bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and molecular characterisation of a fibrinogen binding protein from Streptococcus iniae.
Authors: Baiano Justice CF , Tumbol Reiny A , Umapathy Aarti , Barnes Andrew C 
Published: April 2008

AbstractBackgroundBinding of serum components by surface M-related proteins, encoded by theemmgenes, in streptococci constitutes a major virulence factor in this important group of organisms. The present study demonstrates fibrinogen binding byS. iniae, a Lancefield non-typeable pathogen causing devastating fish losses in the aquaculture industry and an opportunistic pathogen of humans, and identifies the proteins involved and their encoding genes.ResultsFibrinogen binding byS. iniaesignificantly reduced respiratory burst activity of barramundi peritoneal macrophages in primary cultures compared to BSA-treated or untreated controls, indicating a potentially important role for fibrinogen binding cell-surface proteins in avoiding phagocytic attack in fish. We describe a novelemm-like gene,simA, encoding a 57 kDa fibrinogen binding M-like protein inS. iniae. These SiM proteins and their corresponding tetrameric structures from some sequevar types (~230 kDa) bound fibrinogen in Western blots.simAwas most closely related (32% identity) to thedemAgene ofS. dysgalactiae. Genome walking and sequencing determined the genetic organization of thesimAregion had similarities to themgrCregulon in GCS and toS. uberis. Moreover, a putative multigene regulator,mgxwas orientated in the opposite direction to thesimAgene in common withS. uberis, but contrary to findings in GAS and GCS. In GAS, diversity amongemm-genes and consequent diversity of their M-related proteins results in substantial antigenic variation. However, an extensive survey ofS. iniaeisolates from diverse geographic regions and hosts revealed only three variants of the gene, with one sequevar accounting for all but two of the 50 isolates analysed.ConclusionThese proteins play a role in avoiding oxidative attack by phagocytic cells during infection of fish byS. iniae, but genetic diversity amongst these key surface proteins has not yet arisen. This lack of diversity coupled with a functional role in macrophage resistance suggests that these proteins may constitute important targets for future vaccines againstS. iniaein fish.
Intramuscular recurrence in a Hepatocellular carcinoma patient with indolent disease course
Authors: Yau Thomas , Wong Hilda , Chan Pierre , To MC , Poon Ronnie T 
Published: April 2008

Abstract

Background
Hepatocellular carcinoma (HCC) is a common malignancy worldwide and treatment options are depended on the stage of the tumour. In general, the prognosis of HCC patients with extra-hepatic metastasis is poor. The most common sites of extra-hepatic metastasis are the lung, abdominal lymph nodes and bone.

Case presentation
Here, we reported a 54-year-old man with an indolent clinical course of HCC. He had multiple extra-hepatic recurrences after initial hepatectomy for HCC and was benefited from repeated resections with prolonged survival. Eventually, he developed intramuscular recurrence in the thigh, which was initially mistaken as deep vein thrombosis.

Conclusion
Selected patients with indolent disease course of HCC may benefit from repeated resections of extra-hepatic metastases with prolonged survival.
Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Authors: Nadler Yasmine , Camp Robert L , Giltnane Jennifer M , Moeder Christopher , Rimm David L , Kluger Harriet M , Kluger Yuval 
Published: April 2008

Abstract
Introduction
Bcl-2 antanogene-1 (Bag-1) binds the anti-apoptotic mediator Bcl-2, and enhances its activity. Bcl-2 and Bag-1 are associated with chemotherapy resistance in cancer cells. Drugs that target Bcl-2 are currently in clinical development. The purpose of the present study was to examine expression patterns of Bag-1 in a large cohort of breast tumors and to assess the association with Bcl-2, estrogen receptor, progesterone receptor and Her2/neu, and other clinical/pathological variables.

Methods
Tissue microarrays containing primary specimens from 638 patients with 10-year follow-up were employed, and the expression of Bag-1, Bcl-2, estrogen receptor, progesterone receptor and Her2/neu was assessed using our automated quantitative analysis method. We used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and we measured biomarker expression within the mask using Cy5 conjugated antibodies.

Results
High Bcl-2 expression was associated with improved survival in the entire cohort and in the node-positive subset (P = 0.008 and P = 0.002, respectively). High Bag-1 expression was associated with improved survival in the node-positive subset (P = 0.006). On multivariable analysis, neither Bcl-2 nor Bag-1 retained their independence as prognostic markers. Strong associations were found between Bag-1, Bcl-2, estrogen receptor and progesterone receptor.

Conclusion
Bag-1 and Bcl-2 expression in breast tumors is associated with improved outcome and steroid receptor positivity. Evaluation of Bcl-2 and Bag-1 expression in breast cancer may identify a subset of patients with a favorable prognosis, who might not benefit from chemotherapy or who might benefit from Bcl-2 targeting agents in addition to antihormonal therapy.
Differential regulation of naïve and memory CD4+ T cells by alternatively activated dendritic cells
Authors: Anderson Amy E , Sayers Bethan L , Haniffa Muzlifah A , Swan David J , Diboll Julie , Wang Xiao-Nong , Isaacs John D , Hilkens Catharien M U 
Published: April 2008

AbstractPromising immunotherapeutic tools for T cell-mediated pathologies are alternatively activated dendritic cells (aaDC), which exert their effect through the regulation and tolerization of T cells. As naïve and memory T cells have different susceptibilities to tolerogenic signals, it is important to understand the modulatory effects of aaDC on these T cell subsets. We have examined regulation of naïve and memory CD4+ T cells by human aaDC generated with dexamethasone, the active form of vitamin D3, 1α,25-dihydroxyvitamin D3, and LPS. Although aaDC induced low, primary, allogeneic responses by naïve and memory T cells, aaDC regulated the differentiation of these T cell subsets in a distinct manner. Naïve T cells primed by aaDC retained a strong, proliferative capacity upon restimulation but were skewed toward a low IFN-γ/high IL-10 cytokine profile. In contrast, memory T cells primed by aaDC became hyporesponsive in terms of proliferation and cytokine production. Induction of anergy in memory T cells by aaDC was not a result of the presence of CD25hi regulatory T cells and could be partially reversed by IL-2. Both T cell subsets acquired regulatory activity and inhibited primary CD4 and CD8 responses. Addition of exogenous IL-12p70 during T cell priming by aaDC prevented anergy induction in memory T cells and cytokine polarization in naïve T cells, indicating that the lack of IL-12p70 is a key feature of aaDC. Our finding that aaDC differentially regulate naïve and memory T cells is important for understanding and maximizing the therapeutic potential of aaDC.
Synthetic oligonucleotides as modulators of inflammation
Authors: Klinman Dennis , Shirota Hidekazu , Tross Debra , Sato Takashi , Klaschik Sven 
Published: April 2008

AbstractSynthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN directly stimulate human B cells and plasmacytoid dendritic cells, promote the production of Th1 and proinflammatory cytokines, and trigger the maturation/activation of professional APC. CpG ODN are finding use in the treatment of cancer, allergy, and infection. In contrast, ODN containing multiple TTAGGG motifs mimic the immunosuppressive activity of self-DNA, down-regulating the production of proinflammatory and Th1 cytokines. Preclinical studies suggest that “suppressive” ODN may slow or prevent diseases characterized by pathologic immune stimulation, including autoimmunity and septic shock. Extensive studies in animal models suggest that the therapeutic value of CpG and TTAGGG ODN may be optimized by early administration.
Influence of Age at Menarche on Forearm Bone Microstructure in Healthy Young Women
Authors: Chevalley Thierry , Bonjour Jean-Philippe , Ferrari Serge , Rizzoli Rene 
Published: April 2008

Abstract
Background: Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 ± 0.6 (sd) yr.
Methods: At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA).
Results: Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = −0.21; P = 0.018), diaphysis (R = −0.18; P = 0.043), and metaphysis (R = −0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 ± 0.7 (±sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 ± 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 ± 54 vs. 341 ± 56 mg HA/cm3; P = 0.010), cortical volumetric BMD (874 ± 49 vs. 901 ± 44 mg HA/cm3; P = 0.003), and CTh (774 ± 170 vs. 849 ± 191 μm; P = 0.023). CTh was inversely related to CSA (R = −0.46; P &lt; 0.001). In LATER reduced CTh was associated with 5% increased CSA.
Conclusions: In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.
Effect of Weight Loss by Gastric Bypass Surgery Versus Hypocaloric Diet on Glucose and Incretin Levels in Patients with Type 2 Diabetes
Authors: Laferrère Blandine , Teixeira Julio , McGinty James , Tran Hao , Egger Joseph R. , Colarusso Antonia , Kovack Betty , Bawa Baani , Koshy Ninan , Lee Hongchan , Yapp Kimberly , Olivan Blanca 
Published: April 2008

AbstractContext: Gastric bypass surgery (GBP) results in rapid weight loss, improvement of type 2 diabetes (T2DM), and increase in incretins levels. Diet-induced weight loss also improves T2DM and may increase incretin levels.Objective: Our objective was to determine whether the magnitude of the change of the incretin levels and effect is greater after GBP compared with a low caloric diet, after equivalent weight loss.Design and Methods: Obese women with T2DM studied before and 1 month after GBP (n = 9), or after a diet-induced equivalent weight loss (n = 10), were included in the study. Patients from both groups were matched for age, body weight, body mass index, diabetes duration and control, and amount of weight loss.Setting: This outpatient study was conducted at the General Clinical Research Center.Main Outcome Measures: Glucose, insulin, proinsulin, glucagon, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP)-1 levels were measured after 50-g oral glucose. The incretin effect was measured as the difference in insulin levels in response to oral and to an isoglycemic iv glucose load.Results: At baseline, none of the outcome variables (fasting and stimulated values) were different between the GBP and diet groups. Total GLP-1 levels after oral glucose markedly increased six times (peak:17 ± 6 to 112 ± 54 pmol/liter; P &lt; 0.001), and the incretin effect increased five times (9.4 ± 27.5 to 44.8 ± 12.7%; P &lt; 0.001) after GBP, but not after diet. Postprandial glucose levels (P = 0.001) decreased more after GBP.Conclusions: These data suggest that early after GBP, the greater GLP-1 and GIP release and improvement of incretin effect are related not to weight loss but rather to the surgical procedure. This could be responsible for better diabetes outcome after GBP.
PET for Sarcomas Other Than Gastrointestinal Stromal Tumors
Authors: Toner Guy C. , Hicks Rodney J. 
Published: April 2008

Abstract
Positron emission tomography (PET) is increasingly used to diagnose, grade, and stage different types of tumors and to assess tumor response to therapy. Metabolic data acquired by fluorine-18-fluorodeoxyglucose (18FDG)-PET may facilitate accurate grading of sarcomas and have prognostic value when combined with other grading methods and various clinical/radiological features. In addition, 18FDG-PET is currently being evaluated in several cancer types for its utility in biopsy guidance. Whole-body 18FDG-PET also appears to be superior to other imaging modalities in detecting bone metastases in certain sarcoma patients. New PET tracers currently being investigated include 18F-fluorothymidine (18F-FLT) and 18F-misonidazole. 18F-FLT can help to determine tumor growth, rather than tumor shrinkage, which could be used to evaluate treatment response in sarcomas. PET imaging offers invaluable information to help maximize the clinical benefit of patients with sarcoma. This article reviews the use of PET in sarcoma management and its potential applications in the near future.
Other Endpoints in Screening Studies for Soft Tissue Sarcomas
Authors: Verweij Jaap 
Published: April 2008

Abstract
Despite extensive research efforts over the past two decades to identify effective agents for the treatment of soft tissue sarcomas, few agents are available, and with modest utility. There is a high unmet medical need to develop novel therapies for the treatment of patients with soft tissue sarcomas. Clinical trials for soft tissue sarcomas should be optimally designed, and it is crucial that they identify and define the desired clinical outcome. Survival is often the ultimate endpoint; however, physiological and biological markers are often used to predict the potential therapeutic benefit of a new agent. These endpoints can be easily measured, but can lead to false-positive results and do not take into account the complicated nature of soft tissue sarcomas. Alternative endpoints that are currently being evaluated include the progression-free survival rate, time to progression, tumor growth rate, and progression arrest rate. This article discusses some of the limitations of current endpoint criteria and potential endpoint criteria that could be used to evaluate treatment options for patients with soft tissue sarcomas.
The Lessons of GIST—PET and PET/CT: A New Paradigm for Imaging
Authors: Van den Abbeele Annick D. 
Published: April 2008

Abstract
Traditional anatomic tumor response criteria are based on uni- or bidimensional changes in tumor size, and do not take into account changes in tumor metabolism, tumor density, or decrease in the number of intratumoral vessels. These changes are, however, all indicative of response to imatinib therapy in patients with gastrointestinal stromal tumor (GIST). In these patients, metabolic responses seen on positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (18FDG) have been shown to be closely related to clinical benefit. Furthermore, these metabolic changes precede by weeks or months significant decrease in tumor size on computed tomography (CT). Conversely, lack of metabolic response on FDG-PET indicates primary resistance to the drug and may help identify patients who would benefit from another therapy, while re-emergence of metabolic activity within tumor sites following a period of therapeutic response indicates secondary resistance to the drug. Newly proposed CT criteria using either no growth in tumor size or a combination of tumor density and size criteria have shown a close correlation with the predictive value results of FDG-PET. Thus, the integration of FDG-PET and CT, as in the combined hybrid PET/CT scanners now available, will not only optimize the evaluation of patients with GIST treated with molecularly targeted drugs, but may ultimately help shorten clinical trials, and accelerate drug development in this disease and other cancers as well.
Evaluation of the Association of IGF2BP2 Variants With Type 2 Diabetes in French Caucasians
Authors: Duesing Konsta , Fatemifar Ghazaleh , Charpentier Guillaume , Marre Michel , Tichet Jean , Hercberg Serge , Balkau Beverley , Froguel Philippe , Gibson Fernando 
Published: April 2008

OBJECTIVE—We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the “confirmed” type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus.
RESEARCH DESIGN AND METHODS—We genotyped a total of 21 tagging single nucleotide polymorphisms spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects.
RESULTS—IGF2BP2 variants rs4402960 and rs1470579 were not associated with type 2 diabetes in the present study (P = 0.632 and P = 0.896, respectively). Meta-analysis of genotype data from over 34,000 subjects demonstrated that our inability to replicate rs4402960/rs1470579 was consistent with the findings from several previous genome-wide association study (GWAS) datasets that were underpowered to detect this modest association signal (odds ratio [OR] 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% minor allele frequency) in the 3′ downstream region, was associated with type 2 diabetes (P = 0.0002; OR 1.53 [95% CI 1.22–1.91]). This result was corroborated by the meta-analysis of 10,542 genotypes from the current study and GWAS datasets using both fixed (P = 9.47 × 10−6; 1.30 [1.16–1.46]) and random effects (P = 0.001; 1.30 [1.11–1.52)] calculations.
CONCLUSIONS—We were unable to replicate the confirmed rs4402960/rs1470579 susceptibility variants but found novel evidence for a rare variant in the 3′ downstream region of IGF2BP2. Further genetic and functional studies are required to identify the etiological IGF2BP2 variants.
A century of Antarctic science; planning and serendipity
Authors: Fogg G. E. 
Published: April 2008

The British National Antarctic Expedition planned with discreditable bickering, sailed for the Antarctic in 1901 on the Discovery. The venture was well equipped and commanded by R. F. Scott who, without scientific training himself, was nevertheless remarkably in empathy with his scientists. The expedition was foremost among those dispatched around the same time in establishing basic knowledge of the continent. Followed by the second Scott expedition and those of Shackleton and Mawson, a cadre of able and enthusiastic scientists was established. The second involvement of the Discovery in Antarctic exploration was planned without quarrels and with unusual understanding of science by a government department, resulting in a massive accumulation of knowledge about the Southern Ocean. United States expeditions began in 1928, introducing modern technology, thereby extending greatly the scope of Antarctic research. The Norwegian-British-Swedish expedition of 1949–1952 put planned science before geographical exploration. The International Geophysical Year of 1957–1958, supported by governments and planned by international committees, achieved great success. Science has flourished in Antarctica with unplanned and serendipitous findings emerging, for example, the structure of the magnetosphere, collection of meteorites by ice movements, the microbial life of the apparently sterile Dry Valleys and the discovery of the ozone “hole”.
Surveying terrestrial magnetism in time and space
Authors: McConnell Anita 
Published: April 2008

Charts marked with the lines of magnetic variation have been published since Halley's Atlantic chart of 1701. It was already known that the location of the magnetic poles shifted over time, and that the north and south poles were not diametrically opposite. As more seafarers penetrated the Southern Ocean, isogons on the charts were extended southwards with greater confidence. At sea variation was measured by comparing compass direction with the Sun's midday shadow. In polar regions, where horizontal force is too weak to attract a compass needle, the location of the pole was sought by observing the inclination of a dip needle swinging in the magnetic meridian, which would hang vertically at the pole. The Fox dip circle, developed in 1834, was the first instrument capable of measuring dip and intensity at sea, and allowed James Clark Ross to predict the location of the South Magnetic Pole. In 1902 Discovery's crew landed an observatory ashore, but a trek on to the plateau failed to reach the magnetic pole. Success came in 1909 during Shackleton's Nimrod expedition, when T. Edgeworth David's party reached the zone of maximum dip. Over the following years data from photographic magnetometers recording declination, vertical and horizontal intensity were routinely made at the various national bases round Antarctica; they contributed to our knowledge of the Earth's internal magnetism and on the solar influences.
Thing Theory: Towards an Integrated Archaeological Perspective
Authors: HODDER PROFESSOR IAN 
Published: April 2008

Lecture 1.  Humans and things - developing some ideas and terms Lecture 2.  Çatalhöyük: a Neolithic ‘town’ in Turkey Lecture 3.  Humans and things at Çatalhöyük Lecture 4.  Developing a long-term view: the ‘origins of agriculture’ in the Middle East This lecture series has two aims. One is to discuss a new theoretical framework for the relationships between humans and material culture which I am calling ‘Thing Theory’. This framework focuses on the co-dependencies and entanglements between humans and non-humans and argues that long-term change comes about through the dispersed interactions of these entanglements. The theory is integrated in the sense that it adopts aspects of many theoretical agendas in recent archaeology, from experimental and behavioral archaeology to neo-evolutionary and selectionist models. It is also integrated in that it links theoretical agendas with archaeometry and archaeological science. The second aim is to show the application of Thing Theory to the 9000 year old Neolithic site of Çatalhöyük in central Turkey, and to the ‘origins of agriculture’ in the Middle East. My excavations at Çatalhöyük over the past 15 years have uncovered a rich world of human-thing entanglements and have shed light on the complex lived worlds within which agriculture and settled villages were produced.
A Medieval Bloomery Mound in Glen Docherty, Kinlochewe, Highland
Authors: JOHNSON MELANIE , PHOTOS-JONES EFFIE , HICKMAN SAMANTHA 
Published: April 2008

Summary An iron-working bloomery mound was excavated by CFA Archaeology Ltd in 2004 at the head of Glen Docherty, near Kinlochewe, Achnasheen, Highland. A mound of waste material was excavated and dated to the 15th–17th centuries on the basis of radiocarbon analysis. A solidified bed of ferruginous deposit was revealed during the bloomery mound excavations but was found to be of an earlier date (1050–1285 AD). There was no further evidence for metalworking installations. A charcoal-burning platform was also excavated in Glen Docherty in 2005 and radiocarbon dated to the 15th–17th centuries. The above provide evidence for a long involvement with iron making in this part of the western Highlands and prior to the 17th century when the area, and the north shore of Loch Maree in particular, became known as the location for the installation of the first charcoal-operated blast furnace in Scotland.