bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐morbidities and quality of life in elderly persons with haemophilia
Authors: Franchini Massimo , Mannucci Pier Mannuccio 
Published: December 2009

SummaryThe life expectancy and quality of life of persons with haemophilia has dramatically increased since the 1970s, with the exception of the increased rate of deaths observed during the 1980s and the 1990s due to blood‐borne viral infections. Improvements of factor replacement therapy, treatment of infectious diseases and comprehensive health care provided by specialised haemophilia centres are the main determinants of the increasing age of the haemophilia population. As a consequence, a growing number of these patients develop age‐related co‐morbidities, such as cardiovascular disease and cancer. The care of these previously rare conditions is a new challenge for caregivers in haemophilia centres. This review focuses on co‐morbidities in the ageing haemophilia patients, their impact on quality of life and their complex management.
Prospective association between food sensitization and food allergy: results of the LISA birth cohort study
Authors: Schnabel E. , Sausenthaler S. , Schaaf B. , Schäfer T. , Lehmann I. , Behrendt H. , Herbarth O. , Borte M. , Krämer U. , Von Berg A. , Wichmann H.‐E. , Heinrich J. ,   for the LISA Study Group
Published: December 2009

SummaryBackground
Food allergy is common, especially in childhood, where 6–8% of children are affected. Identification of early and efficient markers for later development of food allergy is very important.Objective
We examined the ability of repeated measurements of food sensitization in early childhood to predict doctor‐diagnosed food allergy (DDFA) at the age of 6 years.Methods
The analysis was based on data from a prospective birth cohort study. Information was collected by parental questionnaires, and blood samples were obtained at 2 and 6 years of age. Children with repeated determination of sensitization to food allergens at 2 and 6 years of age were categorized into the sensitization phenotypes: no, early onset, late onset and persistent sensitization. The association between sensitization phenotypes and DDFA was prospectively investigated using multiple logistic regression analyses.Results
Of 3097 children recruited at birth, a complete follow‐up of IgE measurements and questionnaires at 1.5, 2 and 6 years were available for 1082 children. Early food allergen sensitization (fx5) was a strong risk for DDFA at 6 years [odds ratio (OR)=4.7; 95% confidence intervals (95% CI) 2.0–11.2] and for a new onset of DDFA at 6 years (OR=4.1; 95% CI 1.5–11.3). Additionally, persistent food allergen sensitization increased the risk of DDFA at 6 years (OR=6.1; 95% CI 2.7–13.7). Early sensitized children with a history of parental atopy showed the highest risk for DDFA at 6 years.Conclusion
Food‐sensitized children during the first 2 years of life, especially with a family history of atopy, might be considered as a susceptible subgroup that requires specific attention concerning the development of food allergy‐related symptoms.>Cite this as: E. Schnabel, S. Sausenthaler, B. Schaaf, T. Schäfer, I. Lehmann, H. Behrendt, O. Herbarth, M. Borte, U. Krämer, A. von Berg, H.‐E. Wichmann, J. Heinrich, and for the LISA Study Group, Clinical & Experimental Allergy, 2010 (40) 450–457.
Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T‐cell differentiation and modulates responses to Bacille Calmette‐Guérin (BCG) vaccine in HIV‐uninfected infants
Authors: Miles David J. C. , Gadama Louis , Gumbi Anita , Nyalo Flora , Makanani Bonus , Heyderman Robert S. 
Published: December 2009

SummaryHuman immunodeficiency virus (HIV)‐negative infants born to HIV‐positive mothers frequently exhibit a range of immunological abnormalities. We tested the hypothesis that HIV during pregnancy affects the ability of CD4 T cells of HIV‐negative infants to respond to vaccine challenge by recruiting HIV‐negative infants born to HIV‐negative and HIV‐positive mothers and measuring their responses to Bacille Calmette‐Guérin (BCG) vaccine given at birth. At 2 weeks, maternal HIV status did not influence CD4 T‐cell counts or differentiation, but by 10 weeks CD4 counts of infants born to HIV‐positive mothers fell to a level characteristic of HIV‐positive infants. Among the CD4 T‐cell populations, markers of differentiation (CCR7− CD45RA− CD27−) and senescence (CD57, PD‐1) were more common among infants born to HIV‐positive mothers than among infants born to HIV‐negative mothers. At 2 weeks of age, we assessed the effector response to heat‐killed BCG and tuberculin purified protein derivative (PPD) by overnight interferon (IFN)‐γ enzyme‐linked immunosorbent spot‐forming cell assay (ELISpot), but found no measurable effect of maternal HIV status. At 10 weeks, we assessed CD4 T‐cell memory by measuring proliferation in response to the same antigens. We observed a bimodal response that allowed infants to be classified as high or low responders and found that fewer infants born to HIV‐positive mothers were able to mount a robust proliferative response, suggesting that their reduced CD4 counts and increased differentiation indicated a deficiency in their ability to develop immunological memory.
Activation of mannan‐binding lectin‐associated serine proteases leads to generation of a fibrin clot
Authors: Gulla Krishana C. , Gupta Kshitij , Krarup Anders , Gal Peter , Schwaeble Wilhelm J. , Sim Robert B. , O’Connor C. David , Hajela Krishnan 
Published: December 2009

SummaryThe lectin pathway of complement is activated upon binding of mannan‐binding lectin (MBL) or ficolins (FCNs) to their targets. Upon recognition of targets, the MBL‐and FCN‐associated serine proteases (MASPs) are activated, allowing them to generate the C3 convertase C4b2a. Recent findings indicate that the MASPs also activate components of the coagulation system. We have previously shown that MASP‐1 has thrombin‐like activity whereby it cleaves and activates fibrinogen and factor XIII. MASP‐2 has factor Xa‐like activity and activates prothrombin through cleavage to form thrombin. We now report that purified L‐FCN‐MASPs complexes, bound from serum to N‐acetylcysteine‐Sepharose, or MBL‐MASPs complexes, bound to mannan‐agarose, generate clots when incubated with calcified plasma or purified fibrinogen and factor XIII. Plasmin digestion of the clot and analysis using anti‐D‐dimer antibodies revealed that the clot was made up of fibrin and was similar to that generated by thrombin in normal human plasma. Fibrinopeptides A and B (FPA and FPB, respectively) were released after fibrinogen cleavage by L‐FCN‐MASPs complexes captured on N‐acetylcysteine‐Sepharose. Studies of inhibition of fibrinopeptide release indicated that the dominant pathway for clotting catalysed by the MASPs is via MASP‐2 and prothrombin activation, as hirudin, a thrombin inhibitor that does not inhibit MASP‐1 and MASP‐2, substantially inhibits fibrinopeptide release. In the light of their potent chemoattractant effects on neutrophil and fibroblast recruitment, the MASP‐mediated release of FPA and FPB may play a role in early immune activation. Additionally, MASP‐catalysed deposition and polymerization of fibrin on the surface of micro‐organisms may be protective by limiting the dissemination of infection.
CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM‐B
Authors: Leick Marion , Catusse Julie , Follo Marie , Nibbs Robert J. , Hartmann Tanja N. , Veelken Hendrik , Burger Meike 
Published: December 2009

SummaryThe human chemokine receptor CRAM (chemokine receptor on activated macrophages), encoded by the gene CCRL2, is a new candidate for the atypical chemokine receptor family that includes the receptors DARC, D6 and chemocentryx chemokine receptor (CCX‐CKR). CRAM is maturation‐stage‐dependently expressed on human B lymphocytes and its surface expression is up‐regulated upon short‐term CCL5 exposure. Here, we demonstrate that the homeostatic chemokine CCL19 is a specific ligand for CRAM. In radioactive labelling studies CCL19 bound to CRAM‐expressing cells with an affinity similar to the described binding of its other receptor CCR7. In contrast to the known CCL19/CCR7 ligand/receptor pair, CRAM stimulation by CCL19 did not result in typical chemokine‐receptor‐dependent cellular activation like calcium mobilization or migration. Instead, we demonstrate that CRAM is constitutively recycling via clathrin‐coated pits and able to internalize CCL19 as well as anti‐CRAM antibodies. As this absence of classical chemokine receptor responses and the recycling and internalization features are characteristic for non‐classical chemokine receptors, we suggest that CRAM is the newest member of this group. As CCL19 is known to be critically involved in lymphocyte and dendritic cell trafficking, CCL19‐binding competition by CRAM might be involved in modulating these processes.
Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure
Authors: Lima Aline Regina Ruiz , Martinez Paula Felippe , Okoshi Katashi , Guizoni Daniele Mendes , Zornoff Leonardo A. Mamede , Campos Dijon Henrique Salomé , Oliveira Jr Sílvio Assis , Bonomo Camila , Pai‐Silva Maeli Dal , Okoshi Marina Politi 
Published: December 2009

SummarySkeletal muscle abnormalities can contribute to decreased exercise capacity in heart failure. Although muscle atrophy is a common alteration in heart failure, the mechanisms responsible for muscle mass reduction are not clear. Myostatin, a member of TGF‐β family (transforming growth factor), regulates muscle growth and mass. Several studies have shown a negative correlation between myostatin expression and muscle mass. The aim of this study was to evaluate myostatin expression in skeletal muscles of rats with heart failure. As myostatin gene expression can be modulated by follistatin, we also evaluated its expression. Heart failure was induced by myocardial infarction (MI, n = 10); results were compared to Sham‐operated group (n = 10). Ventricular function was assessed by echocardiogram. Gene expression was analyzed by real‐time PCR and protein levels by Western blotting in the soleus and gastrocnemius muscles; fibre trophism was evaluated by morphometric analysis. MI group presented heart failure evidence such as pleural effusion and right ventricular hypertrophy. Left ventricular dilation and dysfunction were observed in MI group. In the soleus muscle, cross‐sectional area (P = 0.006) and follistatin protein levels (Sham 1.00 ± 0.36; MI 0.18 ± 0.06 arbitrary units; P = 0.03) were lower in MI and there was a trend for follistatin gene expression to be lower in MI group (P = 0.085). There was no change in myostatin expression between groups. In gastrocnemius, all MI group parameters were statistically similar to the Sham. In conclusion, our data show that during chronic heart failure, decreased skeletal muscle trophism is combined with unchanged myostatin and reduced follistatin expression.
Oxidized laminin‐1 induces increased monocyte attachment and expression of ICAM‐1 in endothelial cells
Authors: Kostidou Elena , Topouridou Konstantina , Daniilidis Angelos , Kaloyianni Martha , Koliakos George 
Published: December 2009

SummaryAtherosclerosis has been associated with increased oxidative stress and monocyte recruitment by endothelial cells. Sub‐endothelial basement membrane proteins, such as laminins that play a central role in cell adhesion, are exposed to reactive oxygen species. In the present study monocyte attachment on human umbilical cord vein endothelial cells (HUVEC) that were preattached to oxidized or native laminin, was investigated. Intracellular cell adhesion molecule‐1 (ICAM‐1) expression by HUVEC was estimated by an enzyme‐linked immunosorbent assay. HUVEC attachment to oxidized or native laminin‐1 was examined using the Hemacolor kit. Anti‐alphaL, anti‐alphaM, anti‐alpha2 and anti‐beta2 integrin subunit antibodies were used in order to further investigate the above phenomena. HUVEC that were preattached to oxidized laminin expressed higher levels of ICAM‐1 and monocytes attached at a higher degree to these cells as compared to HUVEC that were preattached to native laminin. Incubation of monocytes with monoclonal antibodies against the alphaM and beta2 integrin subunits equalized the above mentioned differences. Moreover, HUVEC attached to oxidized laminin at a higher degree as compared to native laminin. This difference was equalized after incubation with the antibody against the alpha2 integrin subunit. These results indicate a modified interaction between HUVEC and the basement membranes in cases where laminin is oxidatively modified. This modified interaction results in increased ICAM‐1 expression by endothelial cells and consequently increased monocyte recruitment capacity.
Fell‐Muir Lecture: Proteoglycans and more – from molecules to biology
Authors: Heinegård Dick 
Published: December 2009

SummaryIn this article the organization and functional details of the extracellular matrix, with particular focus on cartilage, are described. All tissues contain a set of molecules that are arranged to contribute structural elements. Examples are fibril‐forming collagens forming major fibrillar networks in most tissues. The assembly process is regulated by a number of proteins (thrombospondins, LRR‐proteins, matrilins and other collagens) that can bind to the collagen molecule and in many cases remain bound to the formed fibre providing additional stability and enhancing networking to other structural networks. One such network is formed by collagen VI molecules assembled to beaded filaments in the matrix catalysed by interactions with small proteoglycans of the LRR‐family, which remain bound to the filament providing for interactions via a linker of a matrilin to other matrix constituents like collagen fibres and the large proteoglycans, e.g. aggrecan in cartilage. Aggrecan is contributing an extreme anionic charge density to the extracellular matrix, which by osmotic effects leads to water retention and strive to swelling, resisted by the tensile properties of the collagen fibres. Aggrecan is bound via one end to hyaluronan, including such molecules retained at the cell surface, to form very large molecular entities that interact with other constituents of the matrix, e.g. fibulins that can form their own network. Other important interactions are those with cell surface receptors such as integrins, heparan sulphfate proteoglycans, hyaluronan receptors and others. Many of the molecules with an ability to interact with these receptors can also bind to molecules in the matrix and provide a bridge from the matrix to the cell and induce various responses. In pathology, there is an imbalance in matrix turnover with often excessive proteolytic breakdown. This results in the formation of protein fragments, where cleavage provides information on the active enzyme. Those fragments released can be specifically detected employing antibodies specific to the cleavage site and used to diagnose and monitor e.g. joint disease at early stages.
Interacting effects of density and temperature on body size in multiple populations of Chinook salmon
Authors: Crozier Lisa G. , Zabel Richard W. , Hockersmith Eric E. , Achord Stephen 
Published: December 2009

Summary 1. The size individuals attain reflects complex interactions between food availability and quality, environmental conditions and ecological interactions. A statistical interaction between temperature and the density of conspecifics is expected to arise from various ecological dynamics, including bioenergetic constraints, if population density affects mean consumption rate or activity level. Density effects on behaviour or size‐selective predation could also generate this pattern. This interaction plays an important role in bioenergetic models, in particular, and yet has not been documented in natural populations. 2. The lengths of 131 286 juvenile wild Chinook salmon (Oncorhynchus tshawytscha) across 13 populations spread throughout the Salmon River Basin, Idaho, USA over 15 years were compared to test whether juvenile density alters the relationship between body size and temperature. 3. Strong evidence for a negative interaction between mean summer temperature and density emerged, despite the relatively cool temperatures in this high elevation habitat. Growth correlated positively with temperature at lower densities, but the correlation was negative at the highest densities. 4. This is the first study to document this interaction at such a large spatial and temporal scale, and suggests that warmer temperatures might intensify some density‐dependent processes. How climate change will affect individual growth rates in these populations will depend intimately on ecological conditions, particularly food availability and population dynamics. More broadly, the conditions that led to the interactions observed in our study – limited food availability and temperatures that ranged above those optimal for growth – likely exist for many other natural populations, and warrant broader exploration.
Phylogeography of white spruce (Picea glauca) in eastern North America reveals contrasting ecological trajectories
Authors: de Lafontaine Guillaume , Turgeon Julie , Payette Serge 
Published: December 2009

AbstractAim  The main objective of this study was to investigate the origin of white spruce (Picea glauca) range discontinuities in eastern North America. A first analysis aimed at uncovering the glacial origin and post‐glacial migration route of white spruce in the eastern part of the range. A second analysis aimed at evaluating whether disjunct white spruce populations in central Québec result from a recent expansion or are remnant stands following a northern range contraction.Location  The first analysis covered the North American transcontinental boreal distribution of white spruce, and the second focused on the eastern part of its range.Methods  A total of 589 P. glauca individuals from 51 populations, 24 of which were from a previous published source, were analysed for variation in three chloroplast DNA regions (trnT/L, trnL/F and ndhK/C). At the continental scale, haplotypic diversity, zones of genetic discontinuities, clustering analysis and analysis of molecular variance (AMOVA) were employed. In the eastern part of the range, haplotypic diversity was assessed with a permutation procedure, demographic history with mismatch analyses, and genetic structure with AMOVA.Results  At the continental scale, various lines of evidence (genetic‐diversity hotspots, endemic haplotypes, zones of genetic discontinuities, and pattern of molecular variation) show that different lineages migrated from three glacial refugia (Beringian, Mississippian, east Appalachian). Strong genetic discontinuities, low diversity and lack of evidence for demographic expansion were found among stands from isolated high hills in central Québec.Main conclusions  White spruce in the eastern part of its range has an east Appalachian origin, a lineage genetically distinct from populations west of the Great Lakes. Previous studies have shown that the northward migration of white spruce is still ongoing as the northernmost populations expand into the tundra. In contrast, mixed white spruce and balsam fir (Abies balsamea) stands from isolated high hills in central Québec have already reached their Holocene maxima and are currently declining. This range contraction is probably a result of increased wildfire disturbance, which gradually creates a pattern of regional white spruce isolation and replacement by fire‐prone black spruce (Picea mariana) forest.
Principles of depth‐resolved Kikuchi pattern simulation for electron backscatter diffraction
Authors: WINKELMANN A. 
Published: December 2009

SummaryThis paper presents a tutorial discussion of the principles underlying the depth‐dependent Kikuchi pattern formation of backscattered electrons in the scanning electron microscope. To illustrate the connections between various electron diffraction methods, the formation of Kikuchi bands in electron backscatter diffraction in the scanning electron microscope and in transmission electron microscopy are compared with the help of simulations employing the dynamical theory of electron diffraction. The close relationship between backscattered electron diffraction and convergent beam electron diffraction is illuminated by showing how both effects can be calculated within the same theoretical framework. The influence of the depth‐dependence of diffuse electron scattering on the formation of the experimentally observed electron backscatter diffraction contrast and intensity is visualized by calculations of depth‐resolved Kikuchi patterns. Comparison of an experimental electron backscatter diffraction pattern with simulations assuming several different depth distributions shows that the depth‐distribution of backscattered electrons needs to be taken into account in quantitative descriptions. This should make it possible to obtain more quantitative depth‐dependent information from experimental electron backscatter diffraction patterns via correlation with dynamical diffraction simulations and Monte Carlo models of electron scattering.
Biochemical, immunological and clinical characterization of a cross‐reactive nonspecific lipid transfer protein 1 from mulberry
Authors: Ciardiello M. A. , Palazzo P. , Bernardi M. L. , Carratore V. , Giangrieco I. , Longo V. , Melis M. , Tamburrini M. , Zennaro D. , Mari A. , Colombo P. 
Published: December 2009

To cite this article: Ciardiello MA, Palazzo P, Bernardi ML, Carratore V, Giangrieco I, Longo V, Melis M, Tamburrini M, Zennaro D, Mari A, Colombo P. Biochemical, immunological and clinical characterization of a cross‐reactive nonspecific lipid transfer protein 1 from mulberry. Allergy 2010; 65: 597–605.AbstractBackground:  Mulberry (Morus spp.) is a genus comprising several species of deciduous trees whose fruits are commonly eaten in southern Europe. Subjects with severe systemic reaction have been described. The aim of this study was to isolate the allergens of this species.Methods:  A nonspecific lipid transfer protein 1 (ns‐LTP1) was purified from black mulberry by ion exchange and reverse phase high‐performance liquid chromatography, and the primary structure was elucidated by direct protein sequencing. Its allergenic activity was evaluated in vivo by skin prick test and in vitro by Western Blot, CD203c basophil activation assay and high throughput multiplex inhibition method on immunosolid‐phase allergen chip (ISAC).Results:  Mulberry ns‐LTP (Mor n 3) comprises 91 amino acids producing a molecular mass of 9246 Da. This protein shows high sequence identity with several allergenic ns‐LTP1. Immunoblot analysis and CD203c activation assay demonstrated its allergenic activity in symptomatic subjects and in ns‐LTP allergic patients who are not mulberry consumers. Immunological co‐recognition was studied in vivo on a selected group of well‐characterized ns‐LTP allergic patients showing a high percentage of nMor n 3+ subjects (88.46%) even in patients who have never eaten mulberry before. IgE inhibition on ISAC micro‐array demonstrated an almost complete cross‐reactivity to nArt v 3, rCor a 8 and a very high percentage of inhibition to nPru p 3.Conclusions:  Mor n 3 is the first allergen isolated in black mulberry and immunologically characterized. It displayed allergenic activity among symptomatic and nonconsumer patients and a pattern of cross‐reactivity to other plant‐derived LTPs.