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PubMed1998

Presence of putative neurotransmitters in the myenteric plexus of the gastrointestinal tract and in the musculature of the urinary bladder of the ferret.

The innervation of the musculature in the ferret stomach, ileum, colon and urinary bladder was investigated using immunohistochemistry in noncolchicin-treated tissues. In the gastrointestinal tract two main subpopulations of myenteric neurones were found: cholinergic neurones expressing choline acetyltransferase (ChAT), which made up 68, 67 and 67% of the neurones in the stomach, ileum and colon, respectively, and nitrergic neurones containing nitric oxide synthase and NADPH-diaphorase (stomach: 23%, ileum: 21%, colon: 26%). In the stomach, cholinergic neurones expressed substance P (SP, 2% of all neurones), dopamine-beta-hydroxylase (DBH, 19%) but not tyrosine hydroxylase (TH) or vasoactive intestinal polypeptide (VIP), while nitrergic neurones contained VIP and neuropeptide Y (NPY). TH- but not DBH-immunoreactivity was observed in 4% of gastric neurones. Intense immunoreactivity in the musculature suggests that part of ChAT/SP- and NOS/NPY/VIP-positive neurones function as motorneurones. In the ileum, a high number (32%) of DBH-positive neurones was demonstrated. About half of the SP-positive neurones in the ileum also contained calcitonin gene-related peptide (CGRP). In the urinary bladder, only few intramural ganglia were observed. The smooth muscle was densely innervated by ChAT, NPY and DBH immunoreactive fibres. The data showed that the innervation of the ferret viscera exhibited similarities but also differences as compared with other mammalian species. Some of the chemical coding of myenteric neurones is remarkably similar to that observed in other mammals.

Animals↗
PubMed1990

Alpha 2-adrenoceptors mediate the inhibition of cholinergic transmission in parasympathetic ganglia of the rabbit urinary bladder.

Intracellular recordings were made from neurons of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder and maintained, in vitro. Bath-application of norepinephrine (NE, 500 nM-5 microM) caused a hyperpolarizing response at the postsynaptic membrane of VPG neurons in a concentration-dependent manner. NE blocked the action potential elicited by an orthodromic stimulation of preganglionic (pelvic) nerve fibers. At a relatively low concentration (5-100 nM), NE depressed the fast excitatory postsynaptic potential (EPSP), without producing the hyperpolarization. NE (100 nM) produced 49 +/- 17% (N = 5) decrease in the amplitude of the fast EPSP. NE did not depress the acetylcholine (ACh) potential produced by iontophoretic application of ACh to the ganglion cells. NE did not affect the amplitude of the miniature EPSP, while it reduced the frequency of miniature EPSPs. These results suggest that NE inhibits the nicotinic transmission in the rabbit VPG, probably reducing the ACh release from presynaptic nerve terminals. Epinephrine (1 microM) was more potent than NE (1 microM) in producing the hyperpolarization as well as the blockade of the fast EPSP amplitude. Isoproterenol was ineffective as an agonist for these inhibitory adrenoceptors. Clonidine mimicked the effect of NE on the fast EPSP. Yohimbine and idazoxan antagonized both the inhibition of the fast EPSP and the hyperpolarization produced by NE. These results suggest that alpha 2-adrenoceptors are responsible for the inhibition of the neuronal activity in parasympathetic ganglia of the rabbit urinary bladder. Immunohistochemical study demonstrated the presence of tyrosine hydroxylase (TH)-labelled neuronal elements in the VPG. They were a small proportion of principal neurons, their dendrites, and many varicose fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Diffuse papillomatosis of rat urinary bladder occurring in association with vesical calculi.

Repeated intravesical administrations of 0.9 per cent NaCl solution with or without bladder carcinogen N-butyl-N-(3-carboxypropyl)nitrosamine resulted in a high incidence of calculus formation in the urinary bladder. In all such cases, diffuse papillomatosis of the bladder urothelium was observed. "Invasion" of the tunica muscularis and the tunica adventitia by tumor was demonstrated as early as week 9 of the experiment. Morphologically, the lesions could not be distinguished from the bladder tumors induced by an orally administered carcinogen. Evidence was presented to conclude that they represent neoplasms of low malignant potential. The results indicate that bladder tumors may develop in the absence of known exposure to carcinogen provided the urothelium is chronically stimulated. Tumors solely attributable to N-butyl-N-(3-carboxypropyl)nitrosamine treatment did not occur.

Animals↗
PubMed1993

Fura-2 transport in toad urinary bladder epithelium: effects of antidiuretic hormone, colchicine and osmotic gradients.

Fluorescence is transferred across the toad urinary bladder when fura-2/AM is added to the mucosal or serosal sides of the epithelium. It was now observed that: (1) Oxytocin (20 nM, serosal) increased fluorescence transfer from the mucosal to the serosal but not from the serosal to the mucosal baths. The ratio between the fluorescence intensities recorded with excitation wavelengths of 340 and 380 nm indicates that the calcium sensitive probe (free fura-2) was transferred to the serosal but not to the mucosal compartment by an oxytocin sensitive transport. (2) Preincubation with probenecid did not change fluorescence transfer in basal conditions but significantly reduced the oxytocin induced increase in free fura-2 transport. (3) Fluorescence accumulation inside the tissue was strongly reduced by oxytocin, but only when fura-2/AM was added to the mucosal side. (4) An osmotic gradient, in the presence of oxytocin, further increased the transfer of fluorescence at 380 nm but not at 340 nm. This indicated that the transfer of a calcium-insensitive fraction was being stimulated. (5) Preincubation with colchicine strongly inhibited fluorescence transfer across the tissue, at both 340 and 380 nm (the 340/380 ratio did not change). (6) Tissue accumulation was increased by colchicine. (7) Vanadate did not inhibit fura-2 transfer in the toad urinary bladder. We conclude that intracellularly-generated free fura-2 is only transported across the basolateral border, and that this transfer is stimulated by ADH. The calcium-insensitive fraction is transferred by a temperature-dependent process, sensitive to an osmotic gradient and colchicine.

Animals↗
PubMed1991

High energy underwater shock wave treatment on implanted urinary bladder cancer in rabbits.

The effects of focused high energy shock waves (SW) on the implanted urinary bladder cancer in rabbits were examined. The bladder cancer was exposed to 2000 to 8000 shots of focused SW under ultrasound guidance. Although only focal necrosis of the tumor was seen in the one day SW exposure, wider and deeper tumor necrosis was observed in the tumors following serial SW (2000 to 6000 shots, for two to three days). Eight to 10 day serial SW exposure (6000 to 8000 shots) decreased the tumor growth in comparison with that of the control. Lung metastases examined by periodic chest X-ray after SW treatment revealed that SW did not promote lung metastases. Pathological findings were also in accord with the X-ray examinations. Polyclonal antibody type 4 collagen was used for immunohistochemical staining of vascular wall in bladder cancer. Vascular wall destruction, not found in spontaneous necrotic tumor, were clearly visible in SW induced necrotic area. SW induces vascular damage in the tumor, which may be the primary cause promoting the tumor necrosis.

Animals↗
PubMed1998

High susceptibility of p53(+/-) knockout mice in N-butyl-N-(4-hydroxybutyl)nitrosamine urinary bladder carcinogenesis and lack of frequent mutation in residual allele.

The loss of p53 functions is considered to compromise the growth-suppression machinery of the cell and facilitate neoplastic change. In humans, genetic alteration in the p53 gene is one of the most frequently observed molecular changes in tumors, including urinary bladder carcinomas. We have investigated the susceptibility of heterozygote p53 knockout mice to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in terms of urinary bladder tumor induction. Both p53(+/-) knockout mice and C57BL/6 original parent strain were administered 0, 0.002, 0.004, 0.0075 and 0.025% BBN in the drinking water for 20 weeks. As compared with the C57BL/6 strain, greater lesion yields were observed in knockout mice after 20 weeks of treatment. Transitional cell carcinomas were found in 9 (75%) and 12 (100%) of each 12 mice of the 0.0075 and 0.025% BBN treatment groups, respectively, whereas only 1 (11%) and 6 (67%) of each 9 of the C57BL/6 mice demonstrated tumors. Preneoplastic lesions (dysplasia) were also observed more frequently in the lower dose groups in the knockout mice than C57BL/6 mice. PCR single-strand conformation polymorphism analysis followed by DNA direct sequencing of the p53 gene (exons 5-8) extracted from bladder tumors demonstrated mutations in 3 of 11 (27.3%; exon 7) and 8 of 29 (27.6%; exons 5-8) tumors in C57BL/6 and knockout mice, respectively. There was no significant difference in the mutation rates at the residual p53 gene between the two cases. All mutations observed in knockout mice were restricted to the normal allele, and none were present in the gene-targeted null allele. In a separate experiment, 5-bromo-2'-deoxyuridine labeling indices after treatment with BBN for 2 or 4 weeks were significantly higher in knockout mice than wild-type mice. Measurement of the urinary concentration of N-butyl-N-(3-carboxypropyl)nitrosamine, a proximate carcinogenic metabolite, revealed no significant differences between knockout and original parent strain after administration of 0.0075% BBN in the drinking water for 4 weeks. In conclusion, knockout mice are distinctly more sensitive to urinary bladder carcinogenesis induced by BBN than their original parent strain, as evidenced by elevated DNA synthesis during carcinogen administration and an increased tumor yield. The high susceptibility of p53 knockout mice appeared to be related to the high level of cell proliferation rather than that of N-butyl-N-(3-carboxypropyl)nitrosamine in the urine or that of mutations at the p53 gene.

Alleles↗
PubMed2000

Expression of collagenase-3 (matrix metalloproteinase-13) in transitional-cell carcinoma of the urinary bladder.

Expression of collagenase-3 [matrix metalloproteinase-13 (MMP-13)] has been previously demonstrated in squamous-cell carcinomas of both the head and neck and the vulva, cutaneous basal-cell carcinomas, chondrosarcomas and melanomas. Using in situ hybridization, MMP-13 mRNA expression was detected in 13 of 23 (52%) urinary bladder transitional-cell carcinomas (TCCs). Expression was restricted to cells in the invading edges of tumors. No expression of MMP-13 mRNA could be detected in normal urothelium. As detected by immunohistochemistry, MMP-13 protein showed an expression pattern similar to that of MMP-13 mRNA. Expression of MMP-13 mRNA and protein was also detected in 2 bladder carcinoma cell lines (RT4 and T24). In these cell lines, TNF-alpha potently induced MMP-13 mRNA expression. Retinoids and a selective p38 inhibitor, SB203580, potently inhibited MMP-13 mRNA expression. Our results demonstrate MMP-13 expression in human urinary bladder carcinoma cells in vivo and in vitro and suggest that MMP-13 may serve as a marker for transformation and invasion in urinary bladder TCCs.

Adult↗
PubMed1992

[A clinico-pathological study of inverted papilloma of the urinary bladder. Analysis of histogenesis].

A clinico-pathological study was conducted on 9 cases with inverted papilloma of the urinary bladder. 1. Clinical study: The incidence of inverted papillomas, when compared with transitional cell carcinoma of the urinary bladder, was much higher in men than in women in our study and in the literature dealing with this subject as well. Eight of 9 inverted papillomas were localized in the bladder neck. Cystoscopic examination revealed that all tumors were pedunculated and 8 of the 9 tumors had non-papillary surfaces. These clinical findings suggest that inverted papillomas localized in the bladder neck are very similar to posterior urethral polyps with prostatic type epithelium. Transurethral resection (TUR) was performed in all cases. Recurrence was not observed. 2. Pathological study: Inverted papillomas were classified into two types according to their histological patterns, determined by Hematoxylin-Eosin (H-E) staining. One pattern was glandular and the another was trabecular. Of the 9 cases, 2 were glandular, 5 were trabecular and the remaining 2 were a mixed type. Immunohistochemical staining with anti-prostate specific antigen antibody revealed 3 of the 9 tumors were stained positively, and these tumors were classified a glandular type. Inverted papilloma were classified into two patterns according to their histological patterns, determined by immunohistochemical staining with anti-keratin antibody, namely a bladder tumor pattern and a urethral tumor pattern. Inverted papillomas with a urethral tumor pattern were of the glandular type and included anti-PSA antibody positive staining tumors. These findings suggest that a portion of inverted papillomas may have arisen from neoplastic transformation of prostatic tissue.

Aged↗
PubMedDate not supplied

Computer-based grading of haematoxylin-eosin stained tissue sections of urinary bladder carcinomas.

PURPOSE: A computer-based image analysis system was developed for assessing the malignancy of urinary bladder carcinomas in a more objective manner. Tumours characterized in accordance with the WHO grading system were classified into low-risk (grades I and II) and high-risk (grades III and IV). MATERIALS AND METHODS: Images from 92 haematoxylin-eosin stained sections of urinary bladder carcinomas were digitized and analysed. An adequate number of nuclei were segmented from each image for morphologic and textural analysis. Image segmentation was performed by an efficient algorithm, which used pattern recognition methods to automatically characterize image pixels as nucleus or background. Image classification into low-risk or high-risk tumours was performed by means of the quadratic non-linear Bayesian classifier, which was designed employing 36 textural and morphological features of the nucleus. RESULTS: Automatic segmentation of nuclei on all images was about 90% on average. Overall system accuracy in correctly classifying tumours into low-risk or high-risk was 88%, employing the leave-one-out method and the best combination of three textural and one morphological feature. Classification accuracy for low-risk tumours was 88.8% and for high-risk tumours 86.2%. CONCLUSION: The proposed image analysis system may be of value to the objective assessment of the malignancy of urine bladder carcinomas, since it relies on nuclear parameters that are employed in visual grading and their prognostic value has been proved.

Algorithms↗
PubMed2000

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.

Adenosine Triphosphate↗
PubMed1994

Urinary bladder dysfunction in the BB/W diabetic rat: effect of ganglioside treatment on functional and structural alterations.

Urinary bladder dysfunction in the diabetic BB/W rat is characterized by infrequent irregular contractions of high amplitude. Initially these occur in the absence of detectable neuroanatomical lesions of sensory afferent and parasympathetic fibers of the pelvic nerve, which constitute the micturition reflex arc. Structural lesions consisting of progressive axonal atrophy of myelinated and unmyelinated fibers become detectable only after 4 months of diabetes. In the current study we evaluated the effect of ganglioside treatment (10 mg./kg. body weight) for one month. This drug regimen was initiated at 4 months of diabetes, when functional bladder abnormalities were well established, whereas structural lesions were yet to appear. Animals examined 1 or 3 months after termination of the one-month treatment protocol showed sustained normalization of the characteristic functional abnormalities, accompanied by prevention of the neuroanatomical lesions of sensory afferent and parasympathetic efferent myelinated fibers in the pelvic nerve. These data suggest that ganglioside treatment may be beneficial in delaying the progression of diabetic autonomic neuropathy in this experimental animal model.

Animals↗
PubMedDate not supplied

Immuno-electron microscopic study of tyrosine hydroxylase in the cat urinary bladder and proximal urethra.

The distribution and density of tyrosine hydroxylase (TH)-immunoreactive nerves in the cat urinary bladder and proximal urethra were similar to those of glyoxylic acid fluorescent nerves. Both TH-immunoreactive and fluorescent nerve fibres markedly decreased after 6-hydroxydopamine treatment. Hence, immuno-electron histochemistry of TH was employed to investigate adrenergic termination to the muscle layers of the cat urinary bladder and proximal urethra. A total number of 3728 TH-immunoreactive axon terminals in the lower bladder body, lateral bladder base, trigone, bladder neck and proximal urethra were examined. In the bladder base (the lateral bladder base, trigone and bladder neck) and proximal urethra, most of the TH-immunoreactive axon terminals (57.1-89.2%) lay outside smooth muscle cell fascicles, while most (69.7%) in the bladder body were inside muscle cell fascicles. The proportions of TH-immunoreactive axon terminals accompanying non-TH-immunoreactive axon terminals in the five regions were almost the same (about 70%). The present study demonstrated that the mode of adrenergic termination in the bladder base and proximal urethra notably differed from that in the bladder body, and that approximately 70% of adrenergic axon terminals were associated with non-adrenergic or cholinergic axon terminals in each region.

Animals↗
PubMed2001

[Late metastases of prostatic adenocarcinoma to urinary bladder after radical prostatectomy: a case report].

We report a case of metastasis of prostatic cancer to urinary bladder. A 67-year-old man was admitted with a complaint of macroscopic hematuria, who had undergone radical prostatectomy and surgical castration for prostatic cancer (pT3N0M0) 53 months before. Computed tomographic (CT) scan revealed an invasive tumor on the right wall of the urinary bladder and swelling of paraaortic and pelvic lymph node metastases. These lesions were diagnosed as bladder tumor with lymph node metastases, and then transurethral biopsy of bladder tumor was performed. Because macroscopic hematuria could not be controlled and severe progressive anemia was found after the biopsy, simple cystectomy and bilateral cutaneoureterostomy were performed on the next day. Histopathological analysis showed that the tumor was adenocarcinoma, which was thought to be a metastatic tumor from the prostatic cancer.

Adenocarcinoma↗
PubMed2001

Vascular architecture of normal human urinary bladder and its remodeling in cancer, as revealed by corrosion casting.

The vasculature of normal human urinary bladder wall and its tumors were studied using corrosion casting and scanning electron microscopy. In the normal wall, a regular organization of highly tortuous horizontal and vertical vessels allows accommodation of the vascular system to spatial changes resulting from the filling/voiding cycle. The vasculature of tumors is a result of remodeling of preexisting wall vessels associated with gradual growth of the neoplastic tissue. The shape and arrangement of blood vessels in different regions of the tumor seem to reflect a variable dynamics of tumor development and possible influence of various angiogenesis-promoting growth factors.

Blood Vessels↗
PubMed1982

Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladder tumors in male F344 rats.

Studied were conducted to determine whether initial treatment with N-2-fluorenylacetamide (2-FAA) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) followed by treatment with either phenobarbital sodium (PB) or sodium saccharin (SS) induced or enhanced liver and/or bladder tumorigenesis. Male inbred F344 rats were given 0.05% PB and 5.0% SS in the diet for 32 weeks after 4-week administration of 0.02% 2-FAA treatment and induced hyperplastic liver nodules after BBN treatment. The SS significantly enhanced induction of bladder hyperplasias, but not papilloma after BBN treatment, and induced bladder hyperplasias after 2-FAA treatment. However, PB had no effect on the bladder and SS had no effect on the liver after either 2-FAA or BBN treatment. The data indicate that although 2-FAA and BBN have tumor-initiating effects in the liver and urinary bladder, the tumor-promoting effects of PB and SS are organ-specific. The tumor-promoting effect of PB for the liver is relatively greater than that of SS for the urinary bladder.

2-Acetylaminofluorene↗
PubMed1999

Urinary Bladder Catheterization of Female Mice and Rats.

Catheterization of the urinary bladder of rats and mice is necessary for a variety of clinical and experimental reasons. The anatomy of the female mouse and rat is unique in that the urinary orifice is external and just anterior to the vaginal opening. This characteristic makes the bladder of these species easier to catheterize than that of other species. Methods cited in the literature do not adequately describe techniques that facilitate ease of urinary bladder catheterization (1). We describe a simple technique for urinary catheterization in adult female mice and rats.

Journal Article↗
PubMed1997

Lack of promotion of urinary bladder carcinogenesis by sodium bicarbonate and/or L-ascorbic acid in male ODS/Shi-od/od rats synthesizing alpha 2 mu-globulin but not L-ascorbic acid.

The study was designed to investigate whether sodium bicarbonate (NaHCO3) and/or L-ascorbic acid (AsA) promote urinary bladder carcinogenesis in male ODS/Shi-od/od (ODS) rats, which, unlike male F344 rats, are resistant to sodium L-ascorbate (Na-AsA)-promoting effects. Whereas F344 rats can synthesize AsA and alpha 2 mu-globulin (A2 mu-G), only A2 mu-G in produced in ODS rats. The two strains were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 wk and then were fed basal CA-1 diet supplemented with 3% NaHCO3 plus 5% AsA (NaHCO3 + AsA), 3% NaHCO3, 5% AsA, or no chemicals for 32 wk. ODS rats given BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had only a few small carcinomas in the urinary bladder, like those receiving BBN alone or BBN-AsA. In contrast, F344 rats administered BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had many more, larger, carcinoma than animals of the same strain given BBN alone or BBN-AsA. AsA alone did not have any effect in either strain. Administration of NaHCO3 alone or NaHCO3 + AsA was associated with significant elevation of urinary pH and Na+ concentration to the same extent in both strains but, again, AsA alone was without effect. NaHCO3 + AsA and AsA alone increased the urinary concentration of total ascorbic acid in both strains but the observed levels wer lower in ODS rats. The results indicate that ODS rats are resistant to the modifying effects of NaHCO3 and/or AsA on two-stage urinary bladder carcinogenesis, and thus that the susceptibility to the promotional activity of sodium-salt-type compounds may be regulated by factors other than A2 mu-G-synthesizing ability and urinary levels of pH, Na+ and total ascorbic acid.

Animals↗