Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ureteral obstruction (UO) is one of the most common problems confronting the urologist. Although large amounts of animal and clinical research have been done, the pathophysiologic mechanisms accompanying UO are not fully elucidated. Most of our knowledge on UO has been derived from experimental studies in a variety of animal models. Both antenatal and postnatal UO models have been developed mainly by ligation of the ureter or by burying the ureter into the psoas muscle. Most experimental studies have focused on short-term complete ureteral obstruction. The long-term effects of partial ureteral obstruction have been less intensively studied. It is now clear that obstructive nephropathy is not a simple result of mechanical impairment to urine flow but a complex syndrome resulting in alterations of both glomerular hemodynamics and tubular function caused by the interaction of a variety of vasoactive factors and cytokines that are activated in response to UO. Leukocyte infiltration appears to play an important role in obstructive nephropathy suggesting that UO also has an immunological component. Growth factors such as platelet-derived growth factor, transforming growth factor-beta, epidermal growth factor and insulin-like growth factor I may all play a role in the development and progression of fibrotic and sclerotic changes in the obstructed kidney. At present, the selection of patients with congenital hydronephrosis for operative treatment is controversial. Studies in animals and patients have shown that partial unilateral UO does not always cause a loss of renal function or progression in urinary tract dilation during long-term follow-up. The implications of UO continue to raise many questions and further work is necessary to achieve a better understanding of the pathogenesis in obstructive nephropathy.
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PMID:Obstructive nephropathy: an update of the experimental research. 1009 51

Urine is produced in the kidney by excretory nephrons and is drained by a tree-like system of collecting ducts to the ureter. The collecting ducts develop by arborisation of an initially unbranched epithelial rudiment, the ureteric bud, which ramifies through the surrounding mesenchyme and induces the formation of nephrons by mesenchyme-to-epithelial transition. The question of how collecting duct morphogenesis is controlled is an important one, from the points of view of both basic developmental biology and congenital renal pathology (multi- and polycystic renal disease, and some forms of renal agenesis, arise from defective collecting duct development). We report that neurturin, a neurotrophin related to glial cell line-derived neurotrophic factor and expressed in the developing kidney, acts as a collecting duct morphogen in culture. Applied in culture medium, it promotes epithelial branching and can induced branch initiation that has otherwise been blocked by depleting cultured kidneys of their sulfated proteoglycans or by antibody treatments. Applied locally on agarose beads, neurturin induces supernumerary ureteric buds to emerge from the wolffian duct and causes nearby collecting duct branches to distend to an abnormally large diameter. Like its receptors, neurturin is expressed by the developing collecting ducts themselves, suggesting that it forms an autocrine morphoregulatory control loop. This is in marked contrast to previously identified morphogens such as glial cell line derived neurotrophic factor and hepatocyte growth factor, which act in a paracrine manner.
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PMID:Neurturin: an autocrine regulator of renal collecting duct development. 1032 36

Rapidly progressive renal fibrosis after a slimming regimen including Chinese herbs containing aristolochic acid (AA) has been identified as Chinese-herb nephropathy (CHN). We reported urothelial atypia in three patients with CHN, with the subsequent development in one patient of overt transitional cell carcinoma (TCC). Therefore, it was decided to remove the native kidneys, as well as the ureters, in all patients with CHN. Nineteen kidneys and ureters removed during and/or after renal transplantation from 10 patients were studied to assess critically urothelial lesions and to characterize the cellular expression of p53, a tumor-suppressor gene overexpressed in several types of malignancies. Multifocal high-grade flat TCC in situ (carcinoma in situ; CiS) was observed, mainly in the upper urinary tract, in four patients, a prevalence of 40%. In one of those patients, a superficially invasive flat TCC of the right upper ureter, as well as two additional foci of noninvasive papillary TCC, were found in the right pelvis and left lower ureter, respectively. This patient also presented recurrent noninvasive papillary TCC of the bladder. Furthermore, in all cases, multifocal, overall moderate atypia was found in the medullary collecting ducts, pelvis, and ureter. All CiS and papillary TCC, as well as urothelial atypia, overexpressed p53. These results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect. Carcinogenesis is associated with the overexpression of p53, which suggests a role for a p53 gene mutation. The relationship of this mutation with the reported presence of AA DNA adducts in the kidney remains to be explored.
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PMID:Urothelial lesions in Chinese-herb nephropathy. 1035 10

Aristolochic acid (AA) a naturally occuring nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis, designated Chinese herbs nephropathy (CHN). We identified AA-specific DNA adducts in kidneys and in a ureter obtained from CHN patients after renal transplantation. AA is a plant extract of aristolochia species containing AA I as the major component. Aristolactams are the principal detoxication metabolites of AA, which were detected in urine and faeces from animals and humans. They are activated by cytochrome P450 (P450) and peroxidase to form DNA adducts. Using the 32P-postlabelling assay we investigated the formation of DNA adducts by aristolactam I in these two activation systems. A combination of two independent chromatographic systems (ion-exchange chromatography TLC and reversed-phase HPLC) with reference compounds was used for the identification of adducts. Aristolactam I activated by peroxidase led to the formation of several adducts. Two major adducts were identical to adducts previously observed in vivo. 7-(deoxyguanosin-N2-yl)aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AAI) were formed in DNA during the peroxidase-mediated one-electron oxidation of aristolactam I. Aristolactam I activated by P450 led to one major adduct and four minor ones. Beside the principal AA-DNA adducts identified recently in the ureter of one patient with CHN, an additional minor adduct was detected, which was found to have indistinguishable chromatographic properties on TLC and HPLC from the major adduct formed from aristolactam I by P450 activation. Thus, this minor AA-adduct might be evolved from the AAI detoxication metabolite (aristolactam I) by P450 activation. These results indicate a potential carcinogenic effect of aristolactam I in humans.
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PMID:Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs nephropathy. 1044 9

Although there is permanent increase in incidence of malignant upper urothelial tumours [1, 2], these malignancies are rare neoplasms in relation to both all malignant tumours and urotract tumours. Upper urothelial tumours, i.e. tumours of the renal pelvis and ureter are more frequent in the regions affected by endemic nephropathy [3-5]. The aim of this paper was to describe the main epidemiological characteristics in patients with upper urothelial tumours (UUT) in endemic nephropathic (EN) foci in Lazarevac. We analyzed 73 patients treated at the Institute of Endemic Nephropathy, Lazarevac and the Institute of Urology and Nephrology, Belgrade, from January 1, 1992 to December 31, 1994. The descriptive-epidemiological methods was used. The characteristics in patients with histopathologically confirmed upper urothelial tumours were examined. The diagnosis was made on the basis of the clinical picture, echo-sonographic and radioscopic examinations, intravenous and infusion urography and retrograde pielography. With genealogic analysis, a genealogical tree as far as the fourth degree of kinship for each patient, was made both for urothelial tumours and endemic nephropathy. The average age of the patients at the time of diagnosis was 64.2 years, and the majority of the patients (59%) was in the seventh decade of life (Figure 1). Our results are in accordance with the results of other authors who examined the patients with upper urothelial tumours in the regions with endemic nephropathy and out of them [7, 8, 12, 14]. Females were more affected than males (1.4:1). These results are in accordance with the results of other authors who studied the endemic regions [7, 11, 13]. Foreign authors found that males were more affected by upper urothelial tumours [9, 10]. In view of anatomic localization of tumours (Table 2) our results are in accordance with results of the studies carried out in endemic [11, 12, 15, 19] and non-endemic regions [8]. The majority of patients were rural population and lived in villages known as endemic foci (89%) (Table 1). Agriculture was their main or additional occupation. A large number of UUT patients (67%) had endemic nephropathy as well. The other authors from our country found that farmers were most affected [17, 18]. In foreign studies, there are no data on the fact that farming is risk for the appearance of upper urothelial tumours. The family agglomeration of UUT and EN in UUT patients has been observed in all degrees of relation, especially in the second and third generations (Table 3). The obtained results are comparable with hypotheses on a possible mutual or the same aetiological factor for both diseases, which is in accordance with the results of other authors who studied the endemic regions [6, 7, 12, 13].
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PMID:[Descriptive and epidemiologic characteristics of patients with malignant upper urothelial tumors in the endemic area of Lazarevac]. 1068 18

Several clinical studies have confirmed that histomorphometric changes in the tubulointerstitial compartment contain the best correlating parameters to predict the development of progressive renal insufficiency. The process of interstitial fibrosis is accompanied by an influx of inflammatory cells, up-regulation of fibrogenic cytokines such as transforming growth factor-beta and basic fibroblast growth factor, transient down-modulation of their antagonists, generation and proliferation of myofibroblasts, and, finally, by accumulation of interstitial collagens and proteoglycans. A careful morphometric analysis of interstitial fibrosis requires sensitive parameters through which the severity can be quantified and by which the progression into renal insufficiency can be predicted. We have addressed these issues by morphometric analysis of both human biopsies and by refining existing experimental models in the rat. Morphometric analysis was performed using a Zeiss microscope equipped with a full colour 3CCD camera and KS-400 image analysis software from Zeiss-Kontron. For studies with human material, biopsies were examined from patients with various renal diseases including patients with chronic allotransplant dysfunction. The development of interstitial fibrosis was correlated with clinical parameters. In experimental models, we analysed the interstitial composition and eventual glomerular alterations in rats with bovine serum albumin (BSA)-induced protein overload nephropathy and with human IgG-induced chronic serum sickness nephritis. Finally, we adapted and refined the model of ureter obstruction-induced interstitial fibrosis in the rat. For this purpose, custom-made titanium clips (S&T, Neuhaus, Switzerland) were implanted around the ureter in the abdomen of rats to obstruct the ureter without causing necrosis. The clips were removed at various time points after obstruction of the ureter (1-14 days). The subsequent remodelling of the interstitium was studied thereafter, in order to establish whether uraemia-induced interstitial fibrosis remains reversible at all times. In rat models, we have found that both protein overload-induced and serum sickness-induced interstitial fibrosis are accompanied by the development of focal and segmental glomerulosclerosis. Only in the ureter obstruction model did selective interstitial fibrosis develop, and remained reversible at all times studied. For the reliable assessment of interstitial fibrosis we have found that the best correlating parameters of interstitial fibrosis with renal function were: (i) the ratio of protein accumulation of TGF-beta-1 and its antagonist decorin; (ii) interstitial expression of smooth muscle alpha-actin; and (iii) accumulation of interstitial collagens (as determined by immunoperoxidase and by Sirius red staining).
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PMID:Morphometry of interstitial fibrosis. 1114 98

Malignant tumors of the renal pelvis account for over 78 per cent of all malignant tumors of the kidney, and less than 1 per cent of all urogenital neoplasms. At the time of diagnosing, almost one third of these patients present with tumor of the ipsilateral ureter or bladder, and 40-50 per cent have ureteral tumor located elsewhere (D. Crawford, S. Das, 1990). After World War Two, the frequency of publications on cases of primary tumors of the pelvis show a noticeable increase, e.g. in Yugoslavia and Bulgaria the ratio of parenchymatous renal tumors to those of the renal pelvis is conspicuously altered. S. Petcovic (1970) and S. Lambrev (1972) attribute this fact to the existence of endemic "nephropathy" foci. It is the purpose of this work to analyze twenty-nine patients presenting carcinoma of the upper urinary ways, studied in the Chair of Urology in the period 1991 through 1997. Of them only four come from "endemic" regions. Over the period 1972-1975, fifty-nine patients with the same condition undergo treatment in the aforementioned Chair. It is worth noting that patients from the so-called "endemic" regions lack the typical signs of "endemic" nephropathy. The assumption is warranted that "endemic" nephropathy is a still not well enough clarified nosological entity, bearing resemblance to contamination with radioactive elements with a "boom" during the half-life period gradually subsiding.
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PMID:[Urothelial tumors versus "endemic" nephropathy - myth or reality?]. 1124 69

Chinese herbs nephropathy (CHN), a unique type of nephropathy has been associated with the intake of weight-reducing pills containing the Chinese herb Aristolochia fangchi. Moreover, an association between the use of A. fangchi and urothelial cancer in CHN patients has been reported indicating that aristolochic acid (AA) the major alkaloid of A. fangchi might be the causal agent. Similarities of CHN to the Balkan endemic nephropathy (BEN) have led to the hypothesis of a common etiological agent for both diseases. Evidence has accumulated that BEN is an environmentally-induced disease strongly associated with the fungal mycotoxin ochratoxin A (OTA). Both, AA and OTA are nephrotoxic and carcinogenic and induce the formation of DNA adducts. As OTA has been suspected as fungal contaminant in the herbal batches used for the preparation of the weight-reducing pills we analysed tissues from CHN patients by the 32P-postlabeling procedure for the presence of DNA adducts related to both OTA and AA exposure. Whereas, AA-specific DNA adducts were detected in all five urinary tract tissues from five patients (total RAL: 32-251 adducts per 10(9) nucleotides), OTA-related DNA adducts were detectable in two kidneys and one ureter only (total RAL: 1.5-3.7 adducts per 10(9) nucleotides). Thus, OTA-related DNA adduct levels were about 50 times lower than AA-DNA adduct levels. In female and male rats that were treated with the slimming regimen in the same way like the CHN patients except that the amount of Chinese herbs was 10 times higher, AA-DNA adducts were found in kidney tissues (total RAL ranging from 51 to 83 adducts per 10(9) nucleotides) but adducts derived from OTA were not observed. These results demonstrate that OTA-related DNA adducts do not play a key role in CHN or CHN-associated urothelial cancer.
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PMID:Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patients with Chinese herbs nephropathy. 1142 53

A series of publications in the 1950s described a kidney disease in Bulgaria, the former Yugoslavia and Romania that became known as Balkan endemic nephropathy (BEN). The disease was qualified by World Health Organisation (WHO) experts as 'progressive and very gradually developing renal failure with insidious onset.... The last stage shows marked fibrosis...'. BEN is characterized by tubular degeneration, interstitial fibrosis and hyalinization of glomeruli accompanied by enzymuria and impaired renal function without nephrotic syndrome. Later, an association between BEN and tumours of the kidney pelvis and ureter was recognized, so that the problem of BEN became not only nephrological, but also oncological. There may also be an association with increased urinary bladder cancer incidence, although many confounding factors may interfere in the analysis of data for this organ. In view of the very intimate association between BEN and the urinary tract tumours (UTT), the term 'endemic uropathy' has been proposed. Several hypothesis concerning the aetiology of these diseases has been investigated, which include: predisposing genes factors, environmental factors (heavy metals, minerals, bacteria, leptospira, viruses, fungal toxins and, most recently, pliocene lignites). This paper reviews the different hypotheses about the aetiology of endemic uropathy and pays particular attention to the role of fungal toxins.
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PMID:Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins. 1183 78

For elucidation of the mechanisms by which growth factors and cytokines affect renal epithelial cells, gene array analysis of renal cells cultured in the presence of transforming growth factor-beta1 (TGF-beta1) was performed. Many genes that were not previously considered to be involved in renal cell biologic processes were affected, one of which was jagged-1. The jagged ligand/notch receptor family controls the formation of boundaries between groups of cells and regulates cell fates. On the basis of the array analysis, jagged-1 expression was further evaluated in cultured cells and in C57BL/6 mice with a model of unilateral ureteral obstruction (UUO). Recombinant human TGF-beta1 increased jagged-1 mRNA levels at concentrations between 10(-11) and 10(-10) M. There was a commensurate increase in jagged-1 protein levels, as assessed by Western blotting. The expression of jagged-1 mRNA and protein was observed to be significantly increased in the kidneys of C57BL/6 mice with obstructed ureters, compared with the contralateral kidneys, at 7 and 14 d of UUO. Immunohistochemical analyses demonstrated jagged-1 expression in distal tubules of kidneys from normal mice or contralateral kidneys from mice with UUO. Jagged-1 protein expression was increased in tubules not yet in apparent atrophy in the kidneys with an obstructed ureter. Jagged-1 expression was significantly increased in the kidneys of normal mice treated with TGF-beta1 and was decreased in the kidneys of mice with UUO treated with a TGF-beta receptor II-Fc chimera. These results suggest that jagged-1 is expressed in normal kidneys and that this expression is upregulated during renal disease, in a TGF-beta-dependent manner.
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PMID:Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease. 1203 79


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