Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis

Chronic allograft tubular atrophy/interstitial fibrosis (TA/IF) is a major cause of late allograft loss. A major challenge to the future of kidney transplantation is to dissect the identifiable causes of chronic allograft TA/IF and to develop cause-specific treatment strategies. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is an important event in native and transplant kidney injury, including chronic allograft TA/IF. During EMT, tubular epithelial cells are transformed into myofibroblasts through a stepwise process including loss of cell-cell adhesion and E-cadherin expression, de novo alpha-smooth muscle actin expression, actin reorganization, tubular basement membrane disruption, cell migration, and fibroblast invasion with production of profibrotic molecules such as collagen types I and III and fibronectin. We examined in this review the molecular and cellular pathways of EMT and their involvement in chronic allograft tubulointerstitial fibrosis. We examined the role of alloimmune T cells and oxidative stress in this context and evaluated EMT as a marker of disease progression. Potential therapeutic options are discussed. In conclusion, there is enough evidence demonstrating that EMT is involved in the pathogenesis of chronic allograft tubulointerstitial fibrosis. However, the extent of its contribution to allograft fibrogenesis remains unknown, and only interventional trials will enable us to clarify this question. Furthermore, additional data are required to determine whether EMT may be used as a surrogate marker of disease progression in kidney transplant recipients.     

Deletion analysis of tumor and urinary DNA to detect bladder cancer: urine supernatant versus urine sediment

The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These changes can be detected in the urine by DNA analysis of the cells exfoliated from the bladder wall enabling us to detect bladder cancer. The urine supernatant, besides the urine sediment, contains DNA, however in a much smaller amount. The origin of DNA in these two fractions is probably different. Our aim was to evaluate which fraction (supernatant or sediment) provides more reliable results in detecting tumors. We analyzed blood, urine and tumor samples taken from 80 individuals (44 patients with bladder cancer, 20 control patients and 16 healthy volunteers) by using 12 microsatellite markers mapped on 6 chromosomes. Microsatellite alterations were detected in the urine sediment and supernatant in 86% of the cancer cases. Urine sediment alone had a sensitivity of 68%, while urine supernatant alone indicated aberrations in 80% of the tumors. In the superficial (Ta/T1) cases, a considerable difference in sensitivity, 84 vs. 67%, was found between the two fractions in favor of urine supernatant. We also detected deletions in the control groups, although in a much lower proportion. Loss of the 16q24 chromosomal region showed a significant correlation with tumor stage (p=0.02). Microsatellite analysis of the urine is an efficient and noninvasive molecular method to detect bladder cancer. The analysis of free DNA in the urine supernatant provides a higher detection rate. The marker on the chromosomal region 16q24 is suggested to have a prognostic value.     

Cryosections of pre-irradiated adult rat spinal cord tissue support axonal regeneration in vitro

Neonatal X-irradiation of central nervous system (CNS) tissue markedly reduces the glial population in the irradiated area. Previous in vivo studies have demonstrated regenerative success of adult dorsal root ganglion (DRG) neurons into the neonatally-irradiated spinal cord. The present study was undertaken to determine whether these results could be replicated in an in vitro environment. The lumbosacral spinal cord of anaesthetised Wistar rat pups, aged between 1 and 5 days, was subjected to a single dose (40 Gray) of X-irradiation. A sham-irradiated group acted as controls. Rats were allowed to reach adulthood before being killed. Their lumbosacral spinal cords were dissected out and processed for sectioning in a cryostat. Cryosections (10 μm-thick) of the spinal cord tissue were picked up on sterile glass coverslips and used as substrates for culturing dissociated adult DRG neurons. After an appropriate incubation period, cultures were fixed in 2% paraformaldehyde and immunolabelled to visualise both the spinal cord substrate using anti-glial fibrillary acidic protein (GFAP) and the growing DRG neurons using anti-growth associated protein (GAP-43). Successful growth of DRG neurites was observed on irradiated, but not on non-irradiated, sections of spinal cord. Thus, neonatal X-irradiation of spinal cord tissue appears to alter its environment such that it can later support, rather than inhibit, axonal regeneration. It is suggested that this alteration may be due, at least in part, to depletion in the number of and/or a change in the characteristics of the glial cells.     

Donovanosis (granuloma inguinale) of the oral cavity.

A female patient suffering from donovanosis of the oral cavity without associated lesions elsewhere is reported. The importance of remembering donovanosis in the differential diagnosis of chronic granulomatous ulceration of the mouth is emphasized.     

Osteosarcoma of the scapula arising in osteogenesis imperfecta

A case of osteosarcoma arising in the scapula of a 37 year old woman with severe congenital sporadic white sclera type osteogenesis imperfecta (OI) is presented. Osteosarcoma occurs as a sporadic rather than a related occurrence in patients with OI. A delay in the diagnosis of osteosarcoma may occur due to the similarity in symptomatology between the two conditions and because of the difficulty in differentiating between hyperplastic callus and tumor using conventional radiographic imaging techniques.     

Management of congenital bilateral temporomandibular joint ankylosis with secondary mandibular hypoplasia

The aim of this article is to present the course of the condition in a case of congenital temporomandibular joint ankylosis that caused facial disfigurement, significant reduction of mouth opening, difficulty in feeding and breathing, and general interference with physical development.     

Impact of innate and adaptive immunity on rejection and tolerance

Until recently, research on transplantation rejection and tolerance has been directed toward deciphering the mechanisms of the adaptive immune system. However, the emergence that the innate immune system, the body's first-line defense against pathogens, has a strong influence on adaptive immunity has galvanized interest in elucidating the interplay between these two arms of the immune system. The discovery of Toll-like receptors and the characterization of the cellular mediators involved in innate immunity have provided growing evidence that innate immunity affects the adaptive immune response. Emerging evidence has also shown that early "danger signals"' associated with ischemia-reperfusion injury or brain death contribute to innate immune activation, promoting rejection, and inhibiting tolerance induction. In addition, nonspecific stimuli such as increased donor age or patient disease may also serve to exert a synergistic influence on innate immune activation. Ultimately, controlling the events in innate immune activation may help drive tolerance induction and reduce the rate of rejection.