Fractional excretion of sodium after renal transplantation

Fractional excretion of sodium after renal transplantation. After renal transplantation low urinary sodium concentration (UNa) has been used to diagnose acute rejection (AR), for the early phase of AR is often associated with reduced renal perfusion. Early postoperative graft failure without low UNa favors the diagnosis of ischemic tubular damage (ATN). As fractional excretion of filtered sodium (FENa) better reflects glomerulotubular balance in renal sodium handling, FENa was analyzed during the first 2 weeks in 118 renal allografts. From data on 41 transplants with good early renal function (GEF), a temporal profile of FENa was obtained and used to evaluate the behavior of FFNa by means of standardized FENa (z score). Individual subjects followed their own profile with a small deviation (Δz < 1.4 for 2 days). In 31 instances, acute rejection was diagnosed. In 14 with AR, the z score deviated little; 2 responded to methylprednisolone given intravenously. In 17 with AR, the z score fell significantly (Δz > 1.5 for 2 days), an average of 2.6 days before the first rise in serum creatinine concentration; 15 responded to treatment. The difference between these two groups was significant (P < 0.001). This functional heterogeneity and different responses to treatment may indicate different immunologic mechanisms which damage different target cells in the graft in AR. In 46 patients with acute tubular necrosis after cadaver kidney transplantation FENa was significantly higher than it was in the GEF group as early as the first posttransplantation day and approached normal as the renal function recovered. This behavior of FENa was clearly different from that in AR.Excrétion fractionnelle du sodium après transplantation rénale. Après transplantation rénale une concentration urinaire de sodium (UNa) faible est considérée comme un signe de rejet aigu (AR), du fait que la phase précoce du rejet est souvent associée à une diminution du débit rénal. L'échec précoce d'une greffe sans abaissement de UNa est en faveur d'une tubulopathie ischémique (ATN). Puisque l'excrétion fractionnelle du sodium filtré (FENa) est le meilleur reflet de l'équilibre glomérulo-tubulaire concernant le sodium, FENa a été étudiée pendant les 2 premières semaines d'évolution de 118 allogreffes rénales. A partir de l'observation de 41 transplants ayant eu un bon fonctionnement précoce (GEF) un profil de FENa en fonction du temps a été obtenu et utilisé pour évaluer le comportement de FENa au moyen d'une FENa standardisée (test z). Les sujets ont suivi leur propre profil avec une déviation faible (Δz < 1,4 par 2 jours). Le rejet aigu a été diagnostiqué dans 31 cas. Quatorze d'entre eux avaient une déviation minime de z; deux ont répondu à la methylprednisolone i.v. Dix sept sujets avaient une déviation significative de z (Δz > 1,5 par 2 jours), 2,6 jours en moyenne avant la première augmentation de la créatinine; quinze ont répondu au traitement. La différence entre ces deux groupes est significative (P < 0,001). Cette hétérogénéité fonctionnelle et cette différence de réponse au traitement peuvent être la traduction de mécanismes immunologiques différents qui atteignent des cellules cibles de la greffe différentes au cours du rejet aigu. Chez 46 malades ayant des lésions ischémiques après transplantation de reins de cadavre, FENa était significativement plus élevée que dans le groupe GEF dès le premier jour après la transplantation et revenait vers la normale au fur et à mesure que la fonction rénale s'améliorait. Ce comportement de FENa est nettement différent de celui observé dans les rejets aigus

Systems-Based Design of Bi-Ligand Inhibitors of Oxidoreductases: Filling the Chemical Proteomic Toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases

The Amborella genome: an evolutionary reference for plant biology

The nuclear genome sequence of Amborella trichopoda, the sister species to all other extant angiosperms, will be an exceptional resource for plant genomics

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Evolution of renal function and predictive value of serial renal assessments among patients with acute coronary syndrome:BIOMArCS study

Background: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. Methods: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCr ≥ 30 ml/min/1.73 m2. Survival analyses were adjusted for GRACE risk score and based on data >30 days after the index ACS (mean of 8 sample per patient). Results: Mean age was 63 years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2–3. During hospitalization for index ACS (median [IQR] duration: 5 (3–7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03–2.74]). Conclusion: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score

Genetic Factors Leading to Chronic Epstein–Barr Virus Infection and Nasopharyngeal Carcinoma in South East China: Study Design, Methods and Feasibility

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC

Relative rates of B meson decays into psi(2S) and J/psi mesons

We report on a study of the relative rates of B meson decays into psi(2S) and J/psi mesons using 1.3 fb^-1 of pbar p collisions at sqrt(s) = 1.96 TeV recorded by the D0 detector operating at the Fermilab Tevatron Collider. We observe the channels B^0_s -> psi(2S)phi, B^0_s -> J/psi phi, B^+/- -> psi(2S) K^+/-, and B^+/- -> J/psi K^+/- and we measure the relative branching fractions for these channels to be B(B^0_s -> psi(2S)phi)/B(B^0_s -> J/psi phi) = 0.55 +/- 0.11 (stat) +/- 0.07 (syst) +/- 0.06 (B), B(B^+/- -> psi(2S) K^+/-)/B(B^+/- -> J/psi K^+/-) = 0.65 +/- 0.04 (stat) +/- 0.03 (syst) +/- 0.07 (B) where the final error corresponds to the uncertainty in the J/psi and psi(2S) branching ratio into two muons.Comment: Published in Phys. Rev. D - Rapid Communicatio

Evolution of renal function and predictive value of serial renal assessments among patients with acute coronary syndrome: BIOMArCS study

Background: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. Methods: F