bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes
Authors: Raynauld Jean-Pierre , Martel-Pelletier Johanne , Berthiaume Marie-Josée , Beaudoin Gilles , Choquette Denis , Haraoui Boulos , Tannenbaum Hyman , Meyer Joan M , Beary John F , Cline Gary A , Pelletier Jean-Pierre 
Published: December 2005

AbstractThe objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.
The clinical value of daily routine chest radiographs in a mixed medical–surgical intensive care unit is low
Authors: Graat Marleen E , Choi Goda , Wolthuis Esther K , Korevaar Johanna C , Spronk Peter E , Stoker Jaap , Vroom Margreeth B , Schultz Marcus J 
Published: December 2005

Abstract
Introduction
The clinical value of daily routine chest radiographs (CXRs) in critically ill patients is unknown. We conducted this study to evaluate how frequently unexpected predefined major abnormalities are identified with daily routine CXRs, and how often these findings lead to a change in care for intensive care unit (ICU) patients.

Method
This was a prospective observational study conducted in a 28-bed, mixed medical–surgical ICU of a university hospital.

Results
Over a 5-month period, 2,457 daily routine CXRs were done in 754 consecutive ICU patients. The majority of these CXRs did not reveal any new predefined major finding. In only 5.8% of daily routine CXRs (14.3% of patients) was one or more new and unexpected abnormality encountered, including large atelectases (24 times in 20 patients), large infiltrates (23 in 22), severe pulmonary congestion (29 in 25), severe pleural effusion (13 in 13), pneumothorax/pneumomediastinum (14 in 13), and malposition of the orotracheal tube (32 in 26). Fewer than half of the CXRs with a new and unexpected finding were ultimately clinically relevant; in only 2.2% of all daily routine CXRs (6.4% of patients) did these radiologic abnormalities result in a change to therapy. Subgroup analysis revealed no differences between medical and surgical patients with regard to the incidence of new and unexpected findings on daily routine CXRs and the effect of new and unexpected CXR findings on daily care.

Conclusion
In the ICU, daily routine CXRs seldom reveal unexpected, clinically relevant abnormalities, and they rarely prompt action. We propose that this diagnostic examination be abandoned in ICU patients.
A compendium of Caenorhabditis elegans regulatory transcription factors: a resource for mapping transcription regulatory networks
Authors: Reece-Hoyes John S , Deplancke Bart , Shingles Jane , Grove Christian A , Hope Ian A , Walhout Albertha JM 
Published: December 2005

Abstract
Background
Transcription regulatory networks are composed of interactions between transcription factors and their target genes. Whereas unicellular networks have been studied extensively, metazoan transcription regulatory networks remain largely unexplored. Caenorhabditis elegans provides a powerful model to study such metazoan networks because its genome is completely sequenced and many functional genomic tools are available. While C. elegans gene predictions have undergone continuous refinement, this is not true for the annotation of functional transcription factors. The comprehensive identification of transcription factors is essential for the systematic mapping of transcription regulatory networks because it enables the creation of physical transcription factor resources that can be used in assays to map interactions between transcription factors and their target genes.

Results
By computational searches and extensive manual curation, we have identified a compendium of 934 transcription factor genes (referred to as wTF2.0). We find that manual curation drastically reduces the number of both false positive and false negative transcription factor predictions. We discuss how transcription factor splice variants and dimer formation may affect the total number of functional transcription factors. In contrast to mouse transcription factor genes, we find that C. elegans transcription factor genes do not undergo significantly more splicing than other genes. This difference may contribute to differences in organism complexity. We identify candidate redundant worm transcription factor genes and orthologous worm and human transcription factor pairs. Finally, we discuss how wTF2.0 can be used together with physical transcription factor clone resources to facilitate the systematic mapping of C. elegans transcription regulatory networks.

Conclusion
wTF2.0 provides a starting point to decipher the transcription regulatory networks that control metazoan development and function.
Systematic analysis of gene expression in human brains before and after death
Authors: Franz Henriette , Ullmann Claudia , Becker Albert , Ryan Margaret , Bahn Sabine , Arendt Thomas , Simon Matthias , Pääbo Svante , Khaitovich Philipp 
Published: December 2005

Abstract
Background
Numerous studies have employed microarray techniques to study changes in gene expression in connection with human disease, aging and evolution. The vast majority of human samples available for research are obtained from deceased individuals. This raises questions about how well gene expression patterns in such samples reflect those of living individuals.

Results
Here, we compare gene expression patterns in two human brain regions in postmortem samples and in material collected during surgical intervention. We find that death induces significant expression changes in more than 10% of all expressed genes. These changes are non-randomly distributed with respect to their function. Moreover, we observe similar expression changes due to death in two distinct brain regions. Consequently, the pattern of gene expression differences between the two brain regions is largely unaffected by death, although the magnitude of differences is reduced by 50% in postmortem samples. Furthermore, death-induced changes do not contribute significantly to gene expression variation among postmortem human brain samples.

Conclusion
We conclude that postmortem human brain samples are suitable for investigating gene expression patterns in humans, but that caution is warranted in interpreting results for individual genes.
A novel approach to identifying regulatory motifs in distantly related genomes
Authors: Van Hellemont Ruth , Monsieurs Pieter , Thijs Gert , De Moor Bart , Van de Peer Yves , Marchal Kathleen 
Published: December 2005

AbstractAlthough proven successful in the identification of regulatory motifs, phylogenetic footprinting methods still show some shortcomings. To assess these difficulties, most apparent when applying phylogenetic footprinting to distantly related organisms, we developed a two-step procedure that combines the advantages of sequence alignment and motif detection approaches. The results on well-studied benchmark datasets indicate that the presented method outperforms other methods when the sequences become either too long or too heterogeneous in size.
iVici: Interrelational Visualization and Correlation Interface
Authors: Tarassov Kirill , Michnick Stephen W 
Published: December 2005

AbstractWe have developed an application, iVici, to analyze cellular networks represented as addressable symmetric or asymmetric two-dimensional matrices. iVici was designed to permit simultaneous visualization and correlation of multiple datasets, representing any relationship between a set of genes, mRNAs, or proteins. Visual overlay of datasets and addressable access to gene annotations permits comparison of networks of different types (for example protein-protein interactions and genetic networks) or investigation of the dynamic reorganization of a particular network.
Differential effects of statins on relevant functions of human monocyte-derived dendritic cells
Authors: Yilmaz Atilla , Reiss Christine , Weng Alexander , Cicha Iwona , Stumpf Christian , Steinkasserer Alexander , Daniel Werner G , Garlichs Christoph D 
Published: December 2005

Abstract
Statins were shown to possess immunomodulating properties, but the mechanisms of statin effects on the immune system are poorly understood. We analyzed the influence of statins on professional antigen-presenting dendritic cells (DC). Immature DC were cultivated from monocytes of healthy donors. DC maturation was induced by lipopolysaccharide (LPS; 1 μg/mL). Unstimulated and LPS-stimulated DC were treated with simvastatin or atorvastatin (0.1–1 μM). The expression of CD40, CD83, CD86, and human leukocyte antigen-DR on unstimulated and LPS-stimulated DC was reduced significantly by statins, and the expression of Toll-like receptor 2 (TLR2) and TLR4 on LPS-stimulated DC was enhanced temporarily. Statins caused a significant reduction of endocytosis of fluorescein isothiocyanate-dextran by DC. Statins significantly inhibited the basal secretion of interleukin (IL)-6, IL-8, IL-12, and tumor necrosis factor α from unstimulated DC, and their release from LPS-stimulated DC was enhanced. In mixed leukocyte reaction, preincubation of LPS-stimulated DC with statins significantly suppressed their clustering with T cells and their ability to induce T cell proliferation, CD71, and CD25 up-regulation on T cells and the secretion of interferon-γ and IL-2 from T cells. In conclusion, this study showed that statins suppressed endocytosis, basal secretion of proinflammatory cytokines, and the ability of DC to induce T cell proliferation, activation, and T helper cell type 1 differentiation. However, statin preincubation of LPS-stimulated DC caused a further increase in their secretion of proinflammatory cytokines.
Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide
Authors: Fortin Andrée , Harbour Danielle , Fernandes Maria , Borgeat Pierre , Bourgoin Sylvain 
Published: December 2005

AbstractFour types of adenosine receptors have been identified in different tissues and cell types, namely, A1, A2A, A2B, and A3 receptors. We report that A2AR but not A2BR mRNA in freshly isolated polymorphonuclear neutrophils (PMN) is maximally up-regulated after 4 h stimulation with lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α) and to a lesser extent, with interleukin (IL)-1β. These effects were maintained up to 21 h. Consistent with changes in A2AR mRNA expression, up-regulation of A2AR protein was also detected after 4 h of LPS or TNF-α exposure. Up-regulation of A2AR protein expression was transient and returned to near basal levels after 12 h or 16 h stimulation with TNF-α or LPS, respectively. Conversely, IL-1β failed to promote A2AR protein expression. Suppression of thapsigargin-induced leukotriene synthesis by the selective A2AR agonist CGS-21680 was found to be more pronounced when PMN were cultured for 4 h with LPS or TNF-α. In contrast, the up-regulation of A2AR has no impact on CGS-21680-induced inhibition of phospholipase D activation and superoxide production in response to formyl-Met-Leu-Phe. These results demonstrate that the A2AR is up-regulated by specific T helper cell type 1 cytokines and LPS. Although this could represent a potential feedback mechanism to control inflammation, the effect of A2AR up-regulation varied depending on the stimulus used to stimulate PMN functional responses after their incubation with proinflammatory mediators.
Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular, and biochemical studies
Authors: Saini R , Patel S , Saluja R , Sahasrabuddhe A A , Singh M P , Habib S , Bajpai V K , Dikshit M 
Published: December 2005

Abstract
Nitric oxide (NO) modulates diverse functions of polymorphonuclear neutrophils (PMNs), but localization of NO synthase (NOS) and identification of its interacting proteins remain the least defined. The present study discerns subcellular distribution of NOS and caveolin-1, a prominent NOS-interacting protein in rat PMNs. Localization of NOS was explored by confocal and immunogold electron microscopy, and its activity was assessed by L-[3H] arginine and 4,5-diaminofluorescein diacetate (DAF-2DA). Reverse transcriptase-polymerase chain reaction using NOS primers and Western blotting demonstrated the presence of neuronal NOS (nNOS) and inducible NOS (iNOS) in PMNs. Immunocytochemical studies exhibited distribution of nNOS and iNOS in cytoplasm and nucleus, and L-[3H] citrulline formation and DAF fluorescence confirmed NOS activity in both fractions. NOS activity correlated positively with calmodulin concentration in both of the fractions. nNOS and iNOS colocalized with caveolin-1, as evidenced by immunocytochemical and immunoprecipitation studies. The results thus provide first evidence of nNOS and iNOS in the nuclear compartment and suggest NOS interaction with caveolin-1 in rat PMNs.
A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury
Authors: Li Xiaoling , Schwacha Martin G , Chaudry Irshad H , Choudhry Mashkoor A 
Published: December 2005

Abstract
This study examined the role of protein phosphatase type-1 (PP1), type-2A (PP2A), and mitogen-activated protein kinase phosphatase-1 (MKP-1) in altered mesenteric lymph node (MLN) T cell function in a two-hit model of alcohol (EtOH) intoxication and burn injury. Male rats (250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dL prior to burn or sham injury (25% total body surface area). MLN T cells harvested 24 h after injury show a significant decrease in p38 and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation in T cells from rats receiving a combined insult of EtOH intoxication and burn injury compared with rats receiving EtOH intoxication or burn injury alone. Treatment of cells with inhibitors of PP1/PP2A [calyculin A (CA) and okadaic acid (OA)] prevented the suppression in T cells p38 and ERK-1/2 activation. In addition, the suppression in interleukin-2 and interferon-γ production was attenuated in T cells cultured in the presence of CA and OA. MKP-1 inhibitor triptolide did not prevent the suppression in T cells p38/ERK-1/2 and cytokine production. Furthermore, there was a significant decrease in PP1α phosphorylation (Thr320) and an increase in PP2A (Tyr307) phosphorylation in T cells following a combined insult of EtOH intoxication and burn injury. As phosphorylation of PP1 at Thr320 and PP2A at Tyr307 led to an inhibition of their enzymatic activities, the decrease in the PP1α phosphorylation correlates with an increase in its enzyme activity. Thus, these results suggest that activation of PP1 is likely to play a predominant role in T cell suppression following a combined insult of EtOH intoxication and burn injury.
An in vitro Shwartzman reaction-like response is augmented age-dependently in human peripheral blood mononuclear cells
Authors: Motegi Akira , Kinoshita Manabu , Sato Kengo , Shinomiya Nariyoshi , Ono Satoshi , Nonoyama Shigeaki , Hiraide Hoshio , Seki Shuhji 
Published: December 2005

Abstract
A lethal human septic shock model, mouse generalized Shwartzman reaction (GSR), was elicited by two consecutive lippolysaccharide (LPS) injections (24 h apart) in which interferon-γ (IFN-γ) induced by interleukin (IL)-12 played a critical role in the priming phase, and tumor necrosis factor (TNF) was an important effector molecule in the second phase. We recently reported IL-12/LPS-induced mouse GSR age-dependently enhanced. We herein demonstrate that human peripheral blood mononuclear cells (PBMC) from healthy adults/elderly, cultured with IL-12 for 24 h and with LPS for an additional 24 h, produced a much larger amount of TNF (which increased age-dependently) than did PBMC without IL-12 priming. Whereas macrophages mainly produced TNF following LPS stimulation, macrophages and lymphocytes were necessary for a sufficient TNF production. IL-12-induced IFN-γ up-regulated Toll-like receptor 4 (TLR-4) on macrophages of adults. Although the PBMC from children produced a substantial amount of IFN-γ after IL-12 priming, the GSR response, with augmented TNF production and an up-regulated TLR-4 expression of macrophages, was not elicited by LPS stimulation. CD56+ natural killer cells, CD56+T cells, and CD57+T cells (NK-T cells), which age-dependently increased in PBMC, produced much larger amounts of IFN-γ after IL-12 priming than that of conventional CD56−CD57−T cells and also induced cocultured macrophages to produce TNF by subsequent LPS stimulation. The elder septic patients were consistently more susceptible to lethal shock with enhanced serum TNF levels than the adult patients. The NK cells, NK-T cells, and macrophages, which change proportionally or functionally with aging, might be involved in the enhanced GSR response/septic shock observed in elderly patients.
Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population
Authors: Grimaldi Maria Paola , Candore Giuseppina , Vasto Sonya , Caruso Marco , Caimi Gregorio , Hoffmann Enrico , Colonna-Romano Giuseppina , Lio Domenico , Shinar Yael , Franceschi Claudio , Caruso Calogero 
Published: December 2005

Abstract
A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti-inflammatory status. To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF) may play an opposite role in CHD and in longevity, we examined three FMF-associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infarction (AMI), in 68 centenarians, and in 196 age-matched controls from Sicily. None of the Sicilian subjects studied carried the V726A and the M694I FMF-related mutations. The proinflammatory M694V (A2080G) mutation was the only one we found, which was over-represented significantly in CHD patients and under-represented in oldest old, and intermediate values were in healthy, young controls. After adjustment for well-recognized AMI risk factors, the M694V allele still predicted a significant risk to develop AMI. So, according to these results, we suggest that carrying the proinflammatory M694V pyrin allele may increase the risk to develop AMI. Conversely, the wild-type pyrin genotype may predispose to a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics. All these data indicate a strong relationship among inflammation, genetics, CHD, and longevity.
Uric acid, a nucleic acid degradation product, down-regulates dsRNA-triggered arthritis
Authors: Zare Fariba , Magnusson Mattias , Bergström Tomas , Brisslert Mikael , Josefsson Elisabet , Karlsson Anna , Tarkowski Andrej 
Published: December 2005

Abstract
Uric acid, the naturally occurring degradation product of purine metabolism, is a danger signal, driving maturation of dendritic cells. It is well known that uric acid crystals display potent proinflammatory properties—the cause of gout—whereas the biological properties of soluble uric acid are less well documented. We have demonstrated previously that nucleic acids of endogenous and exogenous origin display proinflammatory properties. The aim of the present study was to assess the impact of soluble uric acid on in vivo inflammatory responses. Mice were administered with uric acid suspension in saline or saline alone prior to induction of neutrophil-mediated inflammation, delayed-type hypersensitivity, histamin-induced edema (measure of vasodilation capacity), as well as double-stranded (ds)RNA-triggered arthritis. Frequency and severity of arthritis were decreased significantly in mice exposed to dsRNA and simultaneously treated with uric acid as compared with saline-treated controls. Also, granulocyte-mediated inflammatory response and vasodilation capacity were reduced significantly in mice treated with uric acid as compared with their control group. The data suggest that down-regulation of inflammation was mediated by skewing the inflammatory response from the peripheral sites to the peritoneal cavity and down-regulating vasodilatatory capacity and thereby affecting leukocyte migration. In contrast, the T cell-mediated delayed-type hypersensitivity reaction was not affected significantly in mice exposed to uric acid. These findings demonstrate that uric acid displays a potent, distant anti-inflammatory effect in vivo. This property seems to be mediated by down-regulation of neutrophil influx to the site of inflammatory insult.
Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72
Authors: Johnson John D , Fleshner Monika 
Published: December 2005

Abstract
Heat shock proteins (Hsp) were first characterized as intracellular proteins, which function to limit protein aggregation, facilitate protein refolding, and chaperone proteins. During times of cellular stress, intracellular Hsp levels increase to provide cellular protection. Recently, it has been recognized that Hsp, particularly Hsp72, are also found extracellularly (eHsp72), where they exhibit potent immunomodulatory effects on innate and acquired immunity. Circulating eHsp72 levels also greatly increase during times of stress (i.e., when an organism is exposed to a physical/psychological stressor or suffers from various pathological conditions). It has been proposed that elevated eHsp72 serves a protective role by facilitating immunological responses during times of increased risk of pathogenic challenge and/or tissue damage. This review focuses on the in vivo releasing signals and immunomodulatory function(s) of endogenous eHsp72. In addition, we present data that emphasize the importance of caution when conducting in vitro immunological tests of Hsp72 function.