Antibody‐mediated rejection (AbAR) is increasingly recognized in the renal allograft population, and successful therapeutic regimens have been developed to prevent and treat AbAR, enabling excellent outcomes even in patients highly sensitized to the donor prior to transplant. It has become critical to develop standardized criteria for the pathological diagnosis of AbAR. This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001. This classification represents a working formulation, to be revisited as additional data accumulate in this important area of renal transplantation.
A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.
The core 3 structure of the O-glycan, GlcNAc1-3GalNAc␣1-Ser͞ Thr, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by 1,3-N-acetylglucosaminyltransferase 6 (3Gn-T6; core 3 synthase). We generated an anti-3Gn-T6 mAb (G8-144 mAb) and performed immunohistochemical analyses. In normal stomach and colon, 3Gn-T6 was strongly expressed in the Golgi region of epithelia. In contrast, its expression was markedly down-regulated in gastric and colorectal carcinomas. Tissue specimens from a familial adenomatous polyposis patient showed a clear correlation between the down-regulation of 3Gn-T6 expression and the degree of dysplasia͞neoplasia. In vitro, the level of 3Gn-T6 transcript was increased according to the differentiation of Caco-2 cells. These results suggested that the expression of 3Gn-T6 is closely regulated during differentiation and dedifferentiation. 3Gn-T6 would be a useful marker for distinguishing between benign adenomas and premalignant lesions. HT1080 FP-10 cells stably transfected with the 3Gn-T6 gene showed a decrease in the core 1 structure, Gal1,3GalNAc␣1-Ser͞ Thr, probably due to competition between the core 1 synthase and core 3 synthase. The migration activity of the transfectants was markedly lower than that of mock transfectants in vitro, and lung metastasis after i.v. injection of the transfectants into nude mice was significantly suppressed. These findings indicated that the core structures of O-glycans are profoundly involved in the metastatic capacity of cancer cells.glycosyltransferase ͉ stomach ͉ familial adenomatous polyposis ͉ immunohistochemical analysis
Background The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007. Methods The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the
The sialyl-Tn (sTn) antigen is a well known cancer-associated antigen, the expression of which is related to the prognosis of cancer patients. We aimed to isolate a human gene encoding an N -acetylgalactosamine alpha2,6-sialyltransferase which synthesizes sTn antigen, and to characterize the enzyme. Degenerate primers encoding sialyl motifs were used for the polymerase chain reaction to amplify complementary DNAs prepared from RNAs of human pyloric mucosae with intestinal metaplasia, which abundantly expressed sTn antigen, followed by screening of full-length cDNAs using the amplified DNA fragment as a probe. We isolated two human cDNA clones, long-form (2.46 kb) and short-form (2.23 kb) cDNAs. The former encodes an active enzyme with a predicted 600 amino acid sequence. The latter, a splice-variant of the long-form, encodes an inactive enzyme. HCT15 human colorectal cancer cells stably expressing the long-form cDNA expressed sTn epitopes on O -glycans. The long form cDNA was considered to encode a human homologue of chick ST6GalNAc I for the following reasons: (1) the putative amino acid sequence showed greater homology to that of chick ST6GalNAc I (55%) compared to other sialyltransferases, (2) it encodes the extraordinarily long stem region that is a typical feature of chick ST6GalNAc I, and (3) the substrate specificity was very similar to that of chick ST6GalNAc I. In situ hybridization demonstrated that the localization of transcripts correlated well with that of sTn antigen in gastric cancer cells and Goblet cells in intestinal metaplastic glands. Thus, we determined that the long-form cDNA of the human ST6GalNAc I gene encodes the probable candidate for the human sTn synthase(s).
123Clin Exp Nephrol (2013) 17:155-173 DOI 10.1007 nephritic syndrome (55.4 % and 50.0 % in 2009 and 2010, respectively), followed by nephrotic syndrome (22.4 % and 27.0 %); the most frequent pathological diagnosis as classified by the pathogenesis was IgA nephropathy (31.6 % and 30.4 %), followed by primary glomerular diseases (except IgA nephropathy) (27.2 % and 28.1 %). Among the primary glomerular diseases (except IgA nephropathy) in the patients with nephrotic syndrome, membranous nephropathy was the most common histopathology in 2009 (40.3 %) and minor glomerular abnormalities (50.0 %) were the most common in 2010 in native kidneys in the J-RBR. Five new secondary and longitudinal research studies by the J-KDR were started in 2009 and one was started in 2010.
A statistical survey conducted at the end of 2005 covered 3985 medical facilities across Japan, and 3940 facilities (98.87%) responded. The dialysis population in Japan at the end of 2005 was 257,765, which showed an increase of 9599 patients (3.87%) from the end of the previous year. The number of patients per million was 2017.6. The crude death rate for one year (from the end of 2004 to the end of 2005) was 9.5%. The mean age of the patients who began dialysis (in 2005) was 66.2 years, and the mean age of the entire dialysis population was 63.9 years. The primary diseases of the patients who began dialysis were diabetic renal disease (42.0%) and chronic glomerulonephritis (27.3%). The mean (+/-SD) serum ferritin concentration of all the dialysis patients was 191 (+/-329) ng/mL. The percentages of antihypertensive agents administered to the hemodialysis patients were as follows: calcium-channel blocker, 50.3%; angiotensin-converting enzyme inhibitor, 11.5%; and angiotensin II-receptor blocker, 33.9%. Of the peritoneal dialysis patients, 33.4% used automated peritoneal dialysis devices. Moreover, 7.3% of the peritoneal dialysis patients received dialysis treatment only in the daytime, and 15% received the treatment only at night. Icodextrin solution was used by 37.2% of the peritoneal dialysis patients. The average amount of dialysis solution used by the peritoneal dialysis patients was 7.43 (+/-2.52) L/day and the average amount of removal fluid was 0.81 (+/-0.60) L/day. A peritoneal equilibration test was conducted on 67% of the patients, and the mean dialysate to plasma creatinine ratio was 0.65 (+/-0.13). The annual incidence of peritonitis in the peritoneal dialysis patients was 19.7%. Of the 126 040 patients who responded to the inquiry of the therapeutic situation of peritoneal dialysis, 676 (0.7%) had a history of encapsulated peritoneal sclerosis and 66 (0.1%) were treated for encapsulated peritoneal sclerosis. The mean life expectancy of the dialysis population in 2003 was calculated according to sex and age. Results showed that the mean life expectancy of the dialysis population was approximately 40-60% of that of the general population of the same sex and age.
Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.
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