Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction

Seven patients with acute renal failure due to gross haematuria caused by glomerulonephritis are described. Gross haematuria lasting 4-40 days led to acute impairment of renal function of variable severity (peak plasma creatinine 1.3-12 mg/dl) and duration. While partial recovery of renal function occurred in all patients within few days, complete remission was observed only some months later. Three patients had IgA nephropathy (2 the primary form and 1 nephritis secondary to Schönlein-Henoch purpura), two patients had acute postinfectious glomerulonephritis, andtwo others had focal necrotizing (pauci-immune) glomerulonephritis. The glomerular changes seen in renal biopsy were not enough to explain per se the renal function impairment. Tubular changes, however, were severe and consisted of tubular necrosis, erythrocyte casts, erythrocyte phagocytosis by tubular cells, accompanied by interstitial damage (oedema, red-cell extravasation, and inflammatory infiltrates). Study of the renal biopsies by immunofluorescence revealed retrodiffusion of Tamm-Horsfall protein into the glomerular Bowman's space, a sign of obstructed tubular flow in any case. It is concluded that acute renal failure due to gross haematuria in glomerulonephritic patients may not occur only in IgA nephropathy, as reported so far, and is not associated with intratubular obstructio

Renal Disease in Essential Mixed Cryoglobulinaemia: LONG-TERM FOLLOW-UP OF 44 PATIENTS

The mode of presentation of renal disease in 44 patients with essential mixed cryoglobulinaemia (EMC) was: acute renal failure (two patients), acute nephritic syndrome (six patients), nephrotic syndrome (eight patients), proteinuria and/or haematuria (28 patients). Renal biopsy, performed in 35 patients, showed proliferative lesions in 33, while only minimal glomerular changes were seen in the remaining two. Immunofluorescence studies showed: IgG (85 per cent), IgA (36 per cent), IgM (90 per cent), C3 (90 per cent), Clq (47 per cent), and C4 (33 per cent) deposits, mainly located in subendothelial position. On electron microscopy, crystalloid structure of deposits and monocyte infiltration of capillary loops were the outstanding feature. The survival rate was 75 per cent at 10 years from the onset of clinical symptoms. Thirty-nine patients were followed for three to 146 months (mean 53·8). Twelve patients died, cardiovascular disease and infection being the commonest cause of death. Thirteen patients showed acute renal failure or acute nephritic syndrome: nine recovered completely, whereas the remaining four died during the acute renal episode. Three patients developed chronic renal failure, but only one required chronic dialysis. The ominous significance of renal impairment in EMC should therefore be revaluated. The high prevalence of hypertension (28/44 patients) which was refractory to treatment in six, may be important to the clinical outcom

The Eurotower Strikes Back

The 2008 global financial crisis came with fears—and, for some, hopes—that a new wave of public mobilization would emerge in industrialized countries. Especially throughout the European Union (EU), the epicenter of the crisis, large protests were expected. Yet, the energy with which social groups mobilized against the proposed austerity measures quickly fizzled. This article provides new evidence for why this was the case. In line with Neo-Keynesian theory, we argue that the interest rate adjustments and political announcements of the European Central Bank (ECB) limited the potential for mass unrest in the member states of the Economic and Monetary Union (EMU) affected by the crisis. We provide evidence for our argument with yearly panel data and a new original data set of monthly political protests between 2001 and 2013. Our analyses support the hypothesis that the ECB was able to successfully assuage dissatisfaction with the limited reform options of the Eurozone member states in the wake of the Eurocrisis

Phosphorylation-Independent Regulation of Atf1-Promoted Meiotic Recombination by Stress-Activated, p38 Kinase Spc1 of Fission Yeast

BACKGROUND:Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. METHODOLOGY/PRINCIPAL FINDINGS:We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. CONCLUSIONS/SIGNIFICANCE:The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1

Risk, responsibilities and rights: reassessing the ‘economic causes of crime’ thesis in a recession

This paper explores competing accounts of an apparent inversion of the previously-prevailing relationship between young people's unemployment and the incidence of youth offending at a time of economic recession. It begins by highlighting the faltering association between unemployment and offending, and considers the paradoxical implications for risk-based methodologies in youth justice practice. The paper then assesses explanations for the changing relationship that suggest that youth justice policies have successfully broken the unemployment-offending link; and alternatively that delayed effects of recession have yet to materialise, by reference to the work of four Inter-governmental organisations and to youth protests beyond the UK. In place of ever more intensive risk analyses, the paper then focusses on the adverse effects of unemployment on social cohesion, and proposes a rights-based approach to youth justice that recognises the growing disjuncture between the rights afforded to young people and the responsibilities expected of them

mTOR Controls Ovarian Follicle Growth by Regulating Granulosa Cell Proliferation

We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of the cell cycle. mTOR specific phosphorylation of p70S6 kinase and 4E-BP, and expression of Raptor are all enhanced during M-phase. The predominant effect of mTOR inhibition by the specific inhibitor Rapamycin (RAP) was a dose-responsive arrest in the G1 cell cycle stage. The fraction of granulosa cells that continued to divide in the presence of RAP exhibited a dose-dependent increase in aberrant mitotic figures known as anaphase bridges. Strikingly, estradiol consistently decreased the incidence of aberrant mitotic figures. In mice treated with RAP, the mitotic index was reduced compared to controls, and a similar increase in aberrant mitotic events was noted. RAP injected during a superovulation regime resulted in a dose-dependent reduction in the numbers of eggs ovulated. Implications for the real-time regulation of follicle growth and dominance, including the consequences of increased numbers of aneuploid granulosa cells, are discussed

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting