bluuebunny/crossref_metadata_2025 huggingface dataset:
Interface effect on thermal conductivity of carbon nanotube composites
Authors: Nan Ce-Wen , Liu Gang , Lin Yuanhua , Li Ming
Published: October 2004

A simple formula for the thermal conductivity enhancement in carbon nanotube composites is presented by incorporating the interface thermal resistance with an effective medium approach. This model well describes the thermal conductivity enhancement observed recently in nanotube suspensions. In particular, this simple formula predicts that a large interface thermal resistance across the nanotube-matrix interface causes a significant degradation in the thermal conductivity enhancement, even for the case with ultrahigh intrinsic thermal conductivity and aspect ratio of the carbon nanotubes embedded.
Hysteretic behavior of the charge injection in single silicon nanoparticles
Authors: Diesinger H. , Mélin T. , Deresmes D. , Stiévenard D. , Baron T.
Published: October 2004

Charge injection in individual silicon nanoparticles has been investigated by electric force microscopy (EFM). Stored charges injected from the EFM tip have been counted using a quantitative method. Injection kinetics reveals the setting-up of an equilibrium regime. Equilibrium charge–voltage characteristics are analyzed, and display an overall linear behavior corresponding to successive tunneling through the nonequivalent tip–nanoparticle and nanoparticle–substrate oxide barriers. A hysteretic behavior is observed in the equilibrium charge–voltage characteristics, and attributed to a secondary charge injection process associated with the nanoparticle oxide surface.
Conversion of localized lower hybrid oscillations and fast magnetosonic waves at a plasma density cavity
Authors: Hall J. O.
Published: October 2004

Analytic expressions are presented for conversion of localized lower hybrid oscillations and magnetosonic waves by scattering off a small scale density cavity. The governing equations are solved in slab geometry with wave vectors perpendicular to both the ambient magnetic field and the density gradient associated with density cavity using a scale length separation method. The theory predicts strong excitation of localized lower hybrid oscillations for a set of frequencies between the lower hybrid frequency of the ambient plasma and the minimum lower hybrid frequency inside the cavity. The theory is relevant for the lower hybrid solitary structures observed in space plasmas.
Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes
Authors: Wang Jen-Chywan , Derynck Mika Kakefuda , Nonaka Daisuke F. , Khodabakhsh Daniel B. , Haqq Chris , Yamamoto Keith R.
Published: October 2004

The global physiological effects of glucocorticoids are well established, and the framework of transcriptional regulation by the glucocorticoid receptor (GR) has been described. However, the genes directly under GR control that trigger these physiological effects are largely unknown. To address this issue in a single cell type, we identified glucocorticoid-responsive genes in A549 human lung adenocarcinoma cells by microarray analysis and quantitative real-time PCR. Reduction of GR expression by RNA interference diminished the effects of dexamethasone on all tested target genes, thus confirming the essential role of GR in glucocorticoid-regulated gene expression. To identify primary GR target genes, in which GR is a component of the transciptional regulatory complex, we developed a strategy that uses chromatin immunoprecipitation to scan putative regulatory regions of target genes for sites occupied by specifically bound GR. We screened 11 glucocorticoid-regulated genes, and we identified GR-binding regions for eight of them (five induced and three repressed). Thus, our approach provides a means for rapid identification of primary GR target genes and glucocorticoid-response elements, which will facilitate analyses of transcriptional regulatory mechanisms and determination of hormone-regulated gene networks.
Immunoglobulin Class Switch Recombination Is Impaired in Atm-deficient Mice
Authors: Lumsden Joanne M. , McCarty Thomas , Petiniot Lisa K. , Shen Rhuna , Barlow Carrolee , Wynn Thomas A. , Morse Herbert C. , Gearhart Patricia J. , Wynshaw-Boris Anthony , Max Edward E. , Hodes Richard J.
Published: October 2004

Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell–dependent antigen (Ag), Atm−/− mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm+/+ controls. To determine whether Atm−/− B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm−/− cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm−/− B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm−/− B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm−/− B cells occurs at the level of genomic DNA recombination as measured by digestion–circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the μ–γ1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR.
Shopping American-Style: The Arrival of the Supermarket in Postwar Italy
Authors: Scarpellini Emanuela
Published: October 2004

This article presents a case study of the establishment of the first Italian supermarket in 1957, carried out by an American industrial group called the International Basic Economy Corporation (IBEC). It raises the question of the export of a model born in the United States in a far different economic and political context. It was necessary to transform the technical and structural aspects of the supermarket as an institution to adapt to Italian society. This article also analyzes how other serious problems, deriving from the particular political and juridical situation of Italy, were confronted. In the end, the Italian supermarket was fundamentally different from the original model.
Prevalence of Low Glomerular Filtration Rate in Nondiabetic Americans
Authors: Clase Catherine M. , Garg Amit X. , Kiberd Bryce A.
Published: October 2004

End-stage renal disease is an important and costly health problem. Strategies for its prevention are urgently needed. Knowledge of the population-based prevalence of renal insufficiency in nondiabetic adults would inform such strategies. Black and white nondiabetic adult participants in the Third National Health and Nutrition Examination Survey were analyzed. The analysis was stratified by age, gender, and race, and four clinically applicable methods were used to assess renal function. There were 13,251 complete records for analysis. By the Modification of Diet in Renal Diseases (MDRD) GFR (GFR) prediction Equation 7, 58% (95% confidence interval [CI], 56 to 60%) of the total adult nondiabetic black and white US population had MDRD GFR below 80 ml/min per 1.73m2, 13% (95% CI, 11 to 14%) below 60 ml/min per 1.73m2, and 0.26% (95% CI, 0.19 to 0.33%) below 30 ml/min per 1.73m2. By the Cockcroft-Gault formula, the equivalent figures were 39% (95% CI, 37 to 41%), 14% (95% CI, 12% - 16%), and 0.81% (95% CI, 0.46 to 1.2%), respectively. The findings of an unexpectedly high prevalence of low clearance and the increased prevalence of low clearance with age were consistent across the four clearance estimation methods used and for each race-sex stratum. The absolute magnitude of the prevalence of low clearance was, however, dependent on the clearance method used. Assessed by estimation from serum creatinine, low clearance may be very common, particularly with advancing age. The prognosis (in terms of risk for progression and end-stage renal disease) of low clearance in unreferred populations may differ from that in referred populations and requires further study.
Vasodilatory N-Methyl-D-Aspartate Receptors Are Constitutively Expressed in Rat Kidney
Authors: Deng Aihua , Valdivielso Jose M. , Munger Karen A. , Blantz Roland C. , Thomson Scott C.
Published: October 2004

N-methyl-D-aspartate receptor (NMDA-R) is an amino acid receptor and membrane calcium channel. NMDA-R is activated by binding of coagonists, L-glutamine and L-glycine. In the brain, calcium entry via NMDA-R activates type I nitric oxide synthase (NOS I). The kidney also contains NOS I and vasodilates in response to L-glycine. In this study, NMDA-R mRNA was demonstrated in rat kidney cortex by reverse transcriptase–PCR and cDNA sequencing. NMDA-R protein was demonstrated in kidney cortex by immunoblotting. To study the functional role of renal NMDA-R, renal hemodynamic effects of NMDA-R inhibition were assessed in rats using a blocker of the NMDA calcium channel (75 mg/kg MK-801 intraperitoneally) or an inhibitor of glycine binding to NMDA-R (30 mg/kg 5,7-dichlorokynurenic acid intraperitoneally). Renal blood flow was measured by perivascular pulse Doppler. GFR was measured by 3H-inulin clearance. Measurements were made before and during glycine infusion. Both NMDA-R antagonists caused renal vasoconstriction and attenuated the renal vasodilatory response to glycine infusion. These effects were not mediated by the renal nerves. The glycine response was not inhibited by aortic snare used to mimic the effects of NMDA-R inhibitors on basal renal blood flow. NMDA-R are expressed in kidney cortex, where they exert a tonic vasodilatory influence and may account for the vasodilatory response to glycine infusion.
Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla
Authors: Castrop Hayo , Vitzthum Helga , Schumacher Karl , Schweda Frank , Kurtz Armin
Published: October 2004

It is well known that loop diuretics enhance the renal excretion of prostanoids; therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA expression unaltered there. In the outer medulla, furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. The downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E2 (PGE2) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/kg; therefore, further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE2 content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE2 under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE2 concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.
N-Linked Glycosylation Is Critical for the Plasma Membrane Localization of Nephrin
Authors: Yan Kunimasa , Khoshnoodi Jamshid , Ruotsalainen Vesa , Tryggvason Karl
Published: October 2004

The expression pattern, subcellular localization, and the role of glycosylation of the human nephrin was examined in transfected cells. Stable cell lines, constitutively expressing a full-length human nephrin cDNA construct, were generated from transfected immortalized mouse podocytes (IMP) and a human embryonic kidney cell line (HEK-293). Immunofluorescence confocal microscopy of transfected cells showed plasma membrane localization of the recombinant nephrin. Immunoblotting showed that the recombinant nephrin expressed in transfected cell lines migrated as a double band with a molecular weight of 185 kD. When cells were treated with the N-glycosylation inhibitor, tunicamycin, the molecular weight of nephrin was decreased to a single immunoband of 150 kD, indicating that the shift in the electrophoretic migration of nephrin is due to N-linked carbohydrate moieties. It was further shown that this glycosylation process is highly sensitive to inhibition by tunicamycin, which is a naturally occurring antibiotic, leading to retention of nonglycosylated nephrin molecules in the endoplasmic reticulum. It was concluded that N-glycosylation of nephrin is crucial for its proper folding and thereby plasma membrane localization; therefore, inhibition of this process might be an important factor in the onset of pathogenesis of some acquired glomerular diseases.
Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy
Authors: Smak Gregoor Peter J. H. , de Sévaux Ruud G. L. , Ligtenberg Gerry , Hoitsma Andries J. , Hené Ronald J. , Weimar Willem , Hilbrands Luuk B. , van Gelder Teun
Published: October 2004

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.
Riboflavin Is a Determinant of Total Homocysteine Plasma Concentrations in End-Stage Renal Disease Patients
Authors: Skoupy Sonja , Fo[Combining Diaeresis]dinger Manuela , Veitl Mario , Perschl Agnes , Puttinger Heidi , Ro[Combining Diaeresis]hrer Claudia , Schindler Karin , Vychytil Andreas , Ho[Combining Diaeresis]rl Walter H. , Sunder-Plassmann Gere
Published: October 2004

The effect of thiamine (vitamin B1) or riboflavin (vitamin B2) availability on fasting total homocysteine (tHcy) plasma levels in end-stage renal disease patients is unknown. A cross-sectional study was performed in a population of non–vitamin supplemented patients maintained on continuous ambulatory peritoneal dialysis. Red blood cell availability of thiamine (α-ETK) and of riboflavin (α-EGR), along with other predictors of tHcy plasma levels, was considered in the analysis. There was a linear association of α-EGR with tHcy plasma concentrations (P = 0.009), which was not observed for α-ETK. Among red blood cell vitamins, α-EGR was the only predictor of tHcy levels (P = 0.035), whereas α-ETK, red blood cell pyridoxal-5-phosphate supply (α-EGOT) and red blood cell folate levels had no effect. The risk for having a high tHcy plasma levels within the fourth quartile (plasma tHcy >38.3 μmol/L) was increased by an α-EGR > median (odds ratio, 4.706; 95% confidence interval, 1.124 to 19.704; P = 0.026). By way of contrast, α-ETK had no effect in these analyses. Independent predictors of tHcy plasma levels were serum albumin, α-EGR, red blood cell folate, and certain MTHFR genotypes. A logistic regression analysis showed that the MTHFR genotype is a predictor for having a tHcy plasma concentration within the fourth quartile. In summary, riboflavin availability, as measured by α-EGR, is a determinant of fasting tHcy plasma levels in peritoneal dialysis patients. This finding may have implications for tHcy lowering therapy in individuals with end-stage renal disease.
Sgk1 Gene Expression in Kidney and Its Regulation by Aldosterone
Authors: Hou Jianghui , Speirs Helen J. L. , Seckl Jonathan R. , Brown Roger W.
Published: October 2004

The serine-threonine kinase sgk1 was recently identified as a gene rapidly induced by mineralocorticoids, resulting in increased sodium transport in vitro. To carefully localize and quantify the renal sgk1 expression response to aldosterone, in situ hybridization was performed on kidneys of mice having aldosterone excess over a range of doses and durations. In control and adrenalectomized animals, the glomeruli and inner medullary collecting ducts were the major sites of sgk1 expression, which was maintained independent of aldosterone. Sgk1 upregulation induced by aldosterone excess exhibited spatio-temporal heterogeneity. Both acute (3-h) and chronic (6-d) aldosterone excess stimulated sgk1 expression in the distal nephron, i.e., from the distal convoluted tubules through to the outer medullary collecting ducts. Treatments for 6 d with low sodium diet (0.03% [I]) and aldosterone infusions (50 μg/kg per d [II], 150 μg/kg per d [III], and 750 μg/kg per d [IV]) generated elevation of circulating aldosterone. Across these treatments (I through IV), the circulating level correlated with the progressive induction of sgk1 expression, with highly stimulated tubules first appearing in cortex (I) and continuing downward (II) until there was a strong stimulation throughout outer medulla (III and IV). Interestingly, chronic but not acute aldosterone excess caused a slight increase of sgk1 expression in glomerulus (30 to 50%; P < 0.01) and a dramatic downregulation in the initial portion of inner medulla, which could result from diminished interstitial osmolarity. Relative quantification (versus control) of sgk1 upregulation in individual tubules revealed: (1) a 1.8-fold increase of sgk1 mRNA at 3 h (150 μg/kg injection) and (2) a dose-dependence of chronic upregulation reaching a ceiling of eightfold elevation.
Henoch-Scho[Combining Diaeresis]nlein Purpura in Adults
Authors: Pillebout Evangéline , Thervet Eric , Hill Gary , Alberti Corinne , Vanhille Philippe , Nochy Dominique
Published: October 2004

Henoch-Scho[Combining Diaeresis]nlein Purpura nephritis (HSPN) has been extensively studied in children but, its natural history in adults is much less known. A cohort of 250 adults suffering HSP was retrospectively analyzed for a median follow-up period of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain. At presentation, palpable purpura was present in 96% of patients, and arthritis was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent of the patients showed renal insufficiency (Creatinine clearance [CrCl] <50 ml/min), usually associated with proteinuria (99%) and/or hematuria (93%). Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy (61%). At the end of follow-up, patient survival was only 74%. The first cause of death was carcinoma (most of them of respiratory or digestive tract). Regarding renal function, 11% of patients reached end-stage renal failure, 13% exhibited severe renal failure (CrCl <30 ml/min), and 14% moderate renal insufficiency (CrCl <50 ml/min). Clinical remission defined as the absence of proteinuria, hematuria, and a normal renal function was achieved in only 20%. This is a retrospective study; therefore, it is not possible to demonstrate any steroid and/or cyclophosphamide efficacy in diminishing the incidence of renal insufficiency. Multivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence of glomeruli with fibrinoid necrosis were associated with a poor renal prognosis. The data indicate that clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children. Identification of clinical and histologic prognostic factors may permit the design of appropriate therapeutic prospective studies.
Comparison of Arteriovenous Grafts in the Thigh and Upper Extremities in Hemodialysis Patients
Authors: Miller Christopher D. , Robbin Michelle L. , Barker Jill , Allon Michael
Published: October 2004

Placement of a thigh graft is an option in hemodialysis patients who have exhausted all upper extremity sites for permanent vascular access. The outcome of thigh grafts has been reported only in retrospective studies. The outcomes of 409 grafts placed at a single institution during a 3.5-yr period were evaluated prospectively, including 63 thigh grafts (15% of the total). Information was recorded on surgical complications, dates of radiologic and surgical interventions, and date of graft failure. The technical failure rate was approximately twice as high for thigh grafts, as compared with upper extremity grafts (12.7 versus 5.8%; P = 0.046). Intervention-free survival was similar for thigh and upper extremity grafts (median, 3.9 versus 3.5 mo; P = 0.55). Thrombosis-free survival was also comparable for thigh and upper extremity grafts (median, 5.7 versus 5.5 mo; P = 0.94). Cumulative survival (time to permanent failure) was similar for thigh and upper extremity grafts (median, 14.8 versus 20.8 mo; P = 0.62). When technical failures were excluded, the median cumulative survival was 27.6 mo for thigh grafts and 22.5 mo for upper extremity grafts (P = 0.72). The frequency of angioplasty (0.28 versus 0.57 per year), thrombectomy (1.58 versus 0.94 per year), surgical revision (0.28 versus 0.18 per year), and total intervention rate (2.15 versus 1.70 per year) was similar between thigh and upper extremity grafts. Access loss as a result of infection tended to be higher for thigh grafts than for upper extremity grafts (11.1 versus 5.2%; P = 0.07). In conclusion, placement of thigh grafts should be considered a viable option among hemodialysis patients who have exhausted all options for a permanent vascular access in both upper extremities. E-mail mdallon@uab.edu
Intrinsic Renal Cell Expression of CD40 Directs Th1 Effectors Inducing Experimental Crescentic Glomerulonephritis
Authors: Ruth Amanda-Jane , Kitching A. Richard , Semple Timothy J. , Tipping Peter G. , Holdsworth Stephen R.
Published: October 2004

Evidence suggests that human and experimental crescentic GN results from Th1-predominant immunity to glomerular antigens. CD40/CD154 signaling plays a key role in initiating Th1 responses and may direct Th1 effector responses. The role of CD40 in the development of GN was assessed in murine experimental anti-glomerular basement membrane GN. In this model, C57BL/6 wild-type (WT) mice sensitized to sheep globulin develop crescentic GN resulting from Th1 effector responses when challenged with sheep globulin planted in glomeruli. CD40−/− mice do not develop immunity in response to sheep globulin and thus fail to develop effector responses or significant GN. CD40 is expressed in nephritic glomeruli, suggesting a potential role for intrarenal CD40-CD154 interactions in injurious effector responses. Immune neutralization of the CD40 ligand (CD154) at the time of challenge significantly reduced accumulation of Th1 effectors and injury. The role of CD40 expression by renal cells was assessed by comparing GN in WT→CD40−/− chimeras (absent renal but intact bone marrow CD40) and sham chimeric mice (WT→WT). Both groups developed strong antigen-specific immune responses (antibody and IFN-γ production). However, WT→CD40−/− chimeras demonstrated reduced renal monocyte chemotactic protein 1 and IFN-inducible protein 10 mRNA levels and minimal T cell and macrophage influx and were protected from renal injury. Sham chimeric mice developed reduced GFR, with prominent renal expression of monocyte chemotactic protein 1 and IFN-inducible protein 10 mRNA and effector cell accumulation. In conclusion, the expression of CD40 by nonimmune renal cells plays a major role in Th1 effector responses by inducing Th1 chemokine production. Therefore, CD40-CD154 interactions are a potential therapeutic target in GN. E-mail: Stephen.Holdsworth@med.monash.edu.au
Hemodialysis and Peritoneal Dialysis
Authors: Termorshuizen Fabian , Korevaar Johanna C. , Dekker Friedo W. , van Manen Jeannette G. , Boeschoten Elisabeth W. , Krediet Raymond T.
Published: October 2004

Various studies indicate that fair comparisons of mortality rates between hemodialysis (HD) patients and peritoneal dialysis (PD) patients are difficult because of differences in patient characteristics, because of nonconstant relative risks of death (RR), and because the survival times of patients who switch treatment modalities can be censored in different ways. The differences in mortality rates between HD and PD patients were investigated in an analysis in which these potential sources of bias were taken into account. The Netherlands Cooperative Study on the Adequacy of Dialysis is a multicenter, prospective, observational, cohort study in which new patients with ESRD are monitored until transplantation or death. A multivariate Cox regression analysis was used to analyze the mortality data according to treatment modality (HD, n = 742; PD, n = 480). No statistically significant differences in adjusted mortality rates between HD and PD patients were observed during the first 2 yr of dialysis. In the years thereafter, increases in mortality rates for PD patients and resulting decreases in RR in favor of HD were observed (e.g., months 24 to 36, adjusted RR, 0.53; 95% confidence interval, 0.31 to 0.91). This tendency was observed especially among patients ≥60 yr of age and was not influenced by the censoring strategy. These results suggest that long-term use of PD, especially among elderly patients, is associated with increases in mortality rates. Further analyses are required to determine the potential role of dialysis adequacy in the observed long-term differences in mortality rates between HD and PD patients and to establish the possible survival benefits for PD patients who switch to HD in time. E-mail: FTermorshuizen@cs.com
Targeting of the VHL-Hypoxia-Inducible Factor-Hypoxia-Induced Gene Pathway for Renal Cell Carcinoma Therapy
Authors: Sosman Jeffrey A.
Published: October 2004

Treatment of advanced renal cancer has made little progress in the past 30 yr. Most clinical efforts have incorporated cytokine-based therapy. The presumption has been that the cytokines may trigger a host immune response against the renal cancer. Only IFN-α and high-dose IL-2 seemed to have positive effects on patient outcomes. IFN has prolonged the lives of patients by a few months, and high-dose IL-2 is capable of inducing very prolonged remissions (>5 yr) for a small number of patients. Nephrectomy in the presence of metastatic disease has been established as an effective procedure for select patients, providing palliation and prolonging survival. Finally, enthusiasm has focused on the use of nonmyeloablative allogeneic stem cell transplantation and donor leukocyte infusion for the induction of graft versus tumor effects. Early results are both provocative and promising. A number of agents that target the critical gene products downstream from pVHL and hypoxia-inducible factor-1, such as vascular endothelial growth factor, PDGF, EGF receptor, and TGF-α, have recently become available. The new agents are capable of inhibiting specific cellular targets, and the biologic characteristics of clear cell carcinoma of the kidney support their application. If the correct targets are carefully selected for inhibition in tumors in which the targets are present (clear cell histologic features and loss of VHL expression), then results should resemble those others have observed with targeted therapy, such as the use of STI-571 (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors or anti-HER2/neu (Herceptin; Genentech, South San Francisco, CA) for treatment of breast cancer. E-mail: jeff.sosman@vanderbilt.edu
Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase
Authors: Kitiyakara Chagriya , Chabrashvili Tina , Chen Yifan , Blau Jonathan , Karber Alex , Aslam Shakil , Welch William J. , Wilcox Christopher S.
Published: October 2004

The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF2α and malonyldialdehyde were measured in groups (n = 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH- and NADH-stimulated superoxide anion (O2
·−) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally two- to threefold with salt intake (P < 0.001), whereas prostaglandin E2 was unchanged. Renal cortical NADH- and NADPH-stimulable O2
·− generation increased (P < 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P < 0.005) increased renal cortical mRNA expression of gp91phox and p47phox and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91phox and p47phox and decreased IC- and Mn-SOD. Thus, salt intake enhances generation of O2
·− accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn-SOD. E-mail: wilcoxch@georgetown.edu
Survival of Functionally Anuric Patients on Automated Peritoneal Dialysis
Authors: Brown Edwina A. , Davies Simon J. , Rutherford Peter , Meeus Frederique , Borras Mercedes , Riegel Werner , Divino Filho Jose C. , Vonesh Edward , Van Bree Monique
Published: October 2004

The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) ≥60 L/wk per 1.73 m2 and ultrafiltration (UF) ≥750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006), nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival. E-mail: e.a.brown@imperial.ac.uk
Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis
Authors: Lods Nadège , Ferrari Paolo , Frey Felix J. , Kappeler Andreas , Berthier Celine , Vogt Bruno , Marti Hans-Peter
Published: October 2004

Equivalent long-term effects on the kidney are attributed to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB). Nevertheless, it is unknown to which degree effects of these compounds on individual inflammatory mediators, including matrix metalloproteinases (MMP), are comparable. On the basis of structural and functional differences, it was hypothesized that ACEI and ARB differentially regulate MMP activity. In a randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20 mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten hypertensive patients with glomerulonephritis and normal or mildly reduced creatinine clearance were studied. MMP activity and tissue inhibitors of metalloproteinase (TIMP) levels were analyzed in serum and urine: without therapy, with ACEI, with ARB, and with both agents combined. Treatment periods continued for 6 wk separated by periods of 4 wk each without therapy. Untreated patients with glomerulonephritis displayed distinctively higher serum levels of MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9 in urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation. In patients with glomerulonephritis, ACEI significantly reduced overall MMP serum activity to 25%, whereas ARB did not show any effect. Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI and ARB differentially regulate MMP activity, which may ultimately have consequences in certain types of MMP-dependent glomerulonephritis. E-mail: hpmarti@bluewin.ch
The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing
Authors: Kaelin William G.
Published: October 2004

Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer and, perhaps more important, on how mammalian cells sense and respond to changes in oxygen availability. This knowledge is already translating into new therapeutic targets for kidney cancer as well as for multiple conditions, such as myocardial infarction and stroke, in which ischemia plays a pathogenic role. This review summarizes the current knowledge of the molecular pathogenesis of von Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney cancer and the mammalian oxygen sensing pathway. E-mail: william_kaelin@dfci.harvard.edu
Nomogram for Predicting the Likelihood of Delayed Graft Function in Adult Cadaveric Renal Transplant Recipients
Authors: Irish William D. , McCollum David A. , Tesi Raymond J. , Owen Art B. , Brennan Daniel C. , Bailly Jane E. , Schnitzler Mark A.
Published: October 2004

Delayed graft function (DGF) is the need for dialysis in the first week after transplantation. Studied were risk factors for DGF in adult (age ≥16 yr) cadaveric renal transplant recipients by means of a multivariable modeling procedure. Only donor and recipient factors known before transplantation were chosen so that the probabilities of DGF could be calculated before transplantation and appropriate preventative measures taken. Data on 19,706 recipients of cadaveric allografts were obtained from the United States Renal Data System registry (1995 to 1998). Graft losses within the first 24 h after surgery were excluded from the analysis (n = 89). Patients whose DGF information was missing or unknown (n = 2820) and patients missing one or more candidate predictors (n = 2951) were also excluded. By means of a multivariable logistic regression analysis, factors contributing to DGF in the remaining 13,846 patients were identified. After validating the logistic regression model, a nomogram was developed as a tool for identifying patients at risk for DGF. The incidence of DGF was 23.7%. Sixteen independent donor or recipient risk factors were found to predict DGF. A nomogram quantifying the relative contribution of each risk factor was created. This index can be used to calculate the risk of DGF for an individual by adding the points associated with each risk factor. The nomogram provides a useful tool for developing a pretransplantation index of the likelihood of DGF occurrence. With this index in hand, better informed treatment and allocation decisions can be made. E-mail: wirish@rti.org
Localization and Regulation of the Epithelial Ca2+ Channel TRPV6 in the Kidney
Authors: Nijenhuis Tom , Hoenderop Joost G. J. , van der Kemp Annemiete W. C. M. , Bindels René J. M.
Published: October 2004

The family of epithelial Ca2+ channels consists of two highly homologues members, TRPV5 and TRPV6, which constitute the apical Ca2+ entry mechanism in active Ca2+ (re)absorption in kidney and small intestine. In kidney, TRPV5 expression has been extensively studied, whereas TRPV6 localization and regulation has been largely confined to the small intestine. The present study investigated the renal distribution of TRPV6 and regulation by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In mouse kidney, TRPV6 was detected by immunohistochemistry at the apical domain of the distal convoluted tubules (DCT2), connecting tubules (CNT), and cortical and medullary collecting ducts (CD). Furthermore, several putative vitamin D-responsive elements were detected upstream of the mouse TRPV6 start codon, and 1,25(OH)2D3 treatment significantly increased renal TRPV6 mRNA and protein expression. In DCT2 and CNT, TRPV6 co-localizes with the other known Ca2+ transport proteins, including TRPV5 and calbindin-D28K. Together, these data suggest a role for TRPV6 in 1,25(OH)2D3-stimulated Ca2+ reabsorption in these segments. Interestingly, distribution of TRPV6 extended to the CD, where it localized to the apical domain of principal and intercalated cells, which are not generally implicated in active Ca2+ reabsorption. In addition, TRPV6 mRNA levels were quantified in a large set of tissues, and in the order of decreasing expression level were detected: prostate > stomach, brain > lung > duodenum, kidney, bone, cecum, heart > colon > skeletal muscle > pancreas. Therefore, additional physiologic functions for TRPV6 are feasible. In conclusion, TRPV6 is expressed along the apical domain of DCT2, CNT, and CD, where TRPV6 expression is positively regulated by 1,25(OH)2D3. E-mail: r.bindels@ncmls.kun.nl
Ureteric Bud Apoptosis and Renal Hypoplasia in Transgenic PAX2-Bax Fetal Mice Mimics the Renal-Coloboma Syndrome
Authors: Dziarmaga Alison , Clark Patsy , Stayner Cherie , Julien Jean Pierre , Torban Elena , Goodyer Paul , Eccles Michael
Published: October 2004

In humans, PAX2 haploinsufficiency causes renal-coloboma syndrome (RCS) involving eye abnormalities, renal hypoplasia, and renal failure in early life. The authors previously showed that heterozygous mutant Pax2 mice have smaller kidneys with fewer nephrons, associated with elevated apoptosis in the ureteric bud (UB). However, PAX2 may have a variety of developmental functions such as effects on cell fate and differentiation. To determine whether apoptosis alone is sufficient to cause a UB branching deficit, the authors targeted a pro-apoptotic gene (Baxα) to the embryonic kidney under the control of human PAX2 regulatory elements. The exogenous PAX2 promoter directed Baxα gene expression specifically to the developing kidney UB, eye, and mid/hindbrain. At E15.5 PAX2Promoter-Baxα fetal mice exhibited renal hypoplasia, elevated UB apoptosis, and retinal defects, mimicking the phenotype observed in RCS. The kidneys of E15.5 PAX2Promoter-Baxα fetal mice were 55% smaller than those of wild-type fetal mice, and they contained 70% of the normal level of UB branching. The data indicate that loss of Pax2 anti-apoptotic activity is sufficient to account for the reduced UB branching observed in RCS and suggest that elevated UB apoptosis may be a key process responsible for renal hypoplasia. The authors propose a morphogenic unit model in which cell survival influences the rate of UB branching and determines final nephron endowment. E-mail: meccles@otago.ac.nz
Differential Usage of Class II Transactivator Promoters PI and PIV during Inflammation and Injury in Kidney
Authors: Takeuchi Oki , Sims Tasha N. , Takei Yutaka , Ramassar Vido , Famulski Konrad S. , Halloran Philip F.
Published: October 2004

Expression of class II transactivator (CIITA), the transcriptional regulator that controls all class II expression, is controlled in cell lines in vitro by three promoters: the dendritic cell promoter PI, the B cell promoter PIII, and the interferon-γ (IFN-γ)–inducible promoter, PIV. The authors examined the promoter usage in vivo in mouse kidney in the basal state and in response to IFN-γ, endotoxin, allostimulation, and renal injury. Genetically modified mice were used to examine the dependency of each promoter on IFN-γ and on the transcription factor interferon regulatory factor 1 (IRF-1). Usage of distinct CIITA promoters was monitored by real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the unique sequences in the 5′ end of the transcript from each promoter. Kidneys in both control mice and IFN-γ knockouts expressed chiefly PI- and PIV–related products. Administration of recombinant IFN-γ activated only promoter PIV. Endotoxin or allogeneic stimulation elevated the PIV-related mRNA, dependent on IFN-γ and on IRF-1. Ischemic renal injury, however, increased the PI- and PIV–driven mRNA expression in wild-type but also in IFN-γ–deficient mice. Thus the in vivo control of CIITA promoters in kidney is similar to that observed in vitro (i.e., basal-state usage of PI and IFN-γ–dependent usage of PIV during inflammation), but it also shows additional levels of control: IFN-γ–independent basal activity of PIV and IFN-γ–independent induction of PIV during tissue injury. E-mail: phil.halloran@ualberta.ca
Origins of the southeastern Australian vegetation
Authors: Hill Robert S.
Published: October 2004

Australia is an ancient continent with an interesting geological history that includes a recent major shift in its position, both globally and compared with neighbouring land masses. This has led to a great deal of confusion over many years about the origins of the Australian biomes. The plant fossil record is now clarifying this, and it is clear that the ancient Gondwanan rainforests that covered Australia while it was still part of that supercontinent contained many of the elements of the modern vegetation. However, major climatic sifting, along with responses to other factors, including soil nutrient levels, disturbance regimes, atmospheric CO2levels, fire frequency and intensity, glaciations and the arrival of humans, have had profound impacts on the Australian vegetation, which today reflects the sum of all these factors and more. The origins of Australian vegetation and its present–day management cannot be properly understood without an appreciation of this vast history, and the fossil record has a vital role to play in maintaining the health of this continent's vegetation into the future.
Epiphytism and pollinator specialization: drivers for orchid diversity?
Authors: Gravendeel Barbara , Smithson Ann , Slik Ferry J. W. , Schuiteman Andre
Published: October 2004

Epiphytes are a characteristic component of tropical rainforests. Out of the 25 000 orchid species currently known to science, more than 70% live in tree canopies. Understanding when and how these orchids diversified is vital to understanding the history of epiphytic biomes. We investigated whether orchids managed to radiate so explosively owing to their predominantly epiphytic habit and/or their specialized pollinator systems by testing these hypotheses from a statistical and phylogenetic standpoint. For the first approach, species numbers of 100 randomly chosen epiphytic and terrestrial genera were compared. Furthermore, the mean number of pollinators per orchid species within the five subfamilies was calculated and correlated with their time of diversification and species richness. In the second approach, molecular epiphytic orchid phylogenies were screened for clades with specific suites of epiphytic adaptations. Epiphytic genera were found to be significantly richer in species than terrestrial genera both for orchids and non–orchids. No evidence was found for a positive association between pollinator specialization and orchid species richness. Repeated associations between a small body size, short life cycle and specialized clinging roots of twig epiphytes in Bulbophyllinae and Oncidiinae were discovered. The development of twig epiphytism in the first group seems repeatedly correlated with speciation bursts.
IMMUNOCYTOCHEMICAL CHARACTERIZATION OF THE INTRAPYRENOID THYLAKOIDS OF CRYPTOMONADS1
Authors: McKay R. Michael L. , Lichtlé Christiane , Gibbs Sarah P.
Published: October 2004

Thylakoid lamellae extend into the pyrenoids of only two genera of cryptomonad algae,ChroomonasandHemiselmis, We used immunoelectron microscopy to assess the photosynthetic competency of cryptomonad intrapyrenoid thylakoids. Intrapyrenoid thylakoids possess phycobiliproteins and the chlorophyll a/c2light‐harvesting complex, both of which are associated with photosystem (PS) II in a light‐harvesting capacity. In addition, thylakoids that extend into the pyrenoid ofHemiselmis brunnescenswere immunolabelled by anti‐PSI. These results indicate that cryptomonad intrapyrenoid thylakoids likely function in a manner analogous to thylakoids of the chloroplast stroma. Moreover, our observation that the Calvin cycle enzyme ribulose 1,5‐bisphosphate carboxylase/oxygenase (Rubisco) is pyrenoid‐localized in these two cryptophytes indicates that the processes of photosynthetic O2‐evolution and ribulose 1,5‐bisphosphate (RuBP) carboxylation/oxygenation are not spatially separated in these algae.