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PubMed2006

Expression of hyperpolarization-activated cyclic nucleotide-gated cation channels in rat dorsal root ganglion neurons innervating urinary bladder.

Afferent pathways innervating the urinary bladder consist of myelinated Adelta- and unmyelinated C-fibers, the neuronal cell bodies of which correspond to medium and small-sized cell populations of dorsal root ganglion (DRG) neurons, respectively. Since hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel currents have been identified in various peripheral sensory neurons, we examined the expression of isoforms of HCN channels in the L6-S1 spinal cord and bladder afferent neurons from L6-S1 DRG in rats. Among HCN-1, HCN-2 and HCN-4 channel subtypes, positive staining with HCN-2 antibodies was found in the superficial dorsal horn of the spinal cord and small- and medium-sized unidentified DRG neurons. In dye-labeled bladder afferent neurons, HCN-2-positive cells were found in approximately 60% of neurons, and HCN-2 was expressed in both small- and medium-sized neurons with a higher ratio (expression ratio: 61% and 50% of neurons, respectively) compared with unidentified DRG neurons, in which the HCN expression ratio was 47% and 21% of small- and medium-sized cells, respectively. These results suggest that HCN-2 is the predominant subtype of HCN channels, which can control neuronal excitability, in small-sized C-fiber and medium-sized Adelta fiber DRG neurons including bladder afferent neurons, and might modulate activity of bladder afferent pathways controlling the micturition reflex.

Animals↗
PubMed1996

Primary staging of urinary bladder carcinoma: the role of MRI and a comparison with CT.

Since the introduction, pelvic MRI has been considered the best non-invasive technique for primary staging of urinary bladder cancer. Before using MRI an understanding of normal and pathological MR images of the urinary bladder is essential. This review therefore describes the MR anatomy of the urinary bladder as well as the appearances of carcinoma. MRI plays an important clinical role in staging the primary tumour. In superficial tumours, clinical staging, which includes transurethral biopsy, is the best technique. For invasive tumours, MRI is superior to other techniques such as CT scanning, transvesical ultrasonography and clinical staging. A limitation of both MRI and CT scanning is their inability to recognize minimal tumour growth in the muscle layer of the bladder wall, or to differentiate between post-transurethral resection oedema and tumour. Therefore, in all patients with urinary bladder cancer staging should preferably start with MRI followed by clinical staging. Unfortunately, however, because of the high cost of this strategy, MRI has to be reserved for staging deeply invasive and superficial poorly differentiated tumours.

Biopsy↗
PubMedDate not supplied

P53 expression in small cell carcinoma of the urinary bladder: biological and prognostic implications.

Small cell carcinoma of the urinary bladder is a rare and highly aggressive tumor. P53 expression has been shown to be associated with poor prognosis in a variety of tumors. This study was undertaken to investigate p53 expression in a large series of small cell carcinomas of the urinary bladder and to correlate the findings with clinicopathologic parameters and clinical outcome. Pathologic findings were reviewed and were correlated with clinical findings and follow-up information. Immunohistochemical staining for p53 was performed on paraffin-embedded tissue sections using the avidin-biotin-peroxidase method. Results were recorded as positive expression (> or =10% of cells with nuclear staining) or negative expression (<10% of cells with nuclear staining). The series included 40 males and 10 females. All 50 patients except one had advanced disease (T2 or above) at presentation. Pathologic stages were as follows: T1 in 1, T2 in 25, T3 in 21, and T4 in 3 patients. During a median follow-up of 12 months (range: 1 month to 122 months), 38 patients died of cancer. Two-year and 5-year cancer-specific survival rates were 45% and 16%, respectively. P53 overexpression was present in 27 out of 50 (54%) cases (7 with 10-25% staining, 4 with 25-50% staining, 11 with 50-75% staining and 5 with 75-100% staining); conversely, negative staining for p53 was observed in 23 out of 50 (46%) cases (19 with no staining and 4 with <10% staining). No correlation was demonstrated between the level of p53 expression and survival (p =0. 16). The 5-year cancer-specific survival was 16.6% for patients with tumors expressing p53 in greater than or equal to 10% of cells and was 14.7% for patients with tumors expressing p53 in less than 10% of tumor cells. There was no correlation between p53 expression and other clinicopathologic characteristics, including age (p =0.20), gender (p=0.84), history of smoking (p=0.25), pathologic Tstage (p=0.38), clinical stage (p=0.60), lymph node metastasis (p=0.17), and distant metastasis (p=0.88). Our data indicate that p53 is frequently expressed in small cell carcinoma of the urinary bladder. However, no correlation is found between p53 expression and clinicopathologic parameters, including long-term survival.

Adult↗
PubMed1986

A prospective randomized study on neodymium-YAG laser irradiation versus TUR in the treatment of urinary bladder cancer.

122 patients with urinary bladder cancer of stage T-1 and T-2 were randomized for Neodymium-YAG laser irradiation (n = 62) or TUR (n = 60). Follow-up was carried out every 3 months for 2 years. Recurrence of tumor in treated area was seen in 3 patients (4.8%) in the laser group and in 19 patients (31.6%) in the TUR group. New tumors in non-treated areas occurred in 12 patients in the laser group and in 13 patients in the TUR group. It is to conclude that Neodymium-YAG laser irradiation is a safe and efficient treatment of bladder tumors of stage T-1 and superior to TUR except in very small tumors which can be completely removed in one piece without resecting into tumor tissue. In muscle invasive tumors of stage T-2, combined treatment with TUR and laser irradiation is superior to TUR alone. Occurrence of new tumors in non-treated areas is independent of treatment modality.

Adult↗
PubMed1979

Carcinosarcoma of the urinary bladder in an adult male.

Carcinosarcoma of the urinary bladder in a 64-year-old man is described. Total cystectomy with bilateral ureteroileostomy was performed. The patient is in good health 12 months after the operation. Histologically the main bulk of the tumour tissue was rhabdomyosarcomatous, but in some areas atypical glands were intermingled with the rhabdomyoblasts. This histologic pattern has not previously been described. The histologic features, clinical manifestations and treatment of these rare bladder tumours are discussed in relation to the literature.

Carcinosarcoma↗
PubMed1995

[Combined penetrating trauma of the rectum and urinary bladder].

Combined penetrating trauma of the rectum and urinary bladder is rare, and constitutes a diagnostic and therapeutic challenge. Most of the literature discusses trauma to either urinary bladder or rectum alone. The combination of penetrating trauma to both rectum and the urinary system is associated with high morbidity and mortality. There is controversy regarding the preferred approach to this type of combined trauma.

Adolescent↗
PubMed1994

An early molecular response induced by acute overdistension of the rabbit urinary bladder.

In the rabbit, partial urinary bladder outlet obstruction rapidly increases bladder mass and alters several parameters of normal bladder function. Previous experiments on this animal model (Buttyan et al. Neurourol. Urodyn. 11:225-238, 1992) had identified an early molecular response to partial outlet obstruction that involved the profound induction of mRNA encoding a heat-shock gene, hsp-70, as well as induced expression of mRNA for basic fibroblast growth factor and certain protooncogenes. Numerous physiological studies of the hypertrophied rabbit bladder indicate that the primary stimulus for bladder growth may be the initial overdistension that occurs as the bladder fills following partial outlet obstruction. The present study was undertaken to determine if the sequence and characteristics of gene activation during the recovery following a brief period of overdistension of the rabbit bladder are comparable with the gene activity previously described in association with partial outlet obstruction. Rabbit bladders were overdistended to 20% above capacity for 1 hr and then relieved. Bladders were recovered from control (untreated) rabbits and from rabbits at 1 hr or at 1, 3 or 5 days following relief of overdistension. RNAs extracted from these tissues were examined by Northern blot assays for a number of different mRNA transcripts previously shown to be altered by partial outlet obstruction. By 1 hr following the relief from acute overdistension, there was already a greater than 10-fold increase in the expression of hsp-70 related transcripts as well as a marked increase in the expression of mRNA encoding bFGF and decreased expression of TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Paraganglioma of the urinary bladder.

A paraganglioma of the urinary bladder in a 60-year-old woman presented with irritative voiding symptoms, without hematuria or hypertension. Sonography revealed a well-limited ovoid mass of the posterior wall, and cystoscopy showed that it was covered by normally appearing mucosa. Treatment consisted of transurethral resection, and the patient has been followed for 2 years without recurrence. Histologically the lesion consisted of small nests of spindle cells with clear to acidophilic cytoplasm; mitotic activity was inconspicuous. Immunohistochemical analyses revealed that the tumor cells were strongly positive for neuron-specific enolase and chromogranin A, and negative for cytokeratin, vimentin, neurofilaments, glial fibrillary acid protein and HMB 45. Sustentacular cells at the periphery of neoplastic cell clusters were positive for S-100 protein.

Biomarkers, Tumor↗
PubMed1970

The effect of smooth muscle on the intercellular spaces in toad urinary bladder.

Phase microscopy of toad urinary bladder has demonstrated that vasopressin can cause an enlargement of the epithelial intercellular spaces under conditions of no net transfer of water or sodium. The suggestion that this phenomenon is linked to the hormone's action as a smooth muscle relaxant has been tested and verified with the use of other agents effecting smooth muscle: atropine and adenine compounds (relaxants), K(+) and acetylcholine (contractants). Furthermore, it was possible to reduce the size and number of intercellular spaces, relative to a control, while increasing the rate of osmotic water flow. A method for quantifying these results has been developed and shows that they are, indeed, significant. It is concluded, therefore, that the configuration of intercellular spaces is not a reliable index of water flow across this epithelium and that such a morphologic-physiologic relationship is tenuous in any epithelium supported by a submucosa rich in smooth muscle.

Acetylcholine↗
PubMed1983

Up-regulation of insulin receptors with dexamethasone in cultured human urinary bladder carcinoma cells.

Cultured human urinary bladder carcinoma cells ( JTC -32) were used to investigate the regulation of insulin receptors by dexamethasone. When the cells were preincubated with dexamethasone at 37 degrees C, insulin binding sites increased up to 24 h. A large increase in insulin binding sites took place for 14 h of preincubation with dexamethasone. At lower concentrations of dexamethasone (less than 1 nM), no significant increase in insulin binding sites was observed, but the maximal increase was observed at more than 10 nM. Scatchard plots showed that dexamethasone increased the number of high affinity insulin binding sites (2.8 fold) without any change in the apparent equilibrium constant in JTC -32 cells. In addition, this steroid hormone also increased the number of low affinity insulin binding sites (1.6 fold) with a small change in the apparent equilibrium constant. Although insulin and dexamethasone did not affect the number of cells or the amount of cellular proteins per dish, dexamethasone plus insulin slightly increased them.

Cells, Cultured↗
PubMed2001

Respiratory response to baroreceptor stimulation and spontaneous contractions of the urinary bladder.

Spontaneous contractions of the urinary bladder (SBCs) and experimental elevations of carotid sinus pressure (CSP) have been shown to result in respiratory inhibition with preferential reduction in hypoglossal (HG) nerve activity as compared with that of phrenic nerve discharge. We assessed the interaction between these respiratory inhibitory stimuli in decerebrate, vagotomized, paralyzed and artificially ventilated cats. We denervated the right carotid sinus and pressurized the isolated left carotid sinus region within the linear range of the baroreflex, while maintaining systemic arterial pressure at approximately 100 mmHg. We monitored the HG and phrenic nerve responses to SBCs, to elevations in CSP between SBCs, and to elevations in CSP during SBCs. Our results show that superimposing these stimuli results in respiratory inhibition, especially of HG activity, that exceeds that resultant from either stimulus alone. We speculate that the combined presence of SBCs and episodic hypertension may contribute to the development of periodic breathing or obstructive apnea, particularly during sleep.

Animals↗
PubMed1982

The role of sodium-channel density in the natriferic response of the toad urinary bladder to an antidiuretic hormone.

Urinary bladders of Bufo marinus were depolarized, by raising the serosal K concentration, to facilitate voltage-clamping of the apical membrane. Passive Na transport across the apical membrane was then studied with near-instantaneous current-voltage curves obtained before and after eliciting a natriferic response with oxytocin. Fitting with the constant-field equation showed that the natriferic effect is accounted for by an increase in the apical Na permeability. It is accompanied by a small increase in cellular Na activity. Furthermore, fluctuation analysis of the amiloride-induced shot-noise component of the short-circuit current indicated that the permeability increase is not due to increased Na translocation through those Na channels which were already conducting prior to hormonal stimulation. Rather, the natriferic effects is found to be based on an increase in the population of transporting channels. It appears that, in response to the hormone, Na channels are rapidly "recruited" from a pool of electrically silent channels.

Animals↗
PubMed1976

Electron microscopic and histological findings on urinary bladder epithelium in interstitial cystitis.

Urinary bladder epithelium was studied with electron microscope in 50 patients with interstitial cystitis (IC) and 9 controls. In addition, biopsies of 14 patients with IC were studied with special stains for the presence of bacteria or viral inclusions in the epithelium. No bacteria or viral inclusions could be demonstrated. On the basis of these and earlier negative findings it appears that simple infection of the epithelium is ruled out as the aetiology in IC. Electron microscopy demonstrated an increase in large swollen epithelial cells with decreased amount of lateral processes in half of the IC samples and inflammatory changes in the mucosa. The similarity of the ultrastructure of epithelial cells in controls and IC patients makes it improbable that the disease process originates in the epithelium. In this study special attention was paid to large cytosomes (diameter 0.4--6.0 mum) in the epithelial cells. These contained small vesicular bodies (diameter 0.04--0.2 mum) and lipid droplets, and were found in controls as well as in IC patients.

Basement Membrane↗
PubMed2004

Advances in intravesical therapy of urinary bladder cancer.

The aim of urinary bladder cancer treatment with intravesical therapy is threefold: to eradicate existing disease, prevent recurrence and prevent tumor progression. The prognostic factors allow differentiation in different risk groups and this is useful in planning treatment. Pharmacokinetic studies have proved the efficacy of a high urine concentration of the chemotherapeutic agent. Comparing resection with and without adjuvant intravesical chemotherapy, an approximately 15% short-term decrease in tumor recurrence with chemotherapy is obtained, although no effect on progression was proven. No chemotherapeutic agent has proved more effective than the other. The importance of early administration has been highlighted by the positive results of a single, early instillation of chemotherapy, with a reported mean reduction in recurrence rate of 12-27%. Immunotherapy in the form of bacillus Calmette-Guerin has generally proven more efficious than chemotherapy. The results in comparison with mitomycin C have not been as conclusive. The best results are found with a maintenance schedule. In this review, several new approaches are explored to improve the efficacy of this therapy.

BCG Vaccine↗
PubMed2004

Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder.

In the rat isolated urinary bladder, NaHS (30 microm-3 mm) and capsaicin (10 nm-3 microm) produced concentration-dependent contractile responses (pEC(50)=3.5+/-0.02 and 7.1+/-0.02, respectively) undergoing dramatic tachyphylaxis. In preparations in which sensory nerves were rendered desensitized (defunctionalized) by high-capsaicin (10 microm for 15 min) pretreatment, neither capsaicin itself nor NaHS produced any motor effect. NaHS-induced contractile effects were totally prevented by the simultaneous incubation with tachykinin NK(1) (GR 82334; 10 microm) and NK(2) (nepadutant; 0.3 microm) receptor-selective antagonists. Tetrodotoxin (1 microm) only partially reduced the response to NaHS. These results provide pharmacological evidence that H(2)S stimulates capsaicin-sensitive primary afferent nerve terminals, from which tachykinins are released to produce the observed contraction by activating NK(1) and NK(2) receptors. While the molecular site of action of H(2)S remains to be investigated, our discovery may have important physiological significance since H(2)S concentrations capable of stimulating sensory nerves overlap those occurring in mammalian tissues under normal conditions.

Animals↗
PubMed1975

The effects of hormones on cyclic adenosine 3':5'-monophosphate accumulation in transitional epithelium of the urinary bladder.

Transitional epithelium lining rabbit urinary bladders was isolated and studied in vitro. The homogeneity of the isolated epithelium was demonstrated by light and electron microscopical monitoring as well as cell culture studies. Transitional epithelium responded to epinephrine and prostaglandin E1 (PGE1) in the presence of 2mM 1-methyl, 3-isobutylxanthine (MIX) with increases in intracellular levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Corticotropin, aldosterone, insulin, parathyroid hormone and vasopressin were slightly but significantly stimulatory under similar conditions. Glucagon and oxytocin were not stimulatory at the concentrations tested. The effects of epinephrine and PGE1 were potentiated by 2mM MIX 20-fold or greater. The cells were slightly more sensitive to PGE1 then to epinephrine. The prostaglandin produced a noticeable response at about 10nM, while effects of epinephrine were discernible at 0.1muM. Maximal responses to both effectors were seen at about 10muM. The action of 10muM epinephrine, but not 10muM PGE1, was completely abolished by 0.1mM propranolol. Responses to combinations of epinephrine and PGE1 were additive. Cyclic AMP accumulated in the incubation medium of transitional epithelial cells exposed to epinephrine, PGE1, MIX, or combinations of the agonists. The appearance of cyclic AMP in the medium was slow compared to the rate of intracellular accumulation, but reached significant levels following prolonged stimulation.

Adrenocorticotropic Hormone↗
PubMed1984

Feedback inhibition of sodium uptake in K+-depolarized toad urinary bladders.

Ouabain-blocked toad urinary bladders were maintained in Na+-free mucosal solutions, and a depolarizing solution of high K+ activity containing only 5 mM Na+ on the serosal side. Exposure to mucosal sodium (20 mM activity) evoked a transient amiloride-blockable inward current, which decayed to near zero within one hour. The apical sodium conductance increased in the initial phase of the current decay and decreased in the second phase. The conductance decrease required Ca2+ to be present on the serosal side and was more rapid when the mucosal Na+ activity was higher. At 20 mM mucosal Na+ and 3 mM serosal Ca2+ the initial (maximal) rate of inhibition amounted to 20% in 10 min. The conductance decrease could be accelerated by raising the serosal Ca2+ activity to 10 mM. The inhibition reversed on lowering the serosal Ca2+ to 3 microM and, in addition, the mucosal Na+ to zero. Exposure of the mucosal surface to the ionophore nystatin abolished the Ca2+ sensitivity of the transcellular conductance, showing that the Ca2+-sensitive conductance resides in the apical membrane. The data imply that in the K+-depolarized epithelia, cellular Ca2+, taken up from the serosal medium by means of a Na+-Ca2+ antiport, cause feedback inhibition by blockage of apical Na+ channels. However, the rate of inhibition is small, such that this regulatory mechanism will have little effect at 1 mM serosal Ca2+ and less than 20 mM cellular Na+.

Animals↗
PubMed1990

Effects of serosal hypertonicity on water permeability in toad urinary bladder.

We studied in toad urinary bladder the effects of serosal hypertonicity on tissue water permeability, granular cell luminal membrane water permeability, and granular cell luminal membrane particle aggregates and compared them with effects of antidiuretic hormone (ADH). In tissues challenged by a hypertonic (447 mosmol/kgH2O) serosal bath, luminal membrane aggregates were structurally similar to those caused by ADH. The tissue water permeability increase induced by serosal hypertonicity was much less than that caused by a maximally stimulating concentration of ADH on tissue in isotonic serosal baths with approximately the same transmural gradient. The difference is explained not only by a reduced incidence of luminal membrane aggregates but also by an increased resistance to water movement at a postluminal membrane site. Measurements of luminal membrane water permeability showed a close correlation with luminal membrane aggregate frequency, indicating that the calculated permeability of an individual aggregate was a constant. Thus the relation of luminal membrane aggregates to tissue osmotic permeability is modified by serosal hypertonicity. Morphological examination of these tissues suggested that luminal membrane aggregates may be less stable in the absence of hormone. This was evident by the proportionally greater number of structures interpreted as aggregates captured in the process of disassembly ("patches"). Membrane depressions containing intramembrane particles ("craters") were also observed. They corresponded in terms of frequency and size to coated pits as seen in thin sections.

Animals↗