Identification of genes involved in human urothelial cell-matrix interactions: implications for the progression pathways of malignant urothelium.
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Interactions between epithelial cells and the extracellular matrix are central to tissue homeostasis and have a dynamic role in tissue remodeling and repair. Regulation of these pathways is balanced by positive and negative feedback elements, many of which have been implicated in the pathways of malignant progression. We have used differential display to identify genes that are up-regulated in normal human urothelial cells in response to exposure to extracellular matrix proteins (Matrigel) in vitro. This approach has identified genes that have key roles in cell-cell and cell-matrix interactions and that have been implicated in the progression of carcinomas of urothelial or other epithelial cell origins. One confirmed but unknown differentially expressed sequence was used to isolate a full-length gene, MIG-C4, from a human urothelial cDNA library. This gene was found to encode a novel urokinase plasminogen-activator receptor-like member of the Ly-6 family of glycosyl-phosphatidylinositol-anchored glycoproteins, and was identified as the human homologue of the rat metastasis-associated C4.4A gene. By in situ hybridization, MIG-C4 was expressed variably in normal urothelium and intensely in the tumor component of some noninvasive superficial lesions and in invasive and metastatic urothelial cancers. Thus, our approach has identified previously nonimplicated gene products involved in normal urothelium-matrix interactions that could be tumor-invasion or suppressor-gene targets in the development of invasive and metastatic tumor phenotypes. (+info)
Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactant protein C.
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Epithelial-mesenchymal tissue interactions regulate the formation of signaling centers that play a role in the coordination of organogenesis, but it is not clear how their activity leads to differences in organogenesis. We report that type XVIII collagen, which contains both a frizzled and an endostatin domain, is expressed throughout the respective epithelial bud at the initiation of lung and kidney organogenesis. It becomes localized to the epithelial tips in the lung during the early stages of epithelial branching, while its expression in the kidney is confined to the epithelial stalk region and is lost from the nearly formed ureter tips, thus displaying the reverse pattern to that in the lung. In recombinants, between ureter bud and lung mesenchyme, type XVIII collagen expression pattern in the ureter bud shifts from the kidney to the lung type, accompanied by a shift in sonic hedgehog expression in the epithelium. The lung mesenchyme is also sufficient to induce ectopic lung surfactant protein C expression in the ureter bud. Moreover, the shift in type XVIII collagen expression is associated with changes in ureter development, thus resembling aspects of early lung type epigenesis in the recombinants. Respecification of collagen is necessary for the repatterning process, as type XVIII collagen antibody blocking had no effect on ureter development in the intact kidney, whereas it reduced the number of epithelial tips in the lung and completely blocked ureter development with lung mesenchyme. Type XVIII collagen antibody blocking also led to a notable reduction in the expression of Wnt2, which is expressed in the lung mesenchyme but not in that of the kidney, suggesting a regulatory interaction between this collagen and Wnt2. Respecification also occurred in a chimeric organ containing the ureter bud and both kidney and lung mesenchymes, indicating that the epithelial tips can integrate the morphogenetic signals independently. A glial cell line-derived neurotrophic factor signal induces loss of type XVIII collagen from the ureter tips and renders the ureter bud competent for repatterning by lung mesenchyme-derived signals. Our data suggest that differential organ morphogenesis is regulated by an intra-organ patterning process that involves coordination between inductive signals and matrix molecules, such as type XVIII collagen. (+info)
Analgesic abuse, ureteric obstruction, and retroperitoneal fibrosis.
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We report two cases of unusual ureteric obstruction in patients with an excessive consumption of analgesics. In a retrospective survey of seven cases of non-malignant retroperitoneal fibrosis seen in the last 15 years it was found that four had taken excessive amounts of analgesics. A careful drug history should be taken in all patients with restroperitoneal fibrosis and ureteric obstruction. (+info)
Intracellular and extracellular regulation of ureteric bud morphogenesis.
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The urinary collecting duct system of the permanent kidney develops by growth and branching of an initially unbranched epithelial tubule, the ureteric bud. Formation of the ureteric bud as an outgrowth of the wolffian duct is induced by signalling molecules (such as GDNF) that emanate from the adjacent metanephrogenic mesenchyme. Once it has invaded the mesenchyme, growth and branching of the bud is controlled by a variety of molecules, such as the growth factors GDNF, HGF, TGFbeta, activin, BMP-2, BMP-7, and matrix molecules such as heparan sulphate proteoglycans and laminins. These various influences are integrated by signal transduction systems inside ureteric bud cells, with the MAP kinase, protein kinase A and protein kinase C pathways appearing to play major roles. The mechanisms of morphogenetic change that produce branching remain largely obscure, but matrix metalloproteinases are known to be necessary for the process, and there is preliminary evidence for the involvement of the actin/myosin contractile cytoskeleton in creating branch points. (+info)
Management of symptomatic ureteric stumps laparoscopically.
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AIM: To study the advantage of excision of the distal symptomatic ureteric stumps with the retroperitoneal laparoscopic approach. METHODS: Four patients who had failed to settle their symptoms with the initial conservative management were included in the study. All underwent excision of the distal symptomatic ureteric stumps with the retroperitoneal laparoscopic approach and then received prophylactic antibiotics. RESULTS: We have achieved better results than those reported in the literature in terms of operating time (mean 1 h 45 min), blood loss (< 10 mL), postoperative recovery (within 12 h) and hospital stay (< 48 h). CONCLUSION: Retroperitoneal laparoscopic excision is a safe, simple and effective method in the management of symptomatic ureteric stumps. (+info)
BACKGROUND: The exact molecular mechanisms that regulate ureteric branching morphogenesis in the developing metanephros have not been fully elucidated. However, in vivo and in vitro evidence indicates that glial cell line-derived neurotrophic factor (GDNF) is a key regulator of the initiation of ureteric branching. GDNF knockout mice show renal agenesis or severe dysgenesis and die 24 hours after birth from renal failure. Inhibition of GDNF activity in metanephric organ culture inhibits ureteric branching. Since nephron initiation only occurs at the tips of ureteric branches, the aim of the present study was to determine whether nephron number in GDNF heterozygous mice is reduced. METHODS: Male GDNF heterozygous mice of hybrid 129/Sv and C57/BL genetic background were mated with C57BL/6 females. Offspring were genotyped at postnatal day 30 (PN30) by polymerase chain reaction. Left kidneys were used for estimating kidney volume and total nephron number. We also estimated absolute and relative volumes of ureteric duct epithelium. Unbiased stereological methods were used throughout (Cavalieri method, physical disector/fractionator combination). RESULTS: GDNF wild-type and heterozygous mice had similar body weights at PN30. However, heterozygous kidneys were 25% smaller than wild-type kidneys (wild-type, 114.75 +/- 16.46 mm3; heterozygous, 87.11 +/- 21.84 mm3, P < 0.001) and contained approximately 30% fewer nephrons (wild-type, 11886 +/- 1277; heterozygous, 8573 +/- 2240, P < 0.01). In addition, the absolute ureteric duct volume was significantly reduced in heterozygous mice (P < 0.001). CONCLUSIONS: : These results indicate that the loss of one GDNF allele results in reduced nephron endowment in the adult kidney, presumably as the result of reduced branching morphogenesis of the ureteric bud. (+info)
Morbidity of 10 110 hysterectomies by type of approach.
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BACKGROUND: Since the late 1980s, the option of laparoscopic hysterectomy has raised questions about the most suitable approach to hysterectomy. METHODS: To evaluate the influence of the type of approach, in causing or avoiding certain complaints in hysterectomies a prospective nationwide study was conducted comprising all hysterectomies for benign disease performed in Finland during 1996. The primary outcomes of interest were the operation-related morbidity, common surgical details and post-operative complications. RESULTS: A total of 10 110 hysterectomies, including 5875 abdominal, 1801 vaginal and 2434 laparoscopic operations showed a low rate of overall complications, 17.2, 23.3 and 19.0% respectively. Infections were the most common complications with incidences of 10.5, 13.0 and 9.0% in the abdominal, vaginal and laparoscopic group respectively. The most severe type of haemorrhagic events occurred in 2.1, 3.1 and 2.7% in the abdominal, vaginal and laparoscopic group respectively. Ureter injuries were predominant in laparoscopic group [relative risk (RR) 7.2 compared with abdominal] whereas bowel injuries were most common in vaginal group (RR 2.5 compared with abdominal). Surgeons who had performed >30 laparoscopic hysterectomies had a significantly lower incidence of ureter and bladder injuries (0.5 and 0.8% respectively) than those who had performed < or =30 operations (2.2 and 2.0% respectively). A decreasing trend of bowel complications was also seen with increasing experience in vaginal hysterectomies. CONCLUSIONS: This large-scale observational study on hysterectomies provides novel information on operation-related morbidity of abdominal, vaginal or laparoscopic approach. The results support the importance of the experience of the surgeon in reducing severe complications, especially in laparoscopic and vaginal hysterectomies. (+info)
Three-dimensional analysis of nephrogenesis in the neonatal rat kidney: light and scanning electron microscopic studies.
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In order to clarify the process of renal development more precisely than previously, the present study observed the rat neonatal kidney by scanning electron microscopy (SEM) of KOH digested tissue as well as by light microscopy of plastic sections. In the subcapsular region, aggregation of the mesenchymal cells was closely associated with the upper side of the ureteric duct ampulla. These mesenchymal cells projected a number of fine irregular processes at the basal portion facing the ureteric duct. A spherical cluster transformed from the mesenchymal cell aggregation was found on the lower side of the terminal ampulla, and was differentiated into the renal vesicle. Some cells at the top of the renal vesicle formed a cone-shaped projection and invaded the ureteric duct ampulla, forming a connection with it. In the advanced stage, a shallow transverse cleft appeared on the outer lateral side of the renal vesicle, and a second cleft was formed on the opposite side close to the junction between the renal vesicle and the ampulla. As the two clefts deepened, the vesicle assumed the well-known S-shaped body. In the advanced S-shaped body, the lower limb became cup-shaped, while the segment between the middle and lower limbs of the "S" elongated to form a tubular structure (i.e., the prospective proximal tubule and Henle's loop). The upper limb of the "S" also increased its length to form a distal tubule. The middle limb of the "S", however, was attached firmly to the cup-shaped lower limb (i.e., the prospective renal corpuscle) and was considered to become the macula densa of the mature nephron. In the maturing renal corpuscle, irregularly shaped cells were observed as a sheet-like aggregation at its vascular pole and were continuous with the vascular smooth muscle cells. These findings will help toward a better understanding of the morphological complexities of nephrogenesis. (+info)