bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21
Authors: Pierce E. M. , Carpenter K. , Jakubzick C. , Kunkel S. L. , Evanoff H. , Flaherty K. R. , Martinez F. J. , Toews G. B. , Hogaboam C. M. 
Published: March 2007

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsy specimens from IPF/UIP patients exhibit focal expression of CC chemokine receptor (CCR) 7, but the identity of these CCR7-positive cells is unknown. The purpose of the present study was to examine the functional and signalling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsy specimens.Primary fibroblasts were cultured from surgical lung biopsy specimens from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analysed for functional, transcriptional and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, and migration, proliferation and Western blot assays.CCR7 was expressed by IPF/UIP fibroblasts, but not normal fibroblasts. IPF/UIP fibroblasts, but not normal fibroblasts, showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralising antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2 and ribosomal S6 kinase (90 kDa) in these cells; this was abrogated by pertussis toxin or CCR7-specific small interfering RNA.Together, these data demonstrate that CC chemokine ligand 21 modulates the functional properties of idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblasts, but not normal fibroblasts.
Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD
Authors: Löfdahl C-G. , Postma D. S. , Pride N. B. , Boe J. , Thorén A. 
Published: March 2007

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events.The current authors performed apost hocanalysis of the European Respiratory Society’s study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 μg·day−1in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia.Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%).The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.
Activation of E-prostanoid4and E-prostanoid2receptors inhibits TNF-α release from human alveolar macrophages
Authors: Ratcliffe M. J. , Walding A. , Shelton P. A. , Flaherty A. , Dougall I. G. 
Published: March 2007

Prostaglandin (PG)E2has been shown to inhibit mediator release from human alveolar macrophages (AMs), but the prostanoid receptor(s) mediating this response have not yet been documented. To investigate this, the present authors conducted a range of pharmacological and expression-based studies in monocyte-derived macrophages (MDMs) and AMs.MDMs were obtained byin vitrodifferentiation of monocytes from the peripheral blood of healthy human volunteers. Human AMs were obtained by perfusion of lung tissue from carcinoma resection patients.In MDMs, PGE2potently inhibited lipopolysaccharide-induced tumour necrosis factor (TNF)-α release (p[A]508.51±0.11, maximum inhibition 95.9±4.8%). In human AMs, PGE2also inhibited TNF-α release but the observed concentration–effect curve was very flat and inhibition was incomplete. The shape of the PGE2curve in AMs suggested that its effects were mediated by activation of a heterogeneous receptor population. Expression studies combined with the use of various E-prostanoid (EP) receptor agonists and a selective EP4-receptor antagonist (Ono-AE2-227) confirmed that the inhibitory effects of PGE2in both AMs and MDMs were mediated by activation of EP4and EP2receptors.These data indicate that both E-prostanoid4and E-prostanoid2selective agonists may have anti-inflammatory properties in lung diseases where macrophages play a role.
Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics
Authors: Simionato Elena , Ledent Valérie , Richards Gemma , Thomas-Chollier Morgane , Kerner Pierre , Coornaert David , Degnan Bernard M , Vervoort Michel 
Published: March 2007

AbstractBackgroundMolecular and genetic analyses conducted in model organisms such asDrosophilaand vertebrates, have provided a wealth of information about how networks of transcription factors control the proper development of these species. Much less is known, however, about the evolutionary origin of these elaborated networks and their large-scale evolution. Here we report the first evolutionary analysis of a whole superfamily of transcription factors, the basic helix-loop-helix (bHLH) proteins, at the scale of the whole metazoan kingdom.ResultsWe identifiedin silicothe putative full complement of bHLH genes in the sequenced genomes of 12 different species representative of the main metazoan lineages, including three non-bilaterian metazoans, the cnidariansNematostella vectensisandHydra magnipapillataand the demospongeAmphimedon queenslandica. We have performed extensive phylogenetic analyses of the 695 identified bHLHs, which has allowed us to allocate most of these bHLHs to defined evolutionary conserved groups of orthology.ConclusionThree main features in the history of the bHLH gene superfamily can be inferred from these analyses: (i) an initial diversification of the bHLHs has occurred in the pre-Cambrian, prior to metazoan cladogenesis; (ii) a second expansion of the bHLH superfamily occurred early in metazoan evolution before bilaterians and cnidarians diverged; and (iii) the bHLH complement during the evolution of the bilaterians has been remarkably stable. We suggest that these features may be extended to other developmental gene families and reflect a general trend in the evolution of the developmental gene repertoires of metazoans.
Serotypes, virulence genes and intimin types of Shiga toxin (verocytotoxin)-producing Escherichia coli isolates from minced beef in Lugo (Spain) from 1995 through 2003
Authors: Mora Azucena , Blanco Miguel , Blanco Jesús E , Dahbi Ghizlane , López Cecilia , Justel Paula , Alonso María Pilar , Echeita Aurora , Bernárdez María Isabel , González Enrique A , Blanco Jorge 
Published: March 2007

Abstract
Background
Shiga toxin-producing Escherichia coli (STEC) have emerged as pathogens that can cause food-borne infections and severe and potentially fatal illnesses in humans, such as haemorrhagic colitis (HC) and haemolytic uraemic syndrome (HUS). In Spain, like in many other countries, STEC strains have been frequently isolated from ruminants, and represent a significant cause of sporadic cases of human infection. In view of the lack of data on STEC isolated from food in Spain, the objectives of this study were to determine the level of microbiological contamination and the prevalence of STEC O157:H7 and non-O157 in a large sampling of minced beef collected from 30 local stores in Lugo city between 1995 and 2003. Also to establish if those STEC isolated from food possessed the same virulence profiles as STEC strains causing human infections.

Results
STEC were detected in 95 (12%) of the 785 minced beef samples tested. STEC O157:H7 was isolated from eight (1.0%) samples and non-O157 STEC from 90 (11%) samples. Ninety-six STEC isolates were further characterized by PCR and serotyping. PCR showed that 28 (29%) isolates carried stx1 genes, 49 (51%) possessed stx2 genes, and 19 (20%) both stx1 and stx2. Enterohemolysin (ehxA) and intimin (eae) virulence genes were detected in 43 (45%) and in 25 (26%) of the isolates, respectively. Typing of the eae variants detected four types: γ1 (nine isolates), β1 (eight isolates), ε1 (three isolates), and θ (two isolates). The majority (68%) of STEC isolates belonged to serotypes previously detected in human STEC and 38% to serotypes associated with STEC isolated from patients with HUS. Ten new serotypes not previously described in raw beef products were also detected. The highly virulent seropathotypes O26:H11 stx1eae-β1, O157:H7 stx1stx2eae-γ1 and O157:H7 stx2eae-γ1, which are the most frequently observed among STEC causing human infections in Spain, were detected in 10 of the 96 STEC isolates. Furthermore, phage typing of STEC O157:H7 isolates showed that the majority (seven of eight isolates) belonged to the main phage types previously detected in STEC O157:H7 strains associated with severe human illnesses.

Conclusion
The results of this study do not differ greatly from those reported in other countries with regard to prevalence of O157 and non-O157 STEC in minced beef. As we suspected, serotypes different from O157:H7 also play an important role in food contamination in Spain, including the highly virulent seropathotype O26:H11 stx1eae-β1. Thus, our data confirm minced beef in the city of Lugo as vehicles of highly pathogenic STEC. This requires that control measures to be introduced and implemented to increase the safety of minced beef.
Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation
Authors: Bautmans Ivan , Gorus Ellen , Njemini Rose , Mets Tony 
Published: March 2007

Abstract

Background
Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons.

Methods
Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed.

Results
In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight.

Conclusion
Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.
SOD2polymorphisms: unmasking the effect of polymorphism on splicing
Authors: Shao Jing , Chen Lishan , Marrs Brian , Lee Lin , Huang Hai , Manton Kenneth G , Martin George M , Oshima Junko 
Published: March 2007

Abstract

Background
The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging.

Results
We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon.
We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism.

Conclusion
Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders.
Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis
Authors: Jiang Yan-Nian , Li Yi-Hung , Ke Meng-Wei , Tseng Ting-Yu , Tang Yueh-Bih , Huang Mu-Chiou , Cheng Winston Teng-Kuei , Ju Yu-Ten 
Published: March 2007

Abstract

Background
Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma.

Results
The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine.

Conclusion
Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.
Knee meniscal extrusion in a largely non-osteoarthritic cohort: association with greater loss of cartilage volume
Authors: Ding Changhai , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Abram François , Raynauld Jean-Pierre , Cicuttini Flavia , Jones Graeme 
Published: March 2007

Abstract
We conducted a longitudinal study (duration 2 years), including 294 individuals (mean age 45 years, 58% female), in order to examine associations between meniscal extrusion, knee structure, radiographic changes and risk factors for osteoarthritis (OA) in a largely non-osteoarthritic cohort. Meniscal extrusion, tibiofemoral cartilage defect score and cartilage volume, and tibial plateau bone area were determined using T1-weighted fat-saturated magnetic resonance imaging. At baseline the presence of medial meniscal extrusion was significantly associated with body mass index (odds ratio [OR] per kg/m2 = 1.13, 95% confidence interval [CI] = 1.02–1.25), past knee injury (positive versus negative history: OR = 3.73, 95% CI = 1.16–11.97), medial tibial bone area (OR per cm2 = 1.37, 95% CI = 1.02–1.85), and osteophytes (OR per grade = 4.89, 95% CI = 1.59–15.02). Two-year longitudinal data revealed that medial meniscal extrusion at baseline was associated with a greater rate of loss of medial tibiofemoral cartilage volume (extrusion versus no extrusion: -1.4%/year; P < 0.05) and greater risk for increased medial femoral cartilage defects (OR = 2.59, 95% CI = 1.14–5.86) and lateral tibial cartilage defects (OR = 2.64, 95% CI = 1.03–6.76). However, the latter two associations became nonsignificant after adjustment for tibial bone area and osteophytes. This study suggests that increasing body mass index and bone size, past knee injury, and osteophytes may be causally related to meniscal extrusion. Most importantly, meniscal extrusion at baseline is associated with greater loss of knee cartilage over 2 years, and this seems to be mediated mostly by subchondral bone changes, suggesting extrusion represents one pathway between bone expansion and cartilage loss.
'I'm OK?' Evaluation of a new walk-in quick-check clinic
Authors: Handy P , Pattman R S , Richards J 
Published: March 2007

Following concerns about asymptomatic people having to wait 2–3 weeks for a standard appointment for screening a new 'I'm OK?' drop-in, nurse-led clinic for the worried well was devised and evaluated after the first 21 weeks (509 patients). Without overt advertising the clinic has run to near capacity and has proved popular, with 98% stating that they would attend such a clinic in the future. The chlamydia detection rate was 9% in women and 4% in men, with one case of asymptomatic rectal gonorrhoea and two of HIV infection diagnosed allowing early treatment intervention. HIV testing was accepted by 94% of attendees and initial hepatitis B vaccination by 93% of homosexual/bisexual men. This approach deflects such routine cases, potentially allowing increased time at standard clinic sessions for those with clinical problems staffed by more experienced nurses and doctors. Its success has encouraged us to develop this concept as a cost-effective way of addressing 48-hour genitourinary medicine access.
HPLC for Simultaneous Quantification of Total Ceramide, Glucosylceramide, and Ceramide Trihexoside Concentrations in Plasma
Authors: Groener Johanna EM , Poorthuis Ben JHM , Kuiper Sijmen , Helmond Mariette TJ , Hollak Carla EM , Aerts Johannes MFG 
Published: March 2007

AbstractBackground: Simple, reproducible assays are needed for the quantification of sphingolipids, ceramide (Cer), and sphingoid bases. We developed an HPLC method for simultaneous quantification of total plasma concentrations of Cer, glucosylceramide (GlcCer), and ceramide trihexoside (CTH).Methods: After addition of sphinganine as internal calibrator, we extracted lipids from 50 μL plasma. We deacylated Cer and glycosphingolipids by use of microwave-assisted hydrolysis in methanolic NaOH, followed by derivatization of the liberated amino-group with o-phthaldialdehyde. We separated the derivatized sphingoid bases and lysoglycosphingolipids by HPLC on a C18 reversed-phase column with a methanol/water mobile phase (88:12, vol/vol) and quantified them by use of a fluorescence detector at λex 340 nm and λem 435 nm.Results: Optimal conditions in the Solids/Moisture System SAM-155 microwave oven (CEM Corp.) for the complete deacylation of Cer and neutral glycosphingolipids without decomposition were 60 min at 85% power, fan setting 7. Intra- and interassay CVs were &lt;4% and &lt;14%, respectively, and recovery rates were 87%–113%. The limit of quantification was 2 pmol (0.1 pmol on column), and the method was linear over the interval of 2–200 μL plasma. In samples from 40 healthy individuals, mean (SD) concentrations were 9.0 (2.3) μmol/L for Cer, 6.3 (1.9) μmol/L for GlcCer, and 1.7 (0.5) μmol/L for CTH. Plasma concentrations of GlcCer were higher in Gaucher disease patient samples and of CTH in Fabry disease patient samples.Conclusions: HPLC enables quantification of total Cer, GlcCer, and CTH in plasma and is useful for the follow-up of patients on therapy for Gaucher or Fabry disease.
Negative-Ion Chemical Ionization Gas Chromatography–Mass Spectrometry Assay for Enantioselective Measurement of Amphetamines in Oral Fluid: Application to a Controlled Study with MDMA and Driving Under the Influence Cases
Authors: Peters Frank T , Samyn Nele , Kraemer Thomas , Riedel Wim J , Maurer Hans H 
Published: March 2007

AbstractBackground: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID).Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S-heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases.Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data.Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.