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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ros1 gene was detected originally by virtue of its transforming potential; the cDNA of the human protooncogene was isolated from a tumor cell line expressing the gene ectopically. It encodes a receptor-type tyrosine specific protein kinase which is closely related to sevenless in Drosophila. Here we report the novel and remarkable in vivo expression pattern of c-ros1, which was determined in the mouse. By a combination of RNase protection and in situ hybridization, we find transient c-ros1 expression during development in the kidney, intestine and lung, coinciding with major morphogenetic and differentiation events in these organs. This temporally restricted nature of expression is unusual for tyrosine kinase receptors and suggests a role for ros1 during development. Furthermore, in kidney development c-ros1 transcripts are confined to subgroups of ureter cells known to be involved directly in inductive interactions between ureter epithelium and metanephric mesenchyme. Thus, this study implicates for the first time a tyrosine kinase receptor in mesenchymal epithelial interactions and suggests a molecular basis for these important inductive events in development.
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PMID:Transient and locally restricted expression of the ros1 protooncogene during mouse development. 171 42

Several mouse genes designated 'Pax genes' contain a highly conserved DNA sequence homologous to the paired box of Drosophila. Here we describe the isolation of Pax8, a novel paired box containing clone from an 8.5 day p.c. mouse embryo cDNA library. An open reading frame of 457 amino acids (aa) contains the 128 aa paired domain near the amino terminus. Another conserved region present in some other paired box genes, the octapeptide Tyr-Ser-Ile-Asn-Gly-Leu-Leu-Gly, is located 43 aa C-terminal to the paired domain. Using an interspecies backcross system, we have mapped the Pax8 gene within the proximal portion of mouse chromosome 2 in a close linkage to the surf locus. Several developmental mutations are located in this region. In situ hybridization was used to determine the pattern of Pax8 expression during mouse embryogenesis. Pax8 is expressed transiently between 11.5 and 12.5 days of gestation along the rostrocaudal axis extending from the myelencephalon throughout the length of the neural tube, predominantly in two parallel regions on either side of the basal plate. We also detected Pax8 expression in the developing thyroid gland beginning at 10.5 days of gestation, during the thyroid evagination. In the mesonephros and metanephros the expression of Pax8 was localized to the mesenchymal condensations, which are induced by the nephric duct and ureter, respectively. These condensations develop to functional units, the nephrons, of the kidney. These data are consistent with a role for Pax8 in the induction of kidney epithelium. The embryonic expression pattern of Pax8 is compared with that of Pax2, another recently described paired box gene expressed in the developing excretory system.
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PMID:Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. 172 50

The aim of the present study was to determine the distribution and density of catecholaminergic nerve fibres and cells in the equine ureter by using immunohistochemical techniques to localise the enzyme tyrosine-hydroxylase (TH). TH-immunoreactive (TH-IR) nerve fibres entered the wall of the ureter as adventitial nerve trunks accompanying the blood vessels. These trunks repeatedly branched as they coursed through the muscular layer towards the epithelium, forming muscular, perivascular and subepithelial nerve plexuses. TH-IR nerve fibres were especially numerous in the pelvic and intravesical ends of the ureter. TH-IR cells have also been identified in the equine ureteral wall, usually grouped as adventitial and intramural nerve ganglia. The results of the present study demonstrated that the equine ureter, like that of other mammals, possesses a rich autonomic supply of catecholaminergic (TH-IR) nerve fibres. These morphological data support a role for the autonomic nervous system in the control of ureteral peristalsis.
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PMID:Catecholaminergic innervation of the equine ureter. 810 62

The distribution of nitric oxide synthase (NOS)-immunoreactive (IR) and haemoxygenase (HO)-IR nerves was investigated in the pig and human intravesical ureter (IVU). NOS activity was measured by monitoring the conversion of [3H]-arginine to [3H]-citrulline. Effects of NO and resulting changes in cyclic nucleotide concentrations were assessed in vitro. The effects of carbon monoxide (CO) on IVU motility was also tested. Immunohistochemistry revealed an abundant overall innervation of the IVU and numerous NOS-IR nerves. Nerve trunks were also found expressing immunoreactivity for HO-1, one of the enzymes synthetising CO. Similar profiles of nerve structures expressing immunoreactivities for NOS and tyrosine-hydroxylase (TH), as well as NOS and vasoactive intestinal peptide (VIP) were demonstrated. In the pig IVU, measurement of NOS activity revealed a moderate calcium-dependent catalytic activity, NO and the NO-donor SIN-1 reduced in a concentration-dependent manner serotonin-induced contractions of pig and human IVU, and the spontaneous contractions of pig IVU. In pig IVU strips precontracted with the thromboxane analogue U-46619, tetrodotoxin-sensitive relaxations were abolished by the NOS inhibitor NG-nitro-L-arginine. CO exerted no significant effect on spontaneous or induced contractions in the pig and human IVU. In precontracted strips of the pig and human IVU exposed to SIN-1 or NO, significant increases of cyclic GMP levels were measured in comparison to control preparations. The results suggest that the L-arginine/NO/cyclic GMP pathway may play a role in the regulation of the valve function in the uretero-vesical junction (UVJ). A role for CO in the UVJ has yet to be established.
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PMID:Localization of nitric oxide synthase and haemoxygenase, and functional effects of nitric oxide and carbon monoxide in the pig and human intravesical ureter. 913 43

Alkaptonuria is an uncommon tyrosine metabolism disorder. Deficit of homogentisic acid oxidase leads to the elimination of large amounts of homogentisic acid in the urine with accumulation of homogentisic acid oxidized pigment in the connective tissue (ochronosis). The ultimate evolution of ochronosis is degenerative arthritis. The clinical case reported is a 57-year old male diagnosed with alkaptonuria in an early stage of the connective tissue disease who comes to the clinic due to a lower urinary obstructive syndrome secondary to benign prostate hyperplasia but is diagnosed with giant prostate lithiasis. The patient undergoes retropubic adenomectomy with lithiasis removal and re-implantation of ectopic ureter from a dual left excretory system. Clinical evolution is completely successful. The rarity of the case calls for circulation and revision of the clinical and therapeutical aspects of this entity.
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PMID:[Alkaptonuria, prostatic calculi, and ectopic ureter]. 921 16

The role of the autonomic innervation of the upper urinary tract for pyeloureteral motility is not completely understood. It is still debatable if the autonomic nervous system might play a modulating role on the ureteral peristalsis. The aim of this study was to investigate the distribution and regional variation of the intramural innervation using whole-mount preparations of the rabbit upper urinary tract. Whole-mount preparation was performed at upper urinary tracts of healthy rabbits. Immunohistochemistry was employed using Neurofilament (NF), Tyrosine Hydroxylase (TH), Choline Acetyltransferase (ChAT) and Substance P (SP) antibodies. NADPH-diaphorase and Acetylcholinesterase (AChE) histochemistry was carried out at the specimens. The stains were evaluated using brightfield, fluorescence and laser confocal microscopy. NF-, TH-, ChAT- and SP-immunoreactive (-IR) nerves formed distinct neuronal plexuses at the submucosal and muscle layers. Perivascular TH-, ChAT- and SP-IR fibres were demonstrated. AChE positive nerves were revealed in all layers, but only moderate NADPH-diaphorase positive innervation was found. Renal pelvis, upper and lower ureter showed enriched intrinsic innervation. Ganglia were found at the ureteropelvic border and the distal ureter. Whole-mount preparation technique revealed detailed informations about morphology and regional variation of the intramural innervation of the rabbit upper urinary tract.
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PMID:The intramural innervation of the rabbit upper urinary tract. 1287 43

1. The mechanisms and receptors involved in the vasoactive intestinal peptide (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38 and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor, omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations. Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro-l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4. The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38, respectively, relaxations. 5. The nonselective and large-conductance Ca(2)-activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1 microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1 microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7. These results suggest that VIP and PACAP relax the pig ureter through smooth muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway. Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at sensory nerves and coupled to NO release, seem also to be involved in the VIP and PACAP 38 relaxations.
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PMID:Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and PACAP-induced relaxations of the pig intravesical ureter. 1466 37

Molecular mechanisms that lead to congenital anomalies of kidneys and the lower urinary tract (CAKUT) are poorly understood. To elucidate the molecular basis for signaling specificity of GDNF-mediated RET signaling in kidney development, we characterized mice that exclusively express either the human RET9 or RET51 isoform, or express these isoforms with individual mutations in docking tyrosines for PTB and SH2-domain-containing adaptors Src (Y981), PLCgamma (Y1015), and Shc (Y1062). Our results provide evidence for differential and isoform-specific roles of these docking sites in murine kidney development. Homozygous Ret(RET9) and Ret(RET51) mice were viable and show normally developed kidneys, indicating redundant roles of human RET isoforms in murine kidney development. In the context of the RET51 isoform, only mutation of the docking Tyr 1015 (Y1015F) resulted in severe renal anomalies. These included bilateral megaureters and multicystic kidneys that were caused by supernumerary ureteric buds that fail to separate from the wolffian duct as well as decreased branching morphogenesis. Similar kidney and ureter defects were observed in RET9(Y1015F) mice that contain the Y1015F mutation in the RET9 isoform. Interestingly, loss of RET9(Y1062)-mediated AKT/MAPK activation resulted in renal agenesis or kidney rudiments, whereas mutation of this residue in RET51 had no obvious effect on AKT/MAPK activity and renal development. These results reveal novel roles of key RET-dependent signaling pathways in embryonic kidney development and provide murine models and new insights into the molecular basis for CAKUT.
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PMID:Critical and distinct roles for key RET tyrosine docking sites in renal development. 1645 4

Primary vesicoureteral reflux (pVUR) is a common, genetically heterogeneous congenital urinary tract abnormality in children. It causes urine to flow backward from the bladder to the ureter due to a developmental defect at the vesicoureteral junction, whose formation requires rearrangement during transformation (Ret)-mediated signaling pathways. To study the genetic causes of pVUR in Quebec patients, we used a sequencing-based candidate gene approach to screen the RET gene and found that 83 out of 118 pVUR patients are carriers of the rare A allele of single nucleotide polymorphism (SNP) rs1799939:G>A that results in a Gly691Ser mutation, a statistically significant increase in allelic frequency, that is absent at six flanking RET SNPs tested. Ser691 is a predicted phosphorylation site and our analysis of transfected cells showed that the Gly691Ser Ret mutant can efficiently interact and associate with a 75-80-kD tyrosine phosphorylated cellular protein, an event not seen with wild-type Ret. This interaction and/or the steric or electric hindrance created by phospho-Ser691 may interfere with the known regulatory functions of the normally phosphorylated phospho-Tyr687 and phospho-Ser696 on the cytoskeleton actin reorganization that are responsible for cell motility and morphology, which consequently may lead to the deficiency in ureteral development observed in pVUR. Our study demonstrates that the Ret Gly691Ser mutation is associated with pVUR and may be one of the genetic causes of this condition in the French-Canadian population in Quebec.
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PMID:RET Gly691Ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from Quebec. 1827 80

The vesico-ureteric junction (VUJ) forms through a complex developmental program that connects the primordium of the upper urinary tract [the nephric duct (ND)] with that of the lower urinary tract (the cloaca). The signals that orchestrate the various tissue interactions in this program are poorly understood. Here, we show that two members of the EphA subfamily of receptor tyrosine kinases, EphA4 and EphA7, are specifically expressed in the mesenchyme surrounding the caudal ND and the cloaca, and that Epha4(-/-);Epha7(+/-) and Epha4(-/-);Epha7(-/-) (DKO) mice display distal ureter malformations including ureterocele, blind and ectopically ending ureters with associated hydroureter, megaureter and hydronephrosis. We trace these defects to a late or absent fusion of the ND with the cloaca. In DKO embryos, the ND extends normally and approaches the cloaca but the tip subsequently looses its integrity. Expression of Gata3 and Lhx1 and their downstream target Ret is severely reduced in the caudal ND. Conditional deletion of ephrin B2 from the ND largely phenocopies these changes, suggesting that EphA4/EphA7 from the pericloacal mesenchyme signal via ephrin B2 to mediate ND insertion. Disturbed activity of this signaling module may entail defects of the VUJ, which are frequent in the spectrum of congenital anomalies of the kidney and the urinary tract (CAKUT) in human newborns.
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PMID:Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme. 2513 58


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