Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.

Allelic loss of chromosome region 3p21 is one of the most frequent events in the development of human cancers including lung, breast and bladder cancer. 1-3 A gene called RASSF1 has been discovered recently in this chromosome region. 4 One of the splice variants of this gene, RASSF1A, is inactivated frequently in many cancers including lung, breast and bladder by promoter hypermethylation. 5,6 Therefore both genetic and epigenetic alterations appeared to be involved in the RASSF1A inactivation. Furthermore, re-expression experiment in lung and renal cell carcinoma found that RASSF1A suppressed tumor growth in soft agar assay and in nude mice model. 5,7 These studies suggest that RASSF1A function as a tumor suppressor gene. Based on the presence of the RAS association domain in protein of RASSF1A, it is suggested that it exerts its function through RAS-mediated pathway. 4 More recently, RASSF1A is found to exert its effect by binding with novel RAS effector, Nore1 and MTS1. 8,9 Bladder cancer is the 6th most common cancer in the world. 10 Transitional cell carcinoma comprising the majority of bladder cancer, displays the multiple metachronous or synchronous features. Bladder cancer patients need a long-term follow-up with repeated urine cytology and cystoscopy for monitoring. 11 Conventional urine cytology has been the standard method for cancer detection. The sensitivity is low, however, especially for low grade transitional cell carcinoma (TCC). Therefore, a more sensitive and non-invasive method is required for cancer detection. We have reported previously that promoter hypermethylation of four cancer-related genes can be detected in voided urine of bladder cancer patients and appears to be more sensitive than conventional cytology in cancer detection. 12 In our study, we investigate the frequency of LOH in 3p21 regions and methylation status of RASSF1A in bladder cancer tissues. We also investigate the feasibility of detecting methylation of RASSF1A in voided urine and its potential role as tumor marker for bladder cancer. MATERIAL AND METHODS Tissues samplesForty bladder tumor tissues samples from transurethral resection specimens (8 frozen samples and 32 paraffin-embedded samples) were obtained at the Prince of Wales Hospital. Paraffin-embedded tissues from 6 samples of carcinoma in situ and 6 samples of normal urothelium from individuals without bladder cancer were also included. The clinical pathological data for all the tissue samples are summarized in Table I. Three human bladder cancer cell lines (T24, UMUC3 and J82) were obtained from American Type Culture Collection (Rockville, MD). Urine samplesPaired voided urine samples were collected from 14 patients ( Table I). The urine samples were spun down and the urine sediments were subjected to subsequent analysis. The corresponding urine samples were also subjected to conventional urine cytology examination by an experienced pathologist without knowledge of the methylation results. In Addition, 10 normal voided urine sediments from age-and gender-match c...

Estrogen receptor-related receptors (ERRs; alpha, beta, gamma) are orphan nuclear receptors and constitutively active without binding to estrogen. Like estrogen receptors (ERs), ERRs bind to estrogen receptor elements and estrogen receptor element-related repeats. Growing evidence suggests that ERRs can cross-talk with ERs in different cell types via competition for DNA sites and coactivators. We hypothesize that ERRs might play regulatory roles in normal and neoplastic prostatic cells by sharing similar ER-mediated pathways or acting independently. In this study, we investigated mRNA and protein expression patterns of three ERR members in normal human prostate epithelial cells, established cell lines, cancer xenografts, and prostatic tissues. Additionally, effects of transient transfection of ERRs on prostatic cell proliferation and ER expression were also examined. RT-PCR showed that ERRalpha and ERRgamma transcripts were detected in most cell lines and xenografts, whereas ERRbeta was detected in normal epithelial cells and few immortalized cell lines but not in most cancer lines. Similar results were demonstrated in clinical prostatic specimens. Western blottings and immunohistochemistry confirmed similar expression patterns that ERR proteins were detected as nuclear proteins in epithelial cells, whereas their expressions became reduced or undetected in neoplastic prostatic cells. Transient transfection confirmed that ERRs were expressed in prostatic cells as nuclear proteins and transcriptionally active in the absence of estradiol. Transfection results showed that overexpression of ERRs inhibited cell proliferation and repressed ERalpha transcription in PC-3 cells. Our study shows that ERRs, which are coexpressed with ERs in prostatic cells, could regulate cell growth and modulate ER-mediated pathways via interference on ERalpha transcription in prostatic cells.

Our finding suggests podocyte markers are reduced in IgAN. An in vitro study implicates that humoral factors (predominantly TNF-alpha and TGF-beta) released from mesangial cells are likely to alter the glomerular permeability in the event of proteinuria and tubulointerstitial injury in IgAN.

We have previously documented that human mesangial cell (HMC)-derived TNF-alpha is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the role of mesangial cells in the activation of podocytes in IgAN. There was no binding of IgA from patients with IgAN to podocytes. Podocytes cultured with IgA from patients with IgAN did not induce the release of growth factors or cytokines. Furthermore, podocytes did not express mRNA of known IgA receptors. In contrast, IgA-conditioned medium (IgA-HMC medium) prepared by culturing HMC with IgA from patients with IgAN for 48 h significantly increased the gene expression and protein synthesis of TNF-alpha by podocytes with a 17-fold concentration above that of IgA-HMC medium. The upregulation of TNF-alpha expression by podocyte was only abolished by a neutralizing antibody against TNF-alpha but not by other antibodies. Exogenous TNF-alpha upregulated the synthesis of TNF-alpha by podocytes in an autocrine fashion. IgA-HMC medium prepared with IgA from patients with IgAN also significantly upregulated the expression of both TNF-alpha receptor 1 and 2 in podocytes. Our in vitro finding suggests podocytes may play a contributory role in the development of interstitial damage in IgAN by amplifying the activation of tubular epithelial cells with enhanced TNF-alpha synthesis after inflammatory changes of HMC.