bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of ERα and ERβ in lobular carcinoma in situ
Authors: Middleton L P , Perkins G H , Tucker S L , Sahin A A , Singletary S E 
Published: June 2007

Aims:  Oestrogen is a modulator of cell growth and differentiation in the breast. It mediates most of its function through members of the oestrogen receptor (ER) family, ERα and ERβ. Lobular carcinoma in situ (LCIS) is a known risk factor for the development of breast cancer; however, the use of tamoxifen for prevention is based upon data for ER+ (ERα) LCIS associated with invasion, but limited data exist on the use of tamoxifen in cases of ER+ (ERα) LCIS occurring in the absence of invasive carcinoma. The aim of this study was to examine ER expression in LCIS to determine the relationship of ERα to ERβ and, thereby, to determine whether it is of clinical value to measure ERβ along with ERα.Methods and results:  Core biopsy specimens from 50 patients were examined retrospectively. Histology was reviewed and histological parameters were assessed. Formalin‐fixed paraffin‐embedded tissue was available for E‐cadherin, ERα and ERβ immunohistochemistry. The degree of ERα and ERβ nuclear reactivity was quantified. The patients' mean age was 55 years. The mean follow‐up duration was 48 months. All 50 cases of LCIS were E‐cadherin‐negative. All cases were ERα+ and ERβ+. The staining intensity of ERβ was strong and included staining of periductal stromal cells. The median percentage of cells immunoreactive for ERα was 75% and for ERβ 70% (range 10% weak positive to 100% strong positive). There was a statistically significant relationship between ERβ staining intensity and incidence of ipsilateral breast cancer (P = 0.010).Conclusions:  The presence and intensity of both stromal and glandular ERβ immunoreactivity suggest that the action of oestrogen on LCIS is on both stromal and glandular cells. Future studies are needed to determine whether the presence of ERβ in LCIS could be targeted to influence the treatment of this disease and perhaps alter its natural history.
Flat epithelial atypia (DIN 1a, atypical columnar change): an underdiagnosed entity very frequently coexisting with lobular neoplasia
Authors: Leibl S , Regitnig P , Moinfar F 
Published: June 2007

Aims:  Flat epithelial atypia of the breast [FEA; synonyms: ductal intraepithelial neoplasia (DIN) 1a, atypical columnar change] is increasingly recognized by pathologists and shows distinct genetic alterations. The aim of this study was to determine its biological significance as an incidental finding in breast biopsy specimens.Methods and results:  On the assumption that both FEA and lobular neoplasia (LN) derive from progenitor cells in the terminal ductal‐lobular unit, we investigated the association between FEA and LN semiquantitatively in 111 excisional breast biopsy specimens which contained LN, but did not contain ductal carcinoma in situ (DCIS) or invasive carcinoma. Ninety‐six cases (86.5%) revealed coexistence of LN and FEA (P < 0001). The distribution of LN was focal in 41 cases (37%), multifocal in 50 (45%) and extensive in 20 (18%) cases. FEA was identified as focal, multifocal and extensive in 29 (26%), 42 (38%) and 25 (23%) cases, respectively. Distribution patterns of LN and FEA showed no statistically significant correlation.Conclusions:  Due to the striking association between LN and FEA in our material, one may speculate that these two lesions are biologically related and that FEA is an early but non‐obligate precursor lesion similar to LN. Based on this assumption, regular clinical and mammographic follow‐up of patients with FEA would be prudent.
Lower reproductive success in hybrid fur seal males indicates fitness costs to hybridization
Authors: LANCASTER MELANIE L. , BRADSHAW COREY J. A. , GOLDSWORTHY SIMON D. , SUNNUCKS PAUL 
Published: June 2007

AbstractHybridization among organisms can potentially contribute to the processes of evolution, but this depends on the fitness of hybrids relative to parental species. A small, recently formed population of fur seals on subantarctic Macquarie Island contains a high proportion of hybrids (17–30%) derived from combinations of three parental species: Antarctic, subantarctic and New Zealand fur seals. Mitochondrial control‐region data (restriction fragment length polymorphisms) and nine microsatellites were used to determine the species composition of breeding adults, and hybrid male fitness was measured by comparing reproductive success (number of genetically inferred paternities) of hybrid and pure‐species territory males over 6 years. No correlations were found between male reproductive success and three genetic measures of outbreeding, but this may be due to a relatively small number of dominant males analysed. Territory males fathered 63% of pups, but hybrid males had lower reproductive success than pure‐species males despite having the same ability to hold territories. A greater proportion of females in hybrid male territories conceived extra‐territorially than those in territories of pure‐species males, and most (70 of 82) mated with conspecifics. This suggests the presence of reproductive isolating mechanisms that promote positive assortative mating and reduce the production of hybrid offspring. Although we found no evidence for male sterility in the population, mechanisms that reduce lifetime reproductive success may act to decrease the frequency of hybrids. Our study has identified a disadvantage of hybridization — reduced reproductive success of hybrid sons — that may be contributing to the persistence of pure lineages at Macquarie Island and the temporal decline in hybridization observed there.
Landscape‐level gene flow inLobaria pulmonaria, an epiphytic lichen
Authors: WERTH SILKE , GUGERLI FELIX , HOLDEREGGER ROLF , WAGNER HELENE H. , CSENCSICS DANIELA , SCHEIDEGGER CHRISTOPH 
Published: June 2007

AbstractEpiphytes are strongly affected by the population dynamics of their host trees. Owing to the spatio‐temporal dynamics of host tree populations, substantial dispersal rates — corresponding to high levels of gene flow — are needed for populations to persist in a landscape. However, several epiphytic lichens have been suggested to be dispersal‐limited, which leads to the expectation of low gene flow at the landscape scale. Here, we study landscape‐level genetic structure and gene flow of a putatively dispersal‐limited epiphytic lichen,Lobaria pulmonaria. The genetic structure ofL. pulmonariawas quantified at three hierarchical levels, based on 923 thalli collected from 41 plots situated within a pasture–woodland landscape and genotyped at six fungal microsatellite loci. We found significant isolation by distance, and significant genetic differentiation both among sampling plots and among trees. Landscape configuration, i.e. the effect of a large open area separating two forested regions, did not leave a traceable pattern in genetic structure, as assessed with partial Mantel tests and analysis of molecular variance. Gene pools were spatially intermingled in the pasture–woodland landscape, as determined by Bayesian analysis of population structure. Evidence for local gene flow was found in a disturbed area that was mainly colonized from nearby sources. Our analyses indicated high rates of gene flow ofL. pulmonariaamong forest patches, which may reflect the historical connectedness of the landscape through gene movement. These results support the conclusion that dispersal inL. pulmonariais rather effective, but not spatially unrestricted.
Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood‐stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
Authors: Nasr A. , Iriemenam N. C. , Troye‐Blomberg M. , Giha H. A. , Balogun H. A. , Osman O. F. , Montgomery S. M. , ElGhazali G. , Berzins K. 
Published: June 2007

AbstractIn a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcγRIIa‐R/H131 polymorphism and anti‐malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria‐free controls. Genotyping of FcγRIIa‐R/H131 dimorphism was performed using gene‐specific polymerase chain reaction (PCR) amplification with allele‐specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood‐stage antigens were assessed by an enzyme‐linked immunosorbent assay. The frequency of the FcγRIIa‐R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcγRIIa‐H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332‐C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcγRIIa‐R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite‐neutralizing immune mechanisms.
De‐aluminated Zeolite Y as a Tool to Study Endocytosis, A Delivery System Revealing Differences between Human Peripheral Dendritic Cells
Authors: Andersson L. I. M. , Eriksson H. 
Published: June 2007

AbstractWe report the use of nanometre‐sized zeolite particles as a novel approach to follow the endosomal acidification and proteolysis inside a viable cell. The method was verified by using human peripheral monocytes, a well known endocytosing cell population. Zeolite particles were subsequently used to investigate the endocytosing mechanisms of human peripheral dendritic cells (DC). Probes detecting pH neutral and acidic endosomes were adsorbed to de‐aluminated zeolite Y, and used to detect endocytosis in immature human peripheral blood DC. Both the myeloid (mDC) and the plasmacytoid (pDC) dendritic cell subsets had an endocytosing capacity comparable with peripheral blood monocytes. However, the majority of both subsets of DC retained their endosomes at a neutral pH during the first hours after endocytosis and only a small number of the mDC showed any formation of acidic endosomes. Proteolytic degradation of endocytosed proteins was detected using self‐quenched DQ‐ovalbumin adsorbed to zeolite particles. Interestingly, a clear difference in proteolytic degradation of endocytosed ovalbumin was observed between the two subsets of DC. The mDC showed an efficient degradation of ovalbumin, while the pDC population displayed no or only minor proteolytic degradation. In conclusion, zeolite particles provide a useful tool to study the endocytosing mechanisms, and an efficient carrier of bio‐molecules into the endosomal pathways of viable cells.
COMT genotype increases risk for bipolar I disorder and influences neurocognitive performance
Authors: Burdick Katherine E , Funke Birgit , Goldberg Joseph F , Bates John A , Jaeger Judith , Kucherlapati Raju , Malhotra Anil K 
Published: June 2007

Objectives:  Bipolar disorder (BPD) is an affective disorder characterized by episodes of depression and mania. Cognitive impairment in patients with BPD is common and recent data suggest that it may represent a trait‐like feature of the illness, as it persists during periods of wellness and co‐segregates in families of bipolar patients. This suggests an underlying genetic predisposition towards cognitive impairment in patients with BPD; however, there have been few studies investigating the effects of candidate genes on this symptom domain. The catechol‐O‐methyl transferase (COMT) gene is located on chromosome 22q11 and is involved in the metabolism of dopamine and norepinephrine. A large body of evidence suggests that COMT is associated with cognitive performance in patients with schizophrenia and in healthy volunteers but there have been no reports of its relationship to cognition in BPD.Methods:  We genotyped 52 Caucasian bipolar I probands and 102 Caucasian healthy controls across four single nucleotide polymorphisms (SNPs) within the COMT gene and administered a cognitive screening battery. We first assessed the relationship between COMT genotype and diagnosis and then tested for effects on cognition.Results:  We observed a modest but significant association between SNP rs165599 and BPD I, with the g allele being over‐represented in cases versus controls (odds ratio, OR = 2.41; allelic p = 0.02; genotypic p = 0.04). Further, we found a relationship between the risk allele at this SNP and poorer performance on measures of verbal memory [California Verbal Learning Test (CVLT) Trials 1–5; p = 0.005, η2 = 0.07] particularly with regard to prefrontal aspects of learning (CVLT semantic cluster; p = 0.037, η2 = 0.04) in patients with BPD and in healthy controls. The common Val158Met polymorphism was not associated with diagnosis (p = 0.32) or cognition in our sample.Conclusions:  These data suggest that COMT genetic variation at SNP rs165599 is associated with BPD I and influences prefrontal aspects of verbal memory in bipolar patients and healthy controls.
Early identification and high‐risk strategies for bipolar disorder
Authors: Correll Christoph U , Penzner Julie B , Lencz Todd , Auther Andrea , Smith Christopher W , Malhotra Anil K , Kane John M , Cornblatt Barbara A 
Published: June 2007

Objectives:  To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD).Methods:  Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high‐risk strategies.Results:  Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first‐degree bipolar relative. On the other hand, emerging work in the clinical‐high‐risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom ‘prodromal’ stages of BPD seems to be an under‐researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent‐onset bipolar, as well as in prospective population‐based phenomenology trials and attenuated symptom‐based high‐risk studies.Conclusions:  Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first‐degree relative with this disorder, clinical high‐risk approaches have great potential to inform early identification and intervention programs.
Use of the DiaMed Impact R to test platelet function in stored platelet concentrates
Authors: Morrison A. , Hornsey V. S. , Prowse C. V. , MacGregor I. R. 
Published: June 2007

Background and Objectives The DiaMed Impact R tests platelet function under close to physiological flow conditions using cone and plate technology. An image analyser quantifies the adhered platelets and results are expressed as percentage of well surface covered by aggregates (SC %) as an index of adhesion and average size of the aggregates (AS µm2) as an index of aggregation. The machine is designed to use whole blood and the aim of this study was to determine if it could be used to assess platelet function in platelet concentrates (PC).Material and Methods  Platelet concentrates were mixed with various ratios of platelet‐poor plasma (PPP) or ABO‐compatible routine leucoreduced red cells in saline–adenine–glucose–mannitol. The effects of platelet counts, haematocrit, shear rate and time of activation upon SC and AS were evaluated to identify optimized assay conditions. Routine PCs were then tested on Days 2, 5 and 7. Samples were also stored at 4 or 37 °C for 1 to 2 h before assay to see if function was altered.Results  Platelet concentrate in PPP resulted in no detectable platelet adhesion. However, addition of red cells to PC resulted in measurable platelet adhesion and aggregation. Optimal conditions were identified as shear rate of 1800 per second, 4‐min activation, platelet count between 250 and 400 × 106 per ml, haematocrit between 30 and 40%. When stored PCs were tested under these conditions we observed median values of 8·2% for SC and 32·7 µm2 for AS at 2 days, which reduced to 6.9% and 25·0 µm2, respectively, after 5‐day storage and 6·8% and 21·0 µm2 after 7 days.Conclusion  We were able to reconstitute PCs by adding red cells and identified conditions to allow platelet adhesion and aggregation functions of PCs to be measurable in the DiaMed Impact R. Platelet functions of adhesion and aggregation were shown to decrease during storage but improved after a 1‐h treatment at 37 °C.
Cryosupernatant and solvent detergent fresh‐frozen plasma (Octaplas) usage at a single centre in acute thrombotic thrombocytopenic purpura
Authors: Scully M. , Longair I. , Flynn M. , Berryman J. , Machin S. J. 
Published: June 2007

Background  Thrombotic thrombocytopenic purpura (TTP) is an acute, life‐threatening disorder and plasma exchange (PEX) remains the mainstay of treatment.Methods  We reviewed 50 acute TTP episodes to establish the efficacy and safety of cryosupernatant (CPP) and Octaplas.Results  Twelve episodes used CPP only and 15 episodes started with CPP and changed to Octaplas. Once Octaplas had been used, it was continued on further admissions. Cryosupernatant was used exclusively in 24% and Octaplas exclusively in 42% of all episodes. The number of citrate reactions and allergic (plasma) reactions were halved in those receiving only Octaplas compared with cryosupernatant. There were 22 line infections and in approximately 70% of cases the infection was associated with a reduction in platelet count. In all 50 episodes, the only documented thrombosis was a superficial non‐central vein. In episodes receiving only cryosupernatant or Octaplas, there was no significant difference in the median number of PEX to remission, 7·0 (interquartile range, IQR 5–8·8) and 8·0 (IQR 6·5–22), respectively. Baseline viral screen in all episodes was negative after discharge following an acute episode.Conclusion  There was no difference in number of PEX to remission with cryosupernatant and solvent/detergent fresh‐frozen plasma (Octaplas). However, allergic/urticarial and citrate reactions were more common with cryosupernatant. There was no documented viral transmission with either product.
Influence of pea lectin expressed transgenically in oilseed rape (Brassica napus) on adult pollen beetle (Meligethes aeneus)
Authors: Lehrman A. , Åhman I. , Ekbom B. 
Published: June 2007

Abstract:Adult pollen beetles were exposed to three transgenic lines of Brassica napus L. expressing pea lectin up to 0.7% of total soluble protein in anthers. Two lines not expressing the pea lectin were used as controls. Adult responses were recorded in two experiments where beetles were fed either racemes or anthers. There was no effect of plant line on feeding rate, weight change or oviposition rate. A slightly reduced egg size was recorded when beetles were feeding on one of the plant lines with high concentration of pea lectin. Previous studies on the effect of pea lectin on pollen beetles have only focused on larval performance. The results of this study suggest that pea lectin has no adverse effect on the pest in its most damaging life stage.
Olfactory response of a predatory mirid to herbivore induced plant volatiles: multiple herbivory vs. single herbivory
Authors: Moayeri H. R. S. , Ashouri A. , Poll L. , Enkegaard A. 
Published: June 2007

Abstract:Plants infested with a single herbivore species can attract natural enemies through the emission of herbivore‐induced plant volatiles (HIPVs). However, under natural conditions plants are often attacked by more than one herbivore species. We investigated the olfactory response of a generalist predators Macrolophus caliginosus to pepper infested with two‐spotted spider mites, Tetranychus urticae, or green peach aphid, Myzus persicae, vs. plants infested with both herbivore species in a Y‐tube olfactometer set up. In addition, the constituents of volatile blends from plants exposed to multiple or single herbivory were identified by gas chromatography‐mass spectrometry (GC‐MS). The mirid bugs showed a stronger response to volatiles emitted from plants simultaneously infested with spider mites and aphids than to those emitted from plants infested by just one herbivore, irrespective of the species. Combined with results from previous studies under similar conditions we infer that this was a reaction to herbivore induced plant volatiles. The GC‐MS analysis showed that single herbivory induced the release of 22 additional compounds as compared with the volatiles emitted from clean plants. Quantitative analyses revealed that the amount of volatile blends emitted from pepper infested by both herbivores was significantly higher than that from pepper infested by a single herbivore. Moreover, two unique substances were tentatively identified (with a probability of 94% and 91%, respectively) in volatiles emitted by multiple herbivory damaged plants: α‐zingiberene and dodecyl acetate.