bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing patterns in the frequency of Hodgkin lymphoma subtypes and Epstein–Barr virus association in Taiwan
Authors: Chang Kung‐Chao , Chen Paul Chih‐Hsueh , Jones Dan , Su Ih‐Jen 
Published: February 2008

Epstein–Barr virus (EBV) infection is a risk factor for Hodgkin lymphoma (HL). To test whether the frequency of HL subtypes and their association with EBV has shifted with rising socioeconomic status in Taiwan, we compared the pathological features and EBV status, detected by in situ hybridization, of HL diagnosed between 1996 and 2007 (99 cases) and 1982 and 1995 (74 cases). The male‐to‐female ratio was 121:52 (2.3:1) and the mean age at presentation was 41.5 years. The overall EBV positivity rate was 50% (86/173 cases). Comparing the distribution of HL cases diagnosed at two different time periods, we found an increased frequency of the nodular sclerosis (NS) subtype (53 vs 68%, P = 0.045), a decreased frequency of the mixed cellularity subtype (35 vs 13%, P < 0.001), a reduced male‐to‐female ratio (2.9:1 compared to 1.4:1) and mean age (42.4 vs 36.6 years) in the NS subtype, and a significant decrease in EBV positivity rates among the NS and lymphocyte‐depletion subtypes (61 vs 39%, P = 0.03). These data indicate shifts in the frequency of histological subtype and EBV association for HL in Taiwan over the last decade, with a trend closer to that seen in Western countries and Japan. (Cancer Sci 2008; 99: 345–349)
Etiologic value of p53 mutation spectra and differences with histology in lung cancers
Authors: Shimmyo Takuo , Okada Akira , Hashimoto Takehisa , Kobayashi Yasuhito , Miyagi Youhei , Ishikawa Yuichi , Nakagawa Ken , Osada Hiroaki , Tsuchiya Eiju 
Published: February 2008

A total of 297 resected Japanese non‐small cell lung cancers (74 squamous cell carcinomas and 223 adenocarcinomas) were analyzed to evaluate the validity of the p53 mutation spectrum as a fingerprint for mutagenic substances as etiological factors. Frequencies of G→T transversions in smokers were significantly higher than in non‐smokers (P = 0.003) and the average incidence of G→T at hot spot codons of adduct formation was higher than that in other codons in smokers and in the hot spots in non‐smokers. Further, the mutation showed a marked strand bias. G→A transitions at CpG sites (CpG→CpA) were equally distributed in smokers and non‐smokers, and on both strands. A→G transitions did not show any variation with smoking status in terms of frequency, but exhibited a marked strand bias. Taken together, the G→T may be a fingerprint of direct mutagenic action of tobacco‐related compounds, the A→G being a new marker for other environmental chemicals, while the CpG→CpA may be attributable to endogenous spontaneous mutation, for active in lung carcinogenesis. (Cancer Sci 2008; 99: 287–295)
Prognostic impact and immunogenicity of a novel osteosarcoma antigen, papillomavirus binding factor, in patients with osteosarcoma
Authors: Tsukahara Tomohide , Kawaguchi Satoshi , Torigoe Toshihiko , Kimura Shigeharu , Murase Masaki , Ichimiya Shingo , Wada Takuro , Kaya Mitsunori , Nagoya Satoshi , Ishii Takeshi , Tatezaki Shin‐ichiro , Yamashita Toshihiko , Sato Noriyuki 
Published: February 2008

To develop peptide‐based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a cytotoxic T lymphocytes (CTL)‐defined osteosarcoma antigen in the context of human leukocyte antigen (HLA)‐B55. In the present study, we analyzed the distribution profile of PBF in 83 biopsy specimens of osteosarcomas and also the prognostic impact of PBF expression in 78 patients with osteosarcoma who had completed the standard treatment protocols. Next, we determined the antigenic peptides from PBF that react with peripheral T lymphocytes of HLA‐A24+ patients with osteosarcoma. Immunohistochemical analysis revealed that 92% of biopsy specimens of osteosarcoma expressed PBF. PBF‐positive osteosarcoma conferred significantly poorer prognosis than those with negative expression of PBF (P = 0.025). In accordance with the Bioinformatics and Molecular Analysis Section score, we synthesized 10 peptides from the PBF sequence. Subsequent screening with an HLA class I stabilization assay revealed that peptide PBF A24.2 had the highest affinity to HLA‐A24. CD8+ T cells reacting with a PBF A24.2 peptide were detected in eight of nine HLA‐A24‐positive patients with osteosarcoma at the frequency from 5 × 10−7 to 7 × 10−6 using limiting dilution/mixed lymphocyte peptide culture followed by tetramer‐based frequency analysis. PBF A24.2 peptide induced CTL lines from an HLA‐A24‐positive patient, which specifically killed an osteosarcoma cell line that expresses both PBF and HLA‐A24. These findings suggested prognostic significance and immunodominancy of PBF in patients with osteosarcoma. PBF is the candidate target for immunotherapy in patients with osteosarcoma. (Cancer Sci 2008; 99: 368–375)
The role of lenalidomide in the management of myelodysplasia with del 5q
Authors: Kelaidi Charikleia , Eclache Virginie , Fenaux Pierre 
Published: February 2008

SummaryDefined by isolated del 5q and no excess of marrow blasts, the ‘5q‐ syndrome’ is a specific type of myelodysplastic syndrome (MDS) with particular characteristics, including severe anaemia, frequent thrombocytosis, typical dysmegakaryopoiesis and favourable outcome. Its pathogenesis remains uncertain, particularly regarding the role of the inactivation of gene(s) situated in 5q. Until the advent of lenalidomide, repeated red blood cell (RBC) transfusions were generally the only treatment for 5q‐ syndrome, which was resistant to other therapeutic approaches. Lenalidomide can lead to RBC transfusion independence in at least two‐thirds of cases of 5q‐ syndrome, and about one half of those responses are maintained after 2 years of treatment. Importantly, frequent complete pathological and cytogenetic responses are also obtained. Grade 3 or 4 neutropenia and thrombocytopenia, especially during the first 6–8 weeks of treatment, are the major side effects of lenalidomide, justifying close clinical and blood counts monitoring. Preliminary results suggest that lenalidomide is also active in MDS with del 5q other than the 5q‐ syndrome. The mechanisms of action of lenalidomide, although uncertain, appear to include targeting of the del 5q clone. Therefore, lenalidomide may have an effect on disease course and survival, which is currently being assessed in clinical trials.
Modulation of the epithelial inflammatory response to rhinovirus in an atopic environment
Authors: Xatzipsalti M. , Psarros F. , Konstantinou G. , Gaga M. , Gourgiotis D. , Saxoni‐Papageorgiou P. , Papadopoulos N. G. 
Published: February 2008

SummaryBackground
Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations.Objective
To evaluate the effect of the environment resulting from an atopic immune response on RV‐induced epithelial inflammation, replication and cytotoxicity.Methods
Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS‐2B) cells were infected with RV in the presence of conditioned media from RV‐stimulated PBMC cultures. IL‐6, IL‐8, RANTES and TGF‐β1 levels were measured by ELISA, RV‐induced cytotoxicity by a colorimetric method and RV titres on Ohio‐HeLa cells.Results
RV‐induced epithelial production of IL‐6, IL‐8 and RANTES was significantly lower, while TGF‐β1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the ‘atopic’ environment also resulted in elevated RV titres and increased RV‐induced cytotoxicity.Conclusions
Under the influence of an atopic environment, the epithelial inflammatory response to RV is down‐regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up‐regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.
Selective induction of nerve growth factor and brain‐derived neurotrophic factor by LPS and allergen in dendritic cells
Authors: Noga O. , Peiser M. , Altenähr M. , Schmeck B. , Wanner R. , Dinh Q. T. , Hanf G. , Suttorp N. 
Published: February 2008

SummaryBackground
Neurotrophins are produced by various cells upon different stimuli and participate in the initiation and regulation of inflammation in various diseases including allergy and asthma, but little is known about the production and control of neurotrophins by dendritic cells (DCs). The aim of this study was to assess whether DCs produce the neurotrophins nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF), and whether inflammatory stimuli or allergens are able to induce the production of neurotrophic factors.Methods
Monocyte‐derived dendritic cells (MoDCs) were generated from different donors. The neurotrophins NGF and BDNF were demonstrated by RT‐PCR, Western blotting, flow cytometry analysis and fluorescence microscopy. MoDCs were cultured and stimulated with lipopolysaccharide (LPS) or allergen for 24 h. The supernatants and cells were collected. Measurement for NGF and BDNF was performed by ELISA.Results
DCs express mRNA for the neurotrophins NGF and BDNF. Proteins were detectable by Western blot, FACS analysis and fluorescence microscopy. LPS led to an up‐regulation of BDNF, while NGF was unaffected. Cell lysates demonstrated an increased amount of BDNF after stimulation with LPS or allergen, while NGF was not affected significantly.Conclusions
DCs are a source of neurotrophins. LPS selectively regulates the production of BDNF. Allergen stimulation leads to an LPS‐independent regulation. This contributes to a complex involvement of neurotrophins in allergic diseases.
Allergological implication of the quaternary hexameric structure of the cockroach allergen Per a 3
Authors: Bellinghausen I. , Häringer B. , Lafargue B. , Strand D. , König B. , Decker H. , Saloga J. 
Published: February 2008

SummaryBackground
Cockroach allergens play a very important role in allergic diseases, especially asthma. The major allergen of the American cockroach (Periplaneta americana), Per a 3, naturally occurs as isoforms of hexamers.Objective
The aim of this study was to investigate whether the hexameric structures of Per a 3 influence their allergenicity and immunogenicity.Methods
Therefore, we compared the different effects of native hexamers and dissociated monomers of cockroach haemolymph (HL), containing almost only Per a 3 proteins (HL‐Per a 3), on proliferation and T‐helper type 1 (Th1)/Th2 cytokine production of human CD4+ T cells in co‐culture with allergen‐pulsed monocyte‐derived autologous dendritic cells (DC) as well as the leukotriene release of basophils.Results
In P. americana‐sensitized and non‐sensitized donors the HL‐Per a 3 monomers were internalized faster by immature DC and induced higher proliferation and IFN‐γ production than the hexamers. While in non‐sensitized donors IL‐4 and IL‐5 as well as IL‐10 production were also increased after stimulation with monomeric HL‐Per a 3‐pulsed DC, Th2 cytokine and IL‐10 production were only enhanced in P. americana‐sensitized donors using hexameric HL‐Per a 3‐pulsed DC. Furthermore, in the leukotriene release assay the monomers were less effective than the hexamers.Conclusion
Our data indicate that the quaternary structure can influence both allergenicity and immunogenicity, also depending on the sensitization status. The monomeric variant of Per a 3 allergens could be a possible candidate for a specific immunotherapy because the IgE‐mediated allergic reaction and the Th2‐inducing capacity are diminished while the Th1‐inducing capacity is retained.
Maternal allergy influences p38‐mitogen‐activated protein kinase activity upon microbial challenge in CD14+ monocytes from 2‐year‐old children
Authors: Saghafian‐Hedengren S. , Holmlund U. , Amoudruz P. , Nilsson C. , Sverremark‐Ekström E. 
Published: February 2008

SummaryBackground
The development of allergic diseases is dependent on genetic and environmental factors. It has been shown previously that cord blood mononuclear cells (CBMCs) from infants with parental allergy have altered cytokine profiles upon bacterial encounter; it might be possible that such impairment persists during the early years of childhood.Objective
The aim of this study was to investigate anti‐microbial responses with regard to p38‐mitogen‐activated protein kinase (MAPK) activity in CD14+ monocytes and IL‐6 release from mononuclear cells in the same group of children at birth and at 2 years of age.Methods
Paired samples of CBMCs and peripheral blood mononuclear cells (PBMCs) were stimulated with either lipopolysaccharide (LPS) or peptidoglycan in vitro. CD14+ monocytes were analysed for p38‐MAPK activity by flow cytometry, and soluble IL‐6 receptor, soluble glycoprotein130 and IL‐6 release from PBMC cultures were quantified by ELISA.Results
CBMCs from newborns with allergic mothers tended to have a lower IL‐6 response following an LPS (P=0.09) challenge compared with the group without maternal allergy while p38‐MAPK activation levels did not differ between the groups. PBMCs from 2‐year‐olds with allergic mothers released significantly less (P<0.05) IL‐6 upon peptidoglycan stimuli compared with age‐matched infants with non‐allergic mothers. Infants with allergic mothers displayed markedly reduced CD14+ monocyte p38‐MAPK phosphorylation after LPS (P<0.05) and peptidoglycan (P<0.01) challenge. This altered anti‐microbial response was attributed to maternal allergy rather than to being IgE‐sensitized at 2 years of age.Conclusion
Monocytes from children with allergic mothers are less responsive to bacterial challenge than monocytes from children with non‐allergic mothers, and this impairment persists during the first 2 years of infancy.
Sulphidoleukotriene release of cord blood basophils in response to allergen stimulation correlates with neither a family history of atopy nor a subsequent development of atopic eczema
Authors: Walaschek C. , Heinzmann A. , Weckmann M. , Kopp M. V. 
Published: February 2008

SummaryObjective
We tested a possible relationship between sulphidoleukotriene (SLT) release of cord blood (CB) basophils, a family history of atopy (HA) and subsequent development of atopic eczema.Population and methods
A cohort of 86 neonates were involved (48.8% males; 46.5% with a positive HA+). CB samples were analysed for in vitro SLT release quantified by ELISA, and in a subgroup for basophilic activation (CD 63 expression) by flow cytometry in response to a positive control (anti‐IgE‐receptor antibody), an allergen‐mix (TOP and PTOP), egg white (EW), egg yolk (EY), and the purified allergens β‐lactoglobulin (BLG) and α‐lactalbumin (ALA).Results
Median concentrations of SLT were 124.2 (negative), 3871.5 (positive), 123.9 (TOP), 128.5 (PTOP), 113.1 (EW), 108.4 (EY), 125.2 (BLG) and 122.3 (ALA) pg/mL. Groups of HA+ and HA– show no difference in all analysed allergens. An allergen‐specific SLT release (defined as SLT>125 pg/mL above individual baseline and a stimulation index >2) was detected in 98% (positive control), 5% (TOP), 7% (BLG), 3% (ALA) and 2% (EW and EY), respectively. After a median observation period of 18 months, n=7 out of 70 children developed an atopic eczema, but we observed no association between CB SLT release (positive response to at least one tested allergen).Conclusion
Allergen‐specific SLT release is detectable in 15.5% of healthy neonates, irrespective of their family history of atopy. However, early allergen‐specific SLT release is not predictive for the development of atopy.
Mechanisms of pathogenesis and the evolution of parasite virulence
Authors: FRANK S. A. , SCHMID‐HEMPEL P. 
Published: February 2008

AbstractWhen studying how much a parasite harms its host, evolutionary biologists turn to the evolutionary theory of virulence. That theory has been successful in predicting how parasite virulence evolves in response to changes in epidemiological conditions of parasite transmission or to perturbations induced by drug treatments. The evolutionary theory of virulence is, however, nearly silent about the expected differences in virulence between different species of parasite. Why, for example, is anthrax so virulent, whereas closely related bacterial species cause little harm? The evolutionary theory might address such comparisons by analysing differences in tradeoffs between parasite fitness components: transmission as a measure of parasite fecundity, clearance as a measure of parasite lifespan and virulence as another measure that delimits parasite survival within a host. However, even crude quantitative estimates of such tradeoffs remain beyond reach in all but the most controlled of experimental conditions. Here, we argue that the great recent advances in the molecular study of pathogenesis provide a way forward. In light of those mechanistic studies, we analyse the relative sensitivity of tradeoffs between components of parasite fitness. We argue that pathogenic mechanisms that manipulate host immunity or escape from host defences have particularly high sensitivity to parasite fitness and thus dominate as causes of parasite virulence. The high sensitivity of immunomodulation and immune escape arise because those mechanisms affect parasite survival within the host, the most sensitive of fitness components. In our view, relating the sensitivity of pathogenic mechanisms to fitness components will provide a way to build a much richer and more general theory of parasite virulence.
The impact of shared ancestral variation on hybrid male lethality – a 16 codon indel in the Drosophila simulans Lhr gene
Authors: NOLTE V. , WEIGEL D. , SCHLÖTTERER C. 
Published: February 2008

AbstractThe Lethal hybrid rescue (Lhr) gene causes hybrid male lethality in crosses between Drosophila simulans and D. melanogaster. Lhr2 is a D. simulans allele, which rescues hybrid males. It has been recently proposed that a 16 codon insertion, which distinguishes the D. melanogaster and the canonical D. simulans allele, and is lacking in Lhr2, may be responsible for the functional divergence of D. melanogaster and D. simulans Lhr alleles. Here, we show that the Lhr2 allele lacking the insertion represents an ancestral polymorphism segregating at a moderate frequency in D. simulans. Crosses of D. melanogaster females to males from two D. simulans strains carrying this deletion showed a severe deficiency of viable hybrid males. Our results suggest that the absence of this insertion alone is not sufficient to explain functional differences between D. melanogaster and D. simulans Lhr alleles.
Social heterosis and the maintenance of genetic diversity at the genome level
Authors: NONACS P. , KAPHEIM K. M. 
Published: February 2008

AbstractSocial heterosis is when individuals in groups or neighbourhoods receive a mutualistic benefit from across‐individual genetic diversity. Although it can be a viable evolutionary mechanism to maintain allelic diversity at a given locus, its efficacy at maintaining genome‐wide diversity is in question when multiple loci are being simultaneously selected. Therefore, we modelled social heterosis in a population of haploid genomes of two‐ or three‐linked loci. With such linkages, social heterosis decreases gametic diversity, but maintains allelic diversity. Genomes tend to survive as complimentary pairs, with alternate alleles at each locus (e.g. the pair AbC and aBc). The outcomes of selection appear similar to fitness epistasis but are novel in the sense that phenotypic interactions occur across rather than within individuals. The model’s results strongly suggest that strong linkage across gene loci actually increases the probability that social heterosis maintains significant genetic diversity at the level of the genome.
Interspecific variation in ejaculate allocation and associated effects on female fitness in seed beetles
Authors: RÖNN J. L. , KATVALA M. , ARNQVIST G. 
Published: February 2008

AbstractWhen ejaculates are costly to produce, males are expected to allocate their ejaculate resources over successive matings in a manner that optimizes their reproductive success and this may have important consequences for their mates. In seed beetles (Coleoptera; Bruchidae), ejaculates vary in size across species from weighing less than 1%, up to as much as 8%, of male body weight. Ejaculates contain not only sperm but also a range of additional substances and females in some species gain benefits from receiving large ejaculates. Male ejaculate allocation may thus affect female fitness. Here, we first characterized the pattern of male ejaculate allocation over successive matings in seven‐seed beetle species. We then assessed how this allocation affected female fitness in each species. Although females generally benefited from receiving large ejaculates, the interspecific variation observed both in ejaculate allocation patterns and in their effects on female fitness was remarkably large considering that the species studied are closely related. Our analyses suggest that variation in ejaculate composition is the key, both within and across species. We discuss possible causes for this variation and conclude that coevolution between male ejaculates and female utilization of ejaculate substances has apparently been rapid in this clade.
LIMITATIONS ON THE USE OF THE STRESS INTENSITY FACTOR, K, AS A FRACTURE PARAMETER IN THE FATIGUE PROPAGATION OF SHORT CRACKS
Authors: Kfouri A. P. 
Published: February 2008

Abstract— It is well known that for very short cracks the stress intensity factor K is not a suitable parameter to estimate the stress level over the small but finite Stage II process zone activation region of size rs near the crack tip, within which crack growth events take place. A critical appreciation of the reasons for the limitations on the applicability of ΔK as a fatigue crack propagation (FCP) parameter, when the crack length a is of the same order of magnitude or smaller than the size of the ‘fatigue‐fracture activation region’, rs is presented. As an alternative to ΔK the range Δσs of the cyclic normal stress at a point situated at the fixed distance s=rs/2, ahead of the crack tip, inside the fatigue‐fracture activation region, is proposed. It is observed that the limitation on the use of ΔK when the crack is short, is mathematical (and not physical) but this inconvenience is easily circumvented if the stress Δσs at the prescribed distance is used instead of ΔK since nowadays Δσs can be obtained numerically by using finite element methods (FEM). It follows that the parameter Δσs is not restricted by the mathematical limitations on ΔK and so it would seem that there is, a priori, no reason why the validity of the parameter Δσs cannot be extended to short cracks. It is shown that if the Paris law is expressed in terms of Δσs (πrrs)½ instead of ΔK the validity of the modified Paris law can be extended to short cracks.A coherent estimate of the value of the fatigue‐fracture activation region rs is derived in terms of the fatigue limit ΔσFL obtained from S‐N tests and of the threshold value ΔKth obtained from tests on long cracks where both relate to Stage II crack growth that ends in failure, namely, rs= (ΔKth/ΔσFL)2/π. An overall, threshold diagram is presented based on the simple criterion that, for sustained Stage II FCP, Δσs must be greater than ΔσFL. The study is based on a simple continuum mechanics approach and its purpose is the investigation of the suitability of both ΔK and Δσs to characterise the crack driving force that activates complex fracture processes at the microstructure's scale. The investigation pertains to conditions that lead to the ultimate failure of the component at values of Δσs > ΔσFL.