REFERENCES

1. Wang, Y., Puri, P., Hassan, J., Miyakita, H. and Reen, D. J.:Abnormal innervation and altered nerve growth factor mes-senger ribonucleic acid expression in ureteropelvic junctionobstruction. J Urol, 154: 679, 1995

2. Solari, V., Piotrowska, A. P. and Puri, P.: Altered expression ofinterstitial cells of Cajal in congenital ureteropelvic junc-tion obstruction. J Urol, 170: 2420, 2003

3. Murakumo, M., Nonomura, K., Yamashita, T., Ushiki, T., Abe,K. and Koyanagi, T.: Structural changes of collagen compo-nents and diminution of nerves in congenital ureteropelvicjunction obstruction. J Urol, 157: 1963, 1997

4. Chevalier, R. L.: Molecular and cellular pathophysiology ofobstructive nephropathy. Pediatr Nephrol, 13: 612, 1999

5. Borges, L. F., Taboga, S. R. and Gutierrez, P. S.: Simultaneousobservation of collagen and elastin in normal and patholog-ical tissues: analysis of sirius-red-stained sections by fluo-rescence microscopy. Cell Tissue Res, 320: 551, 2005

6. Junqueira, L. C., Cossermelli, W. and Brentani, R.: Differen-tial staining of collagens type I, II and III by sirius red andpolarization microscopy. Arch Histol Jpn, 41: 267, 1978

7. Hanna, M. K., Jeffs, R. D., Sturgess, J. M. and Barkin, M.:Ureteral structure and ultrastructure. Part II. Congenitalureteropelvic junction obstruction and primary obstructivemegaureter. J Urol, 116: 725, 1976

8. Seremetis, G. M. and Maizels, M.: TGF-beta mRNA expressionin the renal pelvis after experimental and clinical uretero-pelvic junction obstruction. J Urol, 156: 261, 1996

9. Gosling, J. A. and Dixon, J. S.: Functional obstruction of theureter and renal pelvis. A histological and electron micro-scopic study. Br J Urol, 50: 145, 1978

10. Truong, L. D., Choi, Y. J., Tsao, C. C., Ayala, G., Sheikh-Hamad, D., Nassar, G. et al: Renal cell apoptosis in chronicobstructive uropathy: the roles of caspases. Kidney Int, 60:924, 2001

11. Lama, G., Ferraraccio, F., Iaccarino, F., Luongo, I., Marte, A.,Rambaldi, P. F. et al: Pelviureteral junction obstruction:correlation of renal cell apoptosis and differential renalfunction. J Urol, 169: 2335, 2003

12. Chuang, Y., Chuang, W. and Huang, C.: Myocyte apoptosis inthe pathogenesis of ureteral damage in rats with obstruc-tive uropathy. Urology, 58: 463, 2001

13. Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., West-cott, J. Y. and Henson, P. M.: Macrophages that haveingested apoptotic cells in vitro inhibit proinflammatorycytokine production through autocrine/paracrine mecha-nisms involving TGF-beta, PGE2, and PAF. J Clin Invest,101: 890, 1998

14. Gradl, G., Gaida, S., Gierer, P., Mittlmeier, T. and Vollmar, B.:In vivo evidence for apoptosis, but not inflammation in thehindlimb muscle of neuropathic rats. Pain, 112: 121, 2004

15. Trachtenberg, J. T.: Fiber apoptosis in developing rat musclesis regulated by activity, neuregulin. Dev Biol, 196: 193,1998

16. Kim, W. J., Yun, S. J., Lee, T. S., Kim, C. W., Lee, H. M. andChoi, H.: Collagen-to-smooth muscle ratio helps predictionof prognosis after pyeloplasty. J Urol, 163: 1271, 2000

17. Yoon, J. Y., Kim, J. C., Hwang, T. K., Yoon, M. S. and Park,Y. H.: Collagen studies for pediatric ureteropelvic junctionobstruction. Urology, 52: 494, 1998

18. Kaplan, E. P., Richier, J. C., Howard, P. S., Ewalt, D. H. andLin, V. K.: Type III collagen messenger RNA is modulatedin non-compliant human bladder tissue. J Urol, 157: 2366,1997

19. Keane, D. P., Sims, T. J., Abrams, P. and Bailey, A. J.: Analysisof collagen status in premenopausal nulliparous womenwith genuine stress incontinence. Br J Obstet Gynaecol,104: 994, 1997

20. Kim, D. S., Noh, J. Y., Jeong, H. J., Kim, M. J., Jeon, H. J. andHan, S. W.: Elastin content of the renal pelvis and ureterdetermines post-pyeloplasty recovery. J Urol, 173: 962,2005

EDITORIAL COMMENT

The authors investigate structural and metabolic anomaliesin congenital UPJ obstruction, and the role of programmedcell death in the pathogenesis of intrinsic UPJ obstruction isanalyzed for the first time. They convincingly show thatsmooth muscle cell apoptosis is increased in the obstructedsegment and is accompanied by a reduction of peripheralnerve endings. However, it remains unclear if primary de-fects of innervation cause apoptosis or if a reduction of SMCsalters intramural nerve supply. Others have already dem-onstrated a decrease in nerve growth factor expression con-tributing to a defective nerve supply. Correlation of theapoptotic index with collagen composition, nerve densityand elastin content further underlines the etiological role ofprogrammed cell death. Moreover, persistent apoptosis cor-roborates a progressive nature of intrinsic UPJ stenosis.Further investigations in the field of extracellular matrixchanges, cytokine involvement, the role of innervation andmicrovessel supply might help us to understand the patho-genesis of this frequent congenital disorder.

Christian RadmayrDepartment of Paediatric Urology

Medical University InnsbruckInnsbruck, Austria

REPLY BY AUTHORS

Programmed cell death, associated with many pathologicalconditions, is increasingly viewed as a nexus through whichmany key pathways converge. It has been shown that inmany different organs the empty spaces left by apoptoticcells are filled with fibrotic tissue. In this study we suggestthat this common phenomenon participates in the pathogen-esis of UPJ obstruction. Based on these results, we proposethe defective neural development as the trigger for inductionof apoptosis in myocytes at the site of obstruction. Thus, apersisting congenital defect could be involved in the patho-genesis of intrinsic UPJ obstruction. We entirely agree withRadmayr, and we plan to perform further investigations toexplore extracellular matrix changes, the role of innervationand microvessel supply for better understanding of the UPJpathological process. There is no doubt that the determina-tion of the precise underlying mechanism of congenital UPJobstruction would affect the current therapeutic approach.

URETEROPELVIC JUNCTION OBSTRUCTION AND MYOCYTE APOPTOSIS 723