Abstract
Urinary tract infection occurs more commonly, is more virulent and proves more difficult to eradicate in spinal cord injury persons than in the neurologically intact. In order to find out the peculiarities of the neuropathic bladder which make it vulnerable to recurrent cystitis, we studied the proliferation status of the urothelium in spinal cord injured persons. Eleven consecutive, unselected male spinal cord injury patients (aged 18–73 years) were included in the study. Those with, or undergoing treatment for acute urinary tract infection were excluded. All patients underwent cystoscopy and cold cup bladder biopsy from the trigone and bladder dome. Immunocytochemical analysis was performed using defined, commercially available antibodies for PCNA (PCNA 10, DAKO) and MIB-1 (raised against recombinant DNA defined segment of Ki-67 antigen DAKO) streptavidin/biotin and alkaline phosphatase immunocytochemistry (for MIB-1 with microwave-enhanced antigen retrieval) were used to demonstrate the presence of cell cycling-associated nuclear proteins. Foci of lymphocytic aggregations present in the sections served as in-section controls for antigen preservation. Ten patients showed labelling of 20–70% of cells for PCNA in basal cell layers of dome lining. Higher urothelial layers showed a variable, but generally reduced degree of labelling. Of these 10 patients, three showed complete absence of MIB-1 activity in the basal and other layers of dome urothelium and two demonstrated only a very occasional positive nucleus. MIB-1 labelling was < 5% in four others and it was between 5% and 10% in one. In the trigone, PCNA labelling was 20–70% in nine and < 20% in two others. Of the former nine, MIB-1 labelling was < 5% in five; patchy staining was observed in one; and MIB-1 labelling was completely absent in three. The absence of proliferation was not correlated with urothelium thickness. Absence of MIB-1 expression, with maintained PCNA expression suggests effective arrest due to external factors. The dissociation between MIB-1 and PCNA expression may be an effect of defective innervation of the bladder in spinal cord injured persons. Absence of proliferation would be expected to alter the relative maturity of bladder lining cells. Alterations in the surface structure of urothelium may contribute to changes in the expression of cell adhesion molecules relevant to bacterial adherence and colonisation.
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Weitzman S A, Weitberg A B, Clark E P, Stossel T P . Phagocytes as carcinogens: malignant transformation produced by human neutrophils. Science 1985; 227: 1231–1233.
Case records of the Massachusetts General Hospital, case 31–1993. N Engl J Med 1993; 329: 417–423.
Jie L . Study on infectious mechanism of type 1 fimbriated Escherichia coli in experimental cystitis in mice. Chong-Kuo-I-Hsueh-Ko-Hsueh-Yuan-Hsueh-Pao 1993; 15: 250–254.
Boon M E, Howard C V, van Velzen D . PCNA independence of Ki-67 expression in HPV infection. Cell Biol Int 1993; 17: 1001–1004.
Reid G . Do antibiotics clear bladder infections? J Urol 1994; 152: 865–867.
Reid G et al. Bacterial biofilm formation in the urinary bladder of spinal cord injury patients. Paraplegia 1992; 30: 711.
Reid G et al. Bacterial biofilm formation on the bladder epithelium of spinal cord injured patients II. Toxic outcome on cell viability. Paraplegia 1993; 31: 494.
de Boer W I, Schuller A G P, Vermey M, Vanderjwast T H . Expression of growth factors and receptors during specific phases in regenerating urothelium after acute injury in vivo. Am J Pathol 1994; 145: 1199–1207.
Rebel J M et al. An in vitro model of urothelial regeneration: Effects of growth factors and extracellular matrix proteins. J Pathol 1994; 173: 283–291.
Lezzoni J C et al. Rapid colorimetric detection of epidermal growth factor receptor mRNA by in situ hybridization. J Clin Lab Anal 1993; 7: 247–251.
Border W A, Noble N A . Transforming growth factor beta in tissue fibrosis. N Engl J Med 1994; 31: 1286–1292.
Beck L S et al. One systemic administration of transforming growth factor beta 1 reverses age- or glucocorticoid-impaired wound healing. J Clin Invest 1993; 92: 2841–2849.
Smiddy W E et al. Transforming growth factor-beta 2 significantly enhances the ability to flatten the rim of subretinal fluid surrounding macular holes. Preliminary anatomic results of a multicenter prospective randomized study. Retina 1993 13: 296–301.
Thompson J T et al. Fluorescein angiographic characteristics of macular holes before and after vitrectomy with transforming growth factor beta-2. Am J Ophthalmol 1994; 117: 291–301.
Sporn M B, Roberts A B . A major advance in the use of growth factors to enhance wound healing. J Clin Invest 1993; 92: 2565–2566.
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Velzen, D., Krishnan, K., Parsons, K. et al. Vesical urothelium proliferation in spinal cord injured persons: an immunohistochemical study of PCNA and MIB.1 labelling. Spinal Cord 33, 523–529 (1995). https://doi.org/10.1038/sc.1995.113
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DOI: https://doi.org/10.1038/sc.1995.113
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