Left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular mortality in patients who have end-stage renal disease and are maintained on hemodialysis (HD), and LVH is not always ...correlated with the severity of hypertension in these patients. The purpose of this study was to investigate the role of other factors contributing to LVH.
A total of 50 patients with HD were classified in three groups according to whether their LV mass index (LVMI) was higher than (
n = 15), equal to (
n = 20), or lower than (
n = 15) that predicted by a formula based on their ambulatory blood pressure monitoring (ABPM).
Subjects with higher LVMI than predicted had significantly greater inter-HD weight gain (3.4 ± 0.8
v 2.7 ± 0.8 and 2.6 ± 05 kg, respectively, in the other two groups,
P < .05), and subjects with lower LVMI than predicted had a tendency toward a more pronounced nocturnal dipping pattern of BP (
P = .07
v the other two groups), although daytime and night-time average BP levels did not differ between groups. All other clinical and laboratory parameters were similar among the three groups except higher cardiac output and various indices of LVH, which were more pronounced in the group with higher LVMI by ABPM. This group had also the lowest survival rate over the 2 to 3 years of follow-up, with five deaths versus two in each of the other two groups.
The data suggest that correct management of inter-HD weight gain by nutritional counseling and shorter inter-HD intervals may prevent LVH and improve survival independently of BP control.
We present ROMA, a parallel code to produce joint optimal temperature and polarisation maps out of multidetector CMB observations. ROMA is a fast, accurate, and robust implementation of the iterative ...generalised least-squares approach to map-making. We benchmark ROMA on realistic simulated data from the last polarisation-sensitive flight of BOOMERanG.
We constrain the amplitude of primordial non-Gaussianity in the cosmic microwave background data taking into account the presence of foreground residuals in the maps. We generalize the needlet ...bispectrum estimator marginalizing over the amplitudes of thermal dust, free–free and synchrotron templates. We apply our procedure to Wilkinson Microwave Anisotropy Probe 5-year data, finding fNL= 38 ± 47 (1σ), while the analysis without marginalization provides fNL= 35 ± 42. Splitting the marginalization over each foreground separately, we found that the estimates of fNL are positively cross-correlated of 17 and 12 per cent with the dust and synchrotron, respectively, while a negative cross-correlation of about −10 per cent is found for the free–free component.
Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII ...receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT1) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-week-old angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT1 and type 2 AII (AT2) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.
The pathways downstream of ErbB-family proteins are very important in BC, especially when considering treatment with onco-protein inhibitors. We studied and implemented dynamic simulations of four ...downstream pathways and described the fragment of the signaling network we evaluated as a Molecular Interaction Map. Our simulations, enacted using Ordinary Differential Equations, involved 242 modified species and complexes, 279 reversible reactions and 111 catalytic reactions. Mutations within a single pathway tended to be mutually exclusive; only inhibitors acting at, or downstream (not upstream), of a given mutation were active. A double alteration along two distinct pathways required the inhibition of both pathways. We started an analysis of sensitivity/robustness of our network, and we systematically introduced several individual fluctuations of total concentrations of independent molecular species. Only very few cases showed significant sensitivity. We transduced the ErbB2 over-expressing BC line, BT474, with the HRAS (V12) mutant, then treated it with ErbB-family and phosphorylated MEK (MEKPP) inhibitors, Lapatinib and U0126, respectively. Experimental and simulation results were highly concordant, showing statistical significance for both pathways and for two respective endpoints, i.e. phosphorylated active forms of ERK and Akt, p one tailed = .0072 and = .0022, respectively. Working with a complex 39 basic species signaling network region, this technology facilitates both comprehension and effective, efficient and accurate modeling and data interpretation. Dynamic network simulations we performed proved to be both practical and valuable for a posteriori comprehension of biological networks and signaling, thereby greatly facilitating handling, and thus complete exploitation, of biological data.
Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe ...hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized.
The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed.
Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T p.E1835*, c.7084G>C p.A2343P and c.7093T>C p.W2346R, and four previously reported mutations: c.378C>A p.Y107*, c.886C>T p.R277*, c.1351C>T p.R432* and c.7007G>A p.R2317Q. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*.
In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.
•We report eight patients with hypothyroidism due to thyroglobulin gene mutations.•Molecular analysis reveals three novels and four previously reported mutations.•Aditionally, we analyze a total of 31 unrelated families studied in our laboratory.•33 of the 96 studied TG alleles were the p.R277*.•Our results confirm the genetic heterogeneity of thyroglobulin defects.
Making sky maps from Planck data Ashdown, M. A. J.; Baccigalupi, C.; Balbi, A. ...
Astronomy and astrophysics (Berlin),
05/2007, Letnik:
467, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Aims.We compare the performance of multiple codes written by different groups for making polarized maps from Planck-sized, all-sky cosmic microwave background (CMB) data. Three of the codes are based ...on a destriping algorithm; the other three are implementations of an optimal maximum-likelihood algorithm. Methods.Time-ordered data (TOD) were simulated using the Planck Level-S simulation pipeline. Several cases of temperature-only data were run to test that the codes could handle large datasets, and to explore effects such as the precision of the pointing data. Based on these preliminary results, TOD were generated for a set of four 217 GHz detectors (the minimum number required to produce I, Q, and U maps) under two different scanning strategies, with and without noise. Results.Following correction of various problems revealed by the early simulation, all codes were able to handle the large data volume that Planck will produce. Differences in maps produced are small but noticeable; differences in computing resources are large.
Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the ...renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, i.m., twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, i.m., twice a day for 9 days, and 14 with 0.15 M NaCl , i.m., twice a day for 9 days and PDTC, 50 mg kg(-1) day(-1), i.p., twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm2. Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.
Gaussianity of the cosmological perturbations is one of the key predictions of standard inflation, but it is violated by other models of structure formation such as cosmic defects. We present the ...first test of the Gaussianity of the cosmic microwave background (CMB) on subdegree angular scales, where deviations from Gaussianity are most likely to occur. We apply the methods of moments, cumulants, the Kolmogorov test, the chi(2) test, and Minkowski functionals in eigen, real, Wiener-filtered, and signal-whitened spaces, to the MAXIMA-1 CMB anisotropy data. We find that the data, which probe angular scales between 10 arcmin and 5 deg, are consistent with Gaussianity. These results show consistency with the standard inflation and place constraints on the existence of cosmic defects.
We use the measurement of the cosmic microwave background taken during the MAXIMA-1 flight to estimate the bispectrum of cosmological perturbations. We propose an estimator for the bispectrum that is ...appropriate in the flat sky approximation, apply it to the MAXIMA-1 data, and evaluate errors using bootstrap methods. We compare the estimated value with what would be expected if the sky signal were Gaussian and find that it is indeed consistent, with a chi(2) per degree of freedom of approximately unity. This measurement places constraints on models of inflation.
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