X-ray illumination of the ejecta of supernova 1987A.

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.

A population of mitochondrion-rich cells in the pars recta of mouse kidney.

Following perfusion of adult mouse kidney with a solution of nitroblue tetrazolium (NBT), certain epithelial cells in the pars recta (S3) segments of proximal tubules react to form cytoplasmic deposits of blue diformazan particles. Such cells are characterized by dark cytoplasm, small and often elliptical nuclei, elaborate, process-bearing profiles, and abundant mitochondria. The atypical epithelial cells display the additional characteristic of immunoreactivity for a wide spectrum of antigens, including mesenchymal proteins such as vimentin. Though present in kidneys of untreated or sham-operated animals, they are particularly evident under experimental conditions such as unilateral ureteral obstruction (UUO), appearing in both contralateral and obstructed kidneys over the course of a week's duration, but disappearing from the obstructed kidney as it undergoes the profound atrophy attributable to deterioration of the population of its proximal tubules. The cells do not appear in neonatal kidneys, even those undergoing UUO, but begin to be recognizable soon after weaning (28 days). It is possible that diformazan-positive cells in the mouse S3 tubular segment constitute a resident population of cells that can replenish or augment the tubule. Although somewhat similar cells, with dark cytoplasm and vimentin expression, have been described in human, rat, and transgenic mouse kidney (Smeets et al. in J Pathol 229: 645-659, 2013; Berger et al. in Proc Natl Acad Sci U S A 111: 1533-1538, 2014), those cells-known as "scattered tubule cells" or "proximal tubule rare cells"- differ from the S3-specific cells in that they are present throughout the entire proximal tubule, often lack a brush border, and have only a few mitochondria.

A relativistic type Ibc supernova without a detected gamma-ray burst.

Long duration gamma-ray bursts (GRBs) mark the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested in the pulse of gamma-rays and a long-lived radio afterglow. Until now, central-engine-driven supernovae have been discovered exclusively through their gamma-ray emission, yet it is expected that a larger population goes undetected because of limited satellite sensitivity or beaming of the collimated emission away from our line of sight. In this framework, the recovery of undetected GRBs may be possible through radio searches for type Ibc supernovae with relativistic outflows. Here we report the discovery of luminous radio emission from the seemingly ordinary type Ibc SN 2009bb, which requires a substantial relativistic outflow powered by a central engine. A comparison with our radio survey of type Ibc supernovae reveals that the fraction harbouring central engines is low, about one per cent, measured independently from, but consistent with, the inferred rate of nearby GRBs. Independently, a second mildly relativistic supernova has been reported.

A novel explosive process is required for the gamma-ray burst GRB 060614.

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

Relativistic ejecta from X-ray flash XRF 060218 and the rate of cosmic explosions.

Over the past decade, long-duration gamma-ray bursts (GRBs)--including the subclass of X-ray flashes (XRFs)--have been revealed to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 10(48) erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

The afterglow of GRB 050709 and the nature of the short-hard gamma-ray bursts.

The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates.

New imaging tools to measure nephron number in vivo: opportunities for developmental nephrology.

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Bacillus species at the Canberra Airport: A comparison of real-time polymerase chain reaction and massively parallel sequencing for identification.

Anthrax, caused by the Gram-positive, spore forming bacterium Bacillus anthracis, is a disease with naturally occurring outbreaks in many parts of the world, primarily in domestic and wild herbivores. Due to the movement of people and stock, B. anthracis could, however, be at transportation hubs including airports. The continuous threat to national and international security from a biological agent release, or hoax attack, is a very real concern. Sensitive, robust and rapid (hours-day) methods to identify biological agents, including B. anthracis, and distinguish pathogenic from non-pathogenic species, is an essential cornerstone to national security. The aim of this project was to determine the presence of Bacillus species at the Canberra Airport using two massively parallel sequencing (MPS) approaches and compare with previous results using real-time polymerase chain reaction (qPCR). Samples were collected daily for seven days each month from August 2011-July 2012 targeting movement of people, luggage and freight into and out of the Canberra Airport. Extracted DNA was analysed using qPCR specific for B. anthracis. A subset of samples was analysed using two MPS approaches. Approach one, using the Ion PGM™ (Thermo Fisher Scientific; TFS) and an in-house assay, targeted the two B. anthracis virulence plasmids (cya and capB genes) and a single conserved region of the 16S rRNA gene. Approach two, using the Ion S5™ (TFS) and the commercial Ion 16S™ Metagenomics Kit (TFS), targeted multiple regions within the bacterial 16S rRNA gene. Overall there was consistency between the two MPS approaches and between MPS and qPCR, however, MPS was more sensitive, particularly for plasmid detection. Whilst the broad-range 16S genomic target(s) used in both MPS approaches in this study was able to generate a metagenomic fingerprint of the bacterial community at the Canberra Airport, it could not resolve Bacillus species beyond the level of the Bacillus cereus group. The inclusion of B. anthracis virulence plasmid targets in the in-house assay did allow for the potential presumptive identifications of pathogenic species. No plasmid targets were in the Ion 16S™ Metagenomics Kit. This study shows the choice of target(s) is key in MPS assay development and should be carefully considered to ensure the assay is fit for purpose, whether as an initial screening (presumptive) or a more specific (but not entirely confirmatory) test. Identification approaches may also benefit from a combination of MPS and qPCR as each has benefits and limitations.

Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice.

A novel approach was employed to assess the contribution of the renin-angiotensin system (RAS) to obstructive nephropathy in neonatal mice having zero to four functional copies of the angiotensinogen gene (Agt). Two-day-old mice underwent unilateral ureteral obstruction (UUO) or sham operation; 28 days later, renal interstitial fibrosis and tubular atrophy were quantitated. In all Agt genotypes, UUO reduced ipsilateral renal mass and increased that of the opposite kidney. Renal interstitial collagen increased after UUO linearly with Agt expression, from a fractional area of 25% in zero-copy mice to 54% in two-copy mice. Renal expression of transforming growth factor-beta1 was increased by ipsilateral UUO in mice expressing Agt, but not in zero-copy mice. However, the prevalence of atrophic tubules due to UUO did not vary with Agt expression. Blood pressure was not different in all groups, except for a reduction in sham zero-copy mice. We conclude that a functional RAS is not necessary for compensatory renal growth. This study demonstrates conclusively that angiotensin regulates at least 50% of the renal interstitial fibrotic response in obstructive nephropathy, an effect independent of systemic hemodynamic changes. Angiotensin-induced fibrosis likely is a mechanism common to the progression of many forms of renal disease.

Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction.

Chronic unilateral ureteral obstruction (UUO) in newborn rats activates renin gene expression in the obstructed kidney, and increases renin distribution along afferent glomerular arterioles in both kidneys. To investigate the role of the renal nerves in this response, 2-d-old Sprague-Dawley rats were subjected to UUO or sham operation. Chemical sympathectomy was performed by injection of guanethidine, whereas, control groups received saline vehicle. At 4-5 wk, renal renin distribution was determined by immunocytochemistry, and renin mRNA levels were determined by Northern blot hybridization. Compared to the saline-treated rats with UUO, renin remained localized to the juxtaglomerular region in both kidneys of rats with UUO receiving guanethidine (P less than 0.05). Moreover, renin mRNA levels were eightfold lower in obstructed kidneys of rats receiving guanethidine than in those receiving saline. Additional groups of rats with UUO were subjected to unilateral mechanical renal denervation: renin gene expression in the obstructed kidney was suppressed by ipsilateral but not by contralateral renal denervation. These findings indicate that either chemical or mechanical denervation suppressed the increase in renin gene expression of the neonatal kidney with ipsilateral UUO. We conclude that the renal sympathetic nerves modulate renin gene expression in the developing kidney with chronic UUO.

Renin release and gene expression in intact rat kidney microvessels and single cells.

To investigate whether newborn kidney microvessels and isolated single microvascular cells have the capacity to release renin and/or alter the expression of the renin gene in response to adenylate cyclase stimulation, newborn kidney microvessels were isolated and purified (95%) using an iron perfusion/enzymatic digestion technique. Incubation of microvessels with either vehicle (control; C) or 10(-5) M forskolin (F) in media resulted in an increase in microvessel cAMP (0.67 +/- 0.13 vs. 22 +/- 4.6 pmol/min per mg protein) (P less than 0.005) and renin released into the culture media (1,026 +/- 98 vs. 1,552 +/- 159 pg angiotensin I/h per mg protein) (P = 0.008) (C vs. F). Renin mRNA levels in the newborn kidney microvessels increased 1.6-fold with forskolin treatment. Renin release by isolated, single microvascular cells (with or without forskolin) was assessed using the reverse hemolytic plaque assay. Forskolin administration resulted in an increase in the number of renin-secreting cells without changes in the amount of renin secreted by individual cells. In conclusion, newborn kidney microvessels and isolated renin-releasing microvascular cells possess a functionally active adenylate cyclase whose short-term stimulation results in accumulation of cAMP, a significant increase in renin release, and an enhancement of renin gene expression. The increase in renin release is due to recruitment of microvascular cells secreting renin. Recruitment of hormone-secreting cells in response to stimuli may prove to be a mechanism of general biological importance shared by many endocrine cell types.

Individualizing surgical treatment based on tumour response following neoadjuvant therapy in T4 primary rectal cancer.

BACKGROUND: Rectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b. METHODS: Patients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential resection margin, postoperative morbidity, definitive stoma formation, 3-years local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to both tumours' response and surgical procedures. RESULTS: Among 883 patients with rectal cancer, 101 were included. Responders had a higher rate of induction chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma formation were significantly higher in Non-responders. R0 was not impacted by either the tumour response or the surgical procedures. The 3y-LR was lower in Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02-2.59; p = 0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders, whereas no difference was found in Responders. The 3y-DFS was higher in Responders irrespective to the surgery (71% vs. 47%; p = 0.07). CONCLUSION: In Responders, TME or e-TME are technically and oncollogically feasible and should be considered in preferrence to b-TME. In Non-responders, allowing for high rates of morbidity and local recurrence in patients with e-TME, b-TME procedures should be preferred.

Specific incremental field test for aerobic fitness in tennis.

OBJECTIVES: To compare metabolic and cardiorespiratory responses between subjects undergoing incremental treadmill (non-specific) and tennis field based (sport specific) tests. METHODS: Nine junior competitive tennis players randomly performed two incremental protocols to exhaustion: a treadmill test (TT) and a tennis specific fitness test (FT). The FT consisted of repeated displacements replicating the game of tennis at increasing speed on a court. In both tests, ventilatory variables and heart rate (HR) were determined at the ventilatory threshold (VT), respiratory compensation point (RCP), and maximal loads (max). Blood lactate concentration was determined at the point of volitional fatigue. RESULTS: Percentage (mean (SD)) maximal HR (83.6 (5.1) v 83.0 (2.8) and 92.1 (2.1) v 92.3 (2.1)%, respectively) and percentage maximal oxygen uptake (VO2max) (69.4 (8.1) v 73.5 (6.1) and 84.4 (6.5) v 85.5 (8.7)%, respectively) at the VT and RCP were not different between the FT and TT subjects, whereas VO2max was higher in the FT than in the TT (63.8 (3.0) v 58.9 (5.3) ml/min/kg; p<0.05). Blood lactate concentration (10.7 (3.0) v 10.6 (4.3) mmol/l) did not differ between the TT and FT. CONCLUSIONS: Although cardiorespiratory variables were not different at submaximal intensities between the two tests, VO2max values derived from laboratory measurements were underestimated. Using field testing in addition to treadmill testing provides a better measurement of a player's individual fitness level and may be routinely used to accurately prescribe appropriate aerobic exercise training.

Temporary changes in populations of soil organisms after field application of entomopathogenic nematodes.

To assess the effect of an inundative release of entomopathogenic nematodes on soil organisms, population densities of soil-dwelling organisms were monitored before and after an application of an aqueous suspension of Heterorhabditis megidis to field plots in mown grassland (Exp. I) at a level of 0.38 million/m(2) and to plots (Exp. II) situated in a forested area, a grass sports field and an orchard at a level of 1.5 million/m(2). At the forested site, heat-killed H. megidis (1.5 million/m(2)) also were applied to two plots to compare the impact on soil organisms of a large introduction of living and dead nematodes. Post-treatment, temporary changes in natural population densities of several nematode genera and other organisms were detected in H. megidis-treated plots in both experiments. Temporary changes in the nematode trophic structure occurred in the percentages of nematode omnivores, herbivores and predators in both experiments. Evidence from all sites suggests that the changes were temporary and that the presence of decaying H. megidis following treatment contributed to nutrient enrichment of the soil and to direct and indirect effects on the nematode community.

Specific incremental test in elite squash players.

OBJECTIVES: To compare cardiorespiratory responses between incremental treadmill (non-specific) and field (sport specific) tests in elite squash players. METHODS: Seven elite players (ranked 1 to 25 in their national federation including the World number 1) randomly performed an incremental treadmill test (TT) and a squash specific graded test (ST) to exhaustion. The ST consisted of repeated displacements replicating the game of squash, at increasing speed on the court. In both tests, ventilatory variables and heart rate were determined at the ventilatory threshold, respiratory compensation point, and maximal loads (max). RESULTS: Heart rate and percentage maximal oxygen uptake (VO2MAX) at the ventilatory threshold and respiratory compensation point were not different between the ST and TT, whereas VO2MAX was higher in the ST than in the TT (63.6 (3.0) v 54.9 (2.5) ml/kg/min; p < 0.001). Time to exhaustion was not different between the ST and TT (1056 (180) v 962 (71) seconds) but correlated with the ranking of the players only in the ST (r = -0.96, p < 0.001). CONCLUSIONS: VO2MAX values derived from laboratory testing were not relevant for accurately estimating fitness in elite squash players. So the ST may be used as an additional test for determination of training intensity. Improved training advice for prescribing aerobic exercise or perfecting stroke technique may result from these results.

Fetal expression of the angiotensinogen gene.

To determine whether the angiotensinogen (Ao) gene is expressed in multiple organs of the fetal rat and the changes associated with maturation, fetal (15-20 days of gestation), newborn (1-10 days old), and adult (90 days old) rat tissues were subjected to Northern analysis and hybridization with a full length Ao complementary DNA (cDNA). Whereas Ao messenger RNA (mRNA) was undetectable in fetal livers, Ao sequences were readily detectable 1 h after birth and reached a peak at 24 h of birth. Levels remained elevated at 5 and 10 days after birth to decrease slightly at 90 days of postnatal life. Poly A+ enriched liver RNA was subjected to a similar analysis demonstrating that fetal liver Ao mRNA levels were 50-fold less than the corresponding adult levels. In contrast to the finding in the fetal liver, Ao mRNA was found in fetal brown fat, brains, and kidneys. We conclude that 1) Expression of the Ao gene is developmentally regulated in a tissue-specific manner; 2) Unlike the adult animal, the liver may not be the primary source of Ao in the fetus; 3) Alternate sources of Ao synthesis include fetal brown fat, brain, and kidneys.

Diuresis and natriuresis during continuous dopamine-1 receptor stimulation.

Stimulation of renal dopamine-1 (DA1) receptors for 3 hours produces an increase in renal plasma flow and sustained natriuresis. The present study was designed to assess the response of renal hemodynamic and tubular function to long-term DA1 receptor stimulation. Fenoldopam, a selective DA1 receptor agonist, was infused intravenously for 24 hours in 10 normal male subjects in metabolic balance at 150 mEq sodium and 60 mEq potassium intake in a single-blind, vehicle-controlled protocol. During DA1 receptor activation, urine flow rate and fractional excretion of sodium increased for the first 5 hours, 16.9 +/- 0.9 ml/min compared with a vehicle control value of 12.4 +/- 0.5 ml/min (p less than 0.001) and 2.0 +/- 0.1% compared with a vehicle control value of 1.1 +/- 0.1% (p less than 0.005), respectively. Urinary sodium excretion rose at 5 hours, 0.27 +/- 0.02 mEq/min compared with a vehicle control value of 0.14 +/- 0.01 mEq/min (p less than 0.01). Renal plasma flow increased during fenoldopam at 5 hours, 505 +/- 47 ml/min compared with a vehicle control value of 397 +/- 25 ml/min (p less than 0.01), and was sustained for 24 hours, 523 +/- 40 ml/min compared with 432 +/- 31 ml/min (p less than 0.05). The distal sodium load increased and the percentage of distal sodium reabsorption decreased during fenoldopam. Glomerular filtration rate, blood pressure, heart rate, plasma aldosterone concentration, plasma renin activity, and fractional excretion of potassium were unchanged. Selective DA1 receptor activation produced sustained 5-hour diuresis and 11-hour natriuresis without kaliuresis or a systemic hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans.

Dopamine-1 (DA1) receptors in the renal tubules may be involved in the regulation of sodium homeostasis. To test this hypothesis, fenoldopam, a selective DA1 agonist, was infused at 0.05 microgram/kg/min i.v. in 16 normal male subjects in metabolic balance at 300 or 10 meq sodium. Renal function studies were performed by standard p-aminohippurate, inulin, and lithium clearances for three periods: 1) precontrol (2 hours), 2) experimental (3 hours), and 3) postcontrol (2 hours). DA1 receptor stimulation in sodium-loaded individuals increased the following parameters during the experimental period: urine flow rate, from 12.5 +/- 0.4 to 15.5 +/- 0.5 ml/min (p less than 0.05); urinary sodium excretion, from 309 +/- 12 to 489 +/- 18 mu eq/min (p less than 0.001); renal plasma flow, from 631 +/- 19 to 717 +/- 21 ml/min (p less than 0.005); fractional sodium excretion, from 2.2 +/- 0.1% to 3.4 +/- 0.1% (p less than 0.001); fractional lithium excretion, from 26.2 +/- 0.7% to 32.1 +/- 0.8% (p less than 0.005); and distal sodium load, from 10.7 +/- 0.4 to 13.8 +/- 0.5 ml/min (p less than 0.05). The increase in fractional sodium excretion was greater than that of fractional lithium excretion (p less than 0.0001). Distal sodium reabsorption decreased from 78.3 +/- 0.8% to 73.2 +/- 1.1% but the change was not statistically significant. In contrast, sodium-depleted subjects exhibited no significant changes except in renal plasma flow, which rose from 550 +/- 13 to 625 +/- 17 ml/min (p less than 0.0001). Glomerular filtration rate remained unchanged through the entire study. These results indicate that diuretic and natriuretic responses are mediated by DA1 receptors at both proximal and distal tubular sites. Attenuation of the DA1 natriuretic response during sodium depletion suggests a direct inhibition of cellular DA1 mechanisms in the renal tubule or recruitment of nondopaminergic compensatory homeostatic mechanisms within the kidney.

Prognostic factors in neonatal acute renal failure.

Sixteen infants, 2 to 35 days of age, had acute renal failure, a diagnosis based on serum creatinine concentrations greater than 1.5 mg/dL for at least 24 hours. Eight infants were oliguric (urine flow less than 1.0 mL/kg/h) whereas the remainder were nonoliguric. To determine clinical parameters useful in prognosis, urine flow rate, duration of anuria, peak serum creatinine, urea (BUN) concentration, and nuclide uptake by scintigraphy were correlated with recovery. Nine infants had acute renal failure secondary to perinatal asphyxia, three had acute renal failure as a result of congenital cardiovascular disease, and four had major renal anomalies. Four oliguric patients died: three of renal failure and one of heart failure. All nonoliguric infants survived with mean follow-up serum creatinine concentration of 0.8 +/- 0.5 (SD) mg/dL whereas that of oliguric survivors was 0.6 +/- 0.3 mg/dL. Peak serum creatinine concentration did not differ between those patients who were dying and those recovering. All infants who were dying remained anuric at least four days and revealed no renal uptake of nuclide. Eleven survivors were anuric three days or less, and renal perfusion was detectable by scintigraphy in each case. However, the remaining survivor (with bilateral renal vein thrombosis) recovered after 15 days of anuria despite nonvisualization of kidneys by scintigraphy. In neonates with ischemic acute renal failure, lack of oliguria and the presence of identifiable renal uptake of nuclide suggest a favorable prognosis.

Pathophysiology of obstructive nephropathy in the newborn.

Congenital obstructive nephropathy is a consequence abnormal urinary tract development resulting in renal growth failure and injury manifested by progressive tubular atrophy and interstitial fibrosis. We have studied the renal cellular and physiological response to unilateral ureteral obstruction (UUO) in the neonatal rodent (guinea pig, rat, and mouse). Whereas in the adult, UUO stimulates renal cellular proliferation, UUO in the neonate reduces nephrogenesis, glomerular maturation, and tubular cellular proliferation. This is accompanied by a proportionately greater compensatory growth of the intact opposite kidney in the neonate. Impaired renal growth and tubular atrophy are likely owing at least in part to stimulation of renal tubular apoptosis. This, in turn, may result from a combination of factors, including loss of epithelial cell polarity, a reduction in the oncoprotein bcl-2 and epidermal growth factor (EGF), and increased expression of the fibrogenic cytokine, transforming growth factor-beta1 (TGF-beta1). Infusion of EGF stimulates cellular proliferation, suppresses apoptosis, and reduces tubular atrophy and interstitial fibrosis. TGF-beta1 is regulated by the renin-angiotensin system, which is markedly activated by UUO in the neonate. The functional consequences of obstructive nephropathy in early development are hyperfiltration by remaining nephrons, followed by progressive decrease in glomerular filtration rate that may only develop in later life. Improved management of congenital urinary tract obstruction will depend on a better understanding of the cellular mechanisms, which may lead to specific treatment using gene therapy or modulators of renal growth and development.