bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD59 Efficiently Protects Human NT2‐N Neurons Against Complement‐mediated Damage
Authors: Pedersen E. D. , Aass H. C. D. , Rootwelt T. , Fung M. , Lambris J. D. , Mollnes T. E. 
Published: July 2007

AbstractThe complement regulatory protein CD59 controls cell survival by the inhibition of C5b–9 formation on the cell membrane. Loss of CD59 increases the susceptibility of cells to complement‐mediated damage and lysis. Deposition of IgM can induce complement activation with subsequent cell death. We have previously demonstrated the presence of CD59 on human NT2‐N neurons. In this study, we investigated the functional role of CD59 for NT2‐N cell survival after IgM‐mediated complement activation. Complement activation was induced on NT2‐N neurons with human serum following incubation with the IgM monoclonal antibody A2B5 reacting with a neuronal cell membrane epitope. Deposition of C1q and C5b–9 was detected on the cell membrane and sC5b–9 in the culture supernatant. Specific inhibition of complement was obtained by the C3 inhibitor compstatin, and by anti‐C5/C5a MoAb. CD59 was blocked by the MoAb BRIC 229. Membrane damage of propidium iodide‐stained NT2‐N cells was confirmed by immunofluorescence microscopy and degeneration of neuronal processes was shown with crystal violet staining. A2B5, but not the irrelevant control IgM antibody, induced complement activation on NT2‐N neurons after incubation with a human serum, as detected by the deposition of C1q. A marked membrane deposition of C5b–9 on NT2‐N neurons with accompanying cell death and axonal degeneration was found after the blocking of CD59 with MoAb BRIC 229 but not with an isotype‐matched control antibody. Compstatin and anti‐C5 monoclonal antibodies which blocked C5 activation efficiently inhibited complement activation. In conclusion, CD59 is essential for protecting human NT2‐N neurons against complement‐mediated damage, which is known to occur in a number of clinical conditions including stroke.
CD4+CD25+Foxp3+ Indirect Alloreactive T cells from Renal Transplant Patients Suppress Both the Direct and Indirect Pathways of Allorecognition
Authors: Spadafora‐Ferreira M. , Caldas C. , Faé K. C. , Marrero I. , Monteiro S. M. , Lin‐Wang H. T. , Socorro‐Silva A. , Fonseca S. G. , Fonseca J. A. , Kalil J. , Coelho V. 
Published: July 2007

AbstractAlloreactive T cells recognize donor antigens by two routes: direct and indirect pathways of allorecognition. Although the direct pathway is reported to be dominant in allograft rejection, indirect allorecognition also plays an important role. Indirect alloreactivity is also observed in renal transplant patients irrespective of rejection. Previously we showed a predominance of interleukin (IL)‐10 induced by indirect allorecognition of donor human leucocyte antigen (HLA)‐DR peptides, suggesting the existence of indirect alloreactive T cells displaying regulatory activity. In the present work, our objective was to characterize these regulatory T cells. We detected indirect alloproliferation of peripheral blood mononuclear cells (PBMC) from renal transplant patients, induced by donor HLA‐DR peptides, dependent on IL‐4 or IL‐10, suggesting regulatory activity as part of the alloreactive T‐cell repertoire. PBMC‐derived indirect alloreactive T‐cell lines were established and produced both inflammatory and regulatory cytokines. We showed that two of these T‐cell lines which were able to inhibit both direct and indirect alloproliferation of another T‐cell line from the same patient presented a CD4+CD25+Foxp3+ T‐cell population. These data support the idea that indirect alloreactive T cells may also have regulatory activity and may contribute to the maintenance of the human renal allograft.
Kininogens Coordinate Adaptive Immunity through the Proteolytic Release of Bradykinin, an Endogenous Danger Signal Driving Dendritic Cell Maturation
Authors: Scharfstein J. , Schmitz V. , Svensjö E. , Granato A. , Monteiro A. C. 
Published: July 2007

AbstractStrategically positioned in peripheral tissues, immune sentinel cells sense microbes and/or their shed products through different types of pattern‐recognition receptors. Upon secretion, pre‐formed pro‐inflammatory mediators activate the microvasculature, inducing endothelium/neutrophil adherence and impairing endothelium barrier function. As plasma proteins enter into peripheral tissues, short‐lived proinflammatory peptides are rapidly generated by limited proteolysis of complement components and the kininogens (i.e. kinin‐precursor proteins). While much emphasis has been placed on the studies of the vascular functions of kinins, their innate effector roles remain virtually unknown. A few years ago, we reported that exogenous bradykinin (BK) potently induces dendritic cell (DC) maturation, driving IL‐12‐dependent Th1 responses through the activation of G‐protein‐coupled BK B2 receptors (B2R). The premise that immature DC might sense kinin‐releasing pathogens through B2R was demonstrated in the subcutaneous mouse model of Trypanosoma cruzi infection. Analysis of the dynamics of parasite‐evoked inflammation revealed that activation of TLR2/neutrophils drives the influx of plasma proteins, including kininogens, into peripheral tissues. Once associated to cell surfaces and/or extracellular matrices, the surface‐bound kininogens are cleaved by T. cruzi cysteine proteases. Acting as short‐lived ‘danger’ signals, kinins activate DC via B2R, converting them into Th1 inducers. Fine tuned control of the extravascular levels of these natural peptide adjuvants is exerted by kinin‐degrading metallopeptidases, e.g. Angiotensin converting enzyme (ACE/CD143). In summary, the studies in the subcutaneous model of T. cruzi infection revealed that the peripheral levels of BK, a DC maturation signal, are controlled by TLR2/neutrophils and ACE, respectively characterized as positive and negative modulators of innate/adaptive immunity.
Locally Produced Survival Cytokines IL‐15 and IL‐7 may be Associated to the Predominance of CD8+ T cells at Heart Lesions of Human Chronic Chagas Disease Cardiomyopathy
Authors: Fonseca S. G. , Reis M. M. , Coelho V. , Nogueira L. G. , Monteiro S. M. , Mairena E. C. , Bacal F. , Bocchi E. , Guilherme L. , Zheng X. X. , Liew F. Y. , Higuchi M. L. , Kalil J. , Cunha‐Neto E. 
Published: July 2007

AbstractHuman chronic Chagas disease cardiomyopathy (CCC) is an inflammatory‐dilated cardiomyopathy occurring years after infection by the protozoan Trypanosoma cruzi. The heart inflammatory infiltrate in CCC shows a 2:1 predominance of CD8+ in relation to CD4+ T cells, with a typical Th1‐type cytokine profile. However, in vitro expansion of infiltrating T cells from heart biopsy‐derived fragments with interleukin‐2 (IL‐2) and phytohaemagglutinin leads to the outgrowth of CD4+ over CD8+ T cells. We hypothesized that survival cytokines, such as IL‐2, IL‐7 and IL‐15 might be differentially involved in the growth and maintenance of heart‐infiltrating and peripheral CD8+ T cells from CCC patients. We found that IL‐7 and IL‐15 were superior to IL‐2 in the expansion and viability of CD8+ T cells from both PBMC and heart‐infiltrating T‐cell lines from CCC patients, and the combination of the three cytokines showed synergic effects. Heart‐infiltrating CD8+ T cells showed higher expression of both IL‐15Rα and γc chain than CD4+ T cells, which may explain the improvement of CD8+ T‐cell growth in the presence of IL‐2 + IL‐7 + IL‐15. Immunohistochemical identification of IL‐15 and the higher mRNA expression of IL‐15Rα, IL‐7 and γc chain in CCC heart tissues compared with control individuals indicate in situ production of survival cytokines and their receptors in CCC hearts. Together, our results suggest that local production of IL‐7 and IL‐15 may be associated with the maintenance and predominance of CD8+ T cells, the cells effecting tissue damage in CCC hearts.
Efficacy of Anti‐CD20 Treatment in Patients with Rheumatoid Arthritis Resistant to a Combination of Methotrexate/Anti‐TNF Therapy
Authors: Bokarewa M. , Lindholm C. , Zendjanchi K. , Nadali M. , Tarkowski A. 
Published: July 2007

AbstractRheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty‐six patients with established erosive RA non‐responding to combination treatment with DMARDs and TNF‐α inhibitors were treated with anti‐CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin‐producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12–58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow‐up, B cells returned to circulation in 86% of patients. Fifty‐three percent of the patients were successfully retreated with rituximab or re‐started with anti‐TNF‐α treatment. Of the 11 non‐responders, five were retreated with anti‐CD20 within 2 months, four of them with success, four patients received TNF‐α inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF‐α inhibitors may be effectively treated with anti‐CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities.
The kinetics of Ringer’s solution in young and elderly patients during induction of general anesthesia with propofol and epidural anesthesia with ropivacaine
Authors: Li Y. , Zhu S. , Hahn R. G. 
Published: July 2007

Background:  Different fluid regimens are often adopted for elderly patients, but it is not known whether they handle infused fluids differently during the induction of anesthesia than young patients.Methods:  Mean arterial pressure (MAP), plasma dilution (based on hemoglobin) and volume kinetics were assessed during an intravenous (i.v.) infusion of 1000 ml of lactated Ringer’s solution over exactly 60 min in 29 patients given general anesthesia with propofol (15 < 65 years of age, and 14 > 65 years old) and in 16 patients receiving lumbar epidural anesthesia with titrated doses of ropivacaine (7 patients < 65 years of age and 9 > 65 years old).Results:  General anesthesia caused a greater decrease in MAP than epidural anesthesia (mean 15% vs. 9%; P < 0.001) and was followed by a more pronounced plasma dilution (30% vs. 18%; P < 0.001); the maximum values reaching 50%. The fluid‐induced hemodilution increased after the onset of anesthesia. The distribution rate constant (kt), which governs the preference for infused fluid to retain the plasma, was significantly reduced, with the lowest values being reached during general anesthesia (P < 0.002). However, only the reduction of MAP, and not the patient’s age group or the type of anesthesia per se, had a statistically significant influence on kt after the induction.Conclusion:  Induction of anesthesia greatly increases fluid‐induced hemodilution, the magnitude of which can be expressed as an acute reduction of the distribution rate constant for infused fluid. The post‐induction value of this parameter was closely associated with MAP but not with the patient’s age.
Anti‐inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats
Authors: Hofstetter C. , Boost K. A. , Flondor M. , Basagan‐Mogol E. , Betz C. , Homann M. , Muhl H. , Pfeilschifter J. , Zwissler B. 
Published: July 2007

Background:  Volatile anesthetics and hypothermia attenuate the inflammatory response. We aimed to compare the anti‐inflammatory effects of sevoflurane and mild hypothermia during experimental endotoxemia in the rat.Methods:  Anesthetized, ventilated Sprague–Dawley (SD) rats were randomly treated as follows (n = 6 per group): lipopolysaccharide (LPS) only, animals received LPS [LPS 5 mg/kg, intravenously (i.v.)] with no further treatment. In the LPS‐hypothermia group, rats were cooled down to a temperature of 33 °C 15 min after LPS‐injection (LPS 5 mg/kg i.v.). In animals of the LPS‐sevoflurane group, sevoflurane inhalation (1 MAC) was initiated 15 min after induction of endotoxemia. The LPS‐sevoflurane‐hypothermia group received combined sevoflurane and hypothermia 15 min after induction of endotoxemia. A Sham group served as control without endotoxemia or treatment. After 4 h of endotoxemia, plasma levels of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and IL‐10 were measured. Alveolar macrophages (AM) were ex vivo cultured for nitrite assay.Results:  Inhalation of sevoflurane significantly attenuated plasma levels of TNF‐α (–60%, P < 0.05) and IL‐1β (–68%, P < 0.05) as compared with the LPS‐only group. Hypothermia and its combination with sevoflurane significantly reduced TNF‐α levels (–46% and –58%, each P < 0.05), but not IL‐1β. Application of mild hypothermia and also its combination with sevoflurane resulted in a significant increase in plasma IL‐10 as compared with endotoxemic controls. Nitrite release from AM was found to be significantly suppressed by sevoflurane (–83%), hypothermia (–73%) and by the combination of both (–67%) (P < 0.05, each).Conclusion:  Our data suggest that sevoflurane and mild hypothermia attenuate the inflammatory response during endotoxemia in vivo thus contributing to their beneficial role in clinical organ protection.
Population prevalence and risk factors for iron deficiency in Auckland, New Zealand
Authors: Grant Cameron C , Wall Clare R , Brunt Deborah , Crengle Sue , Scragg Robert 
Published: July 2007

Aim:  Previous prevalence estimates of iron deficiency (ID) in young New Zealand children are inaccurate because of sampling bias and imprecise definition of ID. The aim of this study was to estimate the prevalence of ID in children aged 6–23 months and the factors associated with ID.Methods:  An ethnically stratified sample identified from random residential address start points. Children resident in Auckland, New Zealand were enrolled from 1999 to 2002. Children with elevated C‐reactive protein (>4 mg/L) were excluded. Iron status was determined in 324 (78%) of 416 enrolled children. Analyses adjusted for clustering and weighted for ethnic stratification. ID defined as abnormal values for two or more of serum ferritin (<10 µg/L), iron saturation (<10%) and mean cell volume (<73 fl).Results:  ID was present in 14% (95% confidence interval (CI) 9–17%). ID prevalence varied with ethnicity (Maori 20%, Pacific 17%, other 27%, New Zealand European 7%, P = 0.005), but not with social deprivation. In a multivariate analysis that adjusted for low birthweight, there was an increased risk of ID associated with a body mass index ≥ 18.5 kg/m2 (RR = 4.34, 95% CI 1.08–10.67), and with receiving no infant or follow on formula (RR = 3.60, 95% CI 1.56–6.49).Conclusions:  ID is prevalent in young New Zealand children. Variance in ID prevalence with ethnicity but not social deprivation implies that cultural practices influence iron status. Young children with more rapid growth are at increased risk of ID as are those receiving milk other than that specifically modified for them.
Therapeutic lung lavage in meconium aspiration syndrome: A preliminary report
Authors: Dargaville Peter A , Mills John F , Copnell Beverley , Loughnan Peter M , McDougall Peter N , Morley Colin J 
Published: July 2007

Aim:  To explore the effects of a large volume lung lavage procedure in ventilated infants with meconium aspiration syndrome.Methods:  Infants with severe meconium aspiration requiring high‐frequency ventilation underwent lung lavage using dilute bovine surfactant at a phospholipid concentration of 5 mg/mL. Lavage aliquot volumes were increased through the case series, aiming to deliver two aliquots of 15 mL/kg in rapid sequence. Physiological effects of lavage were documented, and comparison was made with a group of infants with meconium aspiration requiring high‐frequency ventilation, in whom lavage was not performed.Results:  Nine episodes of lavage were performed in eight infants at a median age of 23 h (range 8–83 h). Three infants underwent a lavage that was defined as potentially therapeutic (total lavage volume of at least 25 mL/kg administered before 24 h of age). Lavage was not associated with bradycardia or hypotension. Recovery of arterial oxygen saturation to above 80% was achieved within 12 min in all but one infant in whom oxygen saturation was below 80% at the outset. Mean airway pressure was significantly lower in the Therapeutic lavage group compared with non‐lavaged infants in the first 48 h, with a trend towards improved oxygenation.Conclusion:  Dilute surfactant lavage with aliquots of up to 15 mL/kg appears to be feasible in haemodynamically stable ventilated infants with meconium aspiration syndrome, and its efficacy deserves further investigation in a randomised controlled trial.
Revisiting the effect of nearby supernova remnants on local cosmic rays
Authors: Thoudam Satyendra 
Published: July 2007

Abstract
In an earlier paper, the effect of the nearby known supernova remnants (SNRs) on the local cosmic rays (CRs) was studied, considering different possible forms of the particle injection time. The present work is a continuation of the previous work, but assumes a more realistic model of CR propagation in the Galaxy. The previous work assumed an unbounded three-dimensional diffusion region, whereas the present one considers a flat cylindrical disc bounded in both the radial and vertical directions. The study has found that the effect of the vertical halo boundary H on the local SNR contribution to the observed CR anisotropy is negligible as long as H≳ 2 kpc. Considering the values of the halo height H≳ 2 kpc obtained by different authors, the present work suggests that the study of the effect of local sources on the CR anisotropy can be carried out without having much information on H, and hence using the much simpler three-dimensional unbounded solution. Finally, the present work discusses the possibility of explaining the observed anisotropy below the knee by a single dominant source with properly chosen source parameters, and claims that the source may be an undetected old SNR with a characteristic age of ∼1.5 × 105 yr located at a distance of ∼0.57 kpc from the Sun.
Crustal evolution of Western and Central Europe
Authors: Ziegler P. A. , Dèzes P. 
Published: July 2007

Abstract
A new Moho depth map has been assembled for Western and Central Europe and the Western Mediterranean area that is exclusively based on published regional Moho depth maps. Tectonic overlays summarize Caledonian and Variscan tectonic units, Permo-Carboniferous fault systems and magmatic provinces, Mesozoic and Cenozoic rift-wrench systems, areas of intraplate compression, the outlines of Alpine orogens and the distribution of oceanic crust. Based on a comparison of these overlays with the Moho depth map we assess processes that controlled the evolution of the crust in the various parts of Europe through time. The present-day crustal configuration of Western and Central Europe results from polyphase Late Palaeozoic to recent lithospheric deformation that overprinted the margin of the Proterozoic East European Craton and particularly the Caledonian and Variscan crustal domains. Following consolidation of the Caledonides, their crustal roots were destroyed in conjunction with Devonian wrench tectonics and back-arc rifting. During the Permo-Carboniferous tectonomagmatic cycle, wrench faulting disrupted the crust of the Variscan Orogen and its foreland and the lithosphere of these regions was thermally destabilized. Late Permian and Mesozoic re-equilibration of the lithosphere-asthenosphere system was interrupted by the development of the Arctic-North Atlantic, Tethyan and associated rift systems. During the Alpine orogenic cycle, intraplate compressional stresses controlled basin inversion-related crustal thickening and lithospheric folding, as well as the evolution of the Rhine-Rhone rift system. Variably deep crustal roots characterize the Alpine orogenic chains. Neogene back-arc extension disrupted the eastern Pyrenees, Betic-Balearic, Apennine and Dinarides orogens.
Europe from the Variscan to the Alpine cycles
Authors: Stamfli Gérard M. , Kozur Heinz W. 
Published: July 2007

Abstract
The time span between the Variscan and Alpine cycles is not devoid of any major tectonic activity, and corresponds to the Cimmerian cycle. Between the Early Permian and Late Triassic, the Eocimmerian cycle was marked by the closure of Palaeotethys and opening of Neotethys and of an array of south Eurasian back-arc basins. This was followed by the break-up of Pangaea and the Early Jurassic opening of the central Atlantic and Alpine Tethys. However, in the area of the Eocimmerian collision, the geodynamic evolution is relatively uninfluenced by this event, and a new cycle of Cimmerian deformation affected the Hellenides, Dinarides, Balkans and Pontides in Jurassic-Early Cretaceous times. The anti-clockwise rotation of Africa during the Late Cretaceous heralded the onset of Alpine orogenic processes, characterized first by major east-west shortening, and opening and closure of younger oceanic basins of back-arc type.
European geography in a global context from the Vendian to the end of the Palaeozoic
Authors: Cocks L. R. M. , Torsvik T. H. 
Published: July 2007

Abstract
A succession of palaeogeographical reconstructions is presented, covering half the globe and the time interval from the latest Proterozoic (Vendian) at 550 Ma to the end of the Palaeozoic (latest Permian) at 250 Ma, mostly at 20 or 30 Ma intervals. The various terranes that today constitute Europe are defined and their margins discussed briefly; these are Gondwana, Avalonia, the Rheno-Hercynian Terrane, the Armorican Terrane Assemblage, Perunica, Apulia, Adria, the Hellenic Terrane (including Moesia), Laurentia, and Baltica. As time elapsed, many of these terranes combined to form first Laurussia and subsequently Pangaea. The further terranes of Siberia and Kara adjoined Europe and were relevant to its Palaeozoic development. Brief sections are included on the individual history and geography of the Vendian and the six Palaeozoic systems, with emphasis on their importance in the building of Europe.