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Urinary bladder biopsies in spinal cord injured patients.

STUDY DESIGN: A series of 94 urinary bladder biopsies in spinal cord injured (SCI) patients were histopathologically and statistically analysed. OBJECTIVES: The following hypotheses were examined: (1) The number of clinical bladder infections per year in each patient does not influence the histopathological type of inflammation of the urinary bladder; (2) The duration of the spinal cord lesion does not have a strong effect on the type of inflammation; (3) The different neurological levels (upper and lower motor neuron lesions) do not relate to a specific histopathology. SETTINGS: All patients received their treatment at the Swiss Paraplegic Centre in Nottwil, near Lucerne (Switzerland). METHODS: The samples were taken from the bladder fundus during endoscopic urologic operations. Histopathological standard procedures were carried out. Statistical analysis including Kruskal-Wallis and Chi-square tests were performed. RESULTS: Histopathological analysis showed abnormal alterations of the urinary bladder mucosa in 86 SCI-patients: (91.5%). 63 cases (67.0%) showed a chronic type and 23 cases (24.5%) showed a subacute type of inflammation. A normal urinary bladder was found in eight cases (8.5%). The three hypotheses were statistically not rejected. CONCLUSION: Results demonstrated no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.

Adolescent↗

Sympathetic innervation of the urinary bladder.

The sympathetic innervation of the urinary bladder was studied by fluorescence microscopy using glyoxylic methods, and by electron microscopy, in the normal state, after extirpation of hypogastric ganglia and administration of 6-hydroxydopamine. In the normal state adrenergic fibres could be found along the blood and lymph vessels, within the muscle layers and synaptizing on the surface of the local nerve cells or with other, probably local nerve processes. After extirpation of the hypogastric ganglia, degenerated axons could be observed in the local ganglia and in the connective tissue of the vessels. Many fluorescent fibres could be observed in the muscle layers, too. Four to six weeks after the operation, the animals were treated with 6-hydroxydopamine and no fluorescence was observed. In the muscle layer several degenerated fibres could be found, occasionally in close relation to the smooth muscle cells. It was therefore supposed that part of the sympathetic nerves originates from the hypogastric ganglia and is responsible for the modulation of the local ganglia and the blood supply of the urinary bladder. The other part emanates from the "short adrenergic neurons" and may effect directly the smooth muscle cells.

Animals↗

Cross-organ sensitization of lumbosacral spinal neurons receiving urinary bladder input in rats with inflamed colon.

BACKGROUND & AIMS: Clinical studies show that patients with irritable bowel syndrome and colonic diseases frequently experience sensory and motor dysfunctions of the urinary bladder. The aim of this study was to investigate the spinal neuronal mechanisms responsible for potential cross talk between these visceral organs. METHODS: Colonic inflammation was induced by dextran sulfate sodium (5%) in drinking water for 7-12 days (n = 12); another group of rats without dextran sulfate sodium (n = 12) was used as control. Extracellular potentials of single L6 to S2 spinal neurons were recorded in pentobarbital-anesthetized and paralyzed rats with dextran sulfate sodium-induced colitis or normal colon. Urinary bladder distention (0.5-2.0 mL; 20 seconds) was produced with saline inflation, and colorectal distention was induced by inflation of an air balloon (80 mm Hg; 20 seconds). RESULTS: A total of 58 of 153 (38%) and 55 of 152 (36%) spinal neurons responded to urinary bladder distention in dextran sulfate sodium-treated and control animals, respectively. The mean background activity of neurons excited by urinary bladder distention in rats with dextran sulfate sodium-induced colitis was significantly higher than in the control group. The threshold volume for excitatory responses to urinary bladder distention in rats with inflamed colon (0.024 +/- 0.09 mL; n = 30) was significantly lower than for control rats (0.062 +/- 0.016 mL; n = 31; P < .05). The stimulus-response curves of excitatory responses to graded urinary bladder distention were significantly increased for both viscerovisceral (urinary bladder distention and colorectal distention) convergent neurons and urinary bladder distention-receptive neurons in rats with colitis compared with control animals. CONCLUSIONS: Acute colitis sensitized lumbosacral spinal neurons receiving input from the urinary bladder. Thus, spinal neuronal hyperexcitability may be involved in central cross-organ sensitization of visceral nociception between the colon and urinary bladder.

Animals↗

Correlation between induction of DNA fragmentation in urinary bladder cells from rats and humans and tissue-specific carcinogenic activity.

Seven chemicals, six of which are known to induce epithelial neoplasms of the urinary bladder in rats, were assayed for their ability to induce DNA damage in primary cultures of rat and human cells from urinary bladder mucosa, and in urinary bladder, liver and kidney of intact rats. Significant dose-dependent increases of DNA fragmentation, as measured by the Comet assay, were obtained in cells from both rats and humans with the following concentrations of five test compounds: 2-naphthylamine and N-nitrosodi-n-butylamine 0.5 and 1 mM, phenacetin 2 and 4 mM, cyclophosphamide from 2 to 8 mM, and o-toluidine 16 and 32 mM. Nitrilotriacetic acid (1-4 mM), a rat bladder carcinogen, and 4-aminobiphenyl (0.125-0.5 mM), a bladder carcinogen in humans but not in rats, gave a weak positive response in rats cells and a more marked response in humans cells. In terms of DNA-damaging potency, 4-aminobiphenyl, cyclophosphamide, phenacetin and 4 nitrilotriacetic acid were more active in human than in rat cells, whereas the converse occurred with 2-naphthylamine. Consistently with the results observed in vitro statistically significant dose-dependent increases in the average frequency of DNA breaks were detected in the urinary bladder mucosa of rats given p.o. single doses corresponding to 14 and 12 LD50 of six of the seven test compounds; the only one which gave a substantially negative response was 4-aminobiphenyl. With the exception of N-nitrosodi-n-butylamine which caused DNA damage in liver and of phenacetin and nitrilotriacetic acid which caused damage in kidney in agreement with their tumorigenic activity, any substantial evidence of DNA lesions in these two organs was absent in rats treated with 12 LD50 of the other 4 test compounds. These findings give evidence that urinary bladder genotoxic carcinogens may be identified by the DNA damage/Comet assay using as targets cells of urinary bladder mucosa, and show that the effect may be quantitatively different in cells from rats and from human donors.

Aged↗

[Lymphoid nodules of the urinary bladder in man].

Basing on macro- microscopical investigation of the urinary bladder in 94 persons, died at the period of birth up to old years and by the time of death having not any disease of the urinary apparatus, structure and topography of the lymphoid nodules, their amount, density of distribution in the mucous membrane of various parts of the organ have been studied. The germinative centers in the lymphoid nodules of the urinary bladder are not revealed. The external appearance of the nodules is not the same; some have clear contours others have no clearly manifested borders. We call them prenodules. The lymphoid nodules are situated near to each other without any definite order. And only near the ureteral openings they are always revealed in a small amount, in the area of the triangle; they are oriented, as a rule, from the ureteral openings towards the exit from the urinary bladder. The amount of the lymphoid nodules in the organ's wall varies (at an average) from 18, in newborns, up to 415, in adolescents, and up to 129, in old persons. Distribution density of the lymphoid nodules in the fundal area of the urinary bladder is somewhat greater, than in its superior parts. The size of the lymphoid nodules during all age periods is not more than 900 mcm.

Adolescent↗

Effects of ADH on the apical and basolateral membranes of toad urinary bladder epithelial cells.

Short-circuited urinary bladders from Bufo marinus were supported on their apical surface by an agar mounting method and impaled with microelectrodes via their basolateral membrane. This arrangement provided stable and long-lasting impalements of epithelial cells and yielded reliable membrane potentials and voltage divider ratios (Ra/Rb), where Ra and Rb are apical and basolateral membrane resistances respectively. The membrane potential under short-circuit conditions (Vsc) was -51.4 +/- 2.2 mV (n = 59), while under open-circuit conditions apical membrane potential (Va) and basolateral membrane potential (Vb) were -31.0 +/- 2.4 and 59.5 +/- 2.4 mV, respectively. This yields a "well-shaped" potential profile across the toad urinary bladder, where Va is inversely related to the rate of transport, Isc. Antidiuretic hormone (ADH) produced a hyperpolarisation of Vsc and Vb but had no significant effect on Va. In addition, Ra/Rb was significantly increased by ADH (4.6 +/- 0.5 to 10.2 +/- 3.6). Calculation of individual membrane resistances following the addition of amiloride showed that ADH produced a parallel decrease in Ra and Rb membrane resistance, with the observed increase in Ra/Rb being due to a greater percentage decrease in Rb than in Ra. The ability of ADH to effect parallel changes in apical and basolateral membrane conductance helps to maintain a constant cellular volume despite an increase in transepithelial transport.

Amiloride↗

In vivo motor effects of substance P on the rat urinary bladder.

Intravesical pressure recordings of the urinary bladder in anesthetized rats were performed and the role of substance P (SP) in the motor control of this organ was evaluated. Regional injection of SP (0.4 nmoles i.a.) into the superior vesical artery elicited a prompt bladder contraction; this motor response was dosedependent. The detrusor contraction could be completely inhibited by a SP-analogue, (D-Pro2, D-Trp7,9)-SP (45-90 nmoles i.a.). Furthermore, the detrusor contraction evoked by preganglionic stimulation of the pelvic nerves was partially inhibited by the same antagonist in a higher dose (65% reduction at a total dose of 150-300 nmoles). The contractile response to SP (0.5 nmoles i.a.) was also significantly reduced after blockade of muscarinic receptors with atropine (50% reduction at 1 mg/kg i.a.) or after ganglionic blockade with hexamethonium (75% reduction at 25 mg/kg i.v. + 50 mg/kg hr i.a.). Immunocytochemical studies demonstrated the occurrence of SP-immunopositive nerve terminals in the detrusor part of the rat urinary bladder. Based on these findings it is suggested that SP may act as a neurotransmitter/modulator in this organ. The mechanism of action for SP on the detrusor seems to be complex and may involve ganglionic transmission via both types of cholinoceptors as well as direct activation of smooth muscle.

Animals↗

[Expression of MAGE genes and MAGE gene products in human renal and urinary bladder tumor].

OBJECTIVE: To observe the expression of MAGE-1 MAGE-3 genes and MAGE-3 gene product in renal and urinary bladder tumor, and to explore the possibility of MAGE-1 and MAGE-3 genes encoding proteins or MAGE-3 gene product used as a target for immunotherapy in renal and urinary bladder tumor patients. METHODS: Reverse transcriptase polymerase chain reaction for MAGE-1 and MAGE-3 genes was performed using 39 renal and urinary bladder tumor specimens. Immunohistochemical technique for MAGE-3 antigen was performed using formal infixed paraffin embedded section of 121 renal and urinary bladder tumor specimens. RESULTS: MAGE-1 and MAGE-3 mRNAs were detected in 23(59.0%) and 22(56.4%) of 39 patients with renal and urinary bladder tumor without expression in 10 tumor surrounding tissues.MAGE-3 antigen was detected in 56(46.3%) of 121 patients with renal and urinary bladder tumor without expression in 10 tumor surrounding tissues. The expression rates of MAGE-1 and MAGE-3 mRNA and MAGE-3 gene product were significantly higher in renal and urinary bladder tumors tissues than in tumor surrounding tissues. The frequency of MAGE-3 gene product expression was examined according to clinical stage and differentiation of histopathology. The results revealed no significant differences in MAGE gene product expression among the clinical stage and the grade of differentiation of histopathology according to Logistic Regression test(P>0.05). CONCLUSION: The tumor-specific antigens might be used as molecular markers and targets for human renal and urinary bladder tumor.

Adult↗

Smooth muscle electromyography of the urinary bladder.

To elucidate smooth muscle activity of the urinary bladder, we utilized an optimized animal model and a specially developed, computer-aided data acquisition and analysis system for bioelectrical signals. Twenty-five Wistar rats were pharmacologically paralyzed and artificially respirated. The urinary bladder was exposed by a suprapubic midabdominal incision, and both ureters were ligated to prevent physiological filling of the bladder. The bladder was initially emptied by slight manual pressure and was then filled via a transurethral catheter in 0.1-ml steps to a maximum of 0.45 ml with physiological saline. A custom-made, gold-plated needle electrode was tangentially guided by a micromanipulator to the smooth muscle of the bladder dome, and the recordings commenced. Furthermore, smooth muscle EMG recordings of the bladder were performed after pharmaco-stimulation of the detrusor with carbachol. Initial results demonstrate that, with the animal model presented here, it is possible to record reproducible and almost artifact-free smooth muscle activity from the urinary bladder. All experiments displayed a stochastic distribution of similar electrical events, increasing in appearance and amplitude with increased bladder volume and after pharmacostimulation with carbachol. Two-dimensional power spectrum analysis revealed a main signal frequency below 1 Hz.

Animals↗

Inhibition of carcinogenesis by alpha-difluoromethylornithine in heterotopically transplanted rat urinary bladders.

Inhibitory effects of alpha-difluoromethylornithine (DFMO) on urinary bladder carcinogenesis were examined using the heterotopically transplanted rat urinary bladder (HTB) model. Male Fischer rats with an HTB were arbitrarily divided into four groups. Group 1 rats received into the HTBs 0.25 mg of N-methyl-N-nitrosourea (MNU) once a week for 3 weeks, followed by instillation twice a week of 0.5 ml of 2% DFMO dissolved in normal rat urine. Group 2 rats received the same amount of MNU, followed by instillation of urine without DFMO. Group 3 rats received a single dose of 0.25 mg of MNU, followed by instillation twice a week of urine containing 2% DFMO. Group 4 rats were treated as those in Group 3 but without DFMO. At 8, 14, and 20 weeks after the last MNU administration, urothelial polyamine levels and [3H] thymidine incorporation by the urothelium of HTBs were determined in nine rats of Groups 1 and 2. The remaining animals of Groups 1 and 2 were killed 25 weeks after the beginning of MNU injection, while those of Groups 3 and 4, 30 weeks after the MNU treatment. The contents of 3 polyamines (putrescine, spermidine, and spermine) in urothelial cells were significantly lower in Group 1 as compared with Group 2. The incidences of carcinoma were significantly lower in the groups treated with DFMO (p less than 0.001, Group 1 versus Group 2; p less than 0.005, Group 3 versus Group 4). These observations indicate that administration of DFMO inhibits (or retards) bladder carcinogenesis in HTBs. A possible mechanism for this effect is suppression of polyamine biosynthesis and proliferation of bladder epithelial cells.

Animals↗

LOH and mutational analysis of p53 alleles in mouse urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

In human urinary bladder carcinogenesis, alterations in the p53 tumor suppressor gene are common events. We have previously reported that they are also frequent in invasive urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in NON/Shi mice. To further investigate the significance of the p53 gene status for mouse urinary bladder carcinogenesis, we examined both allele loss and mutational alterations in urinary bladder cancers of (NON/Shi x C3H/He/Shi) F1 hybrid mice exposed to the carcinogen for 12 weeks and then maintained for a further 9 weeks without treatment. An intragenic silent polymorphism within exon 7 of the p53 gene between NON/Shi and C3H/He/Shi mice allows assessment of allele loss of the p53 gene and determination of the parental origin of mutated and/or lost alleles. A tissue microdissection method was employed to obtain carcinoma samples without excessive contamination with normal tissue. Allele losses were detected in one of 14 tumors (7.1%) and nine mutations in eight of 14 (57%) tumors were found in exons 5-8 by polymerase chain reaction-single strand conformation polymorphism followed by DNA direct sequencing analysis. All mutations involved one base substitution with an amino acid change, although the types of base substitution were random. In conclusion, the high incidence of p53 alterations suggests a significant role in the genesis of invasive urinary bladder tumors in BBN-treated mice.

Alleles↗

Presumptive subcutaneous surgical transplantation of a urinary bladder transitional cell carcinoma in a dog.

A urinary bladder mass in a 12-year-old spayed female West Highland White Terrier was diagnosed after exploratory surgery and biopsy as a transitional cell carcinoma. Four months later the dog presented with an ulcerated plaque-like cutaneous lesion at the previous surgical incision site; concurrent inguinal lymphadenopathy and recurrence of the urinary bladder mass were identified. Transitional cell carcinoma was diagnosed at all 3 sites. Although a definitive relationship cannot be established between the initial surgery for urinary bladder mass and the resultant subcutaneous lesion, surgical implantation should be considered as a source for the neoplastic cells.

Animals↗

Nerve fibers in tumors of the human urinary bladder.

Abstract. Exophytic tumors of the urinary bladder were examined by means of transmission electron microscopy for the presence of neural tissue because, as yet, there has been hardly any discussion of a neuronal component in the biology of neoplasms. In the stroma and rarely in the epithelium of bladder tumors, fine nerve strands were found to be irregularly distributed. These strands comprised one to a maximum of five axons containing predominantly colocalized clear and dense-core vesicles. Immunohistochemistry revealed some nerve-like structures showing vasoactive intestinal neuropeptide (VIP) reactivity. This response and the combination of vesicle types indicate that parasympathetic cholinergic neurons contribute to the innervation of the tumors. Thus, a morphological basis for neuronal influence on the behavior of such tumors has been demonstrated.

Aged↗

Primary carcinoid tumor of urinary bladder.

Invasive carcinoid tumor of the urinary bladder in a sixty-five-year-old man who presented with painless gross hematuria was documented by light and electron microscopic studies. The presence of 5-hydroxyindoleacetic acid (5-HIAA) and absence of vanillylmandelic acid (VMA) was determined in the neoplastic tissue by chemical analysis. This was consistent with the findings of elevated 5-HIAA and normal VMA in the twenty-four-hour urine sample. Sections of the tumor yielded negative argentaffin and argyrophil reactions. The relevant literature is reviewed.

Aged↗

[Tissue engineering of the urinary bladder].

In tissue engineering of the urinary bladder with autologous cell transplantation, high differentiation of the cells cultivated in vitro on biocompatible membranes is essential for the functionality of the tissue constructs after implantation. The terminal differentiation of superficial urothelial cells has a key role because of the barrier function of these cells against urine. The aim of this study was to determine optimized conditions for the creation of terminally differentiated urothelium to cover large membrane surfaces. This can bring us closer to the goal of using functioning tissue constructs in clinical trials.

Absorbable Implants↗

'Spontaneous' regression of advanced leiomyosarcoma of the urinary bladder.

A case of advanced leiomyosarcoma of the urinary bladder is reported in a 25-year old man who, in a short time, experienced a complete 'spontaneous' regression of his fatal illness. He first presented with severe haemoperitoneum resulting from an unresectable bleeding tumour of the urinary bladder. Debulking surgery was performed, followed by salvage chemotherapy. Histological and ultrastructural examinations of the tumour confirmed a poorly differentiated leiomyosarcoma. The residual disease failed to respond to salvage chemotherapy, but regressed 'spontaneously' 5 months after cessation of therapy. The patient is alive without evidence of disease 51 months after the diagnosis. This remarkable phenomenon and relatively long survival in a poor-risk leiomyosarcoma of the urinary bladder has never been reported previously.

Adult↗

Neurogenic dysfunction of the urinary bladder in Parkinson's disease.

Involvement of the urinary bladder in Parkinson's disease was recognized in the 1950's, when the accidental discovery of a neurosurgical means of treating the disease brought more attention to it, with increasing research and study. In more recent years, the advent of more specific medical treatment has led to closer examination of the disease, and has enlarged our awareness of its complications. This has been paralleled by progress in the field of urology, with more precise methods of measuring dysfunction of the urinary bladder.

Female↗

Immunohistochemical expression of keratin proteins in urinary bladder carcinoma.

Transitional carcinomas of the urinary bladder were examined immunohistochemically for keratin proteins with the use of polyclonal antiserum (TK, 41-65 kDa) and 3 monoclonal antibodies (KL 1, 55-57 kDa; PKK 1, nos. 19, 18, 8; and K 8.12, nos. 16, 13). Umbrella cells gave particularly strong staining for TK, KL 1 and PKK 1, whereas they were negative for K 8.12. Basal- and intermediate-layer cells in urothelial epithelium were moderately positive for all keratins. Brunn's nests cells showed comparatively slight or moderate keratin staining, and K 8.12 staining of Brunn's nests was higher than in urothelial epithelial cells. Transitional carcinoma (grades I and II) indicated uniform keratin distribution, and staining was strong with TK, while that of KL 1, PKK 1 and K 8.12 varied, and grade III tumors showed the lowest intensity of staining. K 8.12 staining in papillary transitional carcinomas was strongly positive in basal located tumor cells, as compared with apical tumor cells. Squamous cell carcinoma was varying positive to keratin reactions dependent on the degree of keratinization. Heterogenity of keratin distribution in papillary transitional carcinomas was given between basal tumor cells and well differentiated tumor cells including umbrella-like cells.

Antibodies, Monoclonal↗