bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 study of two sequential three‐drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma
Authors: Bensinger William I. , Jagannath Sundar , Vescio Robert , Camacho Elber , Wolf Jeffrey , Irwin David , Capo Gerardo , McKinley Marti , Potts Phyllis , Vesole David H. , Mazumder Amitabha , Crowley John , Becker Pam , Hilger Jacqueline , Durie Brian G.M. 
Published: November 2009

SummaryNovel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three‐drug combinations. Forty‐four previously untreated, symptomatic MM patients received: bortezomib 1·3 mg/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21‐day cycles, followed by bortezomib 1·0 mg/m2, dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%≥ very good partial response. Twenty‐two patients have undergone stem‐cell transplantation. After a median follow‐up of 20·9 months, five patients have died; none was induction therapy‐related. Median event‐free survival (EFS) and overall survival (OS) have not been reached; estimated 1‐year EFS and OS rates were 81% and 91% respectively. Both three‐drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most‐commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three‐drug combination therapy is effective and well‐tolerated in previously untreated MM patients.
Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma
Authors: Geyer Felipe C , Kushner Yael B , Lambros Maryou B , Natrajan Rachael , Mackay Alan , Tamber Narinder , Fenwick Kerry , Purnell Dave , Ashworth Alan , Walker Rosemary A , Reis‐Filho Jorge S 
Published: November 2009

Aims:  Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non‐obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER‐2 overexpression (triple‐negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC‐NST).Methods and results:  We report on a case comprising MGA, AMGA and a high‐grade IDC‐NST. The three components were separately microdissected and subjected to genetic analysis with high‐resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple‐negative phenotype and variable positivity for basal markers.Conclusions:  Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non‐obligate precursor of a subgroup of high‐grade triple‐negative and basal‐like breast carcinomas.
CD98 expression is decreased in papillary carcinoma of the thyroid and Hashimoto’s thyroiditis
Authors: Anderson Catriona E , Graham Catriona , Herriot Michael M , Kamel Hassan M , Salter Donald M 
Published: November 2009

Aims:  CD98 is a component of the large neutral amino acid transporter (LAT), which is a cell surface amino acid transporter. CD98 also binds to and activates β1‐integrin, promoting anchorage‐independent growth. CD98 expression is increased in a variety of carcinomas but its distribution in the normal and neoplastic thyroid gland has not been reported. The aim was to examine the immunohistochemical expression of CD98 in normal and diseased thyroid tissue.Methods and results:  One hundred and forty thyroid cases were selected from the archives of the Department of Pathology, including normal controls, neoplasms (follicular adenoma, follicular carcinoma and papillary carcinoma) and non‐neoplastic conditions (multinodular goitre, Graves’ disease and Hashimoto’s thyroiditis). Immunohistochemistry for CD98 was performed and each case was scored for proportion of cells and intensity of immunoreactivity. In normal thyroid, there was moderately strong expression of CD98 in the lateral cell membranes of follicular cells. A similar pattern of expression was seen in follicular adenoma, minimally invasive follicular carcinoma, multinodular goitre and Graves’ disease. In most cases of papillary carcinoma and in the inflamed areas of Hashimoto’s thyroiditis, expression of CD98 was decreased.Conclusions:  CD98 expression is down‐regulated in thyroid papillary carcinoma; this may relate to the better prognosis associated with many of these tumours.
A comparison between isolated blood dendritic cells and monocyte‐derived dendritic cells in pigs
Authors: Facci Marina R. , Auray Gael , Buchanan Rachelle , Van Kessel Jill , Thompson David R. , Mackenzie‐Dyck Sarah , Babiuk Lorne A. , Gerdts Volker 
Published: November 2009

SummaryVarious dendritic cell (DC) populations exist that differ in phenotype and ability to present antigen to T cells. For example, plasmacytoid DCs (pDCs) are less potent T cell activators compared with conventional DCs (cDCs). Here, we compared porcine blood DCs (BDCs), containing pDCs and cDCs, and monocyte‐derived DCs (MoDC), consisting of cDCs, in their phenotype, ability to uptake antigen, activation and maturation and their ability to present antigen to autologous T cells. Pigs represent an important animal model, whose immune system in many respects closely resembles that of humans. For example, the distribution of Toll‐like receptors is similar to that of humans, in contrast to that of mice. Here we demonstrate that both populations endocytose foreign material. Following lipopolysaccharide stimulation, CD80/86 and chemokine receptor (CCR)7 expression was increased in both populations as was the expression of the chemokine ligands (CCL)‐2, CCL‐4, CCL‐20 and CXCL‐2. Although basal and post‐stimulation protein concentrations of interleukins 6 and 8 and tumour necrosis factor‐α were higher in MoDCs, protein concentrations showed a higher fold increase in BDCs. Antigen‐specific proliferation of autologous T cells was induced by MoDCs and BDCs. Interestingly, while MoDCs induced stronger proliferation in naive T cells, no difference in proliferation was observed when primed T cells were studied. These results demonstrate that isolated porcine BDCs are highly responsive to stimulation with lipopolysaccharide and are functionally able to drive primed T‐cell proliferation to the same extent as MoDCs.
Dendritic cells activated by an anti‐inflammatory agent induce CD4+ T helper type 2 responses without impairing CD8+ memory and effector cytotoxic T‐lymphocyte responses
Authors: Wang Yang , Da’Dara Akram A. , Thomas Paul G. , Harn Donald A. 
Published: November 2009

SummaryPrevalence of pro‐inflammatory diseases is rising in developed country populations. The increase in these diseases has fuelled the search for new, immune suppressive, anti‐inflammatory therapies, which do not impact, or minimally impact, CD4+ and/or CD8+ T‐cell‐mediated immunity. The goal of this study was to determine if antigen‐presenting cells (APCs) activated by the anti‐inflammatory oligosaccharide, lacto‐N‐fucopentaose III (LNFPIII), would have an impaired ability to drive CD4+ T helper (Th) or CD8+ memory and effector T‐cell responses. To investigate this we activated splenic dendritic cells (SDCs) with LNFPIII and examined their ability to drive antigen‐specific CD4+ Th, and CD8+ memory and cytotoxic T‐cell (CTL) responses compared with lipopolysaccharide (LPS) ‐stimulated SDCs. The LNFPIII‐activated SDCs had altered co‐stimulatory molecule expression compared with LPS‐stimulated SDCs, while the levels of SDC chemokines following activation by either compound were similar. LNFPIII‐activated SDCs produced significantly lower levels of interleukin‐12 but surprisingly higher levels of interleukin‐6 than LPS‐activated SDCs. Similar to previous studies using bone‐marrow‐derived DCs, LNFPIII‐activated SDCs induced strong Th2 responses in vivo and ex vivo. LNFPIII activation of APCs was independent of the Toll‐interleukin‐1 receptor adaptor myeloid differentiating factor 88. Importantly, LNFPIII‐matured DCs induced CD8+ memory and effector CTL responses similar to those driven by LPS‐matured DCs, including the frequency of interferon‐γ‐producing CD8+ T cells and induction of CTL effectors. Treatment of APCs by the anti‐inflammatory glycan LNFPIII did not impair their ability to drive CD8+ effector and memory cell‐mediated immunity.
Mesenteric lymph nodes are not required for an intestinal immunoglobulin A response to oral cholera toxin
Authors: Hahn Anika , Thiessen Nadja , Pabst Reinhard , Buettner Manuela , Bode Ulrike 
Published: November 2009

SummaryStimulation of the adaptive immune system in the gut is thought to be mainly initiated in the Peyer’s patches as well as in the mesenteric lymph nodes (mLNs) and results in immunoglobulin A (IgA) secretion by plasma cells in the lamina propria. However, the precise role of the mLNs in the development of IgA immune responses is poorly understood. Thus, cholera toxin (CT) was administered to mLN‐resected and mLN‐bearing animals and the IgA response to CT in the intestine and serum was examined. Levels of CT‐specific IgA antibodies and the numbers of cells producing these antibodies in the intestine were increased in mLN‐resected rats. Particularly in the distal parts of the intestine, the jejunum and the ileum, IgA responses to orally administered antigens developed were stronger in the intestine after removal of the mLNs. This strongly indicates that the mLNs play a critical role in modulating the expansion of specific IgA responses. After removal of the mLNs, the lymph from the gut flows directly into the blood. It was investigated whether the spleen is involved in the initiation of an immune response to orally administered CT after removal of the mLNs. In the spleens of mLN‐resected animals, proliferation was up‐regulated, and germinal centres were formed in the follicles. However, CT‐specific IgM+ cells, but no IgA+ cells, developed. Additionally, an increase of CT‐specific IgM in the serum was found in mLN‐resected animals. Thus, the data indicate that the spleen is involved in the immune response to CT after mLN resection.
Natural colourant from Shiraia bambusicola: stability and antimicrobial activity of hypocrellin extract
Authors: Su Yujie , Yin Xiaoyan , Rao Shengqi , Cai Yujie , Reuhs Brad , Yang Yanjun 
Published: November 2009

SummaryA red pigment, hypocrellin extract, was studied as a natural food additive for the first time. The colour of hypocrellin extract changed with pH value, from bright red in acidic to green in alkaline condition. It was stable to heat, and natural light, but was susceptible under direct sun rays. Hypocrellin extract was resistant to oxidant (H2O2), but was sensitive to reducer such as Na2SO3. No evident influences of food additives in common use on the stability of hypocrellin extract were observed. Most tested metal ions hardly affected pigment stability except for Fe2+, Fe3+, Al3+and Cu2+. It possessed excellent light‐induced antimicrobial activity to the Gram‐positive bacteria usually troublesome in food industry. However, no antimicrobial activity was observed to the Gram‐negative bacteria. Our findings demonstrated that hypocrellin extract may be used as a natural colourant or preservative in food and other allied industries.
Shelf‐life of vacuum packed Alaskan, Scottish and Norwegian cold‐smoked salmon available on the Italian market
Authors: Bernardi Cristian , Ripamonti Barbara , Campagnoli Anna , Stella Simone , Cattaneo Patrizia 
Published: November 2009

SummaryFourteen vacuum packed cold smoked salmon products of different origin purchased in Italian retail were analysed at about half shelf‐life (HSL) and at the expiry date (ED). On ED, eight on fourteen samples had concentration of total volatile basic nitrogen (TVBN) indicating spoilage (values >40 mg N/100 g and up to 71.3 mg N/100 g) and only five samples were not rancid (thiobarbituric acid reactive substances, TBARS <8 nmol/g). Total psychrotrophic count (TPC) at HSL was acceptable (<106 CFU/g) in most samples; at ED, in 13 samples, TPC was very high (range 1.2 × 106– 6.0 × 108 CFU/g) and Lactobacilli were the most representative bacteria. No pathogens were detected. Significant negative differences in declared weight (over 8%) were determined in nine samples. The two months shelf‐life attributed to smoked salmon marketed in Italy proved to be, generally, too long and the consumer is at risk to buy a product in early stage of spoilage.
Industrial processing effects on chestnut fruits (Castanea sativa Mill.). 2. Crude protein, free amino acids and phenolic phytochemicals
Authors: Do Carmo Barbosa Mendes de Vasconcelos Maria , Bennett Richard N. , Rosa Eduardo A. S. , Ferreira‐Cardoso Jorge V. 
Published: November 2009

SummaryThe aim of this study was to analyse the effects of industrial processing on the composition of proteins, free amino acids and phenolics in Castanea sativa Mill. fruits of 2 years. The Portuguese cultivars were Judia, Longal, Martaínha and Lada, and the European cultivars were ‘Spanish’ (Puga do Bolo) and ‘Italian’ (Viterbes). At all processing stages the fruits contained low contents of protein (4.1–5.4 g 100 g−1 d.m.). The essential amino acid Thr had the highest values (3.6–10.0 mg 100 g−1 f.w.), while the highest non‐essential amino acid was Asn (14.9–36.4 g 100 g−1 f.w.). Total phenolics (6.6–18.3 mg g−1 f.w.) were more significantly affected by the processing stage factor. In 2007 the gallic acid contents were more affected by the processing stage and interaction factors (cultivar × processing stage), whereas the cultivar factor had more of an effect on ellagic acid. Industrial processing has some negative effects, specifically reducing the contents of some amino acids.
Microbiological characteristics of poultry patties in relation to packaging atmospheres
Authors: Mastromatteo Marianna , Lucera Annalisa , Sinigaglia Milena , Corbo Maria Rosaria 
Published: November 2009

AbstractMicrobial characteristics under different atmospheres (vacuum, air, MAP1: 80% O2/20% CO2 and MAP2: 5% O2/65% N2/30% CO2) of poultry patties made of a mixture of ostrich, chicken and turkey meat were evaluated. The meat preparations were examined for changes in pH, colour properties (CIE L*, a*, b*), headspace composition, and bacterial counts (total viable cell, psychrotrophs, Enterobacteriaceae, lactic acid bacteria, Staphylococcus spp., Brochothrix thermosphacta, Pseudomonas spp.). The use of a high O2 atmosphere (MAP1) quickly leads to a loss of the appealing red colour. A limited alteration occurred with use of MAP2 and vacuum. For total viable counts a cell load higher than 8 log cfu g−1 for the samples packaged in air, MAP1 and MAP2 at the end of storage was observed. Whereas, for the vacuum packed samples the cell load never reached values higher than 8 log cfu g−1. Enterobacteriaceae, B. thermosphacta and Pseudomonas spp. cell load was less with the vacuum (7.60, 5.06 and 7.17 log cfu g−1, respectively) and MAP2 packaging (7.08, 5.60 and 7.40 log cfu g−1, respectively). However, the high microbial loads suggest that an improvement of the microbiological quality of poultry meat is necessary if the producers are going to propose this new meat preparation on the market.
Do linear landscape elements in farmland act as biological corridors for pollen dispersal?
Authors: Van Geert Anja , Van Rossum Fabienne , Triest Ludwig 
Published: November 2009

Summary 1. Habitat fragmentation in agricultural landscapes has reduced the population sizes of many plant species while increasing their spatial isolation. Restoration or maintenance of the connectivity by gene flow between the fragmented patches may be determinant to sustaining viable populations, especially for insect‐pollinated species. Functional biological corridors facilitating pollen flow between remnants in a human‐dominated matrix might achieve this. 2. Dye dispersal was investigated for the extremely fragmented insect‐pollinated herb Primula vulgaris, using fluorescent dye particles as pollen analogues, in a study site comprising 20 populations, of which 13 pairs were physically connected by a linear landscape elements (LLEs, ditches), and 11 pairs were not connected by an LLE. The dye deposition events were used to fit a model of pollen dispersal at the landscape level. We examined whether existing LLEs in the intensively used agricultural landscape act as functional corridors for pollen dispersal. The effects of LLE length and size and plant density of the recipient population on the dispersal patterns were tested. 3. Dye dispersal showed a leptokurtic decay distribution, with 80% of the dye transfers occurring at less than 85.1 m, and a maximal distance of 1010.8 m. The mean distance travelled by fluorescent dye particles based on the dye dispersal model was δ = 87 m. 4. Dye dispersal between populations was found to be significantly higher when populations were connected by an LLE, than when populations were unconnected. For the group of population pairs connected by an LLE, dye deposition significantly decreased with the distance to dye source, but was not related to recipient population size and plant density. 5. Synthesis. Our study is, to our knowledge, the first to demonstrate that existing LLEs in an intensively used farmland may act as functional biological corridors facilitating pollen dispersal through pollinator movements. The maintenance or restoration of a network of populations connected by LLEs, but also by other landscape structures (e.g. population relays in vegetation patches and networks of small elements allowing indirect connections) should be strongly encouraged.
Higher treefall rates on slopes and waterlogged soils result in lower stand biomass and productivity in a tropical rain forest
Authors: Ferry Bruno , Morneau François , Bontemps Jean‐Daniel , Blanc Lilian , Freycon Vincent 
Published: November 2009

Summary1. Relationships between tropical rain forest biomass and environmental factors have been determined at regional scales, e.g. the Amazon Basin, but the reasons for the high variability in forest biomass at local scales are poorly understood. Interactions between topography, soil properties, tree growth and mortality rates, and treefalls are a likely reason for this variability.2. We used repeated measurements of permanent plots in lowland rain forest in French Guiana to evaluate these relationships. The plots sampled topographic gradients from hilltops to slopes to bottomlands, with accompanying variation in soil waterlogging along these gradients. Biomass was calculated for >175 tree species in the plots, along with biomass productivity and recruitment rates. Mortality was determined as standing dead and treefalls.3. Treefall rates were twice as high in bottomlands as on hilltops, and tree recruitment rates, radial growth rates and the abundance of light‐demanding tree species were also higher.4. In the bottomlands, the mean wood density was 10% lower than on hilltops, the basal area 29% lower and the height:diameter ratio of trees was lower, collectively resulting in a total woody biomass that was 43% lower in bottomlands than on hilltops.5. Biomass productivity was 9% lower in bottomlands than on hilltops, even though soil Olsen P concentrations were higher in bottomlands.6. Synthesis. Along a topographic gradient from hilltops to bottomlands there were higher rates of treefall, which decreased the stand basal area and favoured lower allocation to height growth and recruitment of light‐demanding species with low wood density. The resultant large variation in tree biomass along the gradient shows the importance of determining site characteristics and including these characteristics when scaling up biomass estimates from stand to local or regional scales.
PolY, a transcriptional regulator with ATPase activity, directly activates transcription of polR in polyoxin biosynthesis in Streptomyces cacaoi
Authors: Li Rui , Liu Gang , Xie Zhoujie , He Xihong , Chen Wenqing , Deng Zixin , Tan Huarong 
Published: November 2009

Summary polY, a transcriptional regulatory gene in the polyoxin biosynthetic cluster of Streptomyces cacaoi, was analysed, and its deduced product (PolY) showed amino acid sequence homology to AfsR from Streptomyces coelicolor A3(2). PolY contains an OmpR‐like DNA binding domain at its N‐terminal and an ATPase domain in the middle of the protein. Disruption of polY abolished polyoxin biosynthesis, which could be restored by the integration of a single copy of polY into the chromosome of the disruption mutant. Transcription of polR, a pathway‐specific regulatory gene of polyoxin biosynthesis, was controlled by polY. Electrophoretic mobility shift assay and DNase I protection experiments indicated that PolY bound to the promoter region of polR, and the binding site contained a direct nucleotide repeat typical of Streptomyces antibiotic regulatory protein binding sites. PolY exhibited ATPase activity in vitro. Additionally, binding of ADP/ATPγS to ATPase domain triggered the oligomerization of PolY and enhanced its DNA binding activity. Consistently, further experiments in vivo demonstrated that changes of ADP/ATP concentrations significantly affected PolY activity in the cell. These results suggested that the ATPase domain might be a sensor of endogenous pool of ADP/ATP, whose change modulated PolY activity under the physiological conditions.