bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting of the VHL-Hypoxia-Inducible Factor-Hypoxia-Induced Gene Pathway for Renal Cell Carcinoma Therapy
Authors: Sosman Jeffrey A. 
Published: October 2004

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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

ABSTRACT.
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
IMMUNOCYTOCHEMICAL CHARACTERIZATION OF THE INTRAPYRENOID THYLAKOIDS OF CRYPTOMONADS1
Authors: McKay R. Michael L. , Lichtlé Christiane , Gibbs Sarah P. 
Published: October 2004

ABSTRACTThylakoid 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.
HIGH‐RESOLUTION AIRBORNE REMOTE SENSING OF BLOOM‐FORMING PHYTOPLANKTON1
Authors: Millie David F. , Baker Michael C. , Tucker Craig S. , Vinyard Bryan T. , Dionigi Christopher P. 
Published: October 2004

ABSTRACTRemote sensing of highly turbid finfish aquaculture impoundments using the Calibrated Airborne Multispectral Scanner (CAMS) mounted on a Lear jet flown at 900 m was conducted in central Mississippi on 16 May 1990. Concurrent in situ data consisted of phytoplankton pigment concentrations and standing crop, water color, turbidity, and surface‐water temperature. Surface and near‐surface assemblages of cyanophytes and chlorophytes varied dramatically among impoundments; total chlorophyll concentrations and standing crop values ranged from 8 to 483 mg·m−3 and 8.0 × 102 to 2.2 × 106 cells‐mL−1, respectively. Regression models fit to CAMS data provided reliable estimates for and produced accurate digital cartographs of total chlorophyll and carotenoid concentrations, phytoplankton standing crop, and turbidity. Although a model to effectively estimate in situ c‐phycocyanin concentrations was not identified, the lack of a suitable model may have resulted from variability of pigment extraction during quantification rather than failure of remotely sensed imagery to detect c‐phycocyanin. Models derived from imagery of impoundments directly beneath the aircraft sufficiently described in situ parameters in imagery of adjacent series of impoundments not directly below the aircraft. High‐resolution airborne remote sensing provides a means for monitoring local phytoplankton dynamics in temporal and spatial scales analogous to biotic and abiotic processes affecting such dynamics and necessary for applications to ecological research and fisheries or aquacultural management.
INFLUENCE OF PHOSPHORUS NUTRITION ON COPPER TOXICITY TO THREE STRAINS OF SCENEDESMUS ACUTUS (CHLOROPHYCEAE)1
Authors: Twiss Michael R. , Nalewajko Czeslawa 
Published: October 2004

ABSTRACTThree strains of Scenedesmus acutus f. alternans Hortobagyi with markedly different sensitivities to copper were examined to determine the relative importance of cellular polyphosphate content on acute copper toxicity to photosynthesis. By manipulating the phosphate concentration in semicontinuous cultures, the response of each strain was assessed at three cellular phosphorus states: P‐loaded, P‐sufficient, and P‐deficient. The results demonstrated the importance of cellular polyphosphate content in reducing the toxic effect of copper on photosynthesis; the greater the cellular P content, the less inhibition of photosynthesis occurred during copper exposure. This relationship was evident for both Cu‐tolerant strains (XCu and B‐4) and a Cu‐sensitive strain (X72). The ranges of response to 9.9 μM Cu (measured as the percentage of control rate of photosynthesis within strains) were, from P‐loaded to P‐deficient cells, X72, 78–54%; XCu, 95–77%; and B‐4, 99–94%. The data suggest that polyphosphate plays a passive role in protecting cells from copper; however, with respect to the mechanism of Cu tolerance, polyphosphate appeared to be relatively unimportant because the sensitivity of the Cu‐tolerant strains showed less dependence on cellular polyphosphate than did the Cu‐sensitive strain.
DOESDINOPHYSIS(DINOPHYCEAE) HAVE A SEXUAL LIFE CYCLE?1
Authors: MacKenzie Lincoln 
Published: October 2004

ABSTRACTA variety of morphotypes (of two size classes) within two wild populations ofDinophysis acutaEhrenberg andD.cf.acuminataare described. The observation that these two cell types engaged in the formation of couplets (possibly leading to the engulfment of the smaller by the larger cell) suggests that these species may undergo a process of sexual reproduction involving the fusion of anisogamous gametes. This behavior and asexual cell division involved a small portion of the population at any one time and took place rapidly at specific subsurface depths and time of day, the former during the evening, the latter during the morning. Even though definite proof of sexuality byDinophysiswas not obtained, the possiblity that sexual dimorphism exists in several species of the genus is discussed.
Heightened condition dependence is not a general feature of male eyespan in stalk-eyed flies (Diptera: Diopsidae)
Authors: Cotton S. , Fowler K. , Pomiankowski A. 
Published: October 2004

Abstract
Stalk-eyed flies are exemplars of sexual selection leading to the evolution of exaggerated male ornaments (eyespan). In Sphyracephala beccarri, there is no evidence for female mate choice for exaggerated male eyespan and only minor sex differences in eyespan. We used S. beccarri to test whether heightened condition dependence only evolves when male eyespan becomes sexually exaggerated. Male eyespan showed heightened condition dependence under food stress compared with a control trait (wing length). However, female eyespan displayed a similar pattern and there was no sex difference in the degree of increased eyespan sensitivity. The finding that eyespan is a sensitive indicator of food stress, even in an unexaggerated state, suggests that this may have acted as a pre-adaptation to the role of eyespan in sexual signalling in other Diopsid species. These results are consistent with handicap theory and Fisher's view of how sexual selection is initiated.
In vitro embryo survival and early viability of larvae in relation to male sexual ornaments and parasite resistance in roach, Rutilus rutilus L.
Authors: Kortet Raine , Vainikka Anssi , Rantala Markus J. , Myntti Janne , Taskinen Jouni 
Published: October 2004

Abstract
According to the ‘good genes’ hypothesis, sexual ornaments provide an indication of the ‘quality’ of the bearer. In roach, Rutilus rutilus, breeding tubercles (BTs) may signal resistance against the digenean parasite, Rhipidocotyle campanula. Life history theory predicts that there should be a trade-off between parasite resistance and other life history traits. In roach, this could imply a trade-off between parasite resistance in mature fish and some larval feature. We studied embryo survival and the early viability of larvae of male roach in relation to expression of BTs and parasite resistance in maternal half-sibling families. Highly ornamented males had higher resistance against R. campanula than less ornamented males, but the BTs were not related to either embryo survival or larval viability. However, sires having higher resistance to R. campanula had lower larval viability. These results suggest that BTs of male roach do not indicate ‘quality’ in terms of early survival or viability, but rather in terms of adult parasite resistance.