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)

Mesoblastic nephroma is an uncommon congenital tumor of infancy that rarely occurs in adults. We report three patients (two were female, one was male) who had mesoblastic nephroma of adulthood and who presented at 45, 64, and 66 years of age with hematuria, flank mass, and pain. All underwent nephrectomy without postoperative adjuvant therapy. The tumors were solitary yellow-tan masses with solid and cystic areas involving the renal cortex (three cases) with extension into the renal pelvis and calyces (two) and ureter (one). Microscopically, all consisted of uniform spindle cell proliferations with entrapped dilated renal tubules. Focal necrosis was present in two, but no atypia or mitoses were identified in any case. The spindle cells displayed cytoplasmic immunoreactivity for vimentin, desmin, panmuscle actin (HHF-35), and alpha-smooth-muscle actin, but were nonreactive for keratin (AE1/AE3), epithelial membrane antigen, and S-100 protein. Electron microscopy revealed the presence of smooth-muscle differentiation in two cases and undifferentiated mesenchyme in one. All tumors were DNA diploid by flow cytometry. The patients were free of recurrence 8 months-2 years postoperatively. Because surgical excision may be curative, mesoblastic nephroma in adult patients must be differentiated from spindle cell neoplasms of the kidney that require additional therapy.
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PMID:Mesoblastic nephroma of adulthood. Report of three cases. 839 55

Eighty-nine tissue specimens from the urinary tract and prostate were analyzed for the presence and physical state of BK virus (BKV) DNA. Large T antigen gene sequences were amplified by PCR from prostate, kidney, ureter, and bladder with prevalences ranging from 50 to 83%. Sequence analysis of PCR products from the high variable BKV regulatory region showed that these tissues contained a new BKV strain (URO1). URO1 presents a duplication of part of the 68- and 39-bp elements of the viral enhancer, and a 68-bp deletion spanning part of the 39- and 63-bp enhancer elements. Six neoplastic specimens (11.5%), but none of the control tissues, contained viral DNA in amounts detectable by Southern blot hybridization (P < 0.05). The tumors positive by Southern blot hybridization harbored rearranged and/or integrated DNA sequences whose size was apparently incompatible with assembly into a viral particle. A full-length, macroscopically intact BKV early region was amplified from these tumors by PCR. The restriction pattern of the rearranged sequences was simple, suggesting that tumors were clonal and that DNA rearrangement occurred at an early stage of neoplastic initiation or progression.
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PMID:DNA rearrangements impairing BK virus productive infection in urinary tract tumors. 852 28

Ochratoxin A (OTA) is a ubiquitous nephrotoxic mycotoxin which was shown to be carcinogenic to laboratory animals and may be responsible for kidney pelvis, ureter and urinary bladder tumors associated with Balkan endemic nephropathy in man. Previous evidence from this laboratory demonstrated that OTA exposure results in adduct formation on kidney, testicles, liver and spleen DNA. We show in this study that after a single oral administration of OTA to mice (2 mg/kg body weight) a high level of DNA adducts (150 per 10(9) nucleotides) is also detected in the urinary bladder. The metabolic pathway of OTA leading to genotoxic compounds is not yet known. We demonstrate here that two inhibitors of the prostaglandin H synthase, indomethacin and aspirin, administered to mice before OTA treatment, dramatically reduce the amounts of DNA adducts, particularly in the urinary bladder and kidney. This suggests a role of protaglandin H synthase in the metabolism of OTA leading to active metabolites which react with DNA.
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PMID:Protection by indomethacin and aspirin against genotoxicity of ochratoxin A, particularly in the urinary bladder and kidney. 882 84

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends by using an RNA component as a template. Telomerase extends the telomeric repeats, which prevents telomere shortening during cell division, contributes to chromosomal stability, and, possibly, leads to immortalization of the cells. The telomerase activity in 22 urothelial tumors, including 13 bladder cancers, 8 ureter cancers, and 1 renal pelvic cancer, as well as in 12 adjacent normal tissues, was examined with the use of a nonradioisotope polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Different levels of telomerase activity were detected in the urothelial tumors. No significant activity was observed in normal adjacent tissues; however, two cases exhibited weak activity. Nine tumors retained positive telomerase signals after 100-fold dilution of extracts, which suggests that these tumors express high levels of telomerase activity. These findings indicate that telomerase activation may be a critical step in the pathogenesis of urothelial tumors. Unexpectedly, no significant correlation was observed between high levels of telomerase expression and the clinicopathologic features of the tumors, including clinical stage, pathologic grade, tumor multiplicity, and status of recurrence.
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PMID:Telomerase activity in human urothelial tumors. 912 60

Recently, we reported that aristolochic acid (AA) a naturally occurring nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis, designated Chinese herbs nephropathy (CHN). Indeed, we identified the principal aristolochic acid-DNA adduct in the kidney of five such patients. We now extend these observations and demonstrate the presence of additional AA-DNA adducts by the 32P-post-labelling method not only in the kidneys, but also in a ureter obtained after renal transplantation. Using the nuclease P1 version of the assay not only the major DNA adduct of aristolochic acid, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), but also the minor adducts, 7-(deoxyguanosin-N2-yl)-aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)-aristolactam II (dA-AAII) were detected, and identified by cochromatographic analyses with TLC and HPLC. Quantitative analyses of six kidneys revealed relative adduct levels from 0.7 to 5.3/10(7) for dA-AAI, from 0.02 to 0.12/10(7) for dG-AAI and 0.06 to 0.24/ 10(7) nucleotides for dA-AAII. The detection of the dA-AAII adduct is consistent with the occurrence of aristolochic acid II (AAII) in the herb powder imported under the name of Stephania tetrandra and confirms that the patients had indeed ingested the natural mixture of AAI and AAII. 32P-post-labelling analyses of further biopsy samples of one patient showed the known adduct pattern of AA exposure not only in the kidney, but also in the ureter, whereas in skin and muscle tissue no adduct spots were detectable. In an attempt to explain the higher level of the dA-AAI adduct compared to the dG-AAI adduct level in renal tissue even 44 months after the end of regimen, the persistence of these two purine adducts was investigated in the kidney of rats given a single oral dose of pure AAI. In contrast to the dG-AAI adduct, the dA-AAI adduct exhibited a lifelong persistence in the kidney of rats. Our data demonstrate that AA forms DNA adducts in human tissue by the same activation mechanism(s) reported from animal studies. Thus, the carcinogenic/mutagenic activity of AA observed in animals could also be responsible for the urothelial cancers observed in two of the CHN patients.
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PMID:32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy. 916 97

Insulin-like growth factor I (IGF-I) has been postulated to function as a smooth muscle cell (SMC) mitogen and to play a role in the pathogenesis of bladder hypertrophy, estrogen-induced uterine growth, and restenosis after arterial angioplasty. IGF-binding protein-4 (IGFBP-4) inhibits IGF-I action in vitro and is the most abundant IGFBP in the rodent arterial wall. To explore the function of this binding protein in vivo, transgenic mouse lines were developed harboring fusion genes consisting of a rat IGFBP-4 complementary DNA cloned downstream of either a -724 bp fragment of the mouse smooth muscle alpha-actin 5'-flanking region (SMP2-BP-4) or -1074 bp, 63 bp of 5'-untranslated region, and 2.5 kb of intron 1 of smooth muscle alpha-actin (SMP8-BP-4). SMP2-BP-4 mice expressed low levels of the exogenous IGFBP-4 messenger RNA (mRNA), which was not specifically targeted to SMC-rich tissue environments, and were therefore not analyzed further. Six SMP8-BP-4 transgenic lines derived from separate founders were characterized. Mating of hemizygous SMP8-BP-4 mice with controls produced about 50% transgenic offspring, with equal sex distribution. Expression of IGFBP-4 mRNA in nontransgenic littermates was maximal in liver and kidney. By contrast, transgenic IGFBP-4 mRNA expression, distinguished because of a smaller transcript size, was confined to SMC-containing tissues, with the following hierarchy: bladder > aorta > stomach = uterus. There was no transgene expression in skeletal muscle, brain, or cardiac myocytes. The abundance of IGFBP-4 measured by Western ligand blotting or by immunoblotting, was 8- to 10-fold higher in aorta and bladder of SMP8-BP-4 mice than in their nontransgenic littermates, with no change in plasma IGFBP-4 levels. Transgenic mice exhibited a significant reduction in wet weight of SMC-rich tissues, including bladder, intestine, aorta, uterus, and stomach, with no change in total body or carcass weight. In situ hybridization showed that transgene expression was targeted exclusively to the muscular layers of the arteries, veins, bladder, ureter, stomach, intestine, and uterus. Overexpression of IGFBP-4 was associated with SMC hypoplasia, a reciprocal phenotype to that of transgenic mice overexpressing IGF-I under control of the same promoter (SMP8-IGF-I). Double transgenic mice derived from mating SMP8-BP-4 with SMP8-IGF-I animals showed a modest decrease in wet weight at selected SMC tissues. Although we cannot exclude that the effects of IGFBP-4 may be IGF independent, these data suggest that IGFBP-4 is a functional antagonist of IGF-I action on SMC in vivo.
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PMID:Overexpression of insulin-like growth factor-binding protein-4 (IGFBP-4) in smooth muscle cells of transgenic mice through a smooth muscle alpha-actin-IGFBP-4 fusion gene induces smooth muscle hypoplasia. 956 77

A novel mouse gene, associated with the enhancer-trap mutation TKZ736, has been cloned and sequenced. It encodes a polyspecific transmembrane transporter with 12 putative transmembrane domains, that shares significant homology with the mouse organic cation transporter 1 (Oct1/Slc22a1) called Lx1. Like Oct1/Slc22a1/Lx1, this gene maps to the proximal part of Chromosome (Chr) 17, but shows a different expression pattern from Oct1/Slc22a1/Lx1. The gene identified here is predominantly expressed in the kidney and ureter, but no expression is detectable in liver. Sequence comparisons suggest that this novel gene most likely represents the mouse homolog of the rat organic cation transporter 2 gene. The genomic DNA flanking the 3' transgene integration site in the enhancer-trap mutation TKZ736 encodes the second exon of the Oct2/Slc22a2 gene.
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PMID:Cloning of the mouse organic cation transporter 2 gene, Slc22a2, from an enhancer-trap transgene integration locus. 1005 14

Ig amyloidosis is usually a systemic disease with multisystem involvement. However, in a significant number of cases amyloid deposition is limited to one specific organ. It has not been determined if the Ig light chain (LC) amyloid precursor protein in localized amyloidosis is synthesized by circulating plasma cells with targeting of the amyloid fibril-forming process to one specific organ, or whether the synthesis of Ig LC and fibril formation occurs entirely as a localized process. In the present study local synthesis of an amyloid fibril precursor LC was investigated. Amyloid fibrils were isolated from a ureter that was obstructed by extensive infiltration of the wall with amyloid. Amino acid sequence analysis of the isolated fibril subunit protein proved it to be derived from a lambdaII Ig LC. Plasma cells within the lesion stained positively with labeled anti-lambda Ab and by in situ hybridization using an oligonucleotide probe specific for lambda-LC mRNA. RT-PCR of mRNA extracted from the tumor and direct DNA sequencing gave the nucleotide sequence coding specifically for the lambdaII amyloid subunit protein, thus confirming local synthesis of the LC protein.
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PMID:Organ-specific (localized) synthesis of Ig light chain amyloid. 1022 37

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

We established a unique parental neuroblastoma cell line, NUB-7, which mimics the bipotentiality of neuroblastoma in vivo along neuronal and Schwann cell lineages following dibutyryl cAMP and retinoic acid treatments, respectively. Differential display identified a putative novel zinc finger gene as a potential differentiation-responsive gene coincident with retinoic acid treatment of NUB-7. This cDNA clone, now designated zf5-3, was mapped to chromosome 19 using somatic cell hybrids, and a larger cDNA clone further localized this gene to band 13.1-13.2 by fluorescent in situ hybridization. zf5-3 possesses 4 characteristic zinc finger DNA-binding motifs as determined by its nucleic acid and proposed amino acid sequence. Expression of zf5-3 is restricted to fetal neuronal, hepatic and renal tissues and their tumor-derived cell lines, including 8/9 neuroblastomas and 2/2 malignant rhabdoid tumors of kidney. The restricted expression in the kidney of zf5-3 to collecting tubules and ureter epithelium is suggestive of an ectodermal histogenesis of malignant rhabdoid tumors of kidney. During development of the fetal human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts. Morphological evidence of overt differentiation was generally accompanied by a marked loss in zf5-3 expression. Therefore, the neuronal tissue expression profile and the down-regulation coincident with retinoic acid-induced neuroblastoma maturation implicate zf5-3 as a potential mediator of their differentiation.
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PMID:Identification of a novel zinc finger gene, zf5-3, as a potential mediator of neuroblastoma differentiation. 1036 47


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