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Quantitative analysis for innervation of smooth muscle cells in the wall of the urinary bladder.

The distribution of nerve terminals to different parts of the urinary bladder was studied by electron microscopy with the aid of 6-hydroxydopamine treatment. A quantitative analysis was made for each region. In the sphincter and trigone areas nerve terminals were found to be much more numerous (3 times more) than in sections from the body and the apex of the bladder. In much of the bladder there were 6--7 smooth muscle cells for each nerve fiber, however in the trigone area 1--2 muscle cells were supplied by terminal nerve fiber. The narrowest gap between nerve terminals and smooth muscle cells was found to be 150--250 nm. It was commonly seen that Desmosome-like attachments, called nexuses, connected adjacent smooth muscle cells. After 6-hydroxydopamine treatment degenerated terminals could be found mostly in the fine periarterial plexuses but some were also observed that were not related to blood vessels, especially in the trigone area. Summation of our figures and results for terminal density suggests to us that contractions of the urinary bladder are initiated or controlled in the trigone region and that other parts of the wall are activated by local nerve processes and the numerous nexal contacts.

Animals↗

[A case of invasive squamous carcinoma of the urinary bladder perforated intraperitoneally after intra-arterial chemotherapy].

We report a case of invasive squamous cell carcinoma of the urinary bladder, which was perforated intraperitoneally after intra-arterial chemotherapy. The patient was a 67-year-old woman complaining of macrohematuria and body weight loss. After thorough examination, the diagnosis of clinical stage C of squamous cell carcinoma of urinary bladder was made. At first, balloon occluded intra-arterial infusion with 80 mg, cis-dichlorodiamine platinum 10 mg mitomycin C and 1 mg vincristine was performed, followed by radiotherapy and 15 mg bleomycin injection. On the 5th day, the patient fell into shock with abdominal expansion, and bladder perforation into peritoneal cavity was confirmed by rapid cystography. Emergency cystohysterectomy and drainage were performed. Resected bladder had a large defect on its posterior wall, and tumor had fallen into severe necrosis. Since January, 1986 we performed balloon occluded intra-arterial infusion of antineoplastic drugs for 3 other cases. We obtained a partial response for 2 of these cases. The outcome of intra-arterial chemotherapy in our hospital is also reported.

Aged↗

DPC blockade of transepithelial chloride absorption and single anion channels in teleost urinary bladder.

The columnar cell epithelium of the euryhaline goby (Gillichthys mirabilis) urinary bladder actively absorbs NaCl from the lumen, thereby driving water transport and reducing water loss to the hypertonic external environment. Transcellular transport of Cl- involves apical membrane entry via Na(+)-coupled cotransport driven by the Na+ electrochemical gradient and subsequent basolateral membrane exit. An anion channel in the basolateral cell membrane of columnar epithelial cells was identified using patch-clamp technique. This channel may be one avenue for basolateral Cl- exit from the urinary bladder columnar cell. Single-channel conductance (Gc) of channels in excised, inside-out membrane patches was approximately 75 pS in symmetrical solutions containing 140 mM Cl-. The channel was selective to Cl- over other anions [Cl- > 2-(N-morpholino)ethanesulfonic acid (MES) > F- approximately Br- approximately I- > NO3- approximately SO4(2-)). Channel activity, expressed as the open probability (Po), was voltage dependent in the physiological range of membrane potential, with membrane depolarization increasing Po. Decreasing the pH of the solution bathing the cytoplasmic face of the membrane patch over the range 8.4-6.0 reduced Po. There was no effect of pH on either Gc or ionic selectivity. Radiochloride flux technique was also applied to intact columnar epithelial cell sheets to relate anion channel activity to macroscopic transcellular transport. Serosal exposure to the anion channel blocker diphenylamine-2-carboxylic acid (DPC, 30 microM to 3 mM) reduced and abolished transcellular radiochloride fluxes and net Cl- absorption across short-circuited tissues in a dose-dependent fashion. DPC addition (10 microM to 1 mM) to the solution bathing the cytoplasmic face of excised, inside-out membrane patches reduced Po in a dose-dependent manner and had no effect on Gc. These parallel findings of DPC blockade on intact epithelia and on single anion channels support the notion that this anion channel is a basolateral membrane component of the pathway for Cl- movement in transcellular Cl- absorption.

Absorption↗

[A case of primary signet ring cell carcinoma of urinary bladder].

A 72-year-old female patient presented to our clinic with the chief complaint of gross hematuria and urinary frequency on September 6, 1990. Cystoscopic examination revealed a thumb's head size nonpapillary tumor. The tumor was located adjacent to the orifice of the left ureter. Histological findings of the tumor by transurethral resection (TUR) indicated transitional cell carcinoma with partial signet ring cell carcinoma. No other malignant findings in any other organs including the gastrointestinal tract were noted. Total cystectomy was performed and Indiana pouch was constructed. Histopathological staging was pT1 N0 M0. The patient died of multiple metastasis of the signet ring cell carcinoma on June 22, 1992. This is the thirty-second case of signet ring cell carcinoma of urinary bladder reported in the medical literature in Japan. We investigated 19 alive or unknown cases as follow up and briefly discussed the treatment and outcome of the primary signet ring cell carcinoma of the urinary bladder. The outcome appeared to be somewhat better than previous reports. Total cystectomies were performed in 18 of the 32 cases (56.3%). As noted in past reports, the treatment of our patient consisted of total cystectomy. Twenty-two patients died of signet ring cell carcinoma. Recurrence to the pelvic area was observed in 18 of the 22 (81.8%) patients who died. Because of this high rate of recurrence, we recommend a thorough assessment of the pelvic area of the patients diagnosed with signet ring cell carcinoma of urinary bladder.

Aged↗

[Leiomyoma of urinary bladder: report of a case].

A case of leiomyoma of the urinary bladder in a 46-year-old woman is reported. The patient was referred to us because of incidental finding of a mass in the bladder. Cystoscopy revealed a protruding tumor covered with normal-appearing urothelium on the right posterior wall of the bladder. The tumor was well-demarcated from adjacent organs on echography and computed tomographic scan. Transurethral biopsy revealed a bladder leiomyoma. Partial cystectomy was performed. The patient is now apparently free of disease 7 months after the operation.

Biopsy↗

Sex differences in function and distribution of beta-adrenoceptors in rabbit urinary bladder.

PURPOSE: To examine whether there are sex-related differences in urinary bladder function, we evaluated the function and distribution of beta-adrenoceptor in the male and female rabbit urinary bladder. MATERIALS AND METHODS: Ten male and ten female rabbits were studied. The function and distribution of beta-adrenoceptors were studied by measuring changes in contractile forces from isoproterenol, a beta-adrenoceptor agonist, and forskolin, an adenylate cyclase activator, and by measuring beta-adrenoceptor densities using radioligand receptor binding techniques. RESULTS: Isoproterenol caused significantly greater relaxation in female trigonal muscles than in male trigonal muscles. It caused similar relaxation responses in the male and female detrusors. The Bmax values for [3H]dihydroalprenolol (DHA) binding in trigonal muscles were significantly higher in the female than in the male, whereas Bmax values for [3H]DHA binding in the male and the female detrusor were similar. In contrast, forskolin caused similarly marked relaxations in the male and the female detrusor and trigonal muscles. CONCLUSION: These findings demonstrate that there are sex-related differences in the function and the distribution of beta-adrenoceptors in rabbit trigonal smooth muscles.

Adrenergic beta-Agonists↗

[ImmuCyst intravesical (freeze-dried preparation made from the connaught strain of Bacillus Calmette Guérin) for the treatment of superficial bladder cancer and carcinoma in situ of urinary bladder].

UNLABELLED: BCG has been used as a preventive vaccine of tuberculosis worldwide. However, in 1976, Morales et al. reported the effective use against superficial bladder cancer by intravesical administration. In Japan, in July, 1994, Rhone-Poulenc Rorer Japan Inc, started the cooperative clinical studies with Nippon Kayaku Co. Ltd. as an orphan drug. In the phase I/II studies, BCG preparation at 40.5, 81 and 121.5 mg was given intravesically slowly, keeping it for 2 hrs, in the bladder. This was repeated once weekly for 8 weeks. The CR rates were 60, 68.2 and 75% respectively, but there were no significant differences. The major adverse reactions were polyurea, urination pain, urination difficulty, hematurea and urinary leukocytosis which were frequently observed. Beside these, fever, malaise, loss of appetite and GPT elevation were also observed. In the late phase II study, in which 81 mg were given, CR rates in 39 response evaluable cases, was 61.5% (16/26), response rate (CR + PR) was 85.6% (22/26), and CR rate of CIS was 92.6% (12/13). There were responded cases in the recurred cases and those with previous chemotherapy, and the adverse reactions were polyurea, urination pain, urination difficulty, hematurea, malaise and loss of appetite mainly. CONCLUSION: Compared with anticancer drug treatments, BCG prevented the recurrence the disease for a long time. From these studies, freeze-dried BCG preparation (immu-Cyst) seemed to be very useful for the treatment of superficial bladder cancer and carcinoma in situ of urinary bladder.

Adjuvants, Immunologic↗

Non-cholinergic inotropic responses evoked by electric field stimulation in the isolated rat urinary bladder. Possible participation of substance P.

The present study explores whether a peptide, such as substance P (SP), has some role subserving the atropine-resistant component of electrically-evoked contractions, in isolated rat urinary bladders. The electric field stimulation (EFS) employed herein, consisted in square wave pulses of 5 Hz, 50 ms duration and supramaximal voltage (40 V), applied for 10 sec, every 3 min and conducted to the tissue via a pair of platinum ring electrodes, surrounding the isolated preparations. In order to assess whether electric stimuli, induced urinary bladder inotropism through the activation of nerve structures, degeneration of intramural nerve elements was attempted by cooling the tissue (48 h at 4-5 degrees C). After such procedure, 80-90% inhibition of responses to EFS, was detected. Moreover, tetrodotoxin, at 10(-6) M, evoked similar effects than cooling. Atropine, at 10(-6) M, failed to produce a significant decrement of contractile responses, whereas at 10(-5) M, the electrically-induced inotropism declined around 40%, in comparison with controls. In another set of experiments, atropinized urinary bladders (atropine at 10(-5) M) were exposed to capsaicin (5 X 10(-6) M) and this coincided with decreased (-43%) responses to EFS. Next, SP, at 10(-9) M, was added to the medium containing capsaicin and complete restoration of full contractile responses to EFS, was observed. Inasmuch as it has been proposed that capsaicin releases SP from sensory nerve fibers and since our experiments show that SP restored the inotropism elicited by electric stimuli on capsaicin-exposed preparations, it is suggested that SP could be involved, at least in part, in the non-cholinergic, EFS-evoked, contractile responses of isolated rat urinary bladders.

Acetylcholine↗

Developmental regulation of nerve and receptor mediated contractions of mammalian urinary bladder smooth muscle.

The development of nerve-induced activation, receptor properties and cellular signalling was examined by comparing the urinary bladder of new-born (0-2 days) and adult mice. Tissue strips were isolated and the effects of different neuromuscular agents on force were investigated during electrical field stimulation. The nerve-induced contractions of the urinary bladders from new-born mice were less influenced by desensitisation with alpha, beta-methylene ATP and more sensitive to scopolamine compared with those of the adult bladder. There were no differences in alpha, beta-methylene ATP or ATP responsiveness between adult and new-born tissue, showing that the lower purinergic component of the nerve-induced responses in the new-born mice was due to properties of the transmitter release rather than to a change in receptor function. Dose-response curves for carbachol revealed a lower peak response in new-born bladders compared with adults. The phasic component of the cholinergic contractions was pronounced and initiated at low carbachol concentrations in the new-born tissue. The carbachol contractions of both new-born and adult urinary bladder tissue were inhibited by the Rho kinase inhibitor Y27632 and by the protein kinase G activator 8-Br-cGMP. However, the sustained phase of carbachol contraction was significantly less sensitive to Y27632 and 8-Br-cGMP in new-born tissue. These results suggest that the receptor mediated calcium sensitisation mechanism is less prominent in new-born compared with adult mice and that the contractions of new-born bladders are less influenced by the nitric oxide (NO)-cGMP inhibitory pathway.

Adenosine Triphosphate↗

Detecting homozygous deletions in the CDKN2A(p16(INK4a))/ARF(p14(ARF)) gene in urinary bladder cancer using real-time quantitative PCR.

PURPOSE: 9p21 is a major target in the pathogenesis of human urinary bladder cancer. The locus harbors the CDKN2A/ARF tumor suppressor gene, which encodes two cell cycle regulatory proteins cyclin dependent kinase 2A (p16(INK4a)) and alternate reading frame (p14(ARF)). We have designed a real-time quantitative PCR (QPCR) application to study homozygous deletion (HD) of CDKN2A/ARF in 186 urinary bladder cancer patients. EXPERIMENTAL DESIGN: Real-time QPCR, based on simultaneous amplification of ARF and a reference gene, GAPDH, was developed and evaluated in three melanoma cell lines with HDs at the CDKN2A/ARF locus (IGR-1, SK-MEL-5, and WM-266-4). In addition, loss of heterozygosity was analyzed at the D9S942, D9S1748, and D12S99 markers. Mutation analysis of the CDKN2A/ARF gene was performed using single-strand conformational polymorphism and sequencing. Results from the present investigation were combined with previous p53 analysis of the same urinary bladder neoplasms. RESULTS: Real-time QPCR analysis showed 26 (14%) HDs, 22 (12%) hemizygous deletions, and 3 (2%) multiple duplications. Loss of heterozygosity was determined in 30 (22%) cases at the D9S942 locus, which is located between E1alpha and E1beta of the CDKN2A/ARF gene. No association was established between occurrence of genetic aberrations at 9p21 and tumor stage or grade, supporting previous suggestions that CDKN2A/ARF inactivation is an early event in bladder carcinogenesis. CONCLUSIONS: We have established a fast and efficient method for detection of HDs. Our data support the notion that inactivation, including HDs, of CDKN2A/ARF is an early event in transitional cell carcinoma. We observed separate and specific targeting of the CDKN2A and ARF genes, respectively, and that simultaneous inactivation of ARF and p53 occurs.

Carcinoma, Transitional Cell↗

Bovine papillomavirus type-2 DNA and expression of E5 and E7 oncoproteins in vascular tumours of the urinary bladder in cattle.

Cattles suffering from chronic enzootic haematuria frequently develop urinary bladder tumours of both epithelial and mesenchymal origin mainly haemangioma and its malignant counterpart. The role of the bovine papillomavirus type-2 (BPV-2) and of its major transforming oncoprotein in naturally occurring urothelial carcinogenesis has been recently clarified. E5 interacts in vivo as in vitro with the beta receptor for the platelet-derived growth factor (PDGF). However, studies regarding tumours of mesenchymal origin such as those arising from blood vessels are lacking. We show that the BPV-2 is present in 100% of the vascular tumours of the urinary bladder examined. Twenty-six out of twenty-seven tumour samples (96%) expressed E5 while 20 out of 27 (74%) tumour samples expressed E7. The two viral oncoproteins were not expressed in normal endothelial cells. Additionally, they co-localize in neoplastic endothelial cells as demonstrated by confocal immunofluorescence. PDGFbeta receptor was also shown to be expressed and co-localizes with E5 in neoplastic blood vessels. Our results demonstrate, for the first time, that the BPV-2 is present in high percentage in tumours of mesenchymal origin arising in its natural host. Furthermore, the expression of the two viral oncoproteins confirm that the virus may have a causative role in the neoplastic process.

Animals↗

Pharmacological characterization of the muscarinic receptor subtypes responsible for the contractile response in the rat urinary bladder.

1. Contractile responses of smooth muscle from the Wistar rat urinary bladder were studied with the use of muscarinic agonists and antagonists. 2. McN-A-343 induced only weak contractile responses of the bladder muscle. In contrast, oxotremorine showed higher potency than either acetylcholine or bethanechol in inducing a contractile response (the respective pD2 values were 6.38 +/- 0.25, 4.82 +/- 0.24 and 4.42 +/- 0.14). 3. The M2 antagonists, methoctramine (10(-9) M to 10(-5) M) and gallamine (10(-9) M to 10(-5) M), did not reduce acetylcholine-induced (10(-5) M) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10(-10) M to 10(-7) M), an M3 receptor blocker, effectively antagonized the acetylcholine-induced contractions in a concentration-dependent manner. 4-DAMP had a similar pA2 value to those of the non-selective antagonists, atropine and scopolamine (pA2 values were 8.26 +/- 0.05, 8.36 +/- 0.05 and 8.41 +/- 0.11, respectively). Pirenzepine, and M1 blocker, antagonized the contractions at higher concentrations (10(-8) M to 10(-5) M, pA2 = 6.23 +/- 0.04). 4. It is concluded that (1) the dominant muscarinic receptor subtype responsible for smooth muscle contraction in the rat urinary bladder is M3; and (2) the muscarinic agonist oxotremorine was more potent than acetylcholine and bethanechol in inducing a contractile response.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Microvascular architecture of the human urinary bladder wall: a corrosion casting study.

The vascular system of the urinary bladder wall effectively performs its function in spite of considerable spatial changes due to the filling/voiding cycle. However, only a few studies have dealt with the microvascular architecture of the bladder wall and only two, using old-fashioned techniques, were devoted to the human bladder. This study presents the microvasculature of the human bladder wall visualized by scanning electron microscopy of vascular corrosion casts. Postoperative bladder specimens obtained from patients with advanced bladder tumors were filled with small amount (80 ml) of saline and perfused via at least four largest arteries with anticoagulant-containing saline followed by paraformaldehyde/glutaraldehyde fixative and Mercox resin. After polymerization of the resin, the vascular casts were macerated with potassium hydroxide, cleaned with formic acid and water and freeze dried. Only regions of the bladder wall distant to the tumor were examined in light and scanning electron microscopes. The almost empty state of the bladder was manifested by extensive folding of the mucosa and tortuosity of almost all vessels other than capillaries. The branches of main arteries and veins formed an adventitial/serosal plexus which directly supplied/drained the capillary network of the muscularis and sent long perpendicular vessels to the mucosal plexus. These vessels had straight or coiled course depending on whether they terminated at the top or at the base of the mucosal folds. The rich mucosal plexus followed the folds parallel to their surface and gave off short, straight, mostly perpendicular twigs communicating with the subepithelial capillary network. Apart from very few vascular interconnections between the mucosal plexus and the muscularis, the submucosa was generally avascular. The subepithelial capillary network showed extreme density and uneven contours of the capillaries, only in less folded areas of trigone and urethral orifice the network was looser and capillaries thinner. The capillary system of the muscularis was poorly developed. Due to its architecture, tortuosity, and coiling/uncoiling capabilities, the microvasculature of the human urinary bladder wall seems to efficiently accommodate changes associated with cyclic contraction and stretching. Disturbances in blood flow induced by overdistension of the bladder reported in several studies may be due to pressure of the urine affecting the patency of the vessels rather than to the spatial insufficiency of the vascular system.

Adult↗

Primary localized amyloidosis of the urinary bladder.

We report a rare case of localized form of primary amyloidosis (amyloidoma) of the urinary bladder with CT and MR findings. Clinically, it is difficult to distinguish from invasive transitional cell carcinoma and inflammatory lesion. We think that the MR intensity on T2-weighted images is helpful in making the diagnosis.

Amyloidosis↗

Effects of acetylcholine on the tone and miniature contractions of isolated dog urinary bladder.

Effects of acetylcholine on the tone and miniature contractions of dog urinary bladder were investigated in vitro. In both dome and trigone preparations, cumulative administrations of acetylcholine produced dose-dependent increases in the tone, which were dose-dependently depressed by prior administration of atropine and augmented by neostigmine. The frequency of miniature contractions in the dome and trigone was dose-dependently increased by acetylcholine. The dose-response curves of the frequency for acetylcholine were shifted to the right by atropine and to the left by neostigmine in both preparations. The amplitude of miniature contractions in both preparations was not significantly changed by acetylcholine. A computer analysis showed that changes in the tone of the bladder had the positive correlation to the frequency of miniature contractions. The results indicate that acetylcholine would act on the urinary bladder through activation of muscarinic receptors, and that there is the positive correlation between changes in the tone and the frequency of miniature contractions.

Acetylcholine↗

Inflammatory pseudotumor of the ureter and the urinary bladder.

Inflammatory pseudotumor (IPS) of the urinary bladder was first described in 1980. We report four cases of IPS which occurred during the last four years. One tumor occurred in the bladder of a 49-year-old woman five months after abdominal hysterectomy of uterine leiomyomas, two tumors in a 35- and 39-year-old woman, respectively, without antecedental surgical intervention (though one with recidive after six months). The fourth occurred in a 64-year-old male in the proximal ureter by pyelonephritis. Two cases were initially diagnosed at frozen section during operative treatment, the others on paraffine section after immunohistochemical examination. Two cases showed an aberrant expression of cytokeratines. There is no evidence of recidive tumor within a mean follow up of 25 months (12-49 months). Features to differentiate benign from malignant spindle cell lesions of the lower urinary tract are the absence of atypical mitoses, significant cytologic atypia, absence of necroses within the tumor (rather on its surface), no destructive growth at the tumor margins and low cellularity. Usually, IPS show a submucosal edematous area with a deeper, highly cellular component. The clinical history of a recent bladder operation or gynecologic surgery is of upmost importance in making the diagnosis of IPS. Complete surgical excision, either by transurethral resection or partial cystectomy appears to be curative for IPS.

Female↗

A urinary bladder fibrosarcoma in a young dog.

A 14-month-old female dog, Gos d'Atura Catala was presented for a 7-month-history of reoccurring urinary tract infection. Using sonography, a focal multilobulated thickening of the urinary bladder wall was discovered. The solid mass was arising from the area of the ureteral papllDae and bulging into the lumen of the bladder neck. The wall of the urethra was uniformly thickened. These findings were not considered typical for a generalized urinary tract infection but more indicative of local severe inflammation, neoplasia or hyperplasia in the area of the ureteral openings. The thickening of the urethra was suggestive of urethritis or neoplastic infiltration. Signs of metastasis were not detected on the thoracic radiographs or in the remainder of the abdominal ultrasound examination. A surgical excision of the multilobulated mass was performed and histologic examination was conducted. A fibrosarcoma in the lamina propria of the urinary bladder wall was diagnosed. Because of reoccurence of hematuria and unresponsiveness to therapy the dog was euthanized. Postmortem examination confirmed the diagnosis of fiborsarcoma in the urinary bladder. Additionally, neoplastic infiltration of the urethral wall and metastasis in the lungs and liver were detected histopathologically.

Animals↗

Retrograde flow of spermatozoa into the urinary bladder of boars during collection of semen by electroejaculation.

Boars that had a catheter implanted in the urinary bladder (n = 11) were used to determine the magnitude of retrograde flow of spermatozoa into the urinary bladder during electroejaculation. The overall mean (+/- SD) number of spermatozoa in the electroejaculate of boars was 22 +/- 20 x 10(9), with a mean range for individual boars of 3 +/- 3 to 48 +/- 13 x 10(9). The overall mean adjusted total number of spermatozoa in the post-electroejaculation urine was 1.038 +/- 2.656 x 10(9), and the mean percentage of retrograde flow of spermatozoa into the urinary bladder among boars ranged from 0% to 32.69%, with an overall mean percentage of retrograde flow of 7.51 +/- 17.82%. These findings indicate that in boars electroejaculation is associated with retrograde flow of spermatozoa into the bladder.

Journal Article↗