bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non‐erosive reflux disease
Authors: FASS R. , CHEY W. D. , ZAKKO S. F. , ANDHIVAROTHAI N. , PALMER R. N. , PEREZ M. C. , ATKINSON S. N. 
Published: April 2009

SummaryBackground  The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non‐erosive reflux disease (NERD) than in those with erosive oesophagitis.Aim  To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients.Methods  In this 4‐week, double‐blind, placebo‐controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24‐h heartburn‐free days (primary) and nights without heartburn (secondary) were assessed from patients’ daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires.Results  Dexlansoprazole MR provided significantly greater median percentages of 24‐h heartburn‐free days (54.9% and 50.0% for the 30‐ and 60‐mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment‐emergent adverse events were similar among groups.Conclusions  Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24‐h heartburn‐free days and nights in NERD patients. Treatment was well tolerated.
Meta‐analysis: surveillance with ultrasound for early‐stage hepatocellular carcinoma in patients with cirrhosis
Authors: SINGAL A. , VOLK M. L. , WALJEE A. , SALGIA R. , HIGGINS P. , ROGERS M. A. M. , MARRERO J. A. 
Published: April 2009

SummaryBackground  A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis.Aim  To determine the performance characteristics of surveillance with ultrasound for the detection of HCC, particularly early HCC as defined by the Milan criteria.Methods  A systematic literature review using the MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of ultrasound for HCC at any stage and 13 studies that were specific to early HCC.Results  Surveillance ultrasound detected the majority of tumours before they presented clinically, with a pooled sensitivity of 94%. However, ultrasound was less effective for detecting early HCC with a sensitivity of 63%. Alpha‐fetoprotein provided no additional benefit to ultrasound. Meta‐regression analysis demonstrated a significantly higher sensitivity for early HCC with ultrasound every 6 months than with annual surveillance. Current studies have limitations such as verification bias and are of suboptimal quality.Conclusions  Surveillance with ultrasound demonstrates limited sensitivity for early HCC, although this may be improved by testing at 6‐month intervals. Currently available evidence evaluating surveillance ultrasound has significant limitations and future studies are necessary to determine optimal surveillance methods for early HCC.
Variation in mitochondrial DNA and maternal genetic ancestry of Ethiopian cattle populations
Authors: Dadi H. , Tibbo M. , Takahashi Y. , Nomura K. , Hanada H. , Amano T. 
Published: April 2009

SummaryThis study describes complete control region sequences of mitochondrial DNA (mtDNA) from 117 Ethiopian cattle from 10 representative populations, in conjunction with the available cattle sequences in GenBank. In total, 79 polymorphic sites were detected, and these defined 81 different haplotypes. The haplotype and nucleotide diversity of Ethiopian cattle did not vary among the populations studied. All mtDNA sequences from Ethiopian cattle converged into one main maternal lineage (T1) that corresponds to African Bos taurus cattle. According to the results of this study, no zebu mtDNA haplotypes have been found in Ethiopia, where the most extensive hybridization took place on the African continent.
Genomic structure, chromosomal localization and expression profile of a porcine long non‐coding RNA isolated from long SAGE libraries
Authors: Ren H. , Li Y. , Tang Z. , Yang S. , Mu Y. , Cui W. , Ao H. , Du L. , Wang L. , Li K. 
Published: April 2009

SummaryLong non‐coding RNA (long ncRNA) is a novel class of ncRNA that may be involved in critical cellular processes. A considerable number of mammalian long ncRNAs have now been isolated but only a small number of these nucleic acids have been functionally well characterized. In this study, to determine the structure, regulation and function of long ncRNA in pigs, TncRNA was isolated from this mammal and its potential function during pig foetus development was identified. We anticipated that this would provide new insights into functional genomic studies in the pig. Using LongSAGE libraries generated from Chinese indigenous Tongcheng and Landrace pigs at three prenatal stages, a novel porcine long ncRNA was identified, TncRNA, which was found to be differentially expressed during myogenesis. The full‐length cDNA for this gene is 3409 bp, and it harbours a typical polyadenylation signal sequence located 18 bp upstream from the 3′ poly (A) tail. Genomic sequence analysis showed that pig TncRNA is alternatively spliced and several transcripts were detected. Using the INRA–University of Minnesota porcine radiation hybrid panel, TncRNA was assigned to SSC2 and found to be closely linked to the microsatellite marker SW256. Porcine TncRNA was found to be expressed in all tissues examined but in variable amounts. Comparisons between the expression profiles of TncRNA at different development stages in Tongcheng and Landrace pigs revealed up‐regulation of this molecule in prenatal skeletal muscle, and differential expression in 90‐day‐old foetal skeletal muscle between these two pig breeds. This is the first report to describe a long ncRNA in pig. Moreover, the distinct expression pattern and structure of porcine TncRNA suggest that it performs complex and critical functions during foetal development.
Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease
Authors: Pennisi Angela , Li Xin , Ling Wen , Khan Sharmin , Gaddy Dana , Suva Larry J. , Barlogie Bart , Shaughnessy John D. , Aziz Nazneen , Yaccoby Shmuel 
Published: April 2009

SummaryDipeptidyl peptidase (DPP) IV activity and/or structure homologues (DASH) are serine proteases implicated in tumourigenesis. We previously found that a DASH protease, fibroblast activation protein (FAP), was involved in osteoclast‐induced myeloma growth. Here we further demonstrated expression of various adhesion molecules in osteoclasts cultured alone or cocultured with myeloma cells, and tested the effects of DASH inhibitor, PT‐100, on myeloma cell growth, bone disease, osteoclast differentiation and activity, and expression of adhesion molecules in osteoclasts. PT‐100 had no direct effects on viability of myeloma cells or mature osteoclasts, but significantly reduced survival of myeloma cells cocultured with osteoclasts. Real‐time PCR array for 85 adhesion molecules revealed upregulation of 17 genes in osteoclasts after coculture with myeloma cells. Treatment of myeloma/osteoclast cocultures with PT‐100 significantly downregulated 18 of 85 tested genes in osteoclasts, some of which are known to play roles in tumourigenesis and osteoclastogenesis. PT‐100 also inhibited osteoclast differentiation and subsequent pit formation. Resorption activity of mature osteoclasts and differentiation of osteoblasts were not affected by PT‐100. In primary myelomatous severe combined immunodeficient (SCID)‐hu mice PT‐100 reduced osteoclast activity, bone resorption and tumour burden. These data demonstrated that DASH proteases are involved in myeloma bone disease and tumour growth.
Immunogloblin E‐mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients
Authors: Gómez E. , Blanca‐Lopez N. , Torres M. J. , Requena G. , Rondon C. , Canto G. , Blanca M. , Mayorga C. 
Published: April 2009

SummaryBackgroundPyrazolones are a major cause of immediate IgE‐mediated reactions to drugs in many countries.ObjectiveThe aim of the study was to evaluate a group of patients with this type of reaction by basophil activation test (BAT), focusing on the influence of the time since the reaction on the rate of positive results.MethodsThe study included 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls. Patients were defined by skin testing or a drug provocation test and BATs with pyrazolones were carried out in all cases. Patients who were BAT positive were followed‐up for 30 months to establish the rate of decline in positive tests.ResultsBAT was positive in 28 (54.9%) cases. BAT sensitivity was higher in those who were skin‐test positive (85.7%) compared with those who were skin‐test negative (33.3%). The time between the initial reaction and this study was significantly shorter in those who were skin‐test positive (P=0.005) and those who were BAT positive (P=0.017). Follow‐up of the BAT‐positive patients showed a decrease over time, with 60% of these patients becoming negative after 6 months.ConclusionsBAT is a useful complement to skin testing for the evaluation of immediate allergic reactions to pyrazolones. Although not optimal, BAT sensitivity was also positive in patients with a negative skin test and it is a reasonable alternative in patients with severe reactions who may develop symptoms after skin testing. The time of performance of the test is critical to obtain a positive response.
Allergen dose dependency of the early‐ and late‐phase cutaneous response in the cynomolgus monkey
Authors: Tomkinson A. , Morton M. , Stevens L. , Bowden A. , Tepper J. 
Published: April 2009

SummaryBackground
Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics.Objective
Studies were performed to characterize the allergen‐induced cutaneous early‐ and late‐phase response (EPR and LPR) in the cynomolgus monkey.Methods
Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post‐injection, and skin biopsies were collected at 8–24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes.Results
The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post‐allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02).Conclusion
Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis.
The rise and rise ofStaphylococcus aureus: laughing in the face of granulocytes
Authors: Anwar S , Prince L R , Foster S J , Whyte M K B , Sabroe I 
Published: April 2009

SummaryRecent developments in the study of host–pathogen interactions have fundamentally altered our understanding of the nature of Staphylococcus aureus infection, and previously held tenets regarding the role of the granulocyte are being cast aside. Novel mechanisms of pathogenesis are becoming evident, revealing the extent to which S. aureus can evade neutrophil responses successfully by resisting microbicides, surviving intracellularly and subverting cell death pathways. Developing a detailed understanding of these complex strategies is especially relevant in light of increasing staphylococcal virulence and antibiotic resistance, and the knowledge that dysfunctional neutrophil responses contribute materially to poor host outcomes. Unravelling the biology of these interactions is a challenging task, but one which may yield new strategies to address this, as yet, defiant organism.
The effect of a mixotrophic chrysophyte on toxic and colony‐forming cyanobacteria
Authors: VAN DONK ELLEN , CERBIN SLAWEK , WILKEN SUSANNE , HELMSING NICO R. , PTACNIK ROBERT , VERSCHOOR ANTONIE M. 
Published: April 2009

Summary1. In order to test the effect of Ochromonas sp., a mixotrophic chrysophyte, on cyanobacteria, grazing experiments were performed under controlled conditions. We studied grazing on three Microcystis aeruginosa strains, varying in toxicity and morphology, as well as on one filamentous cyanobacterium, Pseudanabaena sp. Furthermore, we analysed the co‐occurrence of Ochromonas and Microcystis in natural systems in relation to various environmental parameters (TP, TN, DOC, temperature, pH), using data from 460 Norwegian lakes.2. Ochromonas was able to feed on all four cyanobacterial strains tested, and grew quickly on all of them. The chrysophyte caused net growth reductions in all three Microcystis strains (the very toxic single‐celled strain PCC 7806; the less toxic colony‐forming Bear AC and the less toxic single‐celled Spring CJ). The effect of Ochromonas was strongest on the Spring CJ strain. Although the effect of Ochromonas grazing on the growth of Pseudanabaena was relatively smaller, it also reduced the net growth of this cyanobacterium significantly.3. After 4 days of incubation with Ochromonas the total amount of cyanotoxins in the three Microcystis strains was reduced by 91.1–98.7% compared with the controls.4. Ochromonas occurred in similar densities across all 460 Norwegian lakes. Microcystis occurred only at higher TN, TP, temperature and pH values, although its density was often several orders of magnitude higher than that of Ochromonas. Ochromonas co‐occurred in 94% of the samples in which Microcystis was present.5. From our study it is not clear whether Ochromonas could control Microcystis blooms in natural lakes. However, our study does demonstrate that Ochromonas usually occurs in lakes with Microcystis, and our small scale experiments show that Ochromonas can strongly reduce the biomass of Microcystis and its toxin content.
Clusterin expression in cholestasis, hepatocellular carcinoma and liver fibrosis
Authors: Aigelsreiter Ariane , Janig Elke , Sostaric Julia , Pichler Martin , Unterthor Daniela , Halasz Judith , Lackner Carolin , Zatloukal Kurt , Denk Helmut 
Published: April 2009

Aims:  Clusterin shares functional properties with small heat shock proteins. In contrast to other heat shock proteins, it is present in the extracellular space. Its expression is altered in various diseases. The aim was to evaluate the presence and distribution of clusterin in liver diseases associated with cholestasis, in fibrosis and in hepatocellular carcinoma.Methods and results:  Tissue microarrays and biopsy materials were used to evaluate immunohistochemically the expression of clusterin in hepatocellular carcinoma, primary sclerosing cholangitis, primary biliary cirrhosis, mechanical cholestasis, drug‐induced cholestasis, liver fibrosis and cirrhosis. The presence of clusterin in human bile was assessed by Western blotting. Furthermore, real‐time reverse transcriptase‐polymerase chain reaction was performed on liver tissue with mechanical cholestasis. Clusterin colocalized with elastic fibres, but not with collagen, hepatocytes or bile duct epithelia. It was detected in bile plugs in cholestasis and hepatocellular carcinomas with pseudoglandular features within the lumina. Clusterin was demonstrated in bile by Western blotting and its mRNA was expressed in normal and cholestatic livers.Conclusions:  Clusterin may protect bile duct epithelium against offensive biliary components or inhibit precipitation of biliary proteins. The association of clusterin with elastic fibres could reflect an extracellular chaperone function by either protecting elastic fibres or shielding abnormal elastic material.
Antigen retrieval and primary antibody type affect sensitivity but not specificity of CD117 immunohistochemistry
Authors: Wong Newton A C S , Melegh Zsombor 
Published: April 2009

Aims:  To investigate the effects of antigen retrieval and primary antibody selection on specificity and sensitivity of CD117 immunohistochemistry.Methods and results:  A survey and literature review were performed to determine the most commonly used CD117 antibodies. Of six such antibodies, three (Neomarkers polyclonal RB‐1518, Novocastra monoclonal T595 and Santa Cruz polyclonal C19) were rejected as only suboptimal immunoreactivity was produced despite the use of various immunohistochemical protocols. Immunohistochemistry using the three remaining antibodies (Cell Marque polyclonal CMC766, Dako polyclonal A4502 and Epitomics monoclonal YR145) was performed, with and without (for Dako and Epitomics antibodies) antigen retrieval, on 32 gastrointestinal stromal tumours (GISTs) and on 139 neoplasms (comprising 24 neoplasm types) that are differential diagnoses for GIST and/or have been reported to express CD117. Antigen retrieval generally increased the sensitivity but did not alter the specificity of immunoreactivity with the three antibodies. The different antibodies showed variations in sensitivity, but did not stain different spectrums of neoplasm type. A small number of neoplasms showed scattered nuclear immunopositivity (particularly seen without antigen retrieval), which was regarded as representing cross‐reactivity.Conclusions:  Antigen retrieval and changing between the three antibodies tested affect sensitivity but not specificity of CD117 immunohistochemistry. Antigen retrieval does not produce false‐positive CD117 immunostaining.
Progressive cellular response in the lamina propria of the colorectal adenoma–carcinoma sequence
Authors: Cui Guanglin , Yuan Aping , Vonen Barthold , Florholmen Jon 
Published: April 2009

Aims: The lamina propria is inevitably involved in epithelial transformation. The aim was to evaluate the dynamic cellular changes in the tumour lamina propria throughout the colorectal adenoma–carcinoma sequence.Methods and results: Using immunohistochemistry and double immunohistochemistry, we examined lamina propria cellular changes in 41 colorectal adenomas, 25 colorectal cancers and 15 control tissues. The results showed that the proliferation labelling index in lamina propria cells began to increase in the precancerous lesions (adenomas) and became even higher in the colorectal cancers; these proliferative cells were primarily identified as myofibroblasts and lymphocytes. Phenotypic analysis revealed gradually increasing lymphocytic infiltration in both the lamina propria and adenomatous epithelium, as well as myofibroblasts in the lamina propria. However, the intraepithelial macrophage density also showed a tendency to increase gradually. Furthermore, cyclooxygenase‐2‐expressing cell density and microvessel density gradually increased in the tumour lamina propria throughout the adenoma–carcinoma sequence.Conclusions: Progressive cellular responses in the lamina propria could be involved in the adenoma–carcinoma transition.
Nuclear and membrane expression of the angiogenesis regulator delta‐like ligand 4 (DLL4) in normal and malignant human tissues
Authors: Martinez Juan Carlos , Müller Marcus M , Turley Helen , Steers Graham , Choteau Ludovine , Li Ji‐Liang , Sainson Richard , Harris Adrian L , Pezzella Francesco , Gatter Kevin C 
Published: April 2009

Aims:  Delta‐like ligand 4 (DLL4) is one of five known Notch ligands in mammals and interacts predominantly with Notch 1. DLL4 is induced by vascular endothelial growth factor (VEGF) and acts downstream of VEGF as a ‘brake’ on VEGF‐induced vessel growth, forming an autoregulatory negative feedback loop inactivating VEGF. This action was believed to occur only in vascular development, raising hopes that DLL4 could be a specific drug target for controlling vessel growth in tumours and other pathological conditions. Our aim was to pursue this by raising a monoclonal antibody to the internal domain of DLL4 and assess its distribution in normal and malignant tissues in comparison with antibodies against the external domain of DLL4.Methods and results:  The anti‐DLL4 monoclonal antibody was raised using conventional mouse hybridoma techniques. The antibody has been fully characterized by Western blotting and transfectant immunostaining. It has also been comprehensively compared with other antibodies against both the internal and external domains of DLL4. The antigen is widely expressed on human tissues not only on endothelium but also on epithelium and stromal cells. Indeed, in our comprehensive survey only pulmonary alveoli failed to express DLL4. Of a wide range of malignancies, most also expressed DLL4 on tumour cells with a predominantly cytoplasmic pattern, although a number also displayed nuclear positivity.Conclusions:  Contrary to previous beliefs, DLL4 is widely distributed in tissues other than vessels including many malignancies. Furthermore, the molecule is internalized on binding its receptor and often transported to the nucleus. These findings raise many interesting possibilities for further study of DLL4 and its potential as a therapeutic target.
Improvement of the antimicrobial activity of edible mushroom extracts by inhibition of oxidative enzymes
Authors: Santoyo Susana , Ramírez‐Anguiano Ana Cristina , Reglero Guillermo , Soler‐Rivas Cristina 
Published: April 2009

AbstractThe antimicrobial properties of water and methanol extracts from edible mushroom species were evaluated against Escherichia coli, Staphylococcus aureus and Candida albicans. Only water extracts from Lentinus edodes, Boletus edulis and Pleurotus ostreatus showed antimicrobial activity against all tested microorganisms. Their methanol extracts showed antimicrobial activity too but to a lower extent than the water extracts. Moreover, methanol extracts from Cantharellus cibarius and Lactarius deliciosus, showed also a slight activity against S. aureus. However, the antimicrobial properties of the mushroom water extracts might have been always underestimated considering that when oxidative enzymes inhibitors were added before the experimental assay, the water extracts from C. cibarius, L. deliciosus, Agaricus bisporus and Amanita cesarea showed important antimicrobial activity and the water extracts of B. edulis and P. ostreatus increased their activity. These enzymes might degrade potential antimicrobial compounds during the extraction procedure or interfere with their activity.