bluuebunny/crossref_metadata_2025 huggingface dataset:
All-transretinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-δ
Authors: Uruno Akira , Noguchi Naoya , Matsuda Ken , Nata Koji , Yoshikawa Takeo , Chikamatsu Youichiro , Kagechika Hiroyuki , Harigae Hideo , Ito Sadayoshi , Okamoto Hiroshi , Sugawara Akira
Published: March 2011

ATRA and a synthetic RAR agonist tamibarotene (Am80) induce granulocytic differentiation of human acute leukemia HL-60 cells and have been used in antineoplastic therapy. ATRA induces CD38 antigen during HL-60 cell differentiation, which interacts with CD31 antigen on the vascular EC surface and may induce disadvantages in the therapy. We here examined the mechanisms of the ATRA-mediated CD38 induction and compared the difference between ATRA- and tamibarotene-mediated induction. Tamibarotene-induced HL-60 cell adhesion to ECs was 38% lower than ATRA, and NB4 cell adhesion to ECs by tamibarotene was equivalent to ATRA, which induced CD38 gene transcription biphasically in HL-60 cells, the early-phase induction via DR-RARE containing intron 1, and the delayed-phase induction via RARE lacking the 5′-flanking region. In contrast to ATRA, tamibarotene induced only the early-phase induction, resulting in its lower CD38 induction than ATRA. A PKCδ inhibitor, rottlerin, and siRNA-mediated PKCδ knockdown suppressed the ATRA-induced CD38 promoter activity of the 5′-flanking region, whereas a RAR antagonist, LE540, or RAR knockdown did not affect it. Cycloheximide and rottlerin suppressed the delayed-phase induction of CD38 expression by ATRA but did not affect the early-phase induction. Moreover, ATRA, but not tamibarotene, induced PKCδ expression without affecting its mRNA stability. The diminished effect of tamibarotene on CD38-mediated HL-60 cell adhesion to ECs compared with ATRA is likely a result of the lack of its delayed-phase induction of CD38 expression, which may be advantageous in antineoplastic therapy.
Transcriptional Regulation of the Human P450 Oxidoreductase Gene: Hormonal Regulation and Influence of Promoter Polymorphisms
Authors: Tee Meng Kian , Huang Ningwu , Damm Izabella , Miller Walter L.
Published: March 2011

P450 oxidoreductase (POR) is the flavoprotein that acts as the obligatory electron donor to all microsomal P450 enzymes, including those involved in hepatic drug metabolism as well as three steroidogenic P450 enzymes. The untranslated first exon of human POR was located recently, permitting analysis of human POR transcription. Expression of deletional mutants containing up to 3193 bp of the human POR promoter in human adrenal NCI-H295A and liver Hep-G2 cells located the proximal promoter at −325/−1 bp from the untranslated exon. Common human POR polymorphisms at −208 and −173 had little influence on transcription, but the polymorphism at −152 reduced transcription significantly in both cell lines. EMSA and supershift assays identified binding of Smad3/Smad4 between −249 and −261 and binding of thyroid hormone receptor-β (TRβ) at −240/−245. Chromatin immunoprecipitation showed that Smad3, Smad4, TRα, TRβ, and estrogen receptor-α were bound between −374 and −149. Cotransfection of vectors for these transcription factors and POR promoter-reporter constructs into both cell types followed by hormonal treatment showed that T3 exerts major tropic effects via TRβ, with TRα, estrogen receptor-α, Smad3, and Smad4 exerting lesser, modulatory effects. T3 also increased POR mRNA in both cell lines. Thyroid hormone also is essential for rat liver POR expression but acts via different transcription factor complexes. These are the first data on human POR gene transcription, establishing roles for TRβ and Smad3/4 in its expression and indicating that the common polymorphism at −152 may play a role in genetic variation in steroid biosynthesis and drug metabolism.
Glucosensing by GnRH Neurons: Inhibition by Androgens and Involvement of AMP-Activated Protein Kinase
Authors: Roland Alison V. , Moenter Suzanne M.
Published: March 2011

GnRH neurons integrate steroidal and metabolic cues to regulate fertility centrally. Central glucoprivation reduces LH secretion, which is governed by GnRH release, suggesting GnRH neuron activity is modulated by glucose availability. Here we tested whether GnRH neurons can sense changes in extracellular glucose, and whether glucosensing is altered by the steroids dihydrotestosterone (DHT) and/or estradiol (E). Extracellular recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice ± DHT and/or E implants. Firing rate was reduced by a switch from 4.5 to 0.2 mm glucose in cells from OVX, OVX+E, and OVX+DHT+E mice, but not OVX+DHT mice. This suggests that androgens reduce the sensitivity of GnRH neurons to changes in extracellular glucose, but E mitigates this effect. Next we investigated potential mechanisms. In the presence of the ATP-sensitive potassium channel antagonist tolbutamide, glucosensing persisted. In contrast, glucosensing was attenuated in the presence of compound C, an antagonist of AMP-activated protein kinase (AMPK), suggesting a role for AMPK in glucosensing. The AMPK activator N1-(b-d-ribofuranosyl)-5-aminoimidazole-4-carboxamide (AICAR) mimicked the effect of low glucose and was less effective in cells from DHT-treated mice. The effect of DHT to diminish responses to low glucose and AICAR was abolished by blockade of fast synaptic transmission. Both AICAR and low glucose activated a current with a reversal potential near −50 mV, suggesting a nonspecific cation current. These studies indicate that glucosensing is one mechanism by which GnRH neurons sense fuel availability and point to a novel role for AMPK in the central regulation of fertility.
Study of the Tonal Casing Noise of a Centrifugal Fan at the Blade Passing Frequency. Part I. Aeroacoustics
Authors: Jian-Cheng CAI , Da-Tong QI , Fu-An LU , Wen Xuan-Feng
Published: March 2011

This paper is concerned with the simulation of the unsteady turbulent flow and the aerodynamic tonal noise due to pressure fluctuations on the casing wall. Three-dimensional numerical simulations of the complete unsteady flow on the whole impeller-volute configuration were carried out using computational fluid dynamics (CFD) techniques. Pressure fluctuations on the casing wall were obtained, and the blade passing frequency (BPF) component was extracted to be modeled as the dipole source term of the wave equation. In a companion paper, the pressure fluctuations served as the external excitation to the casing vibration. Multi-domain direct boundary element method (BEM) was used to simulate the noise radiation with two domains representing the interior and exterior fields of the volute respectively, in order to take account of the sound scattering effect by the volute casing. Results showed that the dipole on the volute tongue surface was the most dominant noise source of the fan. Sloping-edge volute tongue was introduced to reduce BPF noise radiation through phase cancellation between the dipole sources over the volute tongue.
Disjunctive Decomposition for Two-Stage Stochastic Mixed-Binary Programs with Generalized Upper Bound Constraints
Authors: Keller Brian , Bayraksan Güzin
Published: March 2011

The disjunctive decomposition (D2) algorithm has emerged as a powerful tool to solve stochastic integer programs. In this paper, we consider two-stage stochastic integer programs with binary first-stage and mixed-binary second-stage decisions and present several computational enhancements to D2. First, we explore the use of a cut generation problem restricted to a subspace of the variables, which yields significant computational savings. Then, we examine problems with generalized upper bound constraints in the second stage and exploit this structure to generate cuts. We establish convergence of D2 variants. We present computational results on a new stochastic scheduling problem with an uncertain number of jobs motivated by companies in industries such as consulting and defense contracting, where these companies bid on future contracts but may or may not win the bid. The enhancements reduced computation time on average by 45% on a set of test problems.
A Study of Quality and Accuracy Trade-offs in Process Mining
Authors: Huang Zan , Kumar Akhil
Published: March 2011

In recent years, many algorithms have been proposed to extract process models from process execution logs. The process models describe the ordering relationships between tasks in a process in terms of standard constructs like sequence, parallel, choice, and loop. Most algorithms assume that each trace in a log represents a correct execution sequence based on a model. In practice, logs are often noisy, and algorithms designed for correct logs are not able to handle noisy logs. In this paper we share our key insights from a study of noise in process logs both real and synthetic. We found that all process logs can be explained by a block-structured model with two special self-loop and optional structures, making it trivial to build a fully accurate process model for any given log, even one with inaccurate data or noise present in it. However, such a model suffers from low quality. By controlling the use of self-loop and optional structures of tasks and blocks of tasks, we can balance the quality and accuracy trade-off to derive high-quality process models that explain a given percentage of traces in the log. Finally, new quality metrics and a novel quality-based algorithm for model extraction from noisy logs are described. The results of the experiments with the algorithm on real and synthetic data are reported and analyzed at length.
Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop
Authors: Strohmeier Julian , Hertel Ines , Diederichsen Ulf , Rudolph Markus G. , Klostermeier Dagmar
Published: March 2011

DEAD-box proteins disrupt or remodel RNA and protein/RNA complexes at the expense of ATP. The catalytic core is composed of two flexibly connected RecA-like domains. The N-terminal domain contains most of the motifs involved in nucleotide binding and serves as a minimalistic model for helicase/nucleotide interactions. A single conserved glutamine in the so-called Q-motif has been suggested as a conformational sensor for the nucleotide state. To reprogram theThermus thermophilusRNA helicase Hera for use of oxo-ATP instead of ATP and to investigate the sensor function of the Q-motif, we analyzed helicase activity of Hera Q28E. Crystal structures of the Hera N-terminal domain Q28E mutant (TthDEAD_Q28E) in apo- and ligand-bound forms show that Q28E does change specificity from adenine to 8-oxoadenine. However, significant structural changes accompany the Q28E mutation, which prevent the P-loop from adopting its catalytically active conformation and explain the lack of helicase activity of Hera_Q28E with either ATP or 8-oxo-ATP as energy sources. 8-Oxo-adenosine, 8-oxo-AMP, and 8-oxo-ADP weakly bind to TthDEAD_Q28E but in non-canonical modes. These results indicate that the Q-motif not only senses the nucleotide state of the helicase but could also stabilize a catalytically competent conformation of the P-loop and other helicase signature motifs.
The role of symmetry in the regulation of bacterial carboxyltransferase
Authors: Waldrop Grover L.
Published: March 2011

Carboxyltransferase is one component of the multifunctional enzyme acetyl-CoA carboxylase which catalyzes the first committed step in fatty acid biosynthesis. Carboxyltransferase is an α2β2heterotetramer and possesses two distinct but integrated functions. One function catalyzes the transfer of carbon dioxide from biotin to acetyl-CoA, whereas the other involves binding to the mRNA encoding both subunits. When carboxyltransferase binds to the mRNA both enzymatic activity and translation of the mRNA are inhibited. However, the substrate acetyl-CoA competes with mRNA for binding. Thus, mRNA binding by carboxyltransferase provides an effective mechanism for regulating enzymatic activity and gene expression. This conceptual review takes the position that regulation of enzymatic activity and gene expression of carboxyltransferase by binding to its own mRNA is at its most fundamental level the result of the symmetry in the chemical reaction catalyzed by the enzyme. The chemical reaction is symmetrical in that both substrates generate enolate anions during the course of catalysis. The chemical symmetry led to a structural symmetry in the enzyme where both the α and β subunits contain oxyanion holes that stabilize the enolate anions. Then the region of the mRNA that codes for the oxyanion holes provided the binding sites for carboxyltransferase. Thus, the symmetry of the chemical reaction formed the foundation for the evolution of the mechanism for regulation of carboxyltransferase.
Economic evidence in decision-making process in laboratory medicine
Authors: Brunetti Massimo , Pregno Silvia , Schünemann Holger , Plebani Mario , Trenti Tommaso
Published: March 2011

Laboratory data play a pivotal role in the clinical decision-making process. Major transformations have occurred in laboratory medicine in recent decades. To face the economic pressures, hospital laboratories are forced to enhance efficiency. Decisions on policy and practice take place at many levels. However, decision-making often does not follow Evidence Based Laboratory Medicine principles. Also, the literature shows limited influence of economic evaluations on health care decisions and diagnostic processes. Several barriers to the use of economic evaluation in decision-making process have been identified, and guidelines tend to focus on issues of effectiveness and have not explicitly considered broader issues, particularly cost. As an example, we analyzed recommendations on the use of brain natriuretic peptide (BNP) or N-terminal fragment of the prohormone BNP (NT-proBNP) in patients with chronic heart failure. All guidelines recommend the use of BNP if available. Nevertheless, none included economic data explicitly, even if economic information exists in the literature. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, propose using a balance sheet approach, one way of helping decision makers to explicitly consider resource use along with other outcomes when making recommendations. Key aspects of GRADE, such as the explicit presentation of information and the quality evaluation of the economic data can help overcome barriers in the use of economic evaluations in the decision-making in process. This approach can help to give health decision makers, clinical guideline panels and patients, a better appreciation of the overall health benefits, harms and costs of laboratory tests.
Low-density lipoprotein receptor-related protein 1: new functions for an old molecule
Authors: Franchini Massimo , Montagnana Martina
Published: March 2011

The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor member of the low-density lipoprotein (LDL)-receptor family. As LRP1 plays an important role in endocytosis and regulation of signalling pathways, it is implicated in a number of physiologic processes, including the regulation of lipid metabolism, the proliferation of vascular smooth muscle cells and in neuro-development. More recently, LRP1 has been implicated in the catabolism of factor VIII and regulation of its plasma concentrations. The pathophysiology of the role of LRP1 in hemostasis will be summarized in this review.
Comparison of thyroglobulin antibody interference in first- and second-generation thyroglobulin immunoassays
Authors: Giovanella Luca , Ceriani Luca
Published: March 2011

Background: This study evaluated the impact of thyroglobulin (Tg) antibodies (TgAb) interference on Tg measurements performed with a second-generation immunometric Tg assay, in comparison to a first-generation method.

Methods: Five serum pools without detectable TgAb and containing measurable Tg concentrations were obtained from DTC patients and mixed with sera from patients with measurable TgAb, but undetectable Tg concentrations. Tg and TgAb concentrations were measured by the first- and the second-generation Tg immunoassays and Tg-recovery was also evaluated for both assays.

Results: The decrease in Tg concentrations in the presence of TgAb was more pronounced in the first-generation Tg assay (41.6%) compared with the second-generation assay (31.4%) (p<0.01). Accordingly, the mean Tg-recovery values were 51.4% in the first-generation Tg assay and 68.8% in the second-generation (p<0.01). Measurable Tg concentrations were found in all sera using the second-generation assay, but not the first-generation method.

Conclusions: Our preliminary results indicate that an undetectabIe Tg concentration measured using the second-generation assay is unlikely to be a false-negative result induced by TgAb-interferences.
Could serum measurements of S100 proteins be reliable markers to predict recurrence in meningiomas?
Authors: Abeloos Laurence , Lefranc Florence
Published: March 2011

Predicting which meningiomas will recur and which will not is clinically important, and still represents a major clinical challenge. A number of different molecular, genetic, and/or biochemical markers involved in cell proliferation, invasion, angiogenesis, and cell transformation have been investigated in attempts to predict the risk of post-surgical meningioma recurrence. In this short review we emphasize what has actually been accomplished in this area. Finally, we highlight the potential of S100 serum protein concentrations as a prognostic factor predicting meningioma recurrence. We conclude that serum concentrations of S100 group proteins may prove to be useful as prognostic markers and suggest further pros-pective trials be done.
The integration of a Stat3 specific peptide aptamer into the thioredoxin scaffold protein strongly enhances its inhibitory potency
Authors: Schöneberger Hannah , Weiss Astrid , Brill Boris , Delis Natalia , Borghouts Corina , Groner Bernd
Published: March 2011

We are characterizing peptides which are able to interact with functional domains of oncoproteins and thus inhibit their activity. The yeast two-hybrid system was used to derive a peptide sequence which specifically interacts with the dimerization domain of the transcription factor Stat3. The activated form of Stat3 is required for the survival of many transformed cells and Stat3 inhibition can cause tumor cell death. The genetic selection of specific peptide sequences from random peptide libraries requires the integration into a scaffold protein and the expression in yeast cells. The scaffold protein, a variant of the human thioredoxin protein, has previously been optimized and also allows for effective bacterial expression of the recombinant protein and the cellular uptake of the purified, recombinant protein. We investigated the contributions of the scaffold protein to the inhibitory properties of rS3-PA. For this purpose we compared rS3-PA in which the ligand peptide is embedded within the thioredoxin scaffold protein with a minimal Stat3-interacting peptide sequence. sS3-P45 is a synthetic peptide of 45 amino acids in length and consists only of the Stat3-binding sequence of 20 amino acids, a protein transduction domain (PTD) and a Flag-tag. Both, the recombinant rS3-PA of 19.3 kDa and the synthetic sS3-P45 of 5.1 kDa, were taken up into the cytoplasm of cells by the PTD-mediated transduction process, inhibited Stat3 target gene expression and caused the death of Stat3-dependent tumor cells. Stat3-independent normal cells were unaffected. rS3-PA effectively inhibited Stat3 function at 2 μM, however, sS3-P45 was required at a concentration of 100 μM to exert the same effects. The more potent action of rS3-PA is most probably due to a conformational stabilization of the Stat3-interacting peptide in the context of the scaffold protein.
From Hellenistic to Christian Universal History. Julius Africanus and the Atthidographers on the Origins of Athens
Authors: Roberto Umberto
Published: March 2011

Die Chronographiae des Julius Africanus stehen am Übergang von der Antike zur Spätantike. Als Anhänger des christlichen Glaubens und Begründer der christlichen Universalgeschichte bleibt Africanus zugleich der Tradition der hellenistischen Gelehrsamkeit verbunden. Infolgedessen wird die christliche Idee der Einheit der Menschheit in den Chronographiae durch den Rückgriff auf die hellenistische Kultur verstärkt. Dies zeigt sich besonders deutlich an der Verknüpfung der als synchron angesehenen Ereignisse des Exodus von Israel unter Mose und der Flut zur Zeit von Ogygos in Attika (F34). Interessant ist, wie Africanus die Autochtonie und kulturelle Eigenständigkeit Athens ablehnt. Die Polemik gegen eine idealisierende Beschreibung der Urgeschichte Athens ist eine wichtige Etappe im Wandel von einer klassisch-hellenistischen zu einer christlichen Universalgeschichte.
The Beginnings of Christian Universal History. From Tatian to Julius Africanus
Authors: Wallraff Martin
Published: March 2011

Die Chronographiae des Julius Africanus können als das erste umfangreiche und eigenständige literarische Werk einer Universalgeschichte im Christentum gelten, gleichwohl gab es diverse kleinere Traktate ähnlichen Inhalts, die im zweiten und frühen dritten Jahrhundert abgefasst wurden; sie sind nur teilweise erhalten. Die wichtigsten Texte stammen von Tatian dem Syrer, Theophil von Antiochien und Klemens von Alexandrien.

Oft wird angenommen, dass Geschichtskonzepte im frühen Christentum in enger Beziehung zur Eschatologie stehen, Chronographie und Chiliasmus miteinander verbunden sind. Eine genaue Analyse der Texte zeigt jedoch, dass eine solche Verbindung entweder nicht bewiesen werden kann oder dass sogar – ganz im Gegenteil – einige Autoren kein Interesse an Eschatologie hatten. Obwohl Arithmetik und genaue historische Berechnungen eine grosse Rolle spielen und obwohl der Rahmen der Geschichte in einigen Fällen durchaus als chiliastisch bezeichnet werden kann (in dem Sinn, dass für die Geschichte der Menschheit eine Gesamtdauer von 6000 + 1000 Jahren angenommen wurde), gab es wenig Interesse an einer genauen Berechnung des Endes der Zeit. Außerdem wird die Beziehung zwischen Historiographie und Apologetik diskutiert. Es steht außer Frage, dass die Ursprünge der literarischen Gattung Universalgeschichte in der apologetischen Tradition frühchristlicher Theologie liegen. Im Falle von Tatian und Theophil (bis zum gewissen Grad auch bei Klemens) sind die chronologischen Traktate in größere Werke eingebettet, die einen kritischen Dialog mit zeitgenössischer paganer Philosophie zum Ziel haben. Der Altersbeweis spielt dabei eine zentrale Rolle, im besonderen die chronologische Beziehung zwischen Moses und Homer. Während dieser Gedanke zum Verständnis von Tatian und Theophil weitgehend ausreicht, zeigen spätere Autoren eine Emanzipation der literarischen Gattung Chronographie von den apologetischen Wurzeln. Bis zum gewissen Grad bei Klemens, aber ganz sicher bei Julius Africanus treten diese Wurzeln in den Hintergrund.
Conditional ablation of macrophages disrupts ovarian vasculature
Authors: Turner Emily C , Hughes Jeremy , Wilson Helen , Clay Michael , Mylonas Katie J , Kipari Tiina , Duncan W Colin , Fraser Hamish M
Published: March 2011

Macrophages are the most abundant immune cell within the ovary. Their dynamic distribution throughout the ovarian cycle and heterogenic array of functions suggest the involvement in various ovarian processes, but their functional role has yet to be fully established. The aim was to induce conditional macrophage ablation to elucidate the putative role of macrophages in maintaining the integrity of ovarian vasculature. Using the CD11b-diphtheria toxin receptor (DTR) mouse, in which expression of human DTR is under the control of the macrophage-specific promoter sequence CD11b, ovarian macrophages were specifically ablated in adult females by injections of diphtheria toxin (DT). CD11b-DTR mice were given DT treatment or vehicle and ovaries collected at 2, 8, 16, 24 and 48 h. Histochemical stains were employed to characterise morphological changes, immunohistochemistry for F4/80 to identify macrophages and the endothelial cell marker CD31 used to quantify vascular changes. In normal ovaries, macrophages were detected in corpora lutea and in the theca layer of healthy and atretic follicles. As macrophage ablation progressed, increasing amounts of ovarian haemorrhage were observed affecting both luteal and thecal tissue associated with significant endothelial cell depletion, increased erythrocyte accumulation and increased follicular atresia by 16 h. These events were followed by necrosis and profound structural damage. Changes were limited to the ovary, as DT treatment does not disrupt the vasculature of other tissues likely reflecting the unique cyclical nature of the ovarian vasculature and heterogeneity between macrophages within different tissues. These results show that macrophages play a critical role in maintaining ovarian vascular integrity.
Comment on Kamstra: Reasons for Developing Countries to Be Thrilled about Trills
Authors: Siddiqi Hammad A
Published: March 2011

Shillers trills might prevent the flight of capital from developing to developed countries, according to Hammad Siddiqi of Lahore University of Management Sciences, who suggests they could be used to realign the objectives of developing nations and international lending agencies such the World Bank and the IMF.
Decline in Residual Renal Function in Automated Compared with Continuous Ambulatory Peritoneal Dialysis
Authors: Michels Wieneke Marleen , Verduijn Marion , Grootendorst Diana C. , le Cessie Saskia , Boeschoten Elisabeth Wilhelmina , Dekker Friedo Wilhelm , Krediet Raymond Theodorus
Published: March 2011

Background and objectives

We compared the decline of RRF in patients starting dialysis on APD with those starting on CAPD, because a faster decline on APD has been suggested.

Design, setting, participants, & measurements

NECOSAD patients starting dialysis on APD or CAPD with RRF at baseline were included and followed for 3 years. Residual GFR (rGFR) was the mean of urea and creatinine clearances. Differences in yearly decline of rGFR were estimated in analyses with linear repeated measures models, whereas the risk of complete loss of RRF was estimated by calculating hazard ratios (HRs) for APD compared with CAPD. As-treated (AT) and intention-to-treat (ITT) designs were used. All of the analyses were adjusted for age, gender, comorbidity, and primary kidney disease and stratified according to follow-up and mean baseline GFR.

Results

The 505 CAPD and 78 APD patients had no major baseline differences. No differences were found in the analyses on yearly decline of rGFR. APD patients did have a higher risk of losing RRF in the first year (ITT crude HR 2.43 [confidence interval 95%, 1.48 to 4.00], adjusted 2.66 [1.60 to 4.44]; AT crude 1.89 [1.04 to 3.45], adjusted 2.15 [1.16 to 3.98]). The higher risk of losing all RRF was most pronounced in patients with the highest rGFR at baseline (ITT; crude 3.91 [1.54 to 9.94], adjusted 1.85 to 14.17).

Conclusions

The risk of losing RRF is higher for patients starting dialysis on APD compared with those starting on CAPD, especially in the first year.
Transient Elastography to Assess Hepatic Fibrosis in Hemodialysis Chronic Hepatitis C Patients
Authors: Liu Chen-Hua , Liang Cheng-Chao , Huang Kai-Wen , Liu Chun-Jen , Chen Shih-I , Lin Jou-Wei , Hung Peir-Haur , Tsai Hung-Bin , Lai Ming-Yang , Chen Pei-Jer , Chen Jun-Herng , Chen Ding-Shinn , Kao Jia-Horng
Published: March 2011

Background and objectives

Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan®) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients.

Design, setting, participants, & measurements

A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard.

Results

The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P < 0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P = 0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P = 0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93–100%) and specificity (88–99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively.

Conclusions

TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.
Henoch-Schönlein Purpura Nephritis
Authors: Davin Jean-Claude
Published: March 2011

Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.
Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction
Authors: Bellasi Antonio , Mandreoli Marcora , Baldrati Leopoldo , Corradini Matteo , Di Nicolò Pierpaolo , Malmusi Giulio , Santoro Antonio
Published: March 2011

Background and objectives

Several factors might alter serum phosphate homeostasis and induce hyperhosphatemia in patients with chronic kidney disease (CKD) not requiring dialysis. However, whether and to what extent hyperphosphatemia is associated with a poor prognosis in different CKD patient groups remain to be elucidated.

Design, setting, participants & measurements

We utilized the “Prevenzione Insufficienza Renale Progressiva” (PIRP) database, a large project sponsored by the Emilia-Romagna Health Institute. PIRP is a collaborative network of nephrologists and general practitioners located in the Emilia-Romagna region, Italy, aimed at increasing awareness of CKD complications and optimizing CKD patient care. We identified 1716 patients who underwent a GFR and serum phosphorous assessment between 2004 and 2007. We tested whether phosphate levels ≥4.3 mg/dl are associated with the risk of CKD progression or all causes of death.

Results

Older age and male sex were associated with lower phosphate levels. Instead, higher phosphate levels were noted in patients with diabetes. Patients with phosphate levels ≥4.3 mg/dl were at an increased risk of starting dialysis or dying (hazard ratio 2.04; 95% confidence interval [1.44, 2.90]). Notably, subgroup analyses revealed that the magnitude of the risk associated with hyperphosphatemia varied depending on age, sex, diabetes, and different stages of CKD.

Conclusions

These analyses lend support to the hypothesis that phosphorous abnormalities might have a negative effect on the residual renal function and prognosis in different groups of CKD patients. However, the risk associated with hyperphosphatemia might vary in specific CKD patient subgroups.
Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury
Authors: Grams Morgan E. , Estrella Michelle M. , Coresh Josef , Brower Roy G. , Liu Kathleen D.
Published: March 2011

Background and objectives

Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients.

Design, setting, participants, & measurements

Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria.

Results

306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased.

Conclusions

A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance.
The Efficacy and Safety of the 3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors in Chronic Kidney Disease, Dialysis, and Transplant Patients
Authors: Olyaei Ali , Greer Erin , Delos Santos Rowena , Rueda Jose
Published: March 2011

Coronary heart disease (CHD) is the leading cause of death in Western civilizations, in particular in chronic kidney disease (CKD) patients. Serum total cholesterol and LDL have been linked to the development of atherosclerosis and progression to CHD in the general population. However, the reductions of total and LDL cholesterol in the dialysis population have not demonstrated the ability to reduce the morbidity, mortality, and cost burden associated with CHD. The patients at greatest risk include those with pre-existing CHD, a CHD-risk equivalent, or multiple risk factors. However, data in the dialysis population are much less impressive, and the relationship between plasma cholesterol, cholesterol reduction, use of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and reduction in incidence of CHD or effect on progression of renal disease have not been proven. Adverse event information from published trials indicates that agents within this class share similar tolerability and adverse event profiles. Hepatic transaminase elevations may occur in 1 to 2% of patients and is dose related. Myalgia, myopathy, and rhabodmyolysis occur infrequently and are more common in kidney transplant patients and patients with CKD. This effect appears to be dose related and may be precipitated by administration with agents that inhibit cytochrome P-450 isoenzymes. Caution should be exercised when coadministering any statin with drugs that metabolize through cytochrome P-450 IIIA-4 in particular fibrates, cyclosporine, and azole antifungals. Elderly patients with CKD are at greater risk of adverse drug reactions, and therefore the lowest possible dose of statins should be used for the treatment of hyperlipidemia.
Thrombolysis for Acute Stroke in Hemodialysis
Authors: Palacio Santiago , Gonzales Nicole R. , Sangha Navdeep S. , Birnbaum Lee A. , Hart Robert G.
Published: March 2011

Background and objectives

Although data are absent, it has been stated that thrombolysis is probably not safe in the treatment of acute stroke in patients undergoing hemodialysis. The objective of this study was for stroke experts to define the range of management concerning thrombolytic treatment of acute stroke in hemodialysis.

Design, setting, participants, & measurements

Sixty-five stroke experts in thrombolytic therapy of acute ischemic stroke were queried regarding their personal experience in the use of thrombolysis in hemodialysis patients. Hypothetical case scenarios were presented.

Results

Of the 65 stroke experts who were queried, 40 (62%) responded. One-third of the responders had previously treated hemodialysis patients with recombinant tissue-type plasminogen activator (rt-PA). Most favored use of intravenous rt-PA for hemodialysis patients with acute ischemic stroke. When presented with a case of a patient who had recently undergone dialysis with a mildly prolonged activated partial thromboplastin time (aPTT), 50% favored immediate intravenous thrombolysis. Seventy-eight percent of the experts would have considered an intra-arterial approach and would have preferred mechanical clot retrieval to thrombolysis.

Conclusions

Despite the acknowledged absence of data and prevalent concerns about bleeding risk, most surveyed experts favored its use. One-third reported treating hemodialysis patients with this therapy. Although these results do not substitute for data, they usefully define the range of current practice of stroke experts.
A family of L
2-spaces associated to the jumps of a Markov process
Authors: Grecea Valentin
Published: March 2011

Given the (canonical) Markov process associated with a sufficiently general semigroup (P
t), we establish a result concerning the uniform completeness of a family of L
2-spaces naturally associated with the jumps of the process. An application of this result is presented.
Monotone weak Lindelöfness
Authors: Bonanzinga Maddalena , Cammaroto Filippo , Pansera Bruno
Published: March 2011

The definition of monotone weak Lindelöfness is similar to monotone versions of other covering properties: X is monotonically weakly Lindelöf if there is an operator r that assigns to every open cover U a family of open sets r(U) so that (1) ∪r(U) is dense in X, (2) r(U) refines U, and (3) r(U) refines r(V) whenever U refines V. Some examples and counterexamples of monotonically weakly Lindelöf spaces are given and some basic properties such as the behavior with respect to products and subspaces are discussed.
Omega-3 fatty acids and exercise: a review of their combined effects on body composition and physical performance
Authors: Tiryaki-Sönmez Gül , Schoenfeld Brad , Vatansever-Ozen Serife
Published: March 2011

Omega-3 fatty acids and exercise: a review of their combined effects on body composition and physical performance

Omega-3 (n-3) fatty acids, and the long-chain n-3 derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular, have been extensively researched for their nutritive effects. Among their many purported benefits, n-3 acids have been implicated as positive mediators of cardiovascular health and body composition. It has therefore been speculated that supplementation may enhance the beneficial effects of physical activity, potentiating greater reductions in body fat and improvements in exercise performance. This paper has three objectives: first, to assess the theoretical basis for a synergistic ef-fect when n-3 supplementation is combined with exercise; second, to review the literature as to specific findings on the subject and third, to make relevant conclusions and recommendations for future research.
"Green Chemical" Methods for the Regioselective Synthesis of 1-Hetarylsulfanyl-ω-Cyanoalkanes
Authors: Ābele E. , Ābele R. , Golomba Ļ. , Rubina K. , Višņevska J. , Beresņeva T.
Published: March 2011

"Green Chemical" Methods for the Regioselective Synthesis of 1-Hetarylsulfanyl-ω-Cyanoalkanes

Novel "green chemical" methods for the synthesis of 1-hetarylthio-ω-cyanoalkanes were elaborated. Phase transfer catalyst ((CH3)4NBr) effect on yield of alkylation reaction was demonstrated. 1-Hetarylthio-ω-cyanoalkanes were isolated in 49-86% yields.
Genetic and epigenetic studies on populations of Deschampsia antarctica Desv. from contrasting environments on King George Island
Authors: Chwedorzewska Katarzyna , Bednarek Piotr
Published: March 2011

Genetic and epigenetic studies on populations ofDeschampsia antarcticaDesv. from contrasting environments on King George Island

Populations of Antarctic hairgrassDeschampsia antarcticaDesv. from King George Island exhibit variation in many traits. The reason for that is not evident and could be addressed to variable environmental conditions. Obviously, phenotypic variation could be due to stable or temporal changes in expression pattern as the result of adaptation. Stable changes could be due to mutations or site DNA methylation variation that modified expression pattern. Recently, MetAFLP approach was proposed to study such effects. A variant of methylation sensitive AFLP (Amplified Fragment Length Polymorphism), based on the isoschizomeric combinationsAcc65I/MseI andKpnI/MseI was applied to analyze the sequence and site DNA methylation differences between twoD. antarcticapopulations exhibiting morphological dissimilarities. Both DNA sequence mutations and site methylation pattern alternations were detected among and within analyzed populations. It is assumed that such changes might have originated as the response to environmental conditions that induced site methylation alternations leading to phenotypic variation ofD. antarcticapopulations from South Shetland Islands.
Cenozoic stress field in the southwestern Antarctic Peninsula from brittle mesostructures in Wright Peninsula, Adelaide Island
Authors: Maestro Adolfo , López-Martínez Jerónimo
Published: March 2011

Cenozoic stress field in the southwestern Antarctic Peninsula from brittle mesostructures in Wright Peninsula, Adelaide Island

Palaeostresses inferred from brittle mesostructures in the southern Wright Peninsula show a stress field characterized by compressional, strike-slip and extensional regime stress states. The compressional stress (σ1) shows a main NW-SE direction and the extensional stress (σ3) shows a relative scattering with two main modes: NE-SW to E-W and NW-SE. The maximum horizontal stress (σy) has a bimodal distribution with NW-SE and NE-SW direction. The compressional orientation is related to subduction of the former Phoenix Plate under the Antarctic Plate from the Early Jurassic to the Early Miocene. Extensional structures within a broad-scale compressional stress field can be related to both the decrease in relative stress magnitudes from active margins to intraplate regions and stretching processes occurring in eastern Adelaide Island, which develop a fore-arc or intra-arc basin from the Early Miocene. Stress states with NW-SE-trending σ1are compatible with the dominant pattern established for the western Antarctic Peninsula. NW-SE orientations of σ3suggest the occurrence of tectonic forces coming from fore-arc extension along the western Antarctic Peninsula.
Spesia antarctica gen. et sp. nov. - a new fertile fern spike from the Jurassic of Antarctica
Authors: Ociepa Anna , Barbacka Maria
Published: March 2011

Spesia antarctica gen. et sp. nov. - a new fertile fern spike from the Jurassic of Antarctica

The well-known Jurassic macrofloras from Hope Bay at the northernmost tip of the Antarctic Peninsula continue to yield new taxa. This paper reports on a new type of plant reproductive organ. The affinity of this organ remains unclear; it may be affiliated with the Schizaceae or Osmundaceae, but similarities to pollen organs of the Podocarpaceae are also discussed. Because the fossils differ from hitherto known Mesozoic fertile fronds and conifer pollen organs in some details, the new taxon, Spesia antarctica nov. gen. et sp. is proposed.
A Tentative Report on "American" and "Canadian" Courses in Canadian University Curricula
Authors: COLE WAYNE , ROCK VIRGINIA , WHITE ROBERT L.
Published: March 2011

Two years ago, the secretary of the C.A.A.S. circulated a questionnaire among Canadian university departments in the humanities and social sciences in an effort to find out the extent of "American Studies" course offerings in Canadian curricula. Responses to the questionnaires were slow in coming back, the length and complexity of the questionnaire made analysis of the responses onerous and tricky, and the secretary's time was taken up by other chores; consequently, replies to the ques­tionnaire were but partially tabulated when, during the spring of 1969, Professors Robin Mathews and James Steele raised the question of whether Canadian universities were being "de-Canadianized" by the recent influx of foreign faculty members, many of them American. The unwinnowed data was becoming outdated, and to our minds it was now contextually irrelevant. It now seemed important to know not merely the number of "American Studies" courses offered in Canadian uni­versities, but also the relative importance of such courses in various departments; we were particularly interested to know something of the ratio of such courses to "Canadian Studies" courses.
We stand on guard for thee?"
Authors: Mathews Robin , Steele James
Published: March 2011

Two things must be said at the outset of a discussion on what Professors Robin Mathews and James Steele call the "de-Canadianization" of our universities: first, that it is extremely difficult to discuss this matter at all and, second, it is impossible to discuss it impersonally. As Hugh MacLennan says, "Our conscience, our sensibilities, our notion of cour­tesy are deeply strained by this issue" I have always regarded Canada and its people as characterized by an openness, a tolerance and a generosity that I have found nowhere else.
Who's Afraid of Cultural Identity? or, Stand Up and be Counted Down
Authors: Mathews Robin , Steele James
Published: March 2011

At first glance the title of the Mathews and Steele dossier, The Struggle for Canadian Universities, may seem overly alarmist and tendentious. Ordinary "liberal-minded," non-committed academics may be put off by the apparent tone of provocation, while those who have other fish to fry will make the most of the opportunity offered for subtle, and not so subtle, misrepresentation. That this last has already happened is apparent to anyone who has paid attention to the controversy which erupted in the mass media - and in faculty lounges - after Mathews and Steele chose to break silence, a little over a year ago, about a real problem. In the usual climate of Canadian timidity, indifference, and cultural in­security they made a no-no. Instead of closing their eyes, holding their tongues, and hoping the whole situation would just quietly disappear, with the help, if absolutely necessary, of the red-herring of an "impar­tial" survey of every possible attenuation of the central problem - sup­ported by a grant from the Canada Council or the Rockefeller Founda­tion - they chose to speak out. The violence of the reaction from certain quarters - to give an extreme example, quoted in Time, of course, "We hope we can club these people to death" - clearly shows the im­portance of their action. It's healthy to have the rabid running off at the mouth: their protective colouring of "scholarly objectivity" shows as the camouflage it is, which simplifies seeing what is hidden.