bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn’s disease
Authors: KÜBLER I. , KOSLOWSKI M. J. , GERSEMANN M. , FELLERMANN K. , BEISNER J. , BECKER S. , ROTHFUSS K. , HERRLINGER K. R. , STANGE E. F. , WEHKAMP J. 
Published: June 2009

SummaryBackground  Crohn’s Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the α‐ and β‐defensins. Little is known about in vivo effects of common drugs on their expression.Aim  To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation.Methods  We measured the expression of antimicrobial peptides and pro‐inflammatory cytokines in 75 patients with active CD.Results  Ileal and colonic α‐ and β‐defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell α‐defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples.Conclusions  Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity.
Clinoform quantification for assessing the effects of external forcing on continental margin development
Authors: Kertznus Vanessa , Kneller Ben 
Published: June 2009

ABSTRACTThe Ebro continental margin is characterized by a complex pattern of well‐developed, highly progradational and aggradational, margin‐scale clinoforms. Analysis of conventional 3D seismic reflection data combined with quantitative analyses of margin growth rates, slope geometries, incisional features and shelf‐edge trajectories through time, provides further insights into the signal imposed by externally driven mechanisms on continental margin stratigraphy. Three phases of construction characterize the Ebro continental margin evolution since the Messinian Salinity Crisis. These phases reflect the changes in the climate/sea‐level cyclicity from the Pliocene to the Pleistocene and its effects on sediment supply and sedimentary processes. Nonetheless, morphodynamic feedbacks of the system had a profound effect on the mechanisms of margin growth and sediment distribution. The frequency and amplitude of the progradational pulses of the system follows the trend of climate/sea level as indicated by oxygen isotope records. Generally, major steps of progradation are coeval with pulses towards glacial development. However, the amplitudes of the peaks do not always correlate due to the effects of other variables that are less directly dependent on climate, in particular, modifications of the progradational trends by mass‐wasting processes. The increase in sediment supply and accommodation creation during the Pleistocene along with the progradation of the system into deeper water resulted in progressively steeper slope gradients. Consequently, mass‐wasting processes became the primary sediment delivery mechanism during the Pleistocene. In addition, cross‐shelf incised valleys are not observed throughout the succession, therefore, widely accepted mechanisms of sediment delivery across continental margins and the classic sequence stratigraphic model for margin development are called into question in this system. Quantification of the slope curvature throughout the succession reveal that sigmoidal clinoform profiles correspond to un‐modified slopes while exponential geometries result from a modification of the original shape of the slope by erosional processes.
Influence of point‐source sediment‐supply on modern shelf‐slope morphology: implications for interpretation of ancient shelf margins
Authors: Olariu Cornel , Steel Ronald J. 
Published: June 2009

ABSTRACTPresent sea‐floor bathymetry indicates that the continental‐shelf and shelf‐break morphology have some unique and predictable characteristics in areas with and without high sediment supply. Using a global bathymetry dataset in open shelf areas in front of rivers that discharge over 25 × 106 tons of sediment per year, five distinct accretionary types of shelf‐break are distinguished based on along‐shelf gradient variability and inferred shelf‐break trajectory. Morphological characteristics of river‐mouth shelves (compared with adjacent areas lateral to the immediate fairway of the river) are: (1) an overall lower gradient and greater width, and (2) a relatively high slope gradient/shelf gradient ratio. The exceptions are shelves with active shelf‐edge deltas; these are narrower, steeper and have an attenuated shelf break in front of rivers. These observations are at seismic scale and have direct implications for the recognition and positioning of principal cross‐shelf, supply fairways on ancient shelves or shelf margins, and therefore the potential by‐pass routes for deepwater sands. Higher slope/shelf gradient ratios in areas of actively accreting margins, where the shelf‐break is more prominent and easier to recognize on seismic data compared with adjacent areas, predict areas with high sediment supply. Along‐strike morphological changes on supply‐dominated shelves suggest that identification of the sediment‐feed route and depocenter relative to the shelf break during a relative sea level cycle are critical for understanding/predicting the 3‐D architecture of the shelf‐slope‐basin floor clinoform.
Detailed mapping of marine erosional surfaces and the geometry of clinoforms on seismic data: a tool to identify the thickest reservoir sand
Authors: Rasmussen E. S. 
Published: June 2009

ABSTRACTDeltaic sediments of the Billund and Bastrup sands were deposited in a ramp setting in the storm‐dominated North Sea during the early Miocene. A marked relief in the hinterland and the relatively high precipitation resulted in a high sediment supply to the sea and progradation of major delta‐coastal plains south of the present‐day Norway. The focus of this study is on the forced regressive wedge system tracts of the two delta complexes, which show remarkably well‐developed marine erosional surfaces associated with sand‐rich packages characterised by steeply dipping clinoforms (up to 10°). The well‐developed clinoformal packages indicate that deposition occurred in water depths of 60–100 m even under a sea‐level fall. The sand‐rich delta lobes also demonstrate that it was a high‐energy environment and that wave‐generated re‐suspension at the delta front effectively re‐sorted the sediments and sand‐rich systems became separated from mud‐dominated portions of the delta complexes. The evolution of the above occurred in a basin that has been exposed by inversion tectonism. The sediment supply was consequently high. During deposition, eustatic sea‐level changes strongly controlled the evolution of sequences. The results found in this study may be applicable for mapping reservoir sands in ramp settings and in rift basins especially when looking for reservoir rocks in the basinal setting or when carrying out detailed reservoir mapping in already existing hydrocarbon fields.
Drug cross‐resistance and therapy‐induced resistance in chronic lymphocytic leukaemia by an enhanced method of individualised tumour response testing
Authors: Bosanquet Andrew G. , Richards Sue M. , Wade Rachel , Else Monica , Matutes Estella , Dyer Martin J. S. , Rassam Saad M. B. , Durant Justin , Scadding Sheila M. , Raper Steve L. , Dearden Claire E. , Catovsky Daniel 
Published: June 2009

SummaryPrevious results with individualised tumour response testing (ITRT) in vitro in chronic lymphocytic leukaemia (CLL) have consistently shown good correlation with patient response and survival. We describe here an improved test and report its use with samples from the Leukaemia Research Fund CLL4 randomised clinical trial and previously treated patients. ITRT was performed by the tumour response to anti‐neoplastic compounds (TRAC) assay, a modification of the differential staining cytotoxicity (DiSC) assay. Improvements included drying drugs into wells before assay and using the Octospot system to cytocentrifuge eight spots of cells onto one microscope slide. We successfully tested 765/782 (98%) cellular blood samples received within 48 h of phlebotomy. Cross‐resistance (Pearson’s r > 0·7) in untreated CLL was found between similar drugs. Mitoxantrone (r = 0·31), cyclophosphamide (r = 0·35) and pentostatin (r = 0·29) had low cross‐resistance with fludarabine. Treatment resulted in increased resistance to chlorambucil, cyclophosphamide, doxorubicin, mitoxantrone, corticosteroids, cladribine and fludarabine (P < 0·01) but not to pentostatin. These results provide further rationale for standard drug combinations such as fludarabine‐mitoxantrone and fludarabine‐mitoxantrone‐cyclophosphamide and suggest possible pentostatin salvage in fludarabine‐resistant patients. ITRT results could assist both in determining the best treatment for individual patients and in the design and rationale of future clinical trials.
Cytolytic T‐cell response to the PASD1 cancer testis antigen in patients with diffuse large B‐cell lymphoma
Authors: Ait‐Tahar Kamel , Liggins Amanda P. , Collins Graham P. , Campbell Andrew , Barnardo Martin , Lawrie Charles , Moir Donald , Hatton Chris , Banham Alison H. , Pulford Karen 
Published: June 2009

SummaryThe identification of immunogenic cancer testis antigens (CTAs) as immunotherapeutic targets represents one approach to improve treatment options for diffuse large B‐cell lymphoma (DLBCL). We previously identified PASD1 [PAS (Per ARNT Sim) domain containing 1 (PASD1)], a DLBCL‐associated CTA that was expressed in a range of hematopoietic malignancies. The aim of the present study was to investigate the presence of a cytotoxic T‐cell (CTL) response to PASD1 in DLBCL patients. A significant γ‐interferon (IFN) release was detected in 21/29 HLA‐A*0201‐positive DLBCL patients (18 de novo DLBCL, two transformed DLBCL and one T‐cell rich B‐cell lymphoma) following short‐term culture of their peripheral blood mononuclear cells stimulated with five HLA‐A*0201‐restricted PASD1 peptides. No significant responses were detected in 21 HLA‐A*0201‐negative DLBCL patients (12 de novo DLBCL, seven transformed DLBCL, two T‐cell rich B‐cell lymphoma) or six normal subjects. CTL cell lines were able to lyse PASD1‐positive tumour cells in a major histocompatibility complex‐Class I dependent manner. The presence of a γ‐IFN response correlated with PASD1 protein expression in the tumour cells in 12/15 cases studied. This is the first report of a CTL response to a CTA in DLBCL. Our results provide additional valuable evidence supporting PASD1 as a potential immunotherapeutic target for the treatment of DLBCL and other malignancies.
Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study
Authors: Woodward Mark , Tunstall‐Pedoe Hugh , Rumley Ann , Lowe Gordon D. O. 
Published: June 2009

SummaryPlasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30–74 years, initially free of CVD. After follow‐up for a median of 19·2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio‐economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1·09 (1·02, 1·16) for men and 1·10 (1·02, 1·19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1·3% and 3·2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost‐effective.
Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus
Authors: Skevaki C. L. , Christodoulou I. , Spyridaki I. S. , Tiniakou I. , Georgiou V. , Xepapadaki P. , Kafetzis D. A. , Papadopoulos N. G. 
Published: June 2009

SummaryBackground
Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro‐inflammatory and remodelling‐associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus‐induced inflammation and remodelling are less known.Objective
We investigated whether BUD and FORM synergize in suppressing RV‐induced inflammation and remodelling in the airways.Methods
In vitro models of RV infection of BEAS‐2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post‐infection, at a clinically relevant concentration range (10−6–10−10 m), on the production of CCL5, CXCL10, CXCL8, IL‐6 and the remodelling‐associated VEGF and bFGF, using ELISA and RT‐PCR.Results
BUD effectively suppressed RV‐mediated induction of all mediators studied, in a concentration‐dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration‐dependent, additive or synergistic effects in the suppression of RV‐induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV‐induced IL‐6, and CCL5 at the mRNA level as compared with BUD or FORM alone.Conclusion
BUD and FORM suppress RV‐induced chemokines and growth factors in bronchial epithelial cells in a concentration‐dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.
Prevalence of clinical remission in patients with sporadic idiopathic hypoparathyroidism
Authors: Goswami Ravinder , Goel Siya , Tomar Neeraj , Gupta Nandita , Lumb Vanshika , Sharma Yagya Dutta 
Published: June 2009

SummaryBackground  Remission of disease activity is a characteristic feature of autoimmune endocrine disorders such as Graves’ disease, Addison’s disease and occasionally in patients with premature ovarian failure. Autoimmunity is also implicated in sporadic idiopathic hypoparathyroidism (SIH) with clinical remission of disease reported in three cases.Objective  To assess the rate of remission in patients with sporadic idiopathic hypoparathyroidism and review the cases reported so far.Subjects and methods  Subjects included 53 patients (M:F, 24:29) with SIH who had been symptomatic for at least 1 year (range 1–31 years). They were treated with calcium and 1‐α‐(OH)D3/cholecalciferol therapy and had a mean duration of follow up of 5·0 ± 3·2 years. Treatment was withdrawn in two stages in the patients who maintained normal levels of serum total calcium during the preceding year of treatment. In stage‐1, the dose of therapy was reduced to half and subsequently all treatment was stopped (stage 2) in those patients who maintained normal serum total calcium levels on the reduced dose. Remission of SIH was defined as maintenance of normal serum total (≥2·12 mmol/l) and ionized calcium, inorganic phosphorus and serum intact parathyroid hormone (iPTH) for at least 3 months after withdrawal of calcium and 1‐α‐(OH)D3/cholecalciferol therapy. Calcium sensing receptor autoantibodies (CaSRAb) were determined by Western blot.Results  Two of the 53 patients (3·8%) with SIH stayed in remission for 1 year after complete withdrawal of therapy. CaSRAb was absent in both the cases. The clinical features, age at onset and duration of hypocalcaemic symptoms in cases with remission were comparable to those who did no show remission.Conclusion  Sporadic idiopathic hypoparathyroidism is not irreversible as is widely believed and spontaneous remission of disease may occur in 3·8% of patients.
High cortisol levels in hyperglycaemic myocardial infarct patients signify stress hyperglycaemia and predict subsequent normalization of glucose tolerance
Authors: Carmen Wong K. Y. , Wong Vincent , Ho Jui T. , Torpy David J. , McLean Mark , Cheung N. Wah 
Published: June 2009

SummaryContext  It is unclear if people who develop stress hyperglycaemia have underlying abnormal glucose metabolism, an exaggerated hormonal response to stress, or both. Similarly, it is unknown whether stress hyperglycaemia predicts future glucose intolerance.Objective  To determine the relationship between illness severity and plasma cortisol concentration with the degree of hyperglycaemia in subjects experiencing acute myocardial infarction (AMI), and their later glucose metabolic status.Patients and design  This analysis comprised 55 patients from the HI‐5 Study – a randomized control trial of insulin‐glucose infusion therapy for AMI patients with hyperglycaemia.Main outcome measures  Blood glucose level (BGL) as well as total and free cortisol levels on admission were measured. Patients not previously known to have diabetes were assessed for abnormal glucose metabolism following discharge.Results  Patients with ST segment‐elevation myocardial infarction (STEMI) and higher peak creatinine kinase level had a higher mean admission total and free cortisol level. As many as 38·5% of subjects were found to have newly diagnosed glucose intolerance at follow up. After multiple logistic regression, admission BGL was found to be a positive predictor (P = 0·027) whereas total cortisol level (P = 0·01) was a negative predictor for glucose intolerance.Conclusions  Both the level of hyperglycaemia and cortisol levels on admission are predictive for the subsequent abnormal glucose tolerance development in hyperglycaemic AMI patients. Hyperglycaemia in patients who are more unwell (i.e. higher cortisol) reflects the stressed state rather than underlying glucose intolerance. Conversely, if the patient is less sick (i.e. lower cortisol), hyperglycaemia is more likely to reflect underlying glucose intolerance.
Short‐term overt hypothyroidism induces sympathovagal imbalance in thyroidectomized differentiated thyroid carcinoma patients
Authors: Heemstra Karen A. , Burggraaf Jacobus , Van Der Klaauw Agatha A. , Romijn Johannes A. , Smit Johannes W.A. , Corssmit Eleonora P.M. 
Published: June 2009

SummaryContext  Thyroid hormone impacts on the cardiovascular system. (Subclinical) hyperthyroidism results in sympathovagal imbalance due to decreased vagal tone. However, conflicting data have been reported on the effects of hypothyroidism on the activity of the autonomic nervous system (ANS). In hypothyroidism, both increased and decreased sympathetic activity and increased vagal tone have been found.Objective  To study the effects of acute short‐term overt hypothyroidism and thyroxine replacement therapy on the ANS by measuring urinary excretion of catecholamines and heart rate variability (HRV).Design  Prospective study.Setting  University hospital.Patients  We studied 11 patients, previously treated with thyroidectomy for differentiated thyroid carcinoma, during hypothyroidism caused by cessation of thyroxine substitution for 4 weeks and during thyroxine replacement therapy, and 21 matched healthy controls.Main outcome measures  The activity of the ANS was assessed by measuring urinary excretion of catecholamines and HRV at rest and during a challenge of the ANS by a mental stress test.Results  Urinary dopamine excretion was significantly lower during hypothyroidism. Although in the patients total variability was unchanged, HRV analysis showed a significantly lower low frequency/high frequency ratio, indicating sympathovagal imbalance with sympathetic withdrawal. The mental stress test in the patients resulted in a significant increase in heart rate to the extent of 16–18%. This response was not different between the hypothyroid state and during thyroxine replacement therapy suggesting that cardiovascular reflexes in these patients remain intact.Conclusion  Acute short‐term overt hypothyroidism results in sympathovagal imbalance with sympathetic withdrawal, with preservation of the cardiovascular reflexes to (mental) stress.
Partitioning of metals (Cd, Co, Cu, Ni, Pb, Zn) in soils: concepts, methodologies, prediction and applications – a review
Authors: Degryse F. , Smolders E. , Parker D. R. 
Published: June 2009

SummaryPrediction of the fate of metals in soil requires knowledge of their solid–liquid partitioning. This paper reviews analytical methods and models for measuring or predicting the solid–liquid partitioning of metals in aerobic soils, and collates experimental data. The partitioning is often expressed with an empirical distribution coefficient or Kd, which gives the ratio of the concentration in the solid phase to that in the solution phase. The Kd value of a metal reflects the net effect of various reactions in the solid and liquid phases and varies by orders of magnitude among soils. The Kd value can be derived from the solid–liquid distribution of added metal or that of the soil‐borne metal. Only part of the solid‐phase metal is rapidly exchangeable with the solution phase. Various methods have been developed to quantify this ‘labile’ phase, and Kd values based on this phase often correlate better with soil properties than Kd values based on total concentration, and are more appropriate to express metal ion buffering in solute transport models. The in situ soil solution is the preferred solution phase for Kd determinations. Alternatively, water or dilute‐salt extracts can be used, but these may underestimate in situ concentrations of dissolved metals because of dilution of metal‐complexing ligands such as dissolved organic matter. Multi‐surface models and empirical models have been proposed to predict metal partitioning from soil properties. Though soil pH is the most important soil property determining the retention of the free metal ion, Kd values based on total dissolved metal in solution may show little pH dependence for metal ions that have strong affinity for dissolved organic matter. The Kd coefficient is used as an equilibrium constant in risk assessment models. However, slow dissociation of metal complexes in solution and slow exchange of metals between labile and non‐labile pools in the solid phase may invalidate this equilibrium assumption.