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Urinary bladder endometriosis: a report of two cases.

Endometriosis of the urinary tract is uncommon, and the most common site of involvement is urinary bladder. Two cases of endometriosis of urinary bladder are presented. The first patient, a 39-year-old woman, complained of dysuria during menstruation and the other 37-year-old woman suffered from intermittent gross hematuria. Pre-operative examinations included ultrasonography, computed tomography and cystoscopic biopsy. Case 1 was in premenopausal status, but the serum estrogen level of case 2 was in postmenopausal status because she was given no exogenous estrogen after previous bilateral salpingo-oophorectomy. Endometriosis of urinary bladder rarely occurs in postmenopausal woman without exogenous estrogen replacement. Case 1 received danazole treatment after transurethral resection of bladder tumor and case 2 received partial cystectomy after transurethral resection of bladder tumor. The patients were followed 36 and 4 months, respectively, and the symptoms kept improving during this period.

Adult↗

Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters.

The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs.

3-Hydroxybutyric Acid↗

Light chain amyloidosis of the urinary bladder. A site restricted deposition of an externally produced immunoglobulin.

AIMS: To identify the amyloid protein in a patient with amyloidosis localised to the urinary bladder, and to see whether subtyping of the protein by sequence analysis increases the understanding of the selection of the urinary bladder as the site of amyloid deposition. METHODS: A patient with gross haematuria and a congophilic mass in his urinary bladder was evaluated further. Characterisation of the amyloid protein was performed using conventional histological and immunohistochemical methods. Determination of the N-terminal amino acid sequence of the amyloid protein was performed using protein sequencers. RESULTS: The patient's history, physical examination, and laboratory evaluation excluded the involvement of other organs, justifying a diagnosis of amyloidosis localised to the urinary bladder. Histological and immunological studies showed that the amyloid protein deposited in the urinary bladder of the patient was probably of the amyloid light chain type. No plasma cells or lymphocytes were seen in sections of the urinary bladder and lower ureter adjacent to the amyloid deposits. Molecular analysis showed the sequence NFMLTQPHSISGSPG, which assigned the amyloid protein to either the Vlambda(I) or the Vlambda(VI) immunoglobulin (Ig) light chain families. CONCLUSIONS: The findings suggest that the amyloid protein in this patient originated outside the urinary bladder. The heterogeneity of the Ig proteins in known cases of amyloidosis of the lower urinary tract suggests that the amino acid residues, which determine the Vlambda subtyping, have no major role in restricting the deposited protein to the urinary bladder.

Amino Acid Sequence↗

Specific binding, stimulation of rodent urinary bladder epithelial ornithine decarboxylase, and induction of transitional cell hyperplasia by the skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

The effects of intraurethral or i.p. administration of a mouse skin tumor promoter phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), on rodent urinary bladder transitional epithelium were studied. TPA, when instilled into the urinary bladder of inbred rats (female Fischer, F344) or mice (C3H, ICR, C57BL X DBA/2 F1) at a dose as low as 0.16 nmol, led to a significant (about 10-fold) increase in bladder ornithine decarboxylase (EC 4.1.1.17) (ODC) activity. Peak ODC activity was observed at about 6 hr, and enzyme activity returned to base levels about 14 hr after intravesical TPA. Administration of TPA i.p. in dimethyl sulfoxide also induced vesical ODC at 4 hr after treatment. The magnitude of vesical ODC induction correlated well with the ability of a series of phorbol esters to promote mouse skin tumor formation (TPA greater than phorbol didecanoate greater than phorbol dibenzoate, and phorbol diacetate or phorbol did not induce bladder ODC activity). Mezerein, a second stage mouse skin tumor promoter, induced urinary bladder ODC as much as TPA did. Increased ODC activity by TPA was the result of an increased amount of ODC protein localized mostly (greater than 60%) in urinary bladder mucosa. Intraurethrally administered TPA induced transitional cell hyperplasia starting at Day 2, and it persisted for about 7 days. The urothelium regained normal histology 13 days after TPA treatment. TPA bound specifically and with high affinity to murine bladder mucosa and muscularis particulate preparations. Scatchard analysis of mucosal binding revealed a Kd of 0.82 nM; at saturation, 2.43 pmol were bound per mg protein. Since TPA binds specifically to urinary bladder epithelium, and the induction of ODC activity is one of the properties of tumor promoters, one may conclude that TPA may promote urinary bladder carcinogenesis. Intravesical saccharin also induced urinary bladder ODC activity, but TPA at equimolar quantity was far more potent than saccharin. Thus TPA, being a structurally well-defined molecule, may be a useful compound to study the phenomenon of the tumor promotion stage in urinary bladder carcinogenesis.

Animals↗

Retrograde flow of spermatozoa into the urinary bladder of rams.

Retrograde flow of spermatozoa into the urinary bladder of rams during electroejaculation (EE) was examined. In experiment 1, semen and 4 consecutive samples of the urine released during the first post-EE micturition were collected once a week from 6 rams for 5 weeks during the nonbreeding season. The overall mean concentration per milliliter and the mean total number of spermatozoa in the urine ranged from 3.06 to 4.32 X 10(6) and from 80 to 2,865 X 10(6), respectively. The spermatozoal concentration in sequential urine samples was not different between samples, indicating that these spermatozoa had mixed with the urine before micturition. The percentage of the total number of spermatozoa displaced during EE, which flowed into the urinary bladder (retrograde flow), varied among rams (range 3.9% to 80%). The overall mean percentage of retrograde flow during the nonbreeding season was 28.3%. In experiment 2, a catheter was implanted into the urinary bladder of 6 rams (4 rams were from experiment 1), and semen was collected over 4 weeks during the subsequent breeding season. A urine sample was collected from the implanted catheter before EE. Immediately after semen collection, urine was collected by evacuating the bladder. The spermatozoal concentration in the pre-EE urine ranged from 0 to 1.3 X 10(6) (mean +/- SD, 0.17 +/- 0.38 X 10(6)) and was significantly (P less than 0.0001) lower than the spermatozoal concentration in the post-EE urine, which ranged from 1.10 to 22.55 X 10(6) (mean +/- SD, 9.46 +/- 11.30 X 10(6)).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The modifying effects of indomethacin or ascorbic acid on cell proliferation induced by different types of bladder tumor promoters in rat urinary bladder and forestomach mucosal epithelium.

The effects of indomethacin (IM) or L-ascorbic acid (AsA) on cell proliferation induced by bladder tumor promoters such as butylated hydroxyanisole (BHA), sodium L-ascorbate (Na-AsA), sodium citrate (Na-Cit), and diphenyl (DP) in rat bladder and forestomach epithelium were investigated. Treatment with IM in combination with BHA or Na-AsA diminished DNA synthesis levels of bladder epithelium as compared to the BHA or Na-AsA alone values. On the other hand, AsA further amplified the increase of bladder epithelial DNA synthesis caused by Na-Cit treatment. Histopathologically, administration of Na-AsA in combination with IM reduced the incidence of simple hyperplasia. In contrast, simultaneous treatment with Na-Cit and AsA caused an increase of the hyperplasia development. No apparent combination effects were observed in the DP-treated groups. In forestomach epithelium, AsA enhanced the BHA-induced increase in DNA synthesis and epithelial hyperplasia, characterized by marked basal cell proliferation. The present results thus suggested that IM may exert inhibitory effects on promotion of bladder carcinogenesis by certain tumor promoter types, and AsA may enhance BHA forestomach carcinogenesis.

Animals↗

Effect of chronic atropine administration on the rat urinary bladder.

Micturition is accomplished via a coordinated contraction of the urinary bladder body mediated primarily by muscarinic receptor stimulation. Theoretically, bladder function may be modified by pharmacologically altering either the muscarinic receptor density and/or the magnitude of the response to receptor activation. In the central nervous system, autonomic receptor density can be modified by chronic administration of specific receptor agonists and antagonists. The chronic administration of receptor agonists induces a decrease in the specific receptor density whereas the chronic administration of antagonists induces an increase in the specific receptor density. Although these induced alterations in receptor density occur in the CNS, there have been few studies on peripheral tissue. For the current study, we have administered L-atropine chronically to rats (five mg./kg./day) using implanted osmotic pumps. Using direct radioligand binding techniques, the muscarinic receptor density of the rat brain (cortex) and urinary bladder were determined following six hours, 12 hours, one, two, four, seven, 11 and 14 days of atropine administration. In addition, we have also determined the effect of atropine administration on bladder weight and the response of isolated strips of the bladder to bethanechol, a specific muscarinic agonist. For both the brain and the bladder, the receptor density increased progressively and reached a maximum by seven days. At 14 days of atropine administration, the density of muscarinic receptors in rat brain increased significantly (p less than .05) from 2956 +/-74 fmoles/mg. protein to 3800 +/-170 fmoles/mg. protein. The muscarinic receptor density of the rat urinary bladder increased significantly from 115 +/-10 fmole/mg. protein to 165 +/-14 fmole/mg. protein. Although there was a 42% increase in bladder mass, the contractile response of isolated strips to bethanechol did not change significantly. This study demonstrates that the urinary bladder can respond to the chronic administration of atropine with a significant increase in the density of muscarinic receptors. The magnitude of the increase observed was slightly greater than the magnitude observed for muscarinic receptors isolated from the brain cortex.

Animals↗

Specific p53 gene mutations in urinary bladder epithelium after the Chernobyl accident.

After the Chernobyl accident, the incidence of urinary bladder cancers in the Ukraine population increased gradually from 26.2 to 36.1 per 100,000 between 1986 and 1996. Urinary bladder epithelium biopsied from 45 male patients with benign prostatic hyperplasia living in radiocontaminated areas of Ukraine demonstrated frequent severe urothelial dysplasia, carcinoma in situ, and a single invasive transitional cell carcinoma, combined with irradiation cystitis in 42 cases (93%). No neoplastic changes (carcinoma in situ or transitional cell carcinoma) were found in 10 patients from clean areas (areas without radiocontamination). DNA was extracted from the altered urothelium of selected paraffin-embedded specimens that showed obviously abnormal histology (3 cases) or intense p53 immunoreactivity (15 cases), and mutational analysis of exons 5-8 of the p53 gene was performed by PCR-single-strand conformational polymorphism analysis followed by DNA sequencing. Nine of 17 patients (53%) had one or more mutations in the altered urothelium. Urine sediment samples were also collected from the patients at 4-27 months after biopsy and analyzed by PCR-single-strand conformational polymorphism analysis or yeast functional assay, and identical or additional p53 mutations were found in four of five cases. Interestingly, a relative hot spot at codon 245 was found in five of nine (56%) cases with mutations, and 11 of the 13 mutations determined (73%) were G:C to A:T transitions at CpG dinucleotides, reported to be relatively infrequent (approximately 18%) in human urinary bladder cancers. Therefore, the frequent and specific p53 mutations found in these male patients may alert us to a future elevated occurrence of urinary bladder cancers in the radiocontaminated areas.

Aged↗

Microwave coagulation therapy for urinary bladder tumors.

A new device has been developed for microwave coagulation of urinary bladder tumors. Twenty-one patients with urinary bladder tumors were treated by irradiation with microwave energy of 2,450 MHz. Results were obtained as follows: (1) microwave coagulation was performed in 21 patients with transitional cell carcinoma of the urinary bladder. Excluding 4 patients who subsequently received radical cystectomy, 17 patients showed a complete response, although 2 patients subsequently developed recurrences in different parts of the bladder within the following several months. Histological examination of the excised specimen revealed complete eradication of the tumor in 2 patients. In the remaining 2 patients with high-stage tumor (T4), viable tumor cells were noted in the urethra or vaginal wall. (2) Although neither technical difficulties nor severe complications were encountered, transient urinary frequency and calcification of the bladder wall were noted. The results of this study indicate that microwave coagulation may be used in the treatment of both superficial and invasive tumors.

Aged↗

Promotion by L-ascorbic acid of urinary bladder carcinogenesis in rats under conditions of increased urinary K ion concentration and pH.

Dietary administration of 5% L-ascorbic acid plus 3% K2CO3 to male F344 rats clearly enhanced the development of preneoplastic and neoplastic lesions of the urinary bladder initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Promotion of carcinogenesis by L-ascorbic acid and K2CO3 was associated with changes in urinary parameters: elevation of pH, increased K+ concentration, and increase in total ascorbic acid.

Animals↗

Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder?

Investigation of transitional cell carcinoma of the urinary bladder (TCC) patients classified by recurrence and/or progression has demonstrated that loss of chromosome 9, as detected by FISH analysis of the pericentromeric classical satellite marker at 9q12, occurs early. A total of 105 TCCs from 53 patients were analysed in situ by two independent observers for loss of chromosome 9 using quantitative fluorescence in situ hybridization (FISH). All 53 primary tumours were evaluated for chromosomes 9, 7 and 17. Normal ranges for chromosomal copy number were defined for normal skin epidermis and bladder epithelium. Values for chromosome 9 copy number outwith the range 1.51-2.10 (mean +/- 3 x s.d. of normal values) were significantly abnormal. Twenty-five TCCs were detected with consistent monosomic scores. Of 89 TCCs, in which multiple tumour areas were analysed, 85 tumours (96%) demonstrated the same chromosome 9 copy number in all areas (2-6) analysed; only three tumours demonstrated heterogeneity for this locus. A total of 36% (12 out of 33) of patients with subsequent disease recurrence demonstrated loss of chromosome 9 in their primary and all subsequent TCCs analysed. Only a single patient (n = 20) with non-recurrent TCC showed loss of chromosome 9 (P = 0.0085). Of 53 primary tumours, eight showed significant elevation of chromosome 17. Of these patients, six demonstrated elevation in chromosome 7 copy number. No abnormalities were observed in non-recurrent patients. This study describes rapid quantitation of chromosomal copy number by FISH using a pericentromeric probe for chromosome 9 in TCC of the urinary bladder. Routinely fixed and processed material was evaluated without disaggregation. Strict quality control of FISH demonstrated that this technique was reproducible in a clinical environment and could be used to detect genetic changes relevant to patient outcome. It is proposed that loss of chromosome 9 from primary TCC of the urinary bladder identified patients at high risk of recurrence and possible progression.

Aged↗

Mechanism of action of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine.

The carcinogenic action of N-nitrosodibutylamine in the urinary bladder is related to omega-oxidation of a butyl chain. N-Nitrosobutyl-4-hydroxybutylamine and its proximate metabolite N-nitrosobutyl-3-carboxypropylamine (NBCPA) selectively induce urinary bladder tumours in different animal species. The mechanism by which NBCPA exert its carcinogenic action is not known. We found a small but significant dealkylation of NBCPA with microsomes from rat liver or pig urinary bladder, which could be inhibited by SKF 525A. NBCPA was not mutagenic to Salmonella typhimurium (with or without external metabolizing systems from rat liver or pig urinary bladder) and did not induce DNA strand breaks in tumour cell lines (with or without external activation) or primary cells (rat hepatocytes, pig urinary bladder epithelia). Significant induction of sister chromatid exchange and micronuclei, however, was observed in human tumour cells. N-Nitrosoureas that generate the same electrophiles as NBCPA after alpha- or via beta-oxidation (N-butyl-N-nitrosourea, N-3-carboxypropyl-N-nitrosourea and N-2-oxopropyl-N-nitrosourea) induced single-strand breaks in Namalva cells, the oxopropyl compound being more potent than the butyl or carboxypropyl compounds. Our data suggest that NBCPA is activated via alpha-oxidation in the urinary bladder, even though the activation rate in vitro is so low that a positive response is not detectable by classical short-term tests. Provided that beta-oxidation to a highly genotoxic agent proceeds at an adequate rate, it might also be a relevant activation pathway.

Animals↗

Radiation-induced changes in neuropeptides in the rat urinary bladder.

PURPOSE: To determine whether there was a change in innervation in the rat urinary bladder following x-ray irradiation. MATERIALS AND METHODS: The urinary bladders were obtained from rats irradiated 6 months previously with single doses of 15 Gy and 25 Gy x-radiation, and from nonirradiated (control) animals. They were examined immunohistochemically to localize neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), met-enkephalin (m-ENK), leu-enkephalin (l-ENK), somatostatin (SOM) and the enzyme, tyrosine-hydroxylase (TH). Computer assisted image analysis was used to assess the density of immunoreactive nerve fibres. RESULTS: The greatest density of nerves observed in the bladder from control animals contained NPY, followed (in decreasing order) by CGRP, VIP, SP and TH. The nerves appeared to run predominantly along the longitudinal axis of the circular and longitudinal muscle fibres. SP-, CGRP-, TH- and occasionally VIP-immunoreactive nerves were observed in the lamina propria, at the base of the urothelium. Perivascular nerves containing neuropeptides and TH were observed throughout the bladder wall. There was an absence of m-ENK-, l-ENK- and SOM-immunoreactive nerves in the control and irradiated rat urinary bladders. In the rat urinary bladder irradiated with 25 Gy x-radiation, there was a significant increase (P < 0.05) in the density of NPY-, TH- and SP- but not CGRP- and VIP-immunoreactive nerves. There were regional differences within the bladder, that is, there was an increase in VIP-, CGRP- and SP-immunoreactive nerves around and within the urothelium. NPY-immunoreactive nerves were seen in the connective tissue and elastic fibres of the lamina propria for the first time. An increase in the density or fluorescence intensity of perivascular TH- but not neuropeptide-containing nerves was observed. CONCLUSIONS: The increase in the density of NPY-, SP- and TH-immunoreactive nerves in the irradiated bladders may be due to axonal sprouting which contributes to the symptoms of radiation injury.

Animals↗

Rare pseudotumors of the urinary bladder in childhood.

We report two cases of inflammatory pseudotumors of the urinary bladder, one case of a chronic granulomatous pseudotumor (CGT) and one case of a pseudosarcomatous myofibroblastic (fibromyxoid) tumor (PMT). Both tumors resembled malignancies such as rhabdomyosarcomas regarding clinical appearance and imaging findings and represent rare urinary bladder tumors. The imaging findings on unenhanced and contrast-enhanced MRI as well as histological specimen are presented. Final diagnosis was made following elective surgery. Differential diagnosis of urinary bladder tumors as well as the imaging findings of these clinically comparable cases are discussed. Awareness of these benign lesions may prevent patients from inappropriate therapies such as chemotherapy or radiation therapy.

Adolescent↗

Monoclonal antibodies against human urinary bladder carcinomas: selectivity and utilization for gamma scintigraphy.

Mouse monoclonal antibodies to human urinary bladder carcinoma cells have been examined by indirect membrane immunofluorescence using a panel of 27 human cell lines. Two of the monoclonal antibodies, 7E9 (IgG3) and S2C6 (IgGl), were found to distinguish between urinary bladder carcinoma cells and normal urothelium. The third monoclonal antibody, T24.06.5(IgGl), discriminated among cell lines of urothelial and non-urothelial origin but did not distinguish between urinary bladder carcinoma and normal urothelial cells. None of the of the antibodies was found to be strictly selective, and occasional cross-reactions with unrelated cell types were observed. The monoclonal antibody 7E9, showing the highest degree of selectivity, was further examined by an indirect immunoperoxidase technique on frozen tissue sections from 19 patients. The antibody reacted with all (7/7) bladder carcinomas examined and gave negative results with control normal bladder mucosa (0/8) and unrelated tumor tissue (0/4) sections. The 7E9 antibody was purified by protein A affinity chromatography, labeled with 131I and used for gamma-scintigraphy in nude mice xenografted with human urinary bladder carcinoma T24. The 7E9 antibody was capable of locating the T24 xenografts in nude mice; it localized preferentially in the T24 tissue compared to normal mouse tissues. The T24 xenografts could not be detected by gamma-scintigraphy with 131I-labeled monoclonal antibody against human mammary carcinoma cells and two other control antibodies. Likewise the 131I-labeled 7E9 antibody was not capable of locating human mammary carcinoma xenografts in nude mice.

Animals↗