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Cellular and humoral in vitro cytotoxicity against autologous bladder tumor cells in humans. Differences in autologous cytotoxicity against non-invasive and invasive transitional-cell tumors of the urinary bladder.

Lymphocyte-mediated cytotoxicity (LMC), antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were measured in a 51Cr assay against autologous tumor cells from 7 patients with non-invasive and 9 patients with invasive transitional-cell tumors of the urinary bladder (TCC). Cytotoxicity against the invasive tumor cells were demonstrated in CDC. Heat-inactivation of sera lead to complete loss of cytotoxicity while addition of allogenic serum restored cytotoxicity. The cytotoxicity of allogenic sera from controls against invasive tumor targets showed no differences when compared with autologous sera. No or very weak cytotoxicity was found against non-invasive tumor targets in autologous or allogenic assays. LMC and ADCC showed weak or no reactivities. Intensive wash or trypsinization of effector cells did not affect the cytotoxicity in LMC. The results indicate the occurrence of complement-dependent antibodies directed against target cells from invasive tumors of the urinary bladder while no cytotoxic responses were detectable when the target cells originated from non-invasive tumors.

Adult↗

Cholinergic, adrenergic and purinergic response of sequential strips of rabbit urinary bladder.

In this study, we have characterized the response of five sequential segments of urinary bladder to cholinergic, adrenergic, and purinergic agonists. The results indicate that an abrupt alteration in pharmacological response between bladder body and base occurs at the level of the ureteral orifices. The bladder body responds preferentially to urecholine (muscarinic cholinergic), isoproterenol (beta adrenergic) and ATP (purinergic), whereas the bladder base responds perferentially to methoxamine alpha adrenergic). In parallel studies, the density of both muscarinic cholinergic receptors ([3H]quinuclidinyl benzilate binding sites) and beta adrenergic receptors were significantly higher in the body than in the base, whereas the concentration of alpha adrenergic receptors was greater in the bladder base than in the body. From these studies, we conclude that the differences in the response of the bladder base and body to cholinergic and adrenergic agents are primarily due to differences in the densities of the specific autonomic receptors. In addition, the response of the bladder to ATP (which is a putative neurotransmitter in the urinary bladder) can also be separated between body and base. The distribution is similar to that observed for urecholine.

Adenosine Triphosphate↗

Estrogen-induced alterations in the autonomic responses of the rabbit urinary bladder.

The effect of estrogen administration on the autonomic innervation of the rabbit urinary bladder was studied. Immature female white rabbits were injected twice daily with estrogen (150 microgram/kg) for 4 consecutive days. Control animals received injections of vehicle. The response of bladder strips to the following agonists were determined for control and estrogen-treated animals: methoxamine (alpha adrenergic); isoproterenol (beta adrenergic); bethanechol (muscarinic cholinergic); ATP (purinergic); and potassium chloride (nonreceptor mediated). Additionally, the adrenergic and cholinergic receptor densities were determined by standard radioligand binding techniques. Estrogen induced a marked increase in the response to alpha adrenergic, muscarinic cholinergic and purinergic agonists in the bladder body and midbladder. No significant alterations were noted in the bladder base. In addition, no alterations were noted for isoproterenol or potassium chloride. The receptor densities paralleled closely the physiological responses. Estrogen induced a significant increase in alpha adrenergic and muscarinic receptors in the bladder body and midsection, whereas no change was noted in the receptor density of the bladder base. Estrogen did not alter the beta receptor density. These findings indicate that the urinary bladder responds as a target organ for estrogen-induced alterations in autonomic innervation.

Animals↗

The functional effects of long-term outlet obstruction on the rabbit urinary bladder.

The current study investigated the relationship between duration of outlet obstruction, magnitude of bladder mass, and functional dysfunction on the rabbit urinary bladder. Following the production of obstruction with the "cuff model", bladder wet weight increased to twice control weight within one week, and then slowly to four times control weight by one month, and remained at this level for the six month period. Bladder capacity decreased significantly by one week but returned to control volumes by one month. The in vitro ability of the bladder to empty in response to field stimulation and bethanechol decreased significantly in the one and two week obstructed bladders and remained decreased for six months. One of the major observations of this study was the relatively large variation of bladder weight and histology observed for the one to six month obstructed rabbits. Although the bladders with mild mass increase (less than 3 gm./kg. body weight) had normal distribution of urothelium and muscular elements, the bladders with moderate mass increase (3 to 6 gm./kg.) had thick extrinsic connective tissue deposits and the bladders with severe mass increase (greater than 6 gm./kg.) had thick extrinsic and intrinsic connective tissue deposits and muscular degeneration. The percentage occurrence of mild, moderate and severe mass increase was approximately the same (58%, 30% and 12%, respectively) for the one, three, and six month groups. The bladders with mild mass increase had normal bladder capacities and increased pressure responses to field stimulation and bethanechol. The bladders with moderate-to-severe mass increase showed enlarged bladder capacities and had progressively smaller pressure responses. As the magnitude of bladder mass increased, the ability of the bladder to empty in response to field stimulation and bethanechol decreased proportionally. We conclude that the functional impairment of the bladder is related to the amount of extrinsic and intrinsic connective tissue and the degree of muscle degeneration.

Adenosine Triphosphate↗

The strain-energy density function of the urinary bladder.

In previous articles we proposed a finite deformation theory of the urinary bladder. The present paper is the third article in a series of these works. Our aim is to study more carefully the strain-energy density function W of the urinary bladder, because the determination of this function W is one of the central problems in the finite deformation theory of a hyperelastic continuum. We found that, except for an infinitesimally small deformation region where Hook's law is valid, the third term in W of the Valanis-Landel type takes much smaller values than the other two terms, so that this term can be neglected. Hence, the formula giving the true stress t1 for the uniaxial extension test is reduced to the same one as the true stress t for the equal-biaxial extension test. This may be useful in practical applications.

Animals↗

Absorbability of mucosa in total replacement of urinary bladder with jejunum. An experimental study.

The absorption of urine components in jejunum substitute for the urinary bladder was studied experimentally in dogs. For this purpose, determination of the blood urea, creatinine, and electrolyte levels as well as measurements of the radioactivity in blood samples after intravesical instillations of radioactive iodine, were done at various intervals after total replacement of the urinary bladder with jejunum. The absorption was found to decrease greatly in one month and to be negligible one year postoperatively.

Absorption↗

Rate of urinary bladder blood flow evaluated by 133Xe washout and radioactive microspheres in pigs.

Urinary bladder blood flow as measured by the washout of locally injected 133Xe and by the simultaneously performed radioactive microsphere reference-sample method was studied in pigs. The washout curves were analyzed according to the initial slope, the corrected initial slope and the total curve. The corrected-initial-slope flow rates were not statistically significantly different from the microsphere whole-wall flow rates. The variability between the methods shown by the test-retest difference revealed only a minor lack of agreement. The bladder blood flow tended to decrease after the intravesical pressure had been increased to 20 cmH2O, but the difference was not statistically significant. Washout of locally injected 133Xe can be used for the evaluation of urinary bladder blood flow in humans and in longitudinal animal studies. The corrected-initial-slope method is recommended for the analysis of washout curves.

Animals↗

Effect of bladder outflow obstruction on the innervation of the rabbit urinary bladder.

The effects of bladder outflow obstruction on the innervation of the bladder were studied using a rabbit animal model. Partial occlusion of the bladder neck was obtained by the placement of a silk ligature at that level; control animals underwent a sham procedure. After a 3-month period, the presence of outflow tract obstruction was confirmed using urodynamic studies. The animals were then killed and pharmacological assessments of the bladder innervation undertaken. Detrusor muscle strip studies provided evidence of damage to the cholinergic innervation of the detrusor. Also, muscle strips from obstructed animals showed reduced inhibitory responses to beta-adrenergic stimulation with isoprenaline. In addition to these muscle strip studies, the bladder content of the neuropeptide substance P was assayed, but no significant change was observed in response to obstruction. This finding suggests that substance P-containing sensory nerves may be spared from the denervating effect of bladder outflow obstruction.

Animals↗

Effects of urinary bladder distension on the length of the dog and cat urethra.

Urethral lengths were determined in male and female cats and in female dogs from positive contrast retrograde urethrocystograms at 2 levels of urinary bladder distension. Urethral lengths were longer on urethrograms obtained after urinary bladder distension in female cats and in 7 of 8 female dogs. The intrapelvic and penile urethra were longer after bladder distension in 4 of 6 male cats. In female cats, urethral lengths significantly increased (P less than 0.05) after urinary bladder distension.

Animals↗

Carcinosarcoma with a large cell neuroendocrine epithelial component: first report of an unusual biphasic tumour of the urinary bladder.

This article describes the first reported case of carcinosarcoma of the urinary bladder with a large cell neuroendocrine epithelial component. A 61 year old man presented with gross haematuria and underwent resection of a biphasic bladder tumour. The malignant epithelial component showed large cell neuroendocrine differentiation with immunohistochemical reactivity for neurone specific enolase, synaptophysin, and chromogranin. The malignant mesenchymal component did not show specific differentiation by histological or immunohistochemical examination. The differential diagnosis of biphasic tumours in the urinary bladder is discussed, along with a review of the literature.

Carcinosarcoma↗

Tachykinin NK1 receptor subtypes in the rat urinary bladder.

1. Following the recent proposal that the selective agonist septide, ([pGlu6,Pro9]SP(6-11)), acts on a novel tachykinin receptor distinct from the 'classical' NK1 receptor, the aim of the study was to investigate the possible heterogeneity of tachykinin NK1 receptors in the rat urinary bladder. 2. The synthetic tachykinin receptor agonists, septide (pD2 7.87) and [Sar9]substance P (SP) sulphone (pD2 7.64) produced concentration-dependent contractions of the rat isolated urinary bladder. 3. The NK1 receptor antagonists GR82,334, (+/-)-CP96,345, and RP67,580 competitively antagonized (slopes of Schild plot not significantly different from unity) the response to septide with the rank order of potency (pKB values in parentheses): RP 67,580 (7.57) > GR 82,334 (7.01) > (+/-)-CP 96,345 (6.80). The same antagonists were significantly less potent when tested against [Sar9]SP sulphone, while maintaining the same rank order of potency: RP 67,580 (7.00) > GR 82,334 (5.93) > (+/-)-CP 96,345 (< 6). The antagonists did not affect the concentration-response curve to bombesin. 4. To exclude the involvement of the NK2 receptor, a second series of experiments was performed in the presence of the potent nonpeptide NK2 receptor antagonist, SR 48,968. SR 48,968 (1 microM) produced a rightward shift of the concentration-response curve to the NK2 receptor selective agonist, [beta Ala8]neurokinin A (NKA) (4-10). SR 48,968 did not significantly modify the response to SP, NKA, neurokinin B (NKB), neuropeptide K (NPK), neuropeptide gamma (NP gamma), SP(4-11), SP(6-11), septide or [Sar9]SP sulphone. 5. In the absence or presence of SR 48,968, RP 67,580 antagonized in a competitive manner the response to septide, [Sar9]SP sulphone, SP(4-11) and SP(6-11): pKB values obtained in the absence and presence of SR 48,968 were not significantly different for any of these four agonists.6. RP 67,580 antagonized the response to SP and NKA both in the absence and presence of SR 48,968.In both cases, the slopes of the Schild plots were significantly different from unity. Mean dose-ratios produced by RP 67,580 in the presence of SR 48,968 were larger than those measured without NK2receptor blockade for both SP and NKA.7. RP 67,580 (3 MicroM) did not antagonize the response to NKB in the absence of SR 48,968. In the presence of SR 48,968, RP 67,580 acted as a competitive antagonist of NKB-induced contractions with apKB value (7.63) not significantly different from that measured towards septide. In the present of SR48,968, RP 67,580, GR 82,334 and (+/-)-CP 96,345 antagonized the response to NKB with a rank order of potency identical to that measured towards septide or [Sar9]SP sulphone.8. In the absence of SR 48,968, RP 67,580 (3 MicroM) produced a small shift of the concentration-response curve to neuropeptide K and was ineffective toward neuropeptide T. In the presence of SR 48,968 a clear shift of the curve to both agonists was observed.9. These findings are compatible with the idea that a septide-sensitive tachykinin receptor may exist in the rat urinary bladder. The septide-sensitive receptor is recognized by NK1 receptor antagonists with higher affinity than the 'classical' NK1 receptor recognized by [Sar9]SP sulphone. Our data suggest that NKB, after NK2 receptor blockade, is a more suitable ligand than SP for activation of the 'septidesensitive'receptor. While the final proof for the existence of possible NK1 receptor subtypes must await confirmation at the molecular level, the present findings provide strong pharmacological evidence that either NK, receptor subtypes or a novel type of tachykinin receptor exist in the rat urinary bladder.

Animals↗

Viscerovisceral convergence of urinary bladder and colorectal inputs to lumbosacral spinal neurons in rats.

Extracellular potentials of single L6-S2 spinal neurons were recorded in pentobarbital anesthetized male rats. The urinary bladder was catheterized through the fundus and filled with warm saline for urinary bladder distension (UBD, 0.5-2.0 ml, 20 s). Colorectal distension (CRD) was produced by distending a latex balloon with air (20-80 mmHg, 20 s). Of 171 deeper neurons examined for responses to UBD and CRD, 49 (29%) neurons responded to both UBD and CRD; whereas 6/42 (14%) superficial neurons (depth < 0.3 mm) responded to both organs. Of 55 viscerovisceral convergent neurons, 25 (45%) neurons were excited by both UBD and CRD; the remainder exhibited multiple patterns of excitation and inhibition. In conclusion, responses of superficial and deeper lumbosacral spinal neurons to convergent inputs from urinary bladder and colon suggested that these neurons might contribute to the cross-talk that occurs between visceral organs.

Animals↗

Histochemical demonstration of colonic type mucin in glandular metaplasia and adenocarcinoma of the human urinary bladder.

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.

Adenocarcinoma↗

Simultaneous arterial and urinary bladder pressure recordings in multiple system atrophy and in spinal disorders with detrusor hyperreflexia.

Simultaneous arterial and urinary bladder pressure measurements were recorded during bladder filling in 21 patients with urinary bladder symptoms; seven patients had autonomic failure due to multiple system atrophy (MSA), seven had spinal cord disease of different aetiology with detrusor hyperreflexia (DH) and seven had no neurological abnormalities. A significant increase in average systolic blood pressure (BP) was recorded on bladder filling in the neurologically intact patients (from 110 to 137 mmHg) and in the patients with spinal cord disease and DH (from 109 to 129 mmHg). In those with MSA, the BP rose in four and fell in three patients. The vesicopressor response during cold receptor-mediated DH was not significantly higher when compared with room-temperature saline and when compared with the BP response during bladder filling in the neurologically intact patients. Finally, intravesical lignocaine retained in the bladder for 15 min did not influence the BP response to cold receptor stimulation in patients with spinal cord disease and DH. These findings and their pathophysiological and clinical implications are discussed.

Adult↗

Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor beta receptor in naturally occurring bovine urinary bladder tumours.

Studies regarding the functions of the bovine papillomavirus (BPV) E5 oncoprotein in vivo are lacking and no E5-mediated mechanism underlying epithelial carcinogenesis is known. We have shown that BPV-2 DNA is present in the majority of naturally occurring urinary bladder tumours of cattle and that E5 is expressed in the cancer cells. Here we show that the interaction between the platelet-derived growth factor (PDGF) beta receptor and BPV E5, described in vitro in cultured cells, takes place in vivo in bovine urinary bladder cancers. In these cancers, E5 and PDGF beta receptor colocalize, as shown by confocal microscopy, and physically interact, as shown by coimmunoprecipitation. Furthermore, the PDGF beta receptor associated with E5 is highly phosphorylated, suggesting the functional activation of the receptor upon E5 interaction. Our results demonstrate, for the first time, that E5-PDGF beta receptor interaction occurs during the natural history of bovine urinary bladder tumours, suggesting an important role for E5 in carcinogenesis. Finally, the system provides a suitable animal model of papillomavirus-associated cancer to test therapeutic vaccination against E5. Successful bladder tumour regression would provide a valuable model for therapeutic vaccination against papillomavirus-associated tumours.

Adenocarcinoma↗

Effects of formalin-induced injuries on urinary bladder carcinogenesis.

In multistage carcinogenesis, promotion is a long-term or repeated growth stimulation of initiated cells. Possible effects of regenerative hyperplasia induced by repeated intravesical instillation of 0.3% formalin solution on urinary bladder carcinogenesis were examined using heterotopically transplanted rat urinary bladders (HTBs) initiated by N-methyl-N-nitrosourea. The HTB system was chosen because in this system, transient generalized hyperplasia lasting less than a week can be induced readily and repeatedly by intravesical instillation of the formalin solution. No statistically significant tumor enhancement was observed after 15 formalin treatments administered in 30 weeks. It appears that regenerative cytotoxic stimuli, even multiple, may have no significant tumor-promoting activity. Discussed is the possibility that mild and, more importantly, persistent non-cytotoxic stimuli may be more effective as tumor promoters.

Animals↗

Human papillomaviruses 6/11, 16/18 and 31/33/51 are not associated with squamous cell carcinoma of the urinary bladder.

OBJECTIVE: To assess high-risk human papillomavirus (HPV), mainly HPV type 16, 18, 31 and 33 (an important aetiological factor in squamous cell carcinoma, SCC, of the anogenital region) in SCC of the urinary bladder. MATERIAL AND METHODS: Sixteen SCC from the urinary bladder were evaluated using non-isotopic in situ hybridization with a sensitive detection system for the presence of high-risk HPV 16/18, or 31/33/51, and for HPV6/11, a low-risk type commonly found in condylomata. Previously published studies were also reviewed and assessed. RESULTS: No high-risk HPV was found in any of the SCC of the bladder evaluated. Previous reports identified nine HPV-positive SCC of a total of 105, including the present series. In four of these positive cases, HPV types were found that are considered a high risk in anogenital carcinomas. CONCLUSION: From the present and previous results, we conclude that HPV has no major role in the pathogenesis of SCC of the urinary bladder.

Aged↗

Long-term fate of [14C]nicotine in the mouse: retention in the bronchi, melanin-containing tissues and urinary bladder wall.

N-methyl-14C and 2'-14C-labelled nicotine were used for whole-body autoradiographic distribution studies on C57BL- and NMRI-mice. Radioactivity was retained in the melanin-containing tissues, in the bronchial walls, and in the urinary bladder wall, up to 1 month after administration. The activity levels in the bronchi decreased faster if [2'(14)C] nicotine was used. Quantitative measurements of the retention of the 2 14C-labelled nicotine preparations confirmed the autoradiographic findings. It is proposed that nicotine is N-demthylated in the bronchial mucosa, the off-coming methyl group being incorporated into the cell constituents of the mucosa. Thin-layer chromatographic studies showed that no nicotine was present in the lungs after 24 h. In melanin, however, only unmetabolized nicotine was found from 4 h on. Some reactive nicotine metabolites may be responsible for the retention in the urinary bladder wall. Also in the full-term fetuses radioactivity accumulated in the pigmented eyes and in the respiratory tract. The accumulation and long-term retention of nicotine in the melanin-containing structures might accelerate the development of drug-induced or senile changes in these tissues. The retention in the urinary bladder wall persisted even after rinsing. This may indicate an accumulatory mechanism worth considering in the pathogenesis of urinary bladder cancer.

Animals↗