CHIP probably plays an important role in water transport across the barriers in series with the ADH-sensitive epithelial cells.

Animals↗

The effect of arachidonic acid on the hydroosmotic action of vasopressin in frog urinary bladder.

In experiments on frog urinary bladder it was found that 23 nM arginine-vasopressin (antidiuretic hormone, AVP), 10 min after addition, increased the content of free arachidonic acid (AA) in bladder tissue from 18.6 +/- 1.2 to 33.3 +/- 3.9 ng/mg protein. The exogenous AA (10(-8) - 10(-5) M) added to the serosal Ringer solution did not change the basal level of osmotic water flow, but significantly inhibited the hydroosmotic effect of 23 nM AVP in a dose-dependent manner. The inhibitory effect of AA was not eliminated in the presence of 1 microM indomethacin, 1 microM nordihydroguaiaretic acid, 100 microM ketoconazole, nor if the nonmetabolized analog of AA, eicosatetraynoic acid (1 microM), was used instead of AA. AA inhibited only the action of vasopressin, but had no effect on osmotic water flow induced by 2 mM cAMP + 50 microM 3-isobutyl-1-methylxanthine or 20 microM forskolin. These data suggest that AA is another phospholipid-derived messenger, which modulates the hydroosmotic action of vasopressin in frog urinary bladder at a point prior to cAMP formation.

1-Methyl-3-isobutylxanthine↗

Localized amyloidosis of the urinary bladder.

Localized amyloidosis of the urinary bladder is a rare condition. Five patients, 1 with localized secondary amyloidosis, are described. The symptoms, macroscopic hematuria and tumor-like appearance in cystoscopy, may mimic bladder cancer. Diagnosis is based on histopathological examinations with Congo red staining. In most instances, the treatment of choice is transurethral resection and electrocoagulation. Because of the risk of recurrences, a close follow-up is recommended.

Aged↗

T lymphocytes infiltrating the bladder wall of patients with carcinoma of urinary bladder are in vivo activated.

OBJECTIVES: This paper studies the phenotypical characteristics of the lymphocytes present in mononuclear cell (MNC) preparations from peripheral blood (PBMNC), lymph nodes (LNMNC), tumor bladder (TBMNC), and tumor-free bladder (TFBMNC) from patients with infiltrated transitional cell carcinoma (TCC) of the bladder and PBMNC of healthy controls. METHODS: Eight patients diagnosed with TCC of the bladder, according to UICC criteria, and 10 healthy controls were studied. For immunofluorescence staining, T lymphocytes were incubated with combinations of fluorescein (FITC, green)- and phycoerytrin (PE, red)-labelled monoclonal antibodies. RESULTS: The percentage of NK cells in the LNMNC and TFBMNC was significantly decreased in comparison to that found in the PBMNC from these patients (p < 0.05). A significant enhancement of the expression of class II molecules of the major histocompatibility complex (MHC) by CD3+ T lymphocytes from TBMNC and TFBMNC specimens from bladder walls was found with respect to those quantified in CD3+ T lymphocytes from PBMNC (p < 0.05). In addition, the percentage of CD3+CD25+ T lymphocytes was significantly higher in PBMNC in TCC patients than in healthy controls (p < 0.05). CONCLUSIONS: Our data clearly demonstrate that the presence of infiltrative TCC of the bladder is associated to an infiltration of in vivo activated T lymphocytes of the urinary bladder wall. This in vivo T lymphocyte activation has been considered an expression of the immune response against the tumor cells.

Aged↗

Antagonism of substance P and related peptides by RP 67580 and CP-96,345, at tachykinin NK1 receptor sites, in the rat urinary bladder.

Tonic contraction of rat urinary bladder was elicited in vitro and in vivo by substance P, two selective NK1 receptor agonists, septide ([pGlu6,Pro9]substance P-(6-11)) and [Sar9,Met(O2)11]substance P, and an NK2 agonist, [Lys5,MeLeu9,Nle10]neurokinin A-(4-10), but not by senktide (succinyl[Asp6,MePhe8]substance P-(6-11)), an NK3 agonist. Substance P only stimulated the NK1 receptors of smooth muscle. The non-peptide selective NK1 receptor antagonists, RP 67580 and CP-96,345, both inhibited substance P-induced contraction (pKB values 6.7 and 5.7; ED50 = 1.4 and 5.0 mg/kg i.v., respectively) and septide-induced contraction (pKB values 7.5 and 6.5; ED50 = 0.076 and 0.250 mg/kg i.v., respectively). Both antagonists, at lower doses, also inhibited substance P- and septide-induced plasma extravasation. That both antagonists blocked the effects of septide much more than the effects of substance P suggests the existence of an NK1 receptor subtype or isoform. Selective NK1 receptor antagonists, by blocking both spasm and plasma extravasation in the urinary bladder, would be useful for treating substance P-related motor disorders and cystitis.

Animals↗

Hemangioma of the urinary bladder.

BACKGROUND: Hemangioma of the urinary bladder is rare and the long term outcome of patients is unknown. METHODS: The authors evaluated the clinical and pathologic findings in 19 patients with a vesical hemangioma. All patients were treated at the Mayo Clinic between 1932-1998 and had histologic confirmation of the diagnosis. Hemangioma was classified into cavernous, capillary, or arteriovenous types based on conventional criteria from other sites. Clinical information was obtained from chart review. The mean follow-up of the patients was 6.9 years (range, 0.3-25 years). RESULTS: The mean patient age at the time of diagnosis was 58 years (range, 19-76 years) and the male-to-female ratio was 3.7:1. Patients typically presented with macroscopic hematuria and endoscopic findings usually were nonspecific. The diagnosis of hemangioma was suspected in 3 patients (16%) prior to biopsy. There was a predilection for the posterior and lateral walls and the tumor usually was small (range, 0.2-3 cm; median, 0.7 cm) and solitary. The histologic types of hemangioma were cavernous (15 cases), capillary (2 cases), and arteriovenous (2 cases). All patients were treated with biopsy with or without fulguration, except for one patient who was treated with a partial cystectomy. No patients developed a recurrence during a mean follow-up of 6.9 years. CONCLUSIONS: Patients with hemangioma of the urinary bladder have a favorable outcome. Biopsy and fulguration are effective for hemangioma of the bladder when the lesion is small.

Adult↗

Cancer of the urinary bladder and pyelonephritis.

Successful treatment of cancer of the urinary bladder consists not only in elimination of the tumour process, but also in prophylaxis of various complications. Among complications caused by the tumour process as well as by the applied methods of its therapy a certain place belongs to pyelonephritis. Pyelonephritis develops in consequence of the disturbance of the function of the urinary bladder after hemicystectomy resulting from the change of the bladder's form. With the view of preserving the anatomo-physiological function of the urinary bladder and preventing complications the author suggests a method of reconstruction of the bladder consisting in shaping it in a spherical form after hemicystectomy. Such shape of the urinary bladder ensures nearly normal conditions for both urination act and urinary flow from the upper urinary pathways, this being the prophylaxis of pyelonephritis.

Humans↗

Genetic susceptibility and carcinogen-DNA adduct formation in human urinary bladder carcinogenesis.

Differences in human urinary bladder cancer susceptibility have often been attributed to genetic polymorphisms in carcinogen-metabolizing enzymes, especially those involved in the biotransformation of aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). Metabolic activation generally involves an initial cytochrome P450-dependent oxidation to form N-hydroxy, phenol, or dihydrodiol intermediates that undergo further conjugation or oxidation to form DNA adducts. The acetyltransferases, NAT1 and NAT2, can participate in these pathways by catalyzing detoxification (by AA N-acetylation) or further activation (by N-OH-AA O-acetylation) reactions. NAT2 polymorphisms, which are due to point mutations in the structural gene, have long been associated with higher risk for bladder cancer. In collaborative studies, we now have found that NAT1 is also expressed polymorphically in human bladder due to mutations in the NAT1 polyadenylation signal, which has recently been associated with increased bladder cancer risk. Moreover, we have found that the bladder NAT1*10 genotype and phenotype are correlated with significantly higher levels of putative AA-DNA adducts in human bladder as measured by 32P-postlabelling. Preliminary data have also suggested that putative PAH-DNA adducts in human bladder are correlated with a polymorphism in the total metabolism of benzo[a]pyrene (BP) by bladder microsomes and especially with the formation of BP-7,8-diol. Since each of these correlations was observed without adjusting for carcinogen intake, it would appear that, with ubiquitous human exposure to AAs and PAHs, the expression of carcinogen-metabolizing enzymes may be a more critical determinant of carcinogen-DNA adduct formation and of individual cancer susceptibility.

Arylamine N-Acetyltransferase↗

More than just a barrier: urothelium as a drug target for urinary bladder pain.

Although the urinary bladder urothelium has classically been thought of as a passive barrier to ions/solutes, a number of novel properties have been recently attributed to these cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e., ability to express a number of sensor molecules or respond to thermal, mechanical, and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests these cells may be targets for transmitters released from bladder nerves or that chemicals released by urothelial cells may alter afferent excitability. Taken together, these and other findings highlighted in this review suggest a sensory function for the urothelium. Elucidation of mechanisms impacting on urothelial function may provide insights into the pathology of bladder dysfunction.

Animals↗