Scintillation Counters for the D0 Muon Upgrade

We present the results of an upgrade to the D0 muon system. Scintillating counters have been added to the existing central D0 muon system to provide rejection for cosmic ray muons and out-of-time background, and to provide additional fast timing information for muons in an upgraded Tevatron. Performance and results from the 1994-1996 Tevatron run are presented.Comment: 30 pages, 25 postscript figure

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence

Advanced Maillard reaction products as markers for tissue damage in diabetes and uraemia: relevance to diabetic nephropathy.

Recent work has led to the structural elucidation of three compounds of the advanced Maillard reaction-pyrraline, pentosidine and carboxymethyllysine-which can serve as markers for in vivo studies. Pyrraline is a glucose-derived compound, the presence of which was detected with a monoclonal antibody in elevated amounts in the plasma of diabetic individuals and rodents and in histological sections of renal tissue, especially in sclerosed glomerular and arteriolar regions. The immediate precursor of pyrraline is 3-deoxyglucosone (3-DG), a product formed through degradation of glycated proteins. 3-DG is present in elevated levels in plasma and urine from diabetic humans. Pentosidine is a pentose-derived protein crosslink, which forms from glycated proteins in the presence of oxygen. Pentosidine increases ubiquitously in aging tissues, and at an accelerated rate in diabetes and especially in uraemia. Skin pentosidine levels correlate with the severity of diabetic complications in type I (insulin-dependent) diabetes. Its levels, like those of carboxymethyllysine, an Amadori fragmentation and oxidation product, are not reversible upon tight control of diabetes over a 4-month period. Assuming these advanced products reflect cumulative glycaemia over several years, it would appear that there is a correlation between the severity of complications and total exposure to glucose

Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging and uremia.

Pentosidine is an advanced glycosylation end product and protein cross- link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration >17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications

Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging and uremia.

Collagen undergoes progressive browning with age and diabetes characterized by yellowing, fluorescence, and cross-linking. The present research was undertaken in order to investigate the nature of the collagen-linked fluorescence. Human collagen was exhaustively cleaved into peptides by enzymatic digestion. Upon purification, a highly fluorescent chromophore was identified and purified from old human collagen. Structure elucidation revealed the presence of an imidazo [4,5-b] pyridinium-type structure acting as a cross-link between arginine, lysine, and a pentose. This advanced glycosylation end-product and protein cross-link results from the reaction of pentoses with proteins and was named pentosidine. Further work indicated that long-term glycosylation of proteins with hexoses also leads to pentosidine formation through sugar fragmentation. The proposed mechanism of pentosidine formation involves the dehydration of the pentose-derived Amadori compound to form an intermediate which is attacked under base catalysis by the guanido group of arginine. The strict requriement for the Amadori rearrangement is uncertain. However, oxidation is definitely involved since pentosidine is not formed in the absence of oxygen. Five-carbon sugars contributing to pentosidine formation could be formed from larger sugars by oxidative fragmentation or from trioses, tetroses, and ketoses by condensation and/or reverse aldol reactions. Pentosidine increases exponentially in human skin at autopsy. Mean age-adjusted skin levels were significantly increased in subjects with uremia and especially in type 1 diabetes with uremia vs. controls. In skin biopsy, levels were significantly elevated in all diabetic (type 1) vs. control subjects. The highest degree of association was with the cumulative grade of diabetic complication (retinopathy, nephropathy, arterial stiffness, and joint stiffness). Pentosidine also forms in various proteins other than collagen, although to a much lesser extent. In blood, pentosidine is mainly associated with plasma proteins and is highly elevated during uremia. In the lens, it is associated with both water-soluble and -insoluble protein fractions and is especially elevated during brunescent cataract formation. The origin of pentosidine in vivo is uncertain. Evidence suggests that the pentoses are the most reactive sugars in pentosidine formation in vitro; however, the origin and importance of free pentoses in vivo, especially during the diabetic state, are not certain. Possible origins include hemolysis and/or a defect in the primary pentose metabolism. The more likely precursors of pentosidine are the hexoses; however, it is unclear whether they undergo oxidative fragmentation to form 5-carbon fragments in vivo. This contrasts with ascorbate, a very likely precursor, known to be oxidized to dehydroascorbate and 2,3-diketoglulonate and to fragment to pentoses in vivo. Pentosidine reflects a form of sugar-mediated cumulative damage to protein which increases with aging, diabetes, and uremia. The determination of pentosidine levels may be a useful marker of aging and the risk of developing diabetic complications. It may also be a biochemical end-point for the assessment of therapeutic interventions aimed at preventing or reversing the progression of diabetic complications