bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection
Authors: Wu Wei , Shi Yu , Li Jie , Chen Feng , Chen Zhi , Zheng Min 
Published: March 2011

Abstract

Background and objective
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) represents a novel mechanism of T-cell dysfunction in chronic viral diseases. However, the role of Tim-3 in the pathogenesis of chronic hepatitis B (CHB) is not well understood. We investigated Tim-3 expression on peripheral T cell subsets and analyzed the relationship between Tim-3 expression and disease progression in HBV infection.

Methods
peripheral blood samples were obtained from CHB patients (n = 40), including 23 patients with moderate CHB [MCHB] and 17 with severe CHB [SCHB]. Control samples were obtained from nine acute hepatitis B patients (AHB) and 26 age-matched healthy subjects. The expression of Tim-3 on T cells was determined by flow cytometry.

Results
Tim-3 expression was elevated on peripheral CD4+ and CD8+ T cells from AHB and CHB patients compared to those from healthy controls. The percentage of Tim-3+ T cells was further increased in SCHB patients relative to MCHB patients and showed a positive correlation with conventional markers for liver injury (alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB) and international normalized ratio (INR) level). The frequency of Tim-3-expressing T cells was negatively correlated with T-bet mRNA expression and plasma interferon-gamma (INF-gamma) levels. Further, Tim-3 expression on CD4+ or CD8+ T cells was reduced in CHB patients with disease remission after antiviral treatment and in AHB patients during the convalescence phase.

Conclusions
Our results suggest that over-expression of Tim-3 is involved in disease progression of CHB and that Tim-3 may participate in skewing of Th1/Tc1 response, which contributes to persistency of HBV infection.
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

ABSTRACTATRA 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

AbstractP450 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

Abstract
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.
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

AbstractDEAD-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

AbstractCarboxyltransferase 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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

ZUSAMMENFASSUNG
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

ZUSAMMENFASSUNG
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.
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

Summary

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.