BackgroundThe study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).MethodsPatients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.ResultsDuring 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.ConclusionsThe results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Methylation of CpG sites in the genome, which is generally conserved during cell replication, is considered to play important roles in cell differentiation and carcinogenesis. However, investigations on changes in methylation status have been limited to known genes. To make a genome-wide search for differentially methylated genes, we developed a methylation-sensitive-representational difference analysis (MS-RDA) method. The representation of the genome was prepared using the methylation-sensitive restriction enzyme HpaII, and the mixture ratio of tester and driver DNAs was optimized to detect differences in methylation status of a single copy per diploid mammalian genome.

Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.

Background and objectives: An early histopathologic predictor of the renal prognosis, before the occurrence of advanced glomerular sclerosis/interstitial fibrosis and/or apparent renal dysfunction, remains to be established in IgA nephropathy (IgAN). This study aimed to determine whether the glomerular density (GD; nonsclerotic glomerular number per renal cortical area) of biopsy specimens obtained at an early stage of IgAN could predict the long-term renal outcome.Design, setting, participants, & measurements: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed for 98 patients who had IgAN with an estimated GFR of >60 ml/min per 1.73 m 2 at biopsy (87 ml/min per 1.73 m 2 on average). Results: The individual value of GD in biopsy ranged from 1.2 to 8.1/mm 2 (i.e., approximately a seven-fold variation), and the GD showed a close inverse correlation with mean glomerular volume. Among the various clinicopathologic factors involved, both a cellular/fibrocellular crescent and the GD were found to be significant predictors of progression in multivariate analyses. A low GD in the biopsy specimens was frequently associated with a steeper slope of the renal function and a synergistically enhanced risk for progression with the presence of cellular/fibrocellular crescent. The renal function, proteinuria, degrees of glomerulosclerosis, and interstitial fibrosis at biopsy were not independent predictors of the prognosis in these patients.Conclusions: A strong predictive relationship of low GD with progression observed in this study suggests that GD may serve as an early histopathologic marker of long-term renal prognosis in IgAN.

Germline mutations of BRCA2 were examined in 20 Japanese breast cancer families without BRCA1 mutations, including one demonstrating cancer development in a male. Three different mutations, resulting in truncation of the BRCA2 protein, were detected in 3 different families. They were 9474insA (exon 24, termination at codon 3110), C8729A (exon 20, S2834 ter) and 982del4 (exon 9, termination at codon 275). The 982del4 mutation was detected in the family with a case of male breast cancer. Age at onset was young, with a range of 28-43 years, in the 2 female breast cancer families with truncation mutations. One probable missense mutation, A10462G (I3412V), was further detected in 2 families, although cosegregation of this allele with the breast cancer phenotype was not complete. The rate of BRCA2 mutations in Japanese families was suggested to be almost the same as in Western countries, and larger than it is the case for BRCA1. Int. J. Cancer 74:199-204, 1997.r 1997 Wiley-Liss, Inc.Risk assessment for breast and ovarian cancer development is now available for particular families, due to the discovery of the breast cancer susceptibility genes, BRCA1 and BRCA2. About 5-10% of the cumulative incidence of breast cancer in Japan is associated with familial predisposition. This rate is almost the same as in Western countries, although the incidence of breast cancers in Japan is only about one fifth to one third of that in the United States. We earlier established that the rate of BRCA1 mutations in Japanese breast or breast-ovarian cancer families is smaller than in their North American counterparts, accounting for about 10% of cases on the basis of findings for 20 families examined (Inoue et al., 1995). Thus, clarification of the possible involvement of BRCA2 in the Japanese is important.BRCA2, mapped on chromosome 13q (Wooster et al., 1994), was isolated in 1995 (Tavtigian et al., 1996;Wooster et al., 1995). This gene is composed of 27 exons and encodes a 3,418 amino-acid protein having a certain homology to the BRCA1 protein. Mutational analysis of BRCA2 in breast cancer families has revealed an increased risk in individuals carrying mutations (Couch et al., 1996;Neuhausen et al., 1996;Phelan et al., 1996;Thorlacius et al., 1996). The BRCA2 gene has in fact been reported to be one of the major breast cancer susceptibility genes, accounting for about 70% of the inherited breast cancers not linked to BRCA1 (Wooster et al., 1994). However, BRCA2 mutations were detected in only 17% of site-specific breast cancer families, with a higher rate in those with male breast cancer (Phelan et al., 1996). As for the case of BRCA1, particular types of BRCA2 germline mutations are frequent in some populations. For example, the BRCA2 617delT mutation was identified in 8% of Ashkenazi Jewish breast cancer families , although it has also been detected in non-Jewish individuals (Berman et al., 1996). Further, 999del5 was detected in 40% of male breast cancer patients from Iceland (Thorlacius et al., 1996). If there were a specific type of ...